Detection of Clostridium botulinum toxin by local paralysis elicited with intramuscular challenge. Clostridium botulinum toxin can be identified by a characteristic, acute local paralysis that follows its injection into the gastrocnemius ("calf" muscle) of mice. The local botulism can be elicited with slightly less than one-tenth the toxin amount that is needed to kill mice by the intraperitoneal (i.p.) challenge route. The practical sensitivities of the intramuscular (i.m.) versus i.p. tests are about equal, however, because maximum sample volume injectable i.m. is 0.1 ml as compared to the 0.5-ml range that can be given i.p. i.m. injection of 10 or more mouse i.p. mean lethal doses causes paralysis in about 1 h, and an i.m. injection of about 0.5 i.p. mean lethal doses causes paralysis in 3 to 4 h. Toxin neutralization by homologous type of antitoxin only can be demonstrated with an incubated mixture of toxin and antitoxin. Although not as convenient as the i.p. method for routine use to detect botulinum toxin, the i.m. method has characteristics which could make it a useful supplement to the presently accepted i.p. procedure.


Formation of methyl mercury by bacteria. Twenty-three Hg2+-resistant cultures were isolated from sediment of the Savannah River in Georgia; of these, 14 were gram-negative short rods belonging to the genera Escherichia and Enterobacter, six were gram-positive cocci (three Staphylococcus sp. and three Streptococcus sp.) and three were Bacillus sp. All the Escherichia, Enterobacter, and the Bacillus strain were more resistant to Hg2+ than the strains of staphylococci and streptococci. Adaptation using serial dilutions and concentration gradient agar plate techniques showed that it was possible to select a Hg2+-resistant strain from a parent culture identified as Enterobacter aerogenes. This culture resisted 1,200 mug of Hg2+ per ml of medium and produced methyl mercury from HgCl2, but was unable to convert Hg2+ to volatile elemental mercury (Hg0). Under constant aeration (i.e., submerged culture), slightly more methyl mercury was formed than in the absence of aeration. Production of methyl mercury was cyclic in nature and slightly decreased if DL-homocysteine was present in media, but increased with methylcobalamine. It is concluded that the bacterial production of methyl mercury may be a means of resistance and detoxification against mercurials in which inorganic Hg2+ is converted to organic form and secreted into the environment.


Vitamin B12 production by a methanol-utilizing bacterium. Vitamin B(12) production by a newly isolated strain of a methanol-utilizing bacterium was studied. The maximal yield of the vitamin, 2.6 mg/liter of medium was attained by optimization.


Fermentative accumulation of guanosine polyphosphates by Brevibacterium ammoniagenes. Guanosine-3'-diphosphate-5'-monophosphate (3.35 mg/ml), guanosine-3'-diphosphate-5'-diphosphate (MSI) (5.21 mg/ml), and guanosine-3'-diphosphate-5'-triphosphate (MSII) (0.82 mg/ml), in addition to guanosine 5'-monophosphate, guanosine 5'-diphosphate, and guanosine 5'-triphosphate, were accumulated by microbial conversion of 5'-xanthylic acid with a mutant of Brevibacterium ammoniagenes.


Gamma-aminobutyric acid pathway and modified tricarboxylic acid cycle activity during growth and sporulation of Bacillus thuringiensis. Enzymatic analyses of Bacillus thuringiensis extracts suggest that a modified Krebs tricarboxylic acid cycle (without alpha-ketoglutarate dehydrogenase) can operate during sporulation in conjunction with the glyoxylic acid cycle and the gamma-aminobutyric acid pathway.


Isolation of acetyl T-2 toxin from Fusarium poae. Acetyl T-2 toxin (3,4,15-triacetoxy-8-isovaleroxy-12,13-epoxy-delta9-trichothecene) was isolated and characterized as a naturally occurring emetic trichothecene from liquid cultures of Fusarium poae (NRRL 3287). Acetyl T-2 toxin was shown to be much less toxic than T-2 toxin in pigeon assays.


Carbon monoxide and heart attacks.

Carbon monoxide and heart attacks. A study of the relationship between carbon monoxide exposure and heart attacks was conducted in Baltimore. There was no evidence of clustering of either myocardial infarction or sudden ASHD on a specific day, nor was there correlation between the number of cases per day and ambient CO levels. Postmortem HbCO levels were slightly higher in ASHD sudden deaths than in sudden deaths due to other causes. Any differences were probably primarily due to cigarette smoking. Cigarette smokers who died suddenly due to ASHD had substantially higher postmortem HbCO levels than nonsmokers. Practically all of the elevated HbCO levels could be related to cigarette smoking or specific environmental exposure. There were no differences between HbCO levels in ASHD sudden death patients and in living controls. There was also no relationship between cardiac pathologic findings and postmortem HbCO levels among patients dying suddenly of ASH.


The lead content of teeth. Evidence establishing new minimal levels of exposure in a living preindustrialized human population. Teeth were collected from populations differing in their degree of industrialization and from prehistoric populations. Lead analysis of dentine revealed that in contemporary teeth the lead level was related to the degree of industrialization and that in prehistoric teeth very low concentrations of lead were present. Because tooth lead reflects the body burden of lead, this result suggested that the prehistoric populations and modern nonindustrial populations were exposed to environments low in lead. Teeth from a contemporary population of nonindustrialized Indians of the Lacandon forest in Mexico contain lead in concentrations comparable with those of the prehistoric populations. Comparison of the Indian teeth with teeth from a modern industrial population reveals a 45-fold difference in median tooth lead level. This finding lends support to the hypothesis that high levels of urban lead pollution result in elevated body burdens of lead.


Heavy metals in normal Japanese tissues. Amounts of 15 heavy metals in 30 subjects. To obtain the usual values of arsenic, beryllium, bismuth, cadmium, chromium, cobalt, copper, mercury, methyl mercury, manganese, molybdenum, nickel, lead, antimony, vanadium, and zinc in the normal human body, the amounts of 15 metals were determined in 15 male and 15 female Japanese cadavers (average weight, 55 kg [121 lb]). The content of metals found ranged as follows: Zn, 1,800 mg; Cu, 65 mg; Cd, 35 mg; Pb, 25 mg; Mn, 8 mg; Ni, 6 mg; Cr, 4 mg; Hg, 3 mg; Sb, 0.7 mg; MeHg, 0.4 mg. Cadmium and mercury were higher in Japanese blood than in blood of other people. Cadmium and mercury were absorbed by the metabolic tissues; Cr, Ni, and Pb showed higher concentration in tissue exposed to the environment. Concentrations of Cd, Pb, and Hg tended to be higher in females, and Cr Cu, MeHg, and Mn concentrations tended to be higher in males.


Age, smoking inhalation, and pulmonary function. This study examined the relative effects of age and smoking on pulmonary function. Smoking was measured by six smoking variables, taken singly and as a composite. Subjects were 1,516 male participants in the Normative Aging Study. A stepwise multiple regression with vital capacity (VC) and forced expiratory volume at one second (FEV1.0) as the criteria accounted for 24.4% and 28.3% of the variance, respectively. Two-way analyses of variance showed that the age decline in pulmonary function was substantially greater for high inhalers than it was for low inhalers or nonsmokers. Age and the inhalation index were also noticeably and independently related to a decline in pulmonary function.


A soluble cadmium-binding component in rat and dog spleen. The spleens of cadmium-treated Sprague-Dawley rats and mongrel dogs were examined for cytoplasmic soluble cadmium-binding moieties following the cessation of parenteral cadmium exposure. Cell homogenates prepared in 0.25M sucrose were centrifuged at 29,000 g and the supernatant fractionated on a fractionating column (Sephadex G-75). Ultraviolet absorbing peaks that showed characteristically high 250-nm to 280-nm absorbences were further analyzed for cadmium content by atomic absorption spectrophotometry. Cadmium-binding fractions isolated from the spleens of both species were characteristically similar to rat kidney metallothionein-like substances isolated and identified by the same procedure. Molecular weights for the canine and rat spleen cadmium-binding components were estimated at 14,783 +/- 343 and 13,916 +/- 490, respectively. These preliminary data indicate the production and persistence of soluble metallothionein-like substances in spleen that bind and retain cadmium ions long after cadmium exposure has ceased.


Asbestos, smoking, and laryngeal carcinoma. This study was designed to examine the relationship between exposure to asbestos and laryngeal cancer. A retrospective study of 43 pairs of patients with laryngeal cancer and their matched controls examined a number of variables, including smoking, exposure to asbestos, and other occupational factors. Patients with laryngeal cancer and the controls were matched for age, sex, and place of residence. The data indicate a substantial association between asbestos exposure and laryngeal cancer. Cigarette smoking was also associated with the disease, although the strength of association was not as high as that for asbestos. Exposure to uranium, chromium, nickel, cobalt, arsenic, x-rays, and alcohol did not appear related to later development of carcinoma of the larynx. We conclude that exposure to asbestos and cigarette smoking are potent factors in the development of this disease.


Selection of patients and operative approach in primary aldosteronism. A system for discriminating between adrenal adenoma and hyperplasia based on the levels of aldosterone production, plasma renin concentration, severity of electrolyte disturbances, plasma aldosterone patterns during recumbency and after assuming erect posture, and 131I-19-iodocholesterol scan has been developed. Indicated for operation are patients with adenomas whose elevated blood pressure cannot be continuously controlled with usual doses of medication and patients with documented deterioration of target organ function. Adrenalectomy has been performed 83 times in 81 patients with a diagnosis of primary hyperaldosteronism. Results of excision of adrenal adenomas have been excellent with significant lowering of blood pressure in all cases and cure of hypertension in over 60%. Results of total or subtotal adrenalectomy for hyperplasia have been poor with almost all patients still requiring medication for hypertension. Adenomas have always been unilateral, and usually can be localized so that unilateral exploration is curative. Therefore, we have tried to distinguish preoperatively between adenoma and hyperplasia. Anterior transperitoneal adrenalectomy has been effective with few complications, and no postoperative hypercortisolism after unilateral adrenalectomy for adenoma. The unilateral extraperitoneal approach gives shorter morbidity and potentially fewer serious complications.


The early diagnosis of medullary carcinoma of the thyroid gland in patients with multiple endocrine neoplasia type II. Pentagastrin is a potent stimulator of thyrocalcitonin secretion from "C" cells. Since medulllary carcinoma of the thyroid gland (MCT) is a tumor composed of "C" cells, pentagastrin was used to screen a large kindred with multiple endocrine neoplasia type II (MCT, pheochromocytoma (s), and parathyroid hyperplasia). Four children with no thyroid abnormalities evident on physical examination, with negative thyroid scans, and with normal levels of plasma thyrocalcitonin both before and after calcium infusion, were found to have elevated peripheral levels of this hormone following pentagastrin injection. All four children were found to have very small foci of MCT, in both thyroid lobes at the time of total thyroidectomy. Pentagastrin stimulation used conjointly with selective catheterization of the inferior thyroid vein provided even greater diagnostic accuracy in detecting elevations in thyrocalcitonin secretion. This test has great diagnostic utility, especially in screening patients with multiple endocrine neoplasia type II.


Glycerol: major contributor to the short term protein sparing effect of fat emulsions in normal man. Intravenous fat emulsions have been advocated as acceptable alternatives to hyperosmolar glucose solutions in parenteral nutrition. The ability of a fat emulsion (soy bean oil suspended in glycerol) to produce nitrogen sparing in the absence of nitrogen intake was examined in normal man. The protein conservation obtained by the fat emulsion can be duplicated by the infusion of glycerol alone in the same amount as that available from the fat emulsion.


Body composition in morbidly obese patients before and after jejunoileal bypass. A clinical and body compositional study has been made of 150 patients with morbid obesity and their responses to four different dimensional alterations of jejunoileal bypass. Total body potassium was estimated by measuring 40K with the whole body counter and total body water by tritiated water dilution. Body compositional data derived from these measurements were compared in the 4 groups during followup periods up to 4 years and related to clinical results. Initially, patients were two or more times overweight due to excess (60 to 65%) body fat and increased hydration (21%) of lean tissues. The 80 end-to-end jejunoileal bypass procedures of Groups 3 and 4 (30 cm jejunum to 15 or 20 cm ileum) had better weight losses and clinical results in followup were rated "good" in 60% and 81% respectively. These results were accompanied by a greater degree of improvement in body composition than was observed in the other groups under study.


Optimizing results of gastric bypass.

Optimizing results of gastric bypass. Gastric bypass is an extensive gastric exclusion operation used in patients who are more than twice their ideal weight. Most of the early postoperative deaths observed in 3% of 442 patients during the initial 9 years, could have been prevented by more attention to operative technique and early recognition and correction of leaks when they occurred. The best weight loss can be produced by adherence to three components of the operation: 1) Bypass of stomach and duodenum, 2) a small fundic segment and 3) a small (12 mm diameter) gastroenterostomy stoma. The average patient of 142 kg can expect to have a weight of around 107 kg at 1 year 103 kg at 5 years. Revision of a large stoma to a smaller (9 mm) diameter can induce further weight loss in some patients whose loss has been inadequate. The 1.8% incidence of stoma ulceration may be lowered with the present emphasis on a smaller fundic pouch, but could increase with longer observation. Presently stoma ulcers occur once in every 140 patient years at risk.


Nutritional consequences of total gastrectomy. Nutritional status was investigated in 10 patients who had previously  undergone total gastrectomy without evidence of malignancy. The ability of these patients to ingest and absorb adequate amounts of nutrients was examined. Metabolic balance studies were also performed to discover how effectively these patients could accumulate and use the absorbed nutrients. In the controlled hospital situation, the amount of food ingested was greater than the amount required for maintenance of Ideal Body Weight. Although mild malabsorption of fat and nitrogen was documented, weight gain and positive nitrogen balance occurred. In direct contrast, food intake significantly decreased when the patients returned to their home environment. While severe malabsorption may contribute to malnutrition in the individual patient, the most common mechanism responsible for postoperative malnutrition was inadequate intake. In the occasional patient with severe malabsorption, the universal demonstration of jejunal anaerobic bacterial overgrowth offers important therapeutic implications. The relative importance of pancreatico-biliary insufficiency in promoting malabsorption remains to be determined. Construction of a Hunt-Lawrence jejunal pouch was not found to favorably affect caloric intake, weight gain, degree of malabsorption, or dumping symptoms. Although some degree of malnutrition does result from total gastric resection, in most cases it is mild and potentially correctable. Avoidance of indicated total gastrectomy due to fears of progressive postoperative malnutrition is unwarranted.


Revascularization in treatment of mesenteric infarction. This study compares results of primary revascularization with primary intestinal resection in treatment of acute mesenteric artery occlusion in 48 surgical patients. All cases were verified by surgical exploration, angiography or autopsy. Fifteen occlusions were caused by mesenteric thrombosis and 33 by superior mesenteric artery embolization. Primary revascularization was done in 6 of 15 patients with arteriosclerotic mesenteric thrombosis. Total bowel salvage was achieved in 4 patients but no patient with mesenteric thrombosis treated by any method survived long term. Primary embolectomy was done in 11 patients with superior mesenteric artery embolization. Ttoal bowel salvage was achieved in 8 patients. Three of 11 patients died. Primary exploration and/or resection was done in 11 patients; 9 died. All 11 umoperated patients died. A continuation of attempts at mesenteric revascularization is advocated.


Ex vivo renal artery reconstruction.

Ex vivo renal artery reconstruction. Ex vivo renal artery reconstruction and autotransplantation is a relatively recent addition to the surgical armamentarium for renal vascular hypertension. Ten consecutive patients were considered for this surgical therapy and form the basis of this communication. The patients were treated by a combination of methods including bilateral ex vivo reconstruction, unilateral in situ and contralateral ex vivo reconstruction, and unilateral ex vivo reconstruction and contralateral nephrectomy. Replacement of the diseased segment of the renal artery in all ex vivo reconstruction consisted of arterial autografts including hypogastric artery, splenic artery, common iliac, and external iliac artery. In the ex vivo reconstruction, the ureter was either left intact or was transected and reconstructed by standard ureterovesicle implantation. After surgery all patients became normotensive without antihypertensive medication. Although this is a relatively small series, the uniform good results in these patients with extensive disease suggest that ex vivo renal artery reconstruction is a safe and effective method of treatment. Thus, it should be more widely applicable, expecially in those patients with renal vascular disease who were previously thought to be inoperable or eligible for nephrectomy only.


Treatment of peptic esophageal stricture with combined fundic patch-fundoplication. Forty-five patients treated for peptic esophageal stricture by combined fundic patch-fundoplication are reviewed. The operation afforded an acceptable result in 87% of the patients. There has been no operative mortality. The stricture represents transmural fibrosis of the distal esophagus. The fibrosis interferes with the physiologic function of the LES preventing receptive relaxation. This, however, does not affect the postoperative ability to swallow.


Lesions of the segmental and lobar hepatic ducts. Despite reports to the contrary, unobstructed drainage of 50% of an otherwise normal liver through either the right or left uninfected hepatic duct is adequate to restore normal liver function, even if the obstructed lobe remains in place. An undrained liver lobe, if present, may require no further treatment. As long as it is completely obstructed and uninfected, it will undergo a progressive asymptomatic atrophy. Cholangitis invariably develops behind a partial lobar ductal obstruction, producing jaundice, pruritus, and fever. Unless unobstructed, uninfected biliary flow can be achieved through a segmental or lobar duct, it is better that the duct be completely obstructed and the affected liver parenchyma allowed to atrophy, provided there is normal biliary flow from the residual 50% of liver. This concept is important in the management of injured anomalous segmental or lobar hepatic duct and in the palliative treatment of bile duct carcinoma. Localized intrahepatic infections communicating with abnormal biliary ducts will require hepatic resection of the infected parenchyma and ducts for cure. The abnormality may be saccular dilatation of the intrahepatic ductal system with abscess formation or intrahepatic abscess associated with stenosis of the ductal system from trauma to the duct, to the duct and liver, or to retained intrahepatic stones. Diffusely situated intrahepatic abscesses secondary to ductal abnormalities can be treated with systemic antibiotics, local drainage of a dmoninant abscess, and efforts to improve biliary drainage.


Cholecystokinin metabolism in man and dogs. We have developed a sensitive, specific and reproducible radioimmunoassay for cholecystokinin (CCK) with which basal levels of CCK of between 400-800 pg/ml have been measured in normal man, in patients with diabetes and with duodenal ulcer disease, and in normal dogs. After a meal, circulating levels of CCK rose to 1000-1200 pg/ml in human subjects. Release of CCK was more rapid in diabetic and duodenal ulcer patients than in normal subjects, but elevated postprandial levels persisted much longer in normal subjects. Patients with the Zollinger-Ellison syndrome had elevated values of cholecystokinin which rose after a meal. Lack of correlation between elevated basal levels of gastrin and CCK in patients with the Zollinger-Ellison syndrome suggest that the hypercholecystokininemia may be absolute. The disappearance half-time of exogenous CCK was about 21/2 minutes in normal subjects as well as in diabetic and duodenal ulcer patients. Studies in dogs demonstrated no uptake of basal levels of cholecystokinin by the kidney; on infusion of exogenous CCK-33, the kidney extracted 43% of the total CCK presented and 56% of the integrated CCK. We conclude that: 1) circulating basal and postprandial levels of CCK may be measured in a reproducible fashion; 2) postprandial release of CCK is more rapid in diabetic and duodenal ulcer patients than in normal man; 3) the disappearance half-time of exogenous CCK in man and dogs is about 21/2 minutes; 4) the kidney is a major site for uptake of CCK.


Risk of recurrence of colon polyps.

Risk of recurrence of colon polyps. At Wood Veterans Administration Center, 268 patients who had a polypectomy have been followed up to 20 years with semiannual proctosigmoidoscopic and barium enema examinations. For the present review of benign polyp disease, patients having coexisting carcinoma, chronic inflammatory disease, and those lost to followup have been excluded; 154 patients followed for a mean of 7 years comprise the study group. Thirty per cent of patients developed recurrent polyps. The risk of recurrence during the first year was 16 times that expected in a population of similar age and sex, but thereafter diminished steadily. After 48 months risk of polyp recurrence was little higher than the incidence expected in a normal population. Neither patient age, presenting symptoms nor the site or size of the initial polyp(s) were of any prognostic value regarding recurrence. Patients presenting with a villous adenoma or with more than 3 polyps had a significantly increased risk of recurrence may persist indefinitely. The overall incidence of colonic carcinoma may have been increased, but the location of subsequent cancer was not related to the site of a previously excised polyp.


Definitive treatment of "malignant" polyps of the colon. There has been an unremitting rise in incidence of colonic cancer in this country with no recent improvement in cure rate. As a result the evolution of colorectal cancer has been the focus of considerable attention with an enlarging body of evidence pointing to the common neoplastic polyp as a precursor to malignancy. "Neoplastic" polyps include "adenomatous polyps," "villous adenomas" and, lately recognized, "villo-glandular polyps." Experience with endoscopic removal of over 2,000 colonic polyps (with no mortality) has introduced two questions of prime concern to the surgeon: (1) What constitutes  clinical malignancy in a polyp? AND, (2) When should laparatomy supplant or follow endoscopic removal? Eight hundred and ninety-two consecutive adenomatous (tubular), villous, villoglandular (villo-tubular) and "polypoid cancer" polyps are analyzed, 855 of which have been followed for 6 months to 4 years. Support is offered to the concept that villous and tubular growth patterns are merely variants of a similar base disturbance in cell renewal. Superficial cancer (carcinoma-in-situ) occurred in 6.6% of neoplastic polyps and represents no threat if the polyp is completely removed. Only when the cancer penetrates the muscularis mucosae should it be regarded as "invasive." The term "malignant polyp" should be reserved for this form. Invasive cancer was found in 5.0% of neoplastic polyps in this series. Only in this group need the question of further surgical intervention be raised. Major considerations influencing a decision for subsequent laparotomy are polyp size and gross morphology (i.e. sessile or pedunculated), histologic type (of the polyp and of the cancer itself), adequacy of clearance between depth of invasion and plane of polyp resection, and the patient's age and general condition. These are analyzed. Twenty-five of 46 patients with "malignant polyps" were subjected to abdominal exploration: 17 showed no residual cancer, whereas 8 (5 with recognized incomplete endoscopic removal) had tumor in the bowel wall. Of the remaining 21 patients, for whom endoscopic polypectomy alone was deemed appropriate, none have shown residual or recurrent cancer on clinical and endoscopic followup. Colonoscopy appears to be a most promising approach in terms of the goals of cancer programs, offering both prophylaxis and opportunity for treatment at a favorable stage of disease.


The breeding and feeding of thoracic surgeons. A brief recapitulation of the history of The American Board of Thoracic Surgery reveals that in its 27-year lifetime it has strived to improve the quality of thoracic surgical training. Most recently the Board has decided that candidates from unapproved programs who begin their training after June 30, 1976, will be ineligible for the Board examination. A population of approximately 2,000 thoracic surgeons should be more than adequate to provide patient care in the United Sates. At the present rate of certification the thoracic surgeon population would number about 4,000 within 25 years. With the birth rate in the United States nearing zero population growth, the number of new thoracic surgeons trained and certified each year must be limited, and it is imperative that the profession rather than the federal government be in control of this. Continuing education and evaluation of clinical competence will soon be required in the specialty of thoracic surgery. Cooperation among the major groups concerned with thoracic surgery is necessary for successful development of continuing education and the necessary evaluation of competence.


Esophageal repair following late diagnosis of intrathoracic perforation. Multiple techniques, often complex, have been used to repair the esophagus following spontaneous, instrumental, or postsurgical perforation, especially  when the diagnosis of perforation has been delayed. We have closed such perforations by wrapping a pedicled pleural flap around the esophagus, suturing it firmly over the area of leakage and around its margins. Due to inflammatory changes secondary to perforation, the flap is thickened and easily applied. Four patients were treated with this technique with success in every case. One patient with achalasia had sustained perforation three days prior to repair, another 30 hours following leakage at an esophageal suture line, the third 20 hours following esophagoscopic extraction of a necrosing foreign body, and the fourth 8 hours following hydrostatic bougienage for achalasia.


Clinitest burns of the esophagus.

Clinitest burns of the esophagus. Five children developed esophageal stricture from the ingestion of a Clinitest tablet. The sodium hydroxide contained in these tablets induced a short, dense stricture that was resistant to dilation and necessitated resection. In all patients primary esophageal resection with end-to-end anastomosis was technically possible. Four of the patients needed two or more dilations postoperatively and 1 still requires dilation. Prevention of accidental ingestion by use of a childproof container and parental education about the caustic nature of Clinitest are both essential to eliminate this child health hazard.


Polypoid sarcomas of the esophagus. A rare but potentially curable neoplasm. Five patients with polypoid esophageal sarcoma are reported. All had dysphagia similar to that occurring in epithelial carcinoma of the esophagus. The clinical diagnosis of sarcoma was suspected when barium swallow showed a large polypoid lesion. Biopsy was often inconclusive concerning the nature of the lesion except to identify it as a neoplastic process. In spite of their large size, the tumors remained superficial within the esophageal wall. Nodal or distant organ metastasis was absent in 4 of the 5 patients. The histology of these tumors suggests that so-called carcinosarcoma is an epithelial carcinoma of the esophagus with varying amounts of spindle cell features and should be considered separately from sarcoma arising from mesenchymal tissue. Unlike carcinoma, esophageal sarcoma has a favorable prognosis following radical resection, and recent advances in esophageal surgery have decreased the mortality and morbidity of esophagectomy.


Ventricular fibrillation without left ventricular venting. Observations in humans. Pressures were measured in the heart and great vessels of 52 patients who underwent coronary revascularization. In 25 patients the left ventricle was vented during fibrillation; in the others a vent was not used. Samples for blood gas analysis were obtained twice during fibrillation from the aorta, left atrium, pulmonary artery, and right atrium. Left ventricular venting was found to be effective in keeping mean left heart pressure below 10 mm Hg, although temporary incompetence of the aortic valve or malfunction of the vent occasionally caused higher pressures. Vent use led to air embolism in the aorta in 16% of the patients. In the nonvented patients mean left heart pressures remained between 10 and 20 mm Hg. However, higher values were frequently observed. Blood gas analysis demonstrated that without venting, retrograde pulmonary flow occurred during fibrillation. No abnormality was encountered that could be related to nonventing.


Experimentally reversed pulmonary blood flow. Implications for the surgical management of complex forms of congenital heart disease. Blood flow to the right lung was reversed in 28 dogs, 14 of which survived more than 1 month. Four successful long-term survivors (1 years to 4 years 7 months) were repeatedly studied by cardiac catheterization, angiography, and ventilation/perfusion scans as well as hemodynamically when they were killed. Hemodynamics and gas transfer were normal up to 4 1/2 years after the procedure, and the histology of the right lung was essentially normal. The application of reversed pulmonary blood flow is proposed in the surgical management of forms of congenital heart disease in which the right ventricle is diminutive. The procedure consists of repartitioning of the atria to allow venous blood to flow into the lung through the pulmonary veins and exit to the left atrium through the pulmonary artery.


Local cardiac hypothermia for myocardial protection during correction of congenital heart disease. Eighty-eight operations for correction of intracardiac congenital heart defects were performed using local cardiac hypothermia for protection of the ischemic myocardium. Twenty-six patients underwent repair of tetralogy of Fallot, 23 had patch closure of ventricular septal defect, 24 had correction of various types of congenital aortic stenosis, and 15 were operated upon for other complex lesions. The overall operative mortality was 5.6%. Ischemia times ranged from 9 to 119 minutes (mean, 48 minutes). Ischemic arrest protected by local cardiac hypothermia provides an optimal operative field, permitting repair of uncomplicated intracardiac defects in a precise, unhurried manner. No hemodynamic abnormalities attributable to the technique were encountered.


Ruptured ductus arteriosus. Aneurysm in an infant. Report of a survivor. The diagnosis of a large ductus arteriosus aneurysm was made in a 3 1/2-month-old infant by cardiac catheterization following massive hemoptysis. Prompt surgical correction accounted for the patient's survival. Differential diagnosis of an intrathoracic mass should include a ductus arteriosus aneurysm even in the newborn period.


Congenital coronary artery- cardiac chamber fistula. Review of operative management. Eight patients who had surgical correction of coronary artery-cardiac chamber fistula at our center and 163 from a review of the literature are presented. The patients are usually asymptomatic, and the diagnosis is suspected by observing a continuous cardiac murmur. Electrocardiographic findings are nonspecific. Angina pectoris or electrocardiographic evidence of severe ischemia are surprisingly uncommon since coronary artery steal syndrome is also rare. Cardiac catheterization with angiocardiography is required to establish the diagnosis and identify the involved coronary artery and the cardiac chamber into which the fistula terminates. Left-to-right shunt flow is usually low (average Qp/Qs = 1.5). Indications for operation are not precise. If there should be a large shunt flow (2.0) and symptoms of heart failure are present, the decision to operate is clearly justified. This situation is unusual, and operation is nearly always performed in an asymptomatic patient in whom the fistula is closed to prevent future symptoms or complications. The operation chosen is generally interruption of the fistula by direct ligation. Sometimes cardiopulmonary bypass is required. The results are good, with low morbidity (3.6% myocardial infarction) and low mortality (2%) justifying the operation, to be carried out prophylactically even in asymptomatic patients.


[Venous drainage of the heart with special references to the excito-conduction system]. The venous drainage of the human heart, bovine, the dog's and the cat's was analyzed and classified; in area as well as in depth; establishing relations within the venous systems, with the cardiac cavities and with the conduction cardiac system. The studying techniques, coronariographic, cuts in series, as well as disection, were used in all the hearts. Coronary venous ligations were done at various levels and also thromboflebitis at various levels, in order to demonstrate the function of the venous drainage of the heart, as a "venous-unity" and with a great compensating capacity. It is demonstrated that disturbing the venous drainage of the success-conduction system gives place to blockades of various degrees.


[Role of calcium in the regulation of syncytial formation and the formation of creatine kinase during the development of muscle in the absence of creatine]. 1. It is demonstrated for the first time that typically elongated chick myotubes, with more than 20 nuclei per fiber and creatine kinase, appear in cultures fed all time with partially defined auto-conditioned medium. 2. It was found that the skeletal muscle enzyme of the chick embryo is independent of the presence of creatine and consequently is another constitutive enzyme like the creatine kinase of the early embryonic chick heart. 3. Calcium elicited the activity of the enzyme and promoted fusion of myoblasts in a creatine-free partially defined medium, in the absence of embryo extract. 4. It is suggested that creatine kinase is a dual molecule, working as an ATPasa in the absence of creatine with H2O as the nucleophilic reagent. 5. Alternatively, it is possible that creatine kinase can be synthesized and localized in advance to the advent of creatine in myocardial and skeletal muscle cells.


[Familial occurrence of Wolff-Parkinson-White syndrome. Report of a family group and review of the literature]. A family group of nine members was studied, two of which had W-P-W syndrome; the father type A; and the son type B. These two patients were studied from the clinical electrocardiographic and vectocardiographic point of view; and they were subject to hisian electrogram recordings. The atrial-ventricular conduction under basal conditions and during atrial stimulation is analyzed. In the first case, potential H is registered after the beginning of delta wave of the ventricular complexes in lead II. In th second case, atrial-ventricular conduction can only occur through the abnormal via (no H potential and register of delta wave in the periferial simultaneous lead), or only through the normal via (evidence of potential H with a normal H-V interval and no delta wave in the periferial line of control). The bibliography of the observation that in most family groups described up until now, there is a good correlation concerning sex. This gives the impression to be a genetic disorder linked to sex.


[Electrophysiology of pacemakers by demand. Critical analysis]. The adequate interpretation of cardiac arrhythmias should be done in context with the clinical facts. In case of arrhythmias induced by pacemakers, it is essential to have detailed information about the characteristics of the electronic instrument. This paper shows, that only with precise information about the electrophysiological facts of a certain instrument, it is possible to diagnose the origin of an arrhythmia, its significance related to normal function or disfunction of the apparatus and the proper measures can be taken for correcting the disorder. Examples of clinical cases have been presented, and undoubtedly a growing improvement in the elaboration of the electronic instruments, will enrich, the already ample field of cardiac arrhythmias. All of it will lead to an undoubtful benefit for patients, medical personnel who are involved in the electric treatment of the disturbances in rhythm and conduction.


[Aortapulmonary shunt. Apropos of 4 cases]. Four cases of aorto-pulmonary window are presented, diagnosed in the Section of Pediatric Cardiology during the last six years. The results obtained from clinic; ECG; X-ray; hemodinamic and angiographic studies are described. All of them were clinically diagnosed as left to right shunt through a persistent ductus arteriosus in two cases and of VSD the other two. The final diagnosis was made through cardiac cateterization in one case and at surgery in three. Two of the cases showed additional alterations, in one case it was a PDA, and the other a valvular aortic stenosis. All of them were operated, three successfully and one died immediately after operation. We consider that the study of this relatively rare cardiopaty deserves special attention, because of the similarity to other forms of left to right shunts. We insist on its difficult clinical dianose and the need of making a early diagnosis to do corrective surgery.


[Obstructive pulmonary emphysema. Evolution of various parameters of pulmonary function and its correlation]. A follow-up study was carried on in a series of 20 patients with chronic obstructive pulmonary disease. The parameters analyzed were forced expiratory volume in the first second (FEV1), maximum voluntary ventilation (MVV), forced expiratory flow (FEF), vital capacity (VC), and diffusing capacity of lung (DL). Considering the importance of the parameter changes observed, each of these parameters were divided in three groups. The period of observation was of two and a half years in 9 patients, and between two years and seven months to four years in 11 patients. The follow-up was characterized by stability of the parameters in cases with the greatest degree of changes, and a definite deterioration of the parameter values in patients with minor degree of basal changes. It was observed an excellent correlation between FEV1 and MVV and FEF. As to CV and DL, the relationship was only good. These findings lead us to believe that MVV and FEF values can be predicted about from the FEV1 results.


Cardiovascular histamine receptors in the domestic chicken. The effects of mepyramine (H1-antagonist) and burimamide (H2-antagonist) were studied on histamine, 2-methylhistamine (a selective H1-agonist), 4-methylhistamine (a selective H2-agonist) and acetylcholine-induced changes in systemic arterial and central venous pressure and respiration in anaesthetized chickens. The result of this study suggested a predominance of H1 and some H2 histamine receptors in the cardiovascular system of domestic fowl where both are mediating systemic hypotension. There also appears to be predominance of H1 receptors mediating venous hypertension and respiratory apnoea to large doses of histamine and 2-methylhistamine. In addition, a possible involvement of H2-receptors in the cardiovascular system of chicken is suggested by the finding that burimamide always blocked mepyramine potentiated secondary pressor response to histamine and its analogues.


Antitussive drugs. I. Cardiopulmonary effects of codeine. In the anesthetized dog, codeine causes a combination of pulmonary vasoconstriction and systemic vasodilation. Pulmonary blood flow is either increased or decreased, relating to a primary stimulation or depression of myocardial contractility. The overall effect is an elevation in pulmonary arterial pressure largely due to vasoconstriction of the pulmonary blood vessels.


[Open mitral commissurotomy. Indications and results]. We have reviewed the clinical history of 106 patients that were done an open mitral commissurotomy from june 1971 to march 1974. Hospital mortality was less than 1% and morbility was low. The patients average age was 40 years. Fifteen patients had suffered a previous closed mitral commissurotomy, and systemic embolism occurred in 62.2% of them. Ninety eight of the surviving patients have been followed; 80.6% of them had improved by at least one degree of the N.Y.H.A. functional scale. According to these results we have widened the indications for open mitral commissurotomy. However, we still use the closed technique in young patients without previous mitrol commissurotomy or past history of system embolism, which no fluoroscopic evidence of mitral valve calcifications and without associated valvular lesions.


Antitussive drugs. II. Bronchopulmonary effects of dextromethorphan and doxylamine. Unlike codeine, dextromethorphan does not cause pulmonary vasoconstiction in the anesthetized dog. The other effects of dextromethorphan are as follwos: a rise in pulmonary resistance indicating bronchoconstriction, and increase in pulmonary blood flow relating to a positive inotropic action, and a decrease in aortic blood pressure resulting from systemic vasodilation. These effects are blocked by previous injections of doxylamine, an antihistaminic drug. This interaction suggests a rationale for the combined use of dextromethorphan and doxylamine in the treatment of upper respiratory infection.


[Echocardiographic diagnosis of valvular vegetations. Study of a case]. A case of a 23 year old patient with clinical manifestations of subacute bacterial endocarditis is presented, proven during the surgical treatment, in which it was possible to establish the diagnoses of a vegetation of the mitral valve through echocardiography. The echocardiographic changes produced by vegetations are analyzed and the technical defects which may lead to interpretation mistakes. It is concluded, that this non-ivasive method is of very usefull diagnozing the establishment of vegetations on the cardiac valves.


The mechanism of action of amantadine in Parkinsonism: a review. Studies of the mechanism of action of amantadine are reviewed. Data from pharmacological, behavioural and neurochemical experiments seem to indicate that the most likely effects of amantadine to be important in the alleviation of Parkinsonian symptoms are an indirect dopamine-releasing action and a direct stimulation of dopamine receptors. These effects may have a relative importance of approximately 4 : 1. Evidence favouring inhibition of dopamine uptake does exist, but the balance of opinion seems to be that this action is far too weak to contribute substantially to amantadine's action in vivo.


Effects of suprofen, an inhibitor of prostaglandin biosynthesis, on platelet function, plasma coagulation and fibrinolysis. I. In vitro experiments. ?The effects of suprofen, an inhibitor of prostaglandin biosynthesis, on human platelet function, fibrinolysis, proteolysis and coagulation in vitro were compared to those of reference compounds. Platelet aggregation induced by collagen, adrenaline and arachidonic acid was inhibited by suprofen depending on its concentration. Suprofen and indomethacin proved to have an equally inhibitory effect on platelet aggregation induced by collagen. Thrombin-induced aggregation was more inhibited by suprofen than by indomethacin. While the primary wave of A.D.P.-induced aggregation remained unchanged, the rate of disaggregation was enhanced by both compounds. Experiments on platelet factor-4 and 14C-serotonin release showed that suprofen and indomethacin reduced the platelet release reaction. Based upon results from experiments on synergism of suprofen with other compounds, on inhibition of arachidonic acid-induced platelet reactions and of prostaglandin E2-release, it is suggested that suprofen by inhibiting the prostaglandin biosynthesis in platelets also inhibits the platelet release reaction. In contrast to indomethacin and flufenamic acid, suprofen did not affect fibrinolysis or thrombin clotting activity. Tryptic proteolysis of albumin, however, was reduced by suprofen in a concentration-dependent and a substrate-competitive way. Tryptic decompisition of a synthetic substrate, on the other hand, was not reduced by either suprofen, indomethacin or flufenamic acid. These findings suggest that the observed reduction of albumin proteolysis by suprofen is related to an effect on the protein substrate rather than on the proteolytic enzyme itself.


Diazepam, ethanol and drug metabolizing enzymes in rat liver. The effect of diazepam and/or ethanol treatment of seven days on the drug metabolizing enzymes in rat liver microsomes was studied. Diazepam decreased the metabolism rate of 3,4-benzpyrene by 38% and that of p-nitrobenzoic acid by 15%. Ethanol increased the metabolism rate of N-methylaniline by 15% and decreased the reduction of p-nitrobbenzoic acid by 48%. Although diazepam alone had no inducing effect, its use with ethanol increased the cytochrome P-450 content (56%) and the rate of metabolism of N-methylaniline (44%) more than ethanol alone. The rate of metabolism of diazepam was not affected by any treatment.


Biotransformation and biliary excretion of imipramine in rats under various experimental conditions. 150 Minutes after intraperitoneal administration of 80 mg 14C-imipramine/kg to male rats, the percentage of the dose found in liver and determined as imipramine plus metabolites is 13-15% independently whether a bile fistula has been inserted or not. 1/4 of this percentage is located in the hepatic microsomal fraction. The simultaneous administration of pentobarbital and/or diphenylhydantoin does not alter these findings. The metabolite pattern, however, is shifted in favor of unmetabolized imipramine. In male rats without bile fistula, the enterohepatic circulation has no effect on the amount and the metabolite pattern of imipramine plus metabolites excreted into bile. In male rats with bile fistula, the biliary excretion of imipramine plus metabolites (87% as conjugated metabolites) over 8 h accounts for 26% of the dose (80 mg imipramine/kg) and follows first order kinetics. In female rats without bile fistula, the percentage of an identical imipramine dose found in liver after 150 min is only 7%. 1/7 of this percentage is located in the hepatic microsomal fraction. The percentage of unmetabolized imipramine in liver is double that found in male rats. Simultaneous administration of imipramine and pentobarbital at the same dosage as in male rats is lethal for female rats without bile fistula within 30 min.


Modulation of Hydra attenuata rhythmic activity. Photic stimulation. We investigated in Hydra attenuata the possibility of altering more or less permanently and in different environmental conditions, the frequency of Contraction Pulse Trains (CPT's) associated with the rhythmic spontaneous contraction activity, by repetitive light stimuli of variable duration, frequency and amplitude. The CPT's activity of various pieces of Hydra has been also investigated in indisturbed conditions and under stimulation. The following observations have been performed. 1. A transient effect, consisting of an increase or a decrease of CPT's frequency, occurs respectively after an abrupt decrease or increase of the light level. 2. If Hydra is stimulated by repetitive light pulses of 0.5-10 sec duration, at a frequency different from the CPT's average one, the CPT's frequency modifies; if the stimulation frequency is included in a range not too much up or below that of CPT's the new CPT's frequency equals exactly that of stimulation; close to this range the CPT's frequency is a multiple or submultiple of that of stimulation. 3. No habituation to such repetitive stimulation was found. 4. The phase relation between CPT's at the new frequency and light stimuli is a function of the difference between CPT's and stimulation frequencies. 5. Stimulation with repetition of light and darkness periods of some minutes duration induces activity only or mainly during darkness. 6. Modification of CPT's frequency by means of repetitive light stimulation [of the type mentioned either in 2) or 5)] has been observed also with hypostomal preparations. 7. With cessation of the light stimulation, the new CPT's frequency of the whole animal lasts in darkness for a time (10-85 min) that is about 5-10 times longer than that necessary to obtain CPT's syncronization with stimulation. 8. The influence of the light intensity level on transient CPT's frequency variation (see 1), CPT's inhibition and stimulation, promptness of entrainment, range of entrainability, phase relation between entrained CPT's and stimuli, retention time of entrained rhythm has been examined, together with the influence of the reversal of polarity of light transitions on CPT's inhibition and entrainment.


Responses of nucleus z neurons to vibration of hindlimb extensor muscles in the decerebrate cat. 1. Small sinusoidal changes of length, applied longitudinally to the ddifferented GS muscle, were uused as a specific stimulus to activate the muscle spindle receptors in precollicular decerebrate cats. In order to determine the relative contribution of the primary and secondary endings of muscle spindles to the response of the nucleus z neurons, the effects of muscle vibration on this unit activity were studied under conditions in which the segmental monosynaptic reflexes produced by stimulation of the primary endings of muscle spindles were continuously monitored. 2. Vibration of the GS muscle (at 180-200/sec and amplitudes up to 250-320 mu) affected the frequency and pattern of discharge in 50 out of 168 units recorded from the lower medulla...


[Reverse type of cri du chat disease: 5 p trisomy]. Five patients with a trisomy of the main part of the short arm of a chromosome 5 represented with the clinical picture of the reversetype of the Cri-du-chat syndrome. Its main features are the spurt of gonions, prominent chin, prominent nose root, subnormal skull perimeter, low I.Q. and muscular hypotonia.


Concordance of multiple assessments of the outcome of schizophrenia. On defining the dependent variable in outcome studies. Concordance of multiple assessments of the outcome of schizophrenia are examined from (1) concordance of three different assessments of mental status, and (2) concordance of four different dimensions of outcome. Findings are related to the methodological issue of defining the dependent variable in outcome studies. When the assessment instruments were compared, discordance in overall assessment happened because each instrument taps varying aspects of symptomatology, suggesting that outcome is somewhat instrument-related. Although adjustment in mental status is correlated with social adjustment and role performance, a patient's status at follow-up bears little relationship to rate of rehospitalization or to consumer satisfaction with treatment. A differential impact of the same predictor variables on four dimensions of outcome underscores the discordance in multiple assessments. Since treatment outcome is multifaceted and multidertermined, multiple assessments must continue as vital procedures.


Schizophrenic reasoning about affect-laden material. Drug-free schizophrenic patients (N equals 74) and nonpsychotic subjects (N equals 206) were given a test of affect-laden and affectively neutral multiple choice analogy items. The two subtests were matched on several psychometric characteristics that determine the power of the test to distinguish the more able from the less able normal subjects. Neither newly admitted schizophrenic nor long-term chronic schizophrenic patients performed differently on the affective subtest than on the neutral subtest. The many published findings of a cognitive deficit in schizophrenia in response to affect-laden stimuli can probably be attributed to the inappropriate use of unmatched tested.


Schizophrenia and stimulus intensity control. A group pf 19 acute, medication-free schizophrenic patients was studied, using average-evoked responses (AERs) to four intensities of light. Comparison with age- and sex-matched normal controls and patients with bipolar affective disorders showed that schizophrenics had smaller AER amplitudes and either no increase or an actual decrease in amplitude with increasing stimulus intensity. Normal subjects and schizophrenic patients were discriminated with 71% accuracy using AER variables; normals, patients with bipolar disorders, and schizophrenic patients with 64% accuracy. Patients who evidenced this AER "reducing" pattern to a noticeable extent early in hospitalization showed greater improvement and tended to have relatively good premorbid histories.


Self-disclosure in group therapy with schizophrenics. Self-disclosure was investigated as a process variable in group psychotherapy with chronic schizophrenic patients. Consistent with previous data obtained from nonpsychotic populations, greater perceived therapist interpersonal facillitativeness was associated with higher levels of patient self-disclosure. In contrast to earlier findings, however, patients who were more self-revealing made less therapeutic progress than their counterparts who divulged less personal material. This failure to replicate was tentatively attributed to the limited ability of psychotic persons to integrate social feedback. The results underscore the delicacy of the psychotherapeutic undertaking with schizophrenics.


Integration and sealing over. Clinically distinct recovery styles from schizophrenia. Concepts of integration and sealing over are common clinical psychiatric parlance. Our experience studying and treating acute schizophrenic patients, primarily with psychosocial techniques, has emphasized the meaningfulness of these concepts. By studying the recovered patient's attitude toward his psychotic experiences, we have obtained material from which to formulate definitions and these concepts. Integrators tend to be curious about their symptoms, regard them as part of their life's pattern, and gain information from them, resulting in a more flexible and variable attitude toward illness than patients who seal over. The latter have rather fixed, usually negative, views of their illness, and tend not to strive to understand their psychotic symptoms nor to place their psychotic experiences in perspective with their lives before and after psychosis.


Psychophysiological correlates of meditation. The scientific research that has investigated the physiological changes associated with meditation as it is practiced by adherents of Indian Yoga, Transcendental Meditation, and Zen Buddhism has not yielded a thoroughly consistent, easily replicable pattern of responses. The majority of studies show meditation to be a wakeful state accompanied by a lowering of cortical and autonomic arousal. The investigations of Zen and Transcendental Meditation have thus far produced the most consistent findings. Additional research into the mechanisms underlying the phenomena of meditation will require a shifting from old to new methodological perspectives that allow for adequate experimental control and the testing of theoretically relevant hypotheses.


Perception and cognition in patients with bipolar and unipolar depressive disorders. A study in orschach responding. The Rorschach was administered to 16 bipolar and 13 unipolar patients hospitalized during a depressive episode. Two contrasting styles of Rorschach responding differentiated the two patient groups. The bipolar style of response is characterized by selective attention to the more objective aspects of the inkblots, while the unipolar style of response is characterized by a more subjective approach. Primary response to color was found only in the protocols of bipolar patients. The styles of response were discussed in relation to other studies showing similar results based on self-assessment and clinical tests. It was suggested that perceptual-cognitive structuring of the external environment may be related to, or predispose, mood levels.


Psychiatric illness in fathers of men with bipolar primary affective disorder. A systematic interview regarding family history was administered to 48 men with bipolar affective illness who were attending a lithium clinic. Several families were found in which both the patient and father had affective disorders, but the mother and maternal second-degree relatives were well. Of 30 men who had histories of hospitalization for mania, three had fathers with affective disorder (all bipolar). Of 18 men who had depression and hypomania, one father had unipolar depressive disorder. The hypothesis that bipolar manic-depressive illness may be transmitted by a single dominant genetic factor on the X chromosome is discussed in relation to these ill father-ill son pairs.


Bipolar affective disorder in black and white men. A comparison of symptoms and familial illness. Eleven black and 19 white men with conditions diagnosed as manic-depressive disease, manic type were given a systematic psychiatric interview. In addition, as many of their first-degree relatives as could be contacted were also interviewed. Demographic, clinical, and family history variables were compared for the two races. With the exception of a greater preponderance of alcoholism in the paternal relatives of the black men, few differences were found between the two groups in terms of the variables studied. It was concluded that the clinical and familial expression of bipolar affective disorder is similar in the two races.


The significance of psychotic affective disorders. A study of 253 patients with primary and secondary affective disorders disclosed that psychotic features were more frequent among bipolar patients. Except for more frequent psychiatric hospitalization among unipolar patients with psychotic features, no demographic, family history, or parental home variable was found to distinguish between those with and without psychotic features. Chance variation probably accounted for the few symptoms whose frequencies were different depending on the presence or absence of psychotic features. The results failed to support the validity of a classification of affective disorders based on the presence or absence of psychotic features.


Hostility and depressive illness.

Hostility and depressive illness. This study employs a method of classification based on "information measure" taxonomy to investigate an aspect of hostility in nonendogenously depressed, endogenously depressed and nondepressed patients. Results show that there are no statistically significant differences between the three groups as such, but that a patient's self-rating of anger is substantially related to his position on the endogenous-nonendogenous depression dimension. The greater the anger score, the more likely the patient is to present a depressive syndrome of a nonendogenous type. These observations provide support for previous findings in this area and prompt certain tentative theoretical speculations.


Wrist cutting. Relationship between clinical observations and epidemiological findings. Reports of select samples have described suicide attempt by wrist cutting as a unique clinical syndrome occurring in young, single, attractive women, associated with specific psychological characteristics. A St. Louis study of a large unselected sample found that persons who cut their wrists were similar to other suicide attempters and were not more apt to be single females who made repeated attempts. These findings are repeated in a New Haven, Conn, study suggesting that reports of persons cutting their wrists should be reconsidered in light of these epidemiologic findings. Institutional differences in patient sampling can account for lack of agreement. While clinical observations are important, additional study through epidemiologic approaches is necessary before conclusions about new syndromes can be made. Current evidence on wrist cutting raises questions about the existence of a separate syndrome.


Violence among hospitalized delinquents. We collected data on the extent of violent behavior among 55 male and female hospitalized juvenile delinquents during a period of three years. Violent behavior was correlated with the adolescent self-image and the ratings of staff and psychotherapists. We found that violent adolescent boys have a healthier self-image and are more liked by their therapists than nonviolent adolescent boys. For the female adolescents, we found the opposite. Initially, the mental health staff liked the nonviolent delinquents better; this finding was no longer significant after the adolescents were on the unit for 13 weeks. Our discussion focuses on the individual and staff psychodynamics and cultural factors that contribute to the outbreak of violence. Our plan is to further study our data in order to better understand the phenomena of violence.


A race riot's effect on psychological symptoms. Certain individually stressful events have been observed to increase the psychological distress of persons affected; reduced psychological distress following other events has been attributed to collective processes, including increased group cohesion. These possibilities are investigated by contrasting reported symptom levels of 938 adults interviewed before, during, and after a racial riot. White suburbanites interviewed after the riot and urban black women interviewed during the riot report significantly fewer psychological symptoms. Hypotheses of seasonal symptom changes, sampling biases, and the absence of symptom changes among relatively unimpaired respondents are rejected, suggesting that reductions in symptom level are associated with the riot. Serious methodological problems are raised by our finding that such events may significantly affect not only rates but also patterns of reported psychological symptoms obtained through epidemiological studies.


Lateralized neurologic deficits and psychopathology in a Turner syndrome patient. A Turner syndrome patient has been studied by more extensive neuropsychological testing than has previously been reported with such patients. Testing indicates impairment of a variety of functions normally subserved by the right cerebral hemisphere. If replicated with other Turner patients, a lateralized neurologic deficit is implicated as part of the syndrome. Also, this case illustrates the importance of family support and sensitive professional treatment in determining the psychological outcome of this disorder. As an important therapeutic consideration, we describe psychologically detrimental effects of delayed estrogen treatment with an older Turner syndrome patient.


Transient ictal psychosis.

Transient ictal psychosis. Transient psychotic episodes may result from continuous cerebral epileptiform discharges unaccompanied by clinically observed seizures. Such episodes may mimic depressive, hysterical and schizophrenic psychosis and delirium. I describe two patients here and review eight patient histories from the literature. Diagnosis is established by use of electroencephalography during the psychotic episode. Correct diagnosis is essential because specific treatment is available and additional episodes may be prevented by appropriate long-term anticonvulsant therapy.


[Properties of ribosomes of normal and tumor cells (author's transl)]. On the basis of results showing that the extent and direction of protein biosynthesis essential for cell growth and cell differentiation can be regulated, aside from the transcription level, also on the level of ribosomes (translation), the main results of various properties of ribosomes from normal and tumor tissues are described. The main established difference between the two tissues concerns the organization and localization of the ribosomes within the cell. In tumors, polysomes and inactive dimers and monomeric particles are encountered in considerable amounts freely in the cytosol, i.e. not attached to the membranes. Furthermore, the polysomal profile of tumor cells compared with the normal tissue is characterized by a shift towards fractions with lower sedimentation coefficients. Monomeric ribosomes were not found to differ in physical and chemical properties. In smaller oligonucleotide fragments of ribosomal RNA, differences in the frequency of certain dinucleotides appear likely. Hybridization-competition experiments with DNA do suggest, however, that the ribosomal RNA from tumors is being synthesized at the same cistrons as ribosomal RNA from normal tissues, thus proving its overall sequence homology. Electrophoretic and immunologic methods have not so far revealed any clear differences in the properties of ribosomal proteins from normal and tumor tissues. In in-vitro systems, ribosomes from various tumors show approximately the same incorporation rates for amino acids as ribosomes from normal tissues. The enhanced protein synthesis of the cells, on the basis of data obtained from in-vitro experiments with cell free systems, is to be attributed mainly to the increased content of translation factors in the cytosol.


Intra- and extracellular calcium in Ehrlich ascites tumor cell. Calcium concentration in intra- and extracellular fluid from Ehrlich ascites tumor cells has been studied. The higher content of calcium in the outer cell fluid appears as a possible factor determining the behavior of the cell membrane. While in the cytoplasm macromolecular compounds such as lipo- and nucleoproteins seem to play an important role in calcium-binding, in the extracellular fluid calcium is likely to be bound to small molecules (presumably short chain polyphosphates). The significance of calcium-binding changes at the cell membrane level in the carcinogenesis and in the physiological behavior of the tumor cells is discussed.


[Study on transplantable, melanin containing hamster papova virusinduced skin tumours in Syrian hamster (author's transl)]. A melanin containing skin tumour of trichoepitheliomatic character, induced by a virus some 40 nm large, is described showing neither infiltrative nor metastasizing growth. The multiple, flat, mostly confluent tumour nodes appear in all parts of the skin, especially in dorsal skin, at the chin, eyes, and ears. The tumours are mostly blue black as a result of hemosiderin and melanin deposits; these pigmentations occur in connective-tissue cells, the tumour cells and the abounding keratinizing cysts. The blastomic character of these tumours, which in part are reminiscent of tricho-epitheliomas, can be demonstrated by transplantation experiments, in which with increasing number of passages are observed a decrease of latent period, disappearance of pigment formation, and increase in histologic de-differentiation.


[Stability of clinically used cytostatics (author's transl)]. This paper concerns with the stability of aqueous solutions of clinically used cytostatics. The investigation was carried out with in vitro-activated cyclophosphamide from urine of patients, also with trenimon, vinblastine and methotrexate. The stability was tested by biological determination of tumor cell cultures, NBP-reaction and spectrophotometric investigations at different temperature of storage. The activated cyclophosphamide and the active metabolites from urine too are unstable in contrast to the active metabolites in lyophylisied urine. While vinblastine in our results are stable for ten days and more and methotrexate for fourteen days in the refrigerater in physiological solution, trenimon decomposed relative rapidly.


[Mesenchyme theory on the increase in resistance experienced during repetition of cancer therapy processes (author's transl)]. Experimental observations of pronounced mesenchyme incorporation near the capillaries of cancer tissue occurring three days after therapeutic treatment with a tumour cell killing rate of 50% have led to the conclusion that mesenchyme reaction is one of the most likely causes of the known increase in resistance found with repeated cancer therapy processes. Mesenchyme incorporation especially diminishes the glucose diffusion coefficient and therefore weakens the glucose diffusion field around the capillaries so that proliferation and sensitivity of tumour cells to cancerostaticas and radiation will decrease to a very high degree. The given solution of the glucose diffusion field equation permits a quantitative presentation of regularities and therapeutic results about mesenchyme incorporation within a capillary distance of R approximately 30 mum. So it has been calculated that, in stationary cases, a transition to the conditions obtained with Cancer Multi-step Therapy (CMT) will increase the volume of tumour tissue being accessible to a therapeutic process by a factor of more than 2.5. Viewed from theoretical aspects, the CMT Concept therefore seems to be one of the most promising possibilities to overcome the (mesenchymal) resistance of tumour tissue. Finally, the paper gives a discussion about an actual possibility for reducing the developing resistance in case of repeated therapeutic treatment based on experimental circumstances; i.e., the inhibition of mesenchyme reactions, for instance, by giving a high dosage of prednisolon in the interval between therapeutic processes.


Intramitochondrial dense bodies in the goblet cells of the ileum of muscular dystrophic mice. Mitochondrial osmiophilic bodies were found in the goblet cells of the small intestine in a group of muscular dystrophic mice. They were not found in any littermate normal control mice. The dense bodies were uniformly round in shape but variable in size, approximately 0.2-0.4 mu in diameter. A limiting membrane encircled a dense content. Mitochondria with such dense bodies were distributed throughout the goblet cells. Adjacent absorbing epithelial cells had none of such mitochondrial bodies. Though the site of formation of the mitochondrial bodies remains to be investigated, the Golgi complex did not appear to be involved in the transportation of the dense bodies. Digestion of sections with ether-chlorofolm (1:1) slightly decreased the density of the mitochondrial body. Ruthenium red staining was not visible over the dense bodies but trace of Ru was detected by X-ray microanalysis. X-ray microanalysis indicated very few, if any, amounts of P and Ca, and it was not probable that phospholipid and calcium binding protein were the main constitution of these dense bodies.


Some findings on the fine structure of the neurohypophysis in dehydrated and pitressin-treated mice. The fine structure of the pituitary posterior lobe was observed using normal, dehydrated and Pitressin-treated mice. The normal posterior lobe of the mouse contains numerous neurosecretory granules of about 1,300-2,000 angstrom diameter in the nerve terminals. These granules are often found in contact with neurotubules running longitudinally in the axon. In the 2, 5 and 7 day-dehydrated animals the secretory granules are markedly decreased in number, while small vesicles of about 500 angstrom diameter are conspicuously increased in number in the nerve terminal. It is very difficult to obtain an electron microscopic figure of the exocytosis of the secretory granule. The cluster of small vesicles in the nerve terminal is sometimes surrounded by an electron dense membrane and gradually changed to the cytolysomes. These facts suggest that most of these vesicles are not synaptic vesicles containing acetylcholine but materials derived from the limiting membrane of the released granules and they are gradually disposed of by lysosomes. In Pitressin-treated animals (3 days, 200mU/day), an increase in number of the neurosecretory granules and an appearance of the disposal process of the excess neurosecretory granules are characteristic in the nerve terminal. Some granules are aggregated to become higher in electron density and surrounded by an electron dense membrane. They are positive for acid phosphatase reaction and are degenerated by an autolytic process. In both cases above, the pituicytes showed a marked reaction. The elements of rough endoplasmic reticulum and the Golgi apparatus become well developed and many large lysosomes are seen in the cytoplasm.


The cytological effects of infusion of luminal polyethylene glycol on the rat small intestinal mucosa. An isolated sac of rat upper small intestine was prepared. Its lower end was drained to the skin. Solutions of known volume and composition were infused into the sac and the intestinal mucosa was examined by light and electron microscopy. Infusion of isosmotic (16.8 percent w/v) polyethylene glycol (PEG) resulted in prompt and progressively severe damage to enterocytes at the top of the villus, while goblet cells and basal-granulated cells were apparently unaffected. Thus, after 6-72 hrs a cap of goblet cells and basal-granulated cells accumulated at the tip of the villus, while the enterocytes underwent vacuolation and disintegration. Infusion of an isosmotic mixture of 1 percent PEG and 5.1 percent glucose caused no damage near the site of infusion, but damaged the intestinal sac further distally...


Pliable metacrylate casts of blood vessels: use in a scanning electron microscope study of the microcirculation in rat hypophysis. Methyl methacrylate mixed with 30-50 percent hydroxy ethyl or hydroxy propyl methacrylate produces a pliable replica suited to manipulation. The advantages of this improved casting medium were discussed, demonstrating the scanning electron micrographs of the isolated and dissected blood vascular replica of the rat cerebral hypophysis. In the micrographs it was unequivocally indicated that the vascular bed of the anterior lobe is supplied by the capillary plexus of the median eminence and the neural stalk, and that the vascular meshwork of the intermediate lobe is formed by vessels extended from the posterior lobe and is drained into the anterior lobe. The subependymal network intercalated between the plexus of the median eminence and the meshwork of the hypothalamus is directly supplied by arterial branches. It was also demonstrated that the plexus of the median eminence is, at its periphery, in direct communication with the systemic venous twigs.


Light and electron microscopic studies on the caudate nucleus of the dog with special reference to the classification of nerve cells and to the subsurface cistern. The distribution and classification of the nerve cells in the head, body and tail of the nucleus caudatus of the dog were investigated by light microscopy, fluorescence histochemistry and electron microscopy. A small neuron, a large pale neuron and a large dark neuron were identified submicroscopically in the caudate nucleus. Special attention was given to the differentiation between the dark neuron and the glia. The subsurface cistern could be easily recognized in the nerve cells but was never found in the glia. Its presence might be used as a criterion in the identification of a neuron. Goniometric observation was carried out to determine the three-dimensional configuration of the subsurface cistern. The structure of subsurface cistern was shown to be discoid and not tubular. The physiological role of the subsurface cistern was briefly discussed.


[The attitude of 200 hospitalized psychiatric patients and their doctors toward treatment (author's transl)]. 1 week after their admission to a psychiatric clinic, a representative sample of 200 patients were interviewed as to their attitude toward hospitalization and their opinion of the doctors, nursing personnel, psychopharmaca, as well as the industrial- and creative occupational therapy they underwent. They were also questioned as to the general physical environment. At the same time, the 15 assistants treating these patients were asked their opinion of the attitudes of their patients toward some of the above points. The patients answered less favorably with regard to their wards (particularly if these were closed) and with regard to the hospitalization in general, but they answered more favorably reacted more positively to their doctors and nurses than to the various methods of treatment (counseling, psychopharmaca, occupational therapy). Information on the patients from their doctors concerning noticeable side effects of psychopharmaca proved insufficient. There was no difference in the patients attitude toward occupational therapy that consisted of unpaid industrial work and the creative occupational therapy. Women were more critical than men. The opinions of the patients were in good agreement with those of the doctors.


[Three basic kinds of behaviour, a scheme of their neurobiological correlates (author's transl)]. The psychic sphere is to be regarded as the source of meaningful behaviour, which is carried out in the service of the cell community that makes up our body. Three fundamental types of behaviour can be distinguished: the purely practical, the theoretical-practical, and the purely theoretical. These three types of behaviour have three different reasons: the first a determining reason, the second a motivating reason, and the third a supporting reason. The threefold nature of the reasons is related to the threefold needs of the cell community (in this context man is considered as an example of an animal). Possible neurobiological bases of human behaviour are depicted in a schematic figure showing the relation of cerebral centres and sensorimotor functions of the human face including eye movements. The psychic centre may be located in the thalamus, the areas of the central sulcus are regarded as an objectivation zone. This indicates that the motor zones of the cortex, including the frontal adversive fields, are intention zones, and the sensory zones reproduction, expectation, and recollection zones. A system so composed would render possible what we see in every animal being: decision-making, foresight, and learning.


On the activity of brain phospholipase A2 towards specifically labelled glycerophospholipids during subacute sclerosing panencephalitis. 1,2-Diacyl-sn-glycero-3-phosphorylcholine, -ethanolamine and -serine, specifically labelled with different fatty acids at either the 1- or 2-position, were prepared enzymatically using the acyltransferase system of rat liver microsomes. The substrates were subjected to hydrolysis by phospholipase A2 obtained from brain tissue of a normal and a case of subacute sclerosing panencephalitis (SSPE). In the pathological tissue and increase of approx. 50% in phospholipase A2 activity could be observed in comparison to that from the control brain for all investigated substrates. Experiments with phosphatidylethanolamines, specifically labelled with different fatty acids in the 2-position, revealed that the phospholipase A2 activity of the SSPE brain tissue was enhanced by about 50% when compared to the control brain regardless of the fatty acid constituent at the 2-position of the substrates.


[Experiments on perception in schizophrenia (author's transl)]. Acute and chronic schizophrenic subjects were tested with 6 simple experimental tasks of visual stimulus selection. The 2 control groups were a group of non-psychiatric subjects and one of patients with other psychiatric diagnoses. The 6 experimental tasks represented three different types of attention: 1) differentiation between "figure" and "background", 2) concentration; 3) visual integration (Gestalt completion). The main result was that the acute group with paranoidal psychosis and hallucinations made significantly more mistakes in figure-background differentiation (grouping of patterns). But there was no difference between this group and the other patients in the concentration tasks. Both schizophrenic groups performed more poorly in the Gestalt completion task. The results are discussed in light of the information theory (breakdown of a hypothetical filter mechanism) and Sokolow's psychophysiological model of stimulus selection. The hypothesis is put forward that in the acute schizophrenic group a disturbance in an arousal-modulation system is responsible for attenuation of irrelevant input.


[Diagnosis of language-understanding deficit in aphasia. Methodological considerations and composition of a test for discourse comprehension (author's transl)]. The investigation of language comprehension in aphasics has usually been concerned only with the word and sentence levels. It has not been considered that language in the normal communicative situation has the character of discourse. Furthermore, language understanding should be conceived of as comprising different processes of comprehension which can be selectively affected in aphasia. It was therefore necessary to compose a test for text comprehension. In this test the patient is read a short text and then required to choose that picture from a multiple-choice set which is most appropriate to the story. Texts and pictures were developed according to the linguistic parameters: agent/experiencer, action, situation, metaphorical comment. With the tasks kept uniform this test allows not only quantitative but also qualitative statistical evaluation. Preliminary results show that the test reveals qualitative differences between subtypes of aphasia.


Application of EEG-interval-spectrum-analysis (EISA) to the study of photic driving responses. A preliminary report. Photic driving responses were analyzed by means of Tönnies' EISA method in 65 normal subjects, 20 patients with brain tumor and 4 cases of severe head injury. The response patterns were classified into 5 types, incidence of which in normals were 1. all band-responsive type (38%), 2. Theta-alpha type (8%), 3. Alpha-beta type (32%), 4. Beta type (8%) and 5. non-responsive type (14%). Each response pattern was compared with the resting EEG activities, however, no significant relationship was found between them. The responses of patients with brain tumor or severe head injury were considerably reduced. The reduction of the photic driving responses in brain tumor cases was not specific to the localization of the tumor. It seems to represent the diminution of the general cerebral reactivity corresponding to the severity of the brain damage. Our results have confirmed that EISA is a simple and practical method for the frequency analysis of long duration and suitable for routine clinical examination.


[Course and prognosis of unilateral carotid artery occlucion (author's transl)]. In 80 patients with unilateral carotid artery occlusions who had neurological symptoms, course and prognosis without anticoagulant or surgical therapy were analyzed. 17.5% of these patients died within 4 weeks, 43% of this group from extracerebral complications. The survival-time of those patients, surviving the acute stage, was also shortened: one year later only 67% of the patients were still alive, 5 years later 58% and after 10 years only 42%. Many cases died from further cerebrovascular strokes. In most of the patients carotid artery occlusion is only one of the symptoms of a generalized artery disease, i.e. arteriosclerosis. Resulting poor collateral circulation may be the crucial factor leading to the poor prognosis as to survival and rehabilitation: only 3.8% of the patients returned to work, 19% are able to walk, and 55% need nursing. These facts demand prophylactic measures: first a decisive therapy with respect to the risk factors of stroke, second an alertness to transitory ischemic attacks or small strokes. The latter were found in 56% of our patients. The literature and value of different therapeutic measures will be discussed.


[Psychiatric classification by means of a discriminatory application of Q factor analysis (author's transl)]. An attempt is made to separate different pairs of psychiatric patient groups by means of a modified form of Q factor analysis comparable to discriminant analysis. The psychopathological state of 454 patients had been rated using two psychiatric rating scales, the IMPS (Inpatient Multidimensional Psychiatric Scale) by Lorr et al. and the psychopathological and somatic scales of the AMP documentation system. Out of these patients the four most frequently occurring groups (schizophrenia, paranoid form, n = 45; schizophrenia, unspecified form, n = 47; depressive psychosis, n = 44; depressive neurosis, n = 53) were selected. Each patient group was divided randomly into two samples, an analysis sample and a validation sample. Only those items were selected which discriminated best between any two analysis samples. Using G indices a Q factor analysis was calculated, and the results improved by a criterion-related additional rotation. The resulting weights were transferred to the validation samples in order to have a cross validation. The mean percentage of correct placements within the validation samples was 83%.


[Quantitative clinical assessment of the course in a case of temporal encephalitis (author's transl)]. The neuropsychiatric symptoms and signs of a case of sporadic encephalitis are presented. Psychopathological features are assessed with the IMPS (Lorr-scale). This is shown to be useful for objectivation and differentiation of the psychopathological syndrome. A disadvantage of the IMPS is the limited applicability in states with disturbed verbal communication and insufficient recording of mnestic impairment. Of the 4 states of activation defined for patterns of horizontal and vertical EOG and EMG recordings, state 2 (i.e., electrical activity of the mentalis-EMG, no blinks, no rapid lateral eye movements) and state 4 (i.e., rapid lateral eye movements, electrical activation of the mentalis-EMG) are appropriate measures for a quantitative description of the course of the disease. The relative distribution of state 2 and 4 within one period of registration indicates that the decrease of state 2 and the increase of state 4 are highly correlated with the reduction of psychopathological symptoms. Furthermore, transition among states shows the same correlation during the course of the disease. The ratio of the total number of transitions and non-transitions within one period of registration is proportional to the alleviation of clinical signs.


[Extraversion (e), neuroticism (n), and psychoticism (p) in deaf people (author's transl)]. The personality of deaf people was studied within the framework of the Eysenck concept of personality. Data gathered with the Personality Inventory AUPI could be evaluated in 66 deaf people (43 connatal or early acquired deafness, 25 late deafness, i.e. after full language development). The consistency of the AUPI Scales in the normal population about corresponds to that in the deaf people. -- Those who went deaf "early" showed a statistically significant higher degree of extraversion than the normal population. There was no significant difference in neuroticism (emotional lability). "Early" deaf people had the highest value of psychoticism; and those who developed deafness "late" also differed significantly from the normal population. Psychoticism is--according to Baumann and Dittrich reactive aggressivity and depression (reactive to frustration).


[The logic of decision in symptom rating (author's transl)]. The rating systems used in psychiatry consider sometimes different ways of classifying parameters, such as the valuability and the certainty of decision. Those two parameters have been analysed by means of the AMP-ratings of two samples (Berlin: 1879 patients, Zürich: 786 patients). We have found that the reply "not valuable" appears much less frequently than the reply "questionable valuable". For delusional symptoms and disorders of perception the certainty of decision is lowest. The various analyses carried out lead us to the conclusion that without loosing informatory value of any consequence we can renounce any separate documentation on valuability and certainty of decision.


[Study of efficacy of training emotional behaviour in groups (author's transl)]. A program of training emotional behaviour in groups and a method to prove its efficacy is reported. The objective of this treatment program is to improve recognition of emotional cues and adequate expression of emotions. The methods of behaviour therapy used in this program are: training of adequate behaviour be role-playing, modeling and operant conditioning. The study of efficacy is done as a group comparison between these therapy groups and the assertive training groups. Data are collected using self-rating scales, rating scales filled off by partners or relatives of the patients and direct behaviour ratings. Preliminary results show an improvement of selfrating data for the experimental and the control group, but there is no specific effect of one of the therapy programs.


[The evaluation of community psychiatric services. Some methodological problems (author's transl)]. We have now come to accept that any new pharmacological treatment must be comprehensively and intensively evaluated before it is introduced into general clinical practice. The thalidomide tragedy has illustrated the dangers of inadequate testing. It is less obvious, however, that psychosocial treatments need to be assessed just as stringently. The claims made for new forms of social treatment and new forms of service are very large. The effects, for example, of turning from a predominantly hospital-based service to one which depends on the co-ordination of a large number of smaller community agencies, are potentially much greater than anything that could be expected from the introduction of a new drug. Itis essential that psychiatrists play their full part in this new and rapidly developing field of investigation.


[Methodological problems of clinical trials of psychotropic drugs (author's transl)]. Up to now, clinical studies only succeeded in differentiating between great categories of psychotropic drugs, but failed to prove finer differences of effects within these categories of substances. Two points of the testing-method are discussed: 1. problems which arise when rating pathological behaviour and 2. problems of sampling psychiatric patients. A great part of symptoms that clinicians and psychologists used to consider as relevant proved to be extremely rare. Total scores cannot be taken as a measure of the therapeutic effect, because they don't express adequately the degree of severity of the illness before and after treatment, and there is a symptom that is independent from the observer, i.e. the frequency of the symptom in different clinical pictures. The frequency is an inverse ratio to the specificity of the symptom. It is then argued that even in clinical studies, it would be possible to choose among the variety of descriptive symptoms those which fulfil requirements of the probabilistic test-model of Rasch and to take only those symptoms to characterize the degree of severity of psychic disturbance in trials with psychotropic drugs. Conclusions are then drawn from a study including three groups of physicians (specialists for internal diseases, psychiatrists and general practitioners): failure to differentiate between placebo and a Minor-Tranquilizer was not due to the inefficiency of the drug, but ought to be attributed to the lack of sharpness of the observations made by untrained judges. A significant difference between placebo and the Minor-Tranquilizer was yet found, but only in the group of psychiatrists. The comparison of the first 13 and the last 13 cases in the two remaining groups, however, reveals a learning process in the course of the study. The main problems of sampling are discussed, i.e.: the loss of information as a consequence of taking the mean in a group of psychiatric patients, the role of biological rhythms, which was hitherto insufficiently considered, and finally it is demonstrated in connection with two selected cases of depressive patients that enormous difference of psychophysiological responsiveness can be hidden behind very similar clinical pictures. It is pointed out that the existing research strategy is adjusted to great samples, which were composed on the basis of behavioral characteristics, and that it failed to differentiate subtle effects of psychotropic drugs. Only experiments involving a much greater display, which take into account all aspects of observation of the selected single cases and longitudinal studies can answer the question which is the right medicine for the right patient. Psychophysiological and biochemical methods have here priority over other methods.


Vaccinia virus variants as presumable cause of vaccinial complications. Two vaccinia viruses isolated from patients with vaccinial complications (vaccinial ulcer, postvaccinial seizures) showed qualitative differences from the original parental strain. After intradermal injection of the viruses into the rabbit marked necroses developed, which the original strains did not produce. While the parental virus did not grow on the chorioallantoic membrane at 41 degrees C after 2 days incubation, the vaccinia variant produced typical lesions at that temperature. Also the yield of infectious virus on various cell systems was 1--2.5 logs higher for the virus than for the original vaccine strain. With the plaque technique differences were seen in the appearance and size of plaques between the variant and the parental vaccinia strain. These results indicate that virus of an increased pathogenicity could be isolated from the patients and this might be causally connected with the postvaccinial complications from which they were suffering.


The influence of hyperthermia and poly I:C on Semliki Forest virus infection in mice. In mice infected intraperitoneally with 10(3) intracerebral suckling mice LD50 of Semliki Forest virus an additive reduction in mortality was found when the protective effect of hyperthermia and synthetic polyriboinosinic and polycytidylic aicds (Poly I:C) was combined. The effects of the two treatments seem to be independent of each other as Poly I:C was found to have no influence on the body temperature of mice, nor did hyperthermia increase the amount of interferon induced by Poly I:C.


[Arterial elastin in atherosclerosis and hypertensive disease]. Elasticity and elastin of arteries in 106 dead people aged 14--74 years were investigated using physico-chemical methods. Depending on the character of morphological manifestations, aortas and arteries were divided into following groups: 1) without morphological manifestations of atherosclerosis; 2) affected by atherosclerosis; 3) vessels of patients who had suffered from atherosclerosis and hypertensive disease; 4) aortas and arteries of patients with atherosclerosis in combination with other somatic diseases. In atherosclerosis and hypertensive disease there were observed specific shifts in the character and intensity of fluorescence of elastin and elasticity as a whole. The intensity of primary fluorescence as an atherosclerotic process progressed and in concomitant hypertensive disease gradually changed. In atherosclerosis there were noted changes in transversal bands in elastin. The growth of transversal bands and intensity of fluorescence were found to be interrelated. Optical density of dissolved elastin with wave lengths (lambda) 240, 260, 280, 300, 320, 360, 400, 490 nm and pH 7.7 and 8.6 was studied. The peak of intensity of absorption of the solution of elastin in all groups referred to above was noted at the wave length lambda=240 nm. Amino-acid composition of dissolved elastin was also studied. It was established that as the process of atherosclerosis progressed, the content of lysine in the wall increased depending on the phase of the process -- lipoidosis, atheromatosis, etc. In the vascular wall there were observed changes in monoamino-oxidase, the latter being of particular importance for maintaining the level of cuprum in tissues.


[Atherosclerosis of the vessels of Willis' circle in certain variants in its structure]. Random studies of the base of the brain vessels in 278 men who had died at the age of 50--64 years were carried out; 29 variants of the structure of the circle of Willis were established; the most common were threadlike connective arteries and posterior trifurcations of the inner carotid arteries. The investigation of atherosclerotic changes in every vessel of the base of the brain showed that in the so-called posterior trifurcations there was a statistically reliable growth of the average degree of atherosclerosis in the intracranial region of the inner carotid artery ensuring in these cases the blood supply for a considerably greater region of the brain. In posterior connective arteries atherosclerotic changes were revealed only when their diametre exceeded 0.1 cm which testified to the bloodflow in these arteries.