The diagnosis of bone infarction.

The diagnosis of bone infarction. The radiographic diagnosis of bone infarction is discussed based on the pathological changes that occur. The differences in radiographic density and their significance are emphasized. Bone infarctions are divided into diaphysomethaphyseal and epiphyso-metaphyseal lesions and the radiographic appearance described. Etiologic considerations are outlined.


The potential role of prostaglandins in skeletal and muscular disorders. Musculoskeletal diseases such as rheumatoid arthritis and polymyositis are characterized by chronic inflammation. There is evidence to suggest that prostaglandins participate in the production of the inflammatory response. In several tissues, the production of inflammation has been associated with the release of prostaglandins. The inhibitory effect of some anti-inflammatory agents on prostaglandin synthesis further suggests a prostaglandin role in inflammation. Reduction by prostaglandins of release from cells of mediators of inflammation has been described. Prostaglandin treatment also suppresses acute and chronic inflammation in several experimental models. Thus, prostaglandins may serve to regulate the inflammatory response.


Proline biosynthesis and degradation in mammalian cells and tissue. Radioisotopic assays have been developed for the enzymes of proline metabolism. These assays are specific and sensitive enough to measure enzyme activities in cultured cells and biopsy specimens. Measurements of these enzymes in tissues and cultured cells suggest that endogenous biosynthesis of proline may be an important source of this amino acid.


Effect of probenecid on penetration of oxacillin into fibrin clots in vitro. Probenecid significantly enhanced the in vitro penetration of oxacillin into fibrin clots suspended in rabbit serum or normal saline.


New method for susceptibility testing with antifungal agents. A new method for the determination of minimal inhibitory and fungicidal concentrations of antifungal agents for filamentous fungi is described. 5-Fluorocytosine (5-FC) was used as a representative agent and was tested against the following genera: Allescheria, Aspergillus, Cladosporium, Fonsecaea, and Phialophora. 5-FC was found to be inhibitory but not fungicidal for many of the fungi tested, including eight of clinical origin.


Modified method for analysis of serum iron. An improved method for analysis of serum iron is described which is simple, rapid, precise and convenient for routine use in clinical laboratories. Serum proteins are precipitated with trichloroacetic acid-hydrochloric acid solution, with simultaneous release of Fe(III) from transferrin. Fe(III) is reduced to Fe(II) by sodium ascorbate, and Fe(II) is reacted with ferrozine to form a lavender complex, which is measured by spectrophotometry at 562 nm. Measurements of iron in 183 serum samples by this method were compared with measurements by a "direct" spectrophotometric method without without deproteinization, as previously described. Close agreement was obtained in 171 of these 183 pairs of analyses (93.5 percent). Discrepancies (greater than 12 mug per dl) were noted in the remaining 12 serums, which were attributed to interference in direct spectrophotometric analyses of iron, owing to (1) hemolysis, (2) lipemia, (3) jaundice, (4) protracted storage or (5) repeated freezing and thawing of the serums.


Absorption of pivampicillin in postoperative patients. The absorption of orally administered pivampicillin was studied in nine postoperative patients and compared with that of intravenously administered ampicillin. The absorption of pivampicillin was calculated on the basis of comparison of the areas under the serum concentration curves for both modes of administration. After an oral dose of 700 mg the absorption ranged from 40 to 95% (mean, 60%).


Inhibitory effects of citrates in the determination of trace amounts of penicillin. In the microbiological assay for the determination of trace amounts of penicillin, it has been shown that sodium citrate and penicillin act synergistically against Sarcina lutea. The inhibitory action of citrate appears to involve a sequestering of divalent cations essential to the growth of the organism as shown by minimal inhibitory concentration and agar diffusion studies. The addition of calcium or magnesium to broth or agar at various concentrations overcomes this inhibition, and 0.02 M magnesium was found to be the most effective concentration. On agar supplemented with magnesium chloride, penicillin dose-response curves with and without citrate present were practically superimposable, and larger inhibition zones against a greater amount to total growth resulted in improved assay susceptibility and an interference-free method. Misleading results can be obtained when pharmaceutical products containing citrates are tested by conventional methods for penicillin cross-contamination.


Gentamicin blood levels: a guide to nephrotoxicity. Gentamicin blood levels were monitored in 86 patients. Twenty-one patients had valley levels over 2 mug/ml and 36% of these patients developed abnormal serum creatinine or a further rise in creatinine. No patient had a rise in creatinine without a valley level over 2. The peak levels in patients with valleys over 2 were above 10 mug/ml in only one case, whereas four patients had peaks over 10 mug/ml without nephrotoxicity. The mean peak blood levels in patients with a normal creatinine were dose related. An initial dose of 2.0, 1.5, and 1.3 or less mpk (mg/kg) yielded mean peak blood levels of 5.2, 4.7, and 3.7, respectively. To assure an initial peak blood level over 4 mug/ml a loading dose of 2 mpk was required. A rise in peak and valley levels during therapy appeared dose related, being observed in all patients treated with 4.5 mpk daily but not in those receiving 3.0 mpk daily. A radioenzymatic assay was used to validate the standard agar diffusion assay method. The results from the two assays were statistically identical. Valley blood levels of gentamicin may be useful for predicting accumulation of gentamicin which in turn may be correlated with early renal impairment before potentially toxic serum levels of gentamicin develop.


Effects of renal failure and dialysis on cefazolin pharmacokinetics. Serum and urinary levels of cefazolin were determined after a 500-mg parenteral dose in eight azotemic volunteers. The mean peak serum concentration was 1.5 to 5 times the levels obtained in nonazotemic patients. The serum half-life of cefazolin was increased significantly. In patients on dialysis, the mean serum half-life of cefazolin was 4.05 h during (or after) hemodialysis, and 32.1 h during (or after) peritoneal dialysis. There was a significant decrease in cefazolin removal when dialysate flow or membrane surface area of the dialyzer were decreased. It was also shown that one circuit through the dialysis unit caused measurable decrease in cefazolin concentration. These data and previously published reports suggest: (i) the maintenance dose of cefazolin can be decreased in azotemic patients; (ii) patients on hemodialysis will require an additional half dose after dialysis because of efficient removal during hemodialysis; and (iii) patients on peritoneal dialysis do not require an extra dose.


Pharmacological evaluation of amikacin in neonates. The in vitro bacterial susceptibilities and pharmacokinetic properties of amikacin (BB-K8) were studied in newborn infants. Gram-negative bacteria and Staphylococcus aureus isolated from neonates were uniformly susceptible to 10 mug or less of amikacin per ml, and five Escherichia coli strains resistant to kanamycin were inhibited and killed by 5 mug or less of amikacin per ml. Mean peak serum concentrations of 17 to 20 mug/ml were observed 30 min after 7.5-mg/kg amikacin doses, and accumulation of drug in serum was not detected after repeated doses for 5 to 7 days. Intravenous infusion of amikacin over a 20-min period resulted in extremely low peak serum levels in four of eight infants studied. Serum half-life values were correlated inversely with postnatal age and renal clearances of amikacin. The volumes of drug distribution indicate that amikacin remains primarily in the extracellular fluid space of neonates. The lack of efficacy and safety data preclude the use of amikacin in neonates at this time.


Microwave sanitization of color additives used in cosmetics: feasibility study. Microwave exposure has been explored as a method of microbiologically sanitizing color additives used in cosmetic products. Selected microbiologically unacceptable cosmetic color additives, D&C red no. 7 Ca lake (certified synthetic organic color), carmine (natural organic color not subject to certification), and chromium hydroxide green (inorganic color not subject to certification), were submitted to microwave exposure. Gram-negative bacteria were eliminated, as verified by enrichment procedures, and levels of gram-positive bacteria were reduced. Generally, analytical and dermal safety studies indicated no significant alterations in physical, chemical, and toxicological properties of the colors. Sanitization was also successfully performed on other colors (D&C red no. 9 Ba lake, D&C red no. 12 Ba lake, D&C green no. 5, and FD&C red no. 4); initial physical and chemical tests were satisfactory. Results indicated that this method of sanitization is feasible and warrants further investigation.


Characterization of radiation-resistant vegetative bacteria in beef. Ground beef contains numerous microorganisms of various types. The commonly recognized bacteria are associated with current problems of spoilage. Irradiation, however, contributes a new factor through selective destruction of the microflora. The residual microorganisms surviving a nonsterilizing dose are predominantly gram-negative coccobacilli. Various classifications have been given, e.g., Moraxella, Acinetobacter, Achromobacter, etc. For a more detailed study of these radiation-resistant bacteria occurring in ground beef, an enrichment procedure was used for isolation. By means of morphological and biochemical tests, most of the isolates were found to be Moraxella, based on current classifications. The range of growth temperatures was from 2 to 50 C. These bacteria were relatively heat sensitive, e.g., D10 of 5.4 min at 70 C or less. The radiation resistance ranged from D10 values of 273 to 2,039 krad. Thus, some were more resistant than any presently recognized spores. A reference culture of Moraxella osloensis was irradiated under conditions comparable to the enrichment procedure used with the ground beef. The only apparent changes were in morphology and penicillin sensitivity. However, after a few subcultures these bacteria reverted to the characteristics of the parent strain. Thus, it is apparent that these isolates are a part of the normal flora of ground beef and not aberrant forms arising from the irradiation procedure. The significance, if any, of these bacteria is not presently recognized.


Incidence of Vibrio parahaemolyticus in Chesapeake Bay. A Bay-wide survey of the distribution of Vibrio parahaemolyticus was carried out in Chesapeake Bay during May 1972, to determine whether the annual cycle of V. parahaemolyticus which was observed to occur in the Rhode River subestuary of Chesapeake Bay took place in other parts of Chesapeake Bay. In an earlier study, April to early June, when the water temperature rises from 14 to 19 C, was found to be a critical period in the annual cycle of the organism in the Rhode River, since this is the time period when the annual cycle is initiated. Results of this study, however, revealed that V. parahaemolyticus could not be found in the water column during May 1972. Nevertheless, several samples of sediment and plankton yielded V. parahaemolyticus isolates. Comparison of data with those for the Rhode River area examined in the earlier studies of the annual cycle of V. parahaemolyticus suggests that the time of initiation of the annual cycle of V. parahaemolyticus in the open Bay proper may be influenced by various factors such as temperature and salinity, i.e., deeper water locations may show initiation of the V. parahaemolyticus annual cycle later than shallow areas. Confirmation of the presence of the organisms in the samples studied was accomplished using numerical taxonomy with 19 reference strains also included in the analyses.


Estimate of the genome size by renaturation studies in Streptomyces. The genome sizes of Streptomyces coelicolor and Streptomyces rimosus as calculated by deoxyribonucleic acid reassociation kinetics are approximately 10.5 X 10(6) nucelotide pairs.


Reduction of endotoxin levels in influenza virus vaccines by barium sulfate adsorption-elution. The level of endotoxin in influenza virus vaccine lots was reduced 10- to 20-fold after barium sulfate adsorption-elution. The amount of viral antigen lost was negligible.


Lymphatic transport and phagocytosis of melanosomes in blue nevus. The present paper describes ultrastructural aspect of lymphatic transport of dermal melanosomes in blue nevus. At least two processes may be responsible for the transport across the lymphatic endothelial wall in vivo; one is the passage of melanophages through the intercellular junctions and the another of free melanosomes. Phagocytosis of melanosomes by lymphatic endothelial cells is discussed.


[Penetration of radioactive hydrocortisone in human skin from various ointment bases. II. In vivo-experiments (author's transl)]. Absolute concentrations in the horny layer, epidermis, and dermis of therapeutical doses of topically applied hydrocortisone to human skin (in vivo) are reported. Using vaseline as vehicle 2-10(-4) molar concentrations are found in the epidermis and 3-10(-5) molar concentrations in the dermis. Further, three vehicles revealed minor concentrations. Comparison of the results with similar in vitro-investigations, reported earlier, allow to judge the resorption rate by the intact capillary system. Uptake of hydrocortisone by the vessels is observed. With high rates of penetration vasoconstriction seems to limit the resorption, while this is not the case with low rates, for instance with polyethyleneglycol as vehicle. Thus a differing drug liberation from the vehicle causes qualitatively different permeation kinetics. The elimination by urine, however, was practically the same. It is concluded that different vehicles may cause different therapeutic concentrations of the drug in the skin, but equal systemic side effects.


[Isolation and amino acid composition of two pathologically augmented proteins from psoriatic scales (author's transl)]. Two protein bands of water soluble extracts of psoriatic scales, which appear intensified in disc-electrophoretical separation, were isolated and their amino acid compositions were determined. It could be demonstrated that band 9 was rich of glycine, alanine, aspartic acid, leucine, and serine and that band 10 was rich of glycine, threonine, and serine. Both proteins contained an amino-sugar (galactosamine).


Fine structure and x-ray microanalysis of melanosomes in pigmented nevi and melanomas. Further finestructural characteristics of melanosomes in pigmented nevi and melanomas are described. The differences in the calcium, iron and surphur content of melanosomes derived from melanocytes, nevocytes and malignant melanoma cells are pointed out.


Fluorescence microscopy test in porphyrias, photodermatoses and lead exposed persons. Fluorescence microscopy tests were carried out in different groups of patients Peripheral blood diluted with saline was used and 200 high power fields were inspected in every case. The results were presented as the number of fluorescing erythrocytes (FE) per 100000 red blood cells (or 200 fields). In the controls, porphyria cutanea tarda patients and patients with photodermatoses other than erythopoietic protoporphyria and pellagra almost no FE were detected. In erythropoietic protoporphyria the mean value was 10600, in lead poisoning 1032, in patients exposed to lead 48.2, in sideropenic anaemia 123 and in patients with pellagra 8.1 FE/100000 red blood cells. The conclusion is made that one has to take care, when using this test for detection of latent carriers in genetic studies of the relatives of patients with erythropoietic protoporphyria. The test is useful for the confirmation of the diagnosis of erythropoietic protoporphyria.


Experimental studies on human health effects of air pollutants: I. Design considerations. Because of the possible threat to public health posed by photochemical air pollution, a need exists for experimental studies of short-term respiratory effects of air pollutant exposure in humans. Such studies require rigorous control and comprehensive documentation of the experimental air environment and exposure conditions to ensure that results are both reliable and relevant to public health questions. In addition to biochemical, behavioral, and clinical evaluations, comprehensive pulmonary testing is required to assure that effects at different levels of the respiratory tract are detected. An experimental design based on these principles is described. Studies using this design have shown a wide range of sensitivity to the pollutant ozone and important adverse health effects in sensitive individuals under exposure conditions similar to those experienced during ambient pollution episodes.


Biochemical and physiological parameters on the skin surface of healthy test persons: a contribution towards the interpretation of the results obtained by a screening program. Biochemical and physiological examinations were carried out on the skin surface of a total of 115 healthy persons ranging from the age of 7-79 years. In these investigations the following striking findings were made: 1. There is a significant correlation between the results obtained by the ferricyanide, the phenol sulfuric acid and the ninhydrin methods in the so called water solubles. 2. The relationship between the fraction of wax and cholesterol esters and the squalene fraction in the skin surface lipids influences the release of free fatty acids by bacterial lipases. 3. With regards to most parameters tested there are great differences between the 8-12 year age group and the older age groups. 4. There are significant differences in the 8-12 year age group between the male and female test persons. 5. With regards to the parameters tested there are also significant differences between the various test areas.


The role of carbon monoxide in cigarette smoking. I. Carbon monoxide yield from cigarettes. The carbon monoxide deliveries of 20 major Canadian brands of cigarettes, determined by gas chromatography and using standard smoking conditions, were estimated and found to vary by a factor of about two. The CO yields were found to increase with puff volume and tobacco moisture, decrease with increased paper porosity, but remain essentially constant with puff duration. The data suggest that reduced CO deliveries can be achieved by increasing the cigarette paper porosity. Combustion temperature presumably also influences CO deliveries, but the relative role ascribed to dilution and combustion is not clear. It may be concluded that smokers can lower their CO exposure by reducing their puff volume, smoking cigarettes manufactured from high porosity paper, by taking fewer puffs, and decreasing their tendency to inhale. Since CO and tar deliveries are correlated, these measures would also tend to decrease a smoker's exposure to tar.


Ghetto hiring.

Ghetto hiring. A review was conducted of the medical charts of random samples of "hard-core unemployed" hired in 1968 and of "ghetto hires" in 1972. No unusual medical problems were found. The attendance pattern appears worse than that of the general employee population but seems unrelated to underlying medical problems. A very high rate of on-duty accidents was found in both groups. The explanation is not immediately apparent, but will be pursued further.


Repeated exposure to acetaldehyde vapor. Studies in Syrian golden hamsters. The subacute inhalation toxicity of acetaldehyde was examined with four groups of 20 hamsters each, exposed repeatedly to acetaldehyde vapor at concentrations of 0, 390, 1,340, and 4,560 ppm (six hr day, five days/week) for a 90-day period. The highest level induced growth retardation, ocular and nasal irritation, increased numbers of erythrocytes, increased weights of heart and kidneys, and severe histopathological changes in the respiratory tract that mainly consisted of necrosis, inflammatory changes, and hyper- and metaplasia of the epithelium. The upper segments of the respiratory tract were much more severely injured than the lower parts. At 1,340 ppm treatment-releated changes included increased kidney weights in males and slight hyper- and metaplastic changes of the tracheal epithelium; 390 ppm was considered a no toxic effect level.


Octabromobiphemyl-induced ultrastructural changes in rat liver. Single oral administration of octabromobiphenyls at 1,000 mg/kg, or two consecutive doses of 3,000 mg/kg, to rats produced liver enlargement. Light microscopic examination revealed hepatocellular hyperplasia, margination of basophillic cytoplasm, and foamy cytoplasmic alteration on the third day posttreatment. Laminated cytoplasmic inclusions developed seven days after treatment and subsequently disappeared about one week later. Under electron microscopy, the cytoplasmic margination corresponded to peripherally displaced granular reticulum and the foamy cytoplasm was recognizable as proliferating agranular reticulum with depletion of particualte glycogen. The cytoplasmic inclusions were identified as myelin configurations enclosing lipid bodies, membrane-bound vacuoles with whorled figures, and vesicular agranular reticulum. In the early developmental stages, the myelin figures were studded with ribosomes and associated with the granular reticulum.


Oral inhalation system for exposing rabbits to cigarette smoke. An oral inhalation system for exposing rabbits to cigarette smoke has been developed. The essential components of the system comprise a smoke delivery device that adapts to the oral cavity, a molded face mask, and a sealable body enclosure. The functional capability of the system has been validated by detecting the presence of nicotine in plasma and by measuring the deposition of dotricontane labeled with radioactive carbon (14C) in lungs after exposure to cigarette smoke.


The treatment and postoperative complications of congenital megacolon: A 25 year followup. In 1948 one of us (O.S.) proposed a new method of treatment, abdominoperineal resection, for patients with congential megacolon. Since then, 483 patients have been treated by 13 pediatric surgeons in Chicago and Boston using this technique. Two hundred and eight-two of the patients were last interviewed and examined more than 5 years after the resection. There were 16 postoperative deaths (3.3%) and 6 late deaths (1.2%) from enterocolitis. Both early and late complications were infrequent and are discussed in detail. Almost 90% of the patients reported that they now have normal bowel habits. None of the patients developed urinary incontinence or impotence, although ten patients (2.1%) reported permanent fecal soiling. This is the first large group of patients treated for congenital megacolon who have been followed to adulthood. The low incidence of postoperative complications and minimal frequency of long-term complications indicate that the abdominoperineal resection is a safe, effective method of treatment for congenital megacolon.


Necrotizing enterocolitis in the newborn: operative indications. Fifty-two premature, low birth weight infants presented mainly in the first week of life with sudden manifestations of intestinal ileus and an x-ray picture of pneumatosis intestinalis. Twenty-two of 32 patients treated with gastric decompression, antibiotics, intensive supportive therapy and intravenous hyperalimentation survived. Twenty other patients had progression of their disease and required operation. Twelve of these patients survived. Review of this material indicated that some medically treated patients might have survived if they had been operated upon. Indications for operation included free perforation and clinical signs of deterioration. Abdominal physical findings and x-rays were not reliable except as signs of far advanced pathology. Confirmation of ascites by paracentesis and gram stain of fluid was helpful when present. If patients were adequately treated and then developed sudden hyponatremia or progressive acidosis, they invariably had gangrenous bowel and required operation. The most striking finding was that a sudden, profound drop in the platelet count to levels below 100,000 reliably predicted the presence of gangrenous bowel and the need for operation. Other clotting studies indicated that disseminated intravascular coagulation is an important accompaniment of NNE with the complication of bowel gangrene prior to perforation. Gastrostomy and resection of involved bowel with staged anastomosis proved to be the most successful form of surgical management. Overall suvival was 66 per cent.


Coronary revascularization in "high" versus "low-risk" patients: The role of myocardial protection. Postoperative mortality, infarction, and need for inotropic support are reportedly increased following myocardial revascularization in "high-risk" patients. We believe these complications result from inadequate protection of the compromised myocardium and should not occur with greater frequency in "high-risk" than "Low-risk" patients if the heart is optimally protected during the entire course of the operative procedure. Results following revascularization in 50 consecutive "low-risk" and 50 consecutive "high-risk" patients were analyzed. One or more of the followin factors were present in the "high-risk" group: ventricular dysfunction--ejection fraction less than 0.4, preinfarction angina, evolving infarction, recent infarction (less than 2 weeks), and refractory ventricular tachyarrhythmia. The following principles were used in all patients to minimize ischemic injury: 1) avoidance of pre-bypass hypo- or hypertension, 2) limitation of ischemic arrest to less than 12 minutes, 3) avoidance of ventricular fibrillation, and 4) prolongation of total bypass as necessary to repay the myocardial oxygen debt. Postoperative inotropic support was required in 10% of "high" and 10% of "low-risk" patients, new postoperative infarction developed in 10% of "high" vs. 10% "low-risk" patients; death occurred in 2% of "high" vs. 4% "low-risk" patients. These results are comparable and indicate that optimum myocardial protection allows safe revascularization in the "high-risk" patient.


Selection of the optimum surgical treatment of stage I melanoma by depth of microinvasion: Use of the combined microstage technique (Clark-Breslow). The methods of histologic staging of primary Stage I melanoma and the relation to lymph node metastases and survival after surgery was evaluated in 151 patients with extremity melanoma only. Microstaging by depth of invasion showed a better prognostic correlation than by histologic typing (into superficial spreading, or nodular melanoma). A correlation existed between depth of invasion (Clark's levels) and incidence of nodal metastases at elective node dissection. This incidence was 5% at Level II, 4% at Level III, 25% at Level IV and 75% at Level V. The measured depth of invasion added prognostic insight to each Clark's level; the minimal invasion at which nodal metastases occurred was 0.6 mm for Level II, 0.9 mm for Level III, 1.5 mm for Level IV and over 4 mm for Level V. The 5 year disease-free survival after surgery was 100% for Clark Level II, 88% for Level III, 66% for Level VI and 15% for Level V. There was a direct relation between the measured depth of invasion and survival and mortality from disease at 5 years. Mortality from disease at 5 years could be directly equated with 10 times microinvasion in mm. Microstaging by direct measurement gave a better prognostic correlation than was found using Clark's levels for more deeply invading melanoma. At this time there is suggestive evidence that patients with certain higher risk lesions may do significantly better with wide excision and elective node dissection than with wide excision alone. These high risk lesions include Clark Level III to V, lesions measuring 0.9 mm or greater and all nodular melanomas.


Prophylactic isolation-perfusion as the primary therapy for invasive malignant melanoma of the limbs. The most common causes of treatment failure in patients with malignant melanoma treated by surgical therapy alone are local or regional recurrences. These are presumed to be due to occult metastasis present at the time of the initial treatment. In an effort to control this occult regional disease, 202 patients with Stage I malignant melanoma underwent isolation-perfusion with 1-phenylalanine mustard between the years 1960 and 1970. The 2-5 and 10-year determinate survival rates were 98%, 86% and 83%, respectively. In these patients, 2% developed local recurrences, 3% developed intransit metastasis, 18% developed positive regional lymph nodes and 6% developed disseminated disease, as their first evidence of recurrence. Over 40% of these patients were benefitted by further therapy. When regional perfusion is used, the question of prophylactic lymph node dissection need not arise. There was one surgical death in this series and only a few patients had symptomatology referable to their limbs beyond 3 months.


Secundum atrial septal defect and mitral valve incompetence. Mitral regurgitation associated with secundum atrial septal defect is described in 4 patients, each with a different mitral lesion: rheumatic valvular disease, congenitally cleft valve, subacute bacterial endocarditis with disruption of the chordae tendineae, and traumatic valve rupture. The pathological spectrum of mitral valve disease associated with atrial septal defect is reviewed, and it is suggested that structural abnormality of the mitral valve may accompany the atrial septal defect. More general awareness of this association will allow the surgeon more accuracy in defining and repairing this rather unusual combination of lesions.


Tracheostomy and endotracheal tube cuff volume and pressure changes during thoracic operations. The effects of oxygen and 60% nitrous oxide and oxygen on the pressure and volume of Portex low-pressure (LP) and high-pressure (HP) endotracheal tube cuffs were determined in 120 intubated patients undergoing thoracic surgical procedures. Cuffs were filled with either room air or a sample of the inspired gases. All cuffs had sustained significant increases in cuff volume and pressure by the end of the procedure except those filled with inspired gases. LP cuffs had lower initial and final cuff pressures than HP cuffs, but pressure and volume changes were similar with both types. Cuff gas analysis revealed that cuff volume changes were due to diffusion of oxygen and nitrous oxide into the cuff and failure of nitrogen to diffuse out. These findings suggest that cuff overexpansion during anesthesia or prolonged ventilation may be an important cause of tracheal trauma.


The effects of preoperative irradiation on primary tracheal anastomosis. Preoperative radiotherapy was used in the management of selected patients with cancer of the lung or trachea who might subsequently require segmental resection of bronchus or trachea and reconstruction by primary anastomosis. This study was designed to determine the effects of varying dosages of preoperative irradiation on anastomotic healing. Two rings were resected from the cervical trachea of 20 dogs following irradiation with varying doses of cesium. There were no important adverse effects on healing of the trachea or adjacent organs in dogs receiving up to 3,500 rads. All dogs receiving a higher dose than this developed some anastomotic stenosis, which was severe in 6 of 8 animals. Similar adverse effects were observed in 2 patients managed by preoperative radiotherapy (4,000 rads in three weeks) and tracheal resection with primary anastomosis.


Pulmonary sequestration. A broad spectrum of bronchopulmonary foregut abnormalities. We believe the broad clinical, embryological, and radiological spectrum of pulmonary sequestration has not been adequately emphasized. In order to gain clearer understanding of these foregut abnormalities, all cases from the files of three Army Medical Centers were reviewed. Thirty-two patients, the largest single series in the literature, met the criteria for a diagnosis of bronchopulmonary sequestration. Clinical manifestations varied from no symptoms to recurrent pulmonary infection, hemoptysis, and intrapleural hemorrhage. The presence of symptoms strongly correlated (23/32) with air-containing cystic sequestrations. The embryological and radiological spectra as well as appropriate operative therapy are reviewed.


Clinical effects of membrane lung support for acute respiratory failure. Extrapulmonary support in respiratory failure has become possible for prolonged periods with clinical application of the membrane lung oxygenator. The membrane lung may be perfused in a venovenous circuit, in which case it functions by prepulmonary venous oxygenation, or it may be pumped in venoarterial perfusion as partial or total cardiopulmonary bypass. Four patients were placed on venovenous membrane lung (GE-Peirce) perfusion for periods ranging from 6 to 112 hours. In oxygenating blood flows of less than 50% of the cardiac output, a viable PaO2 (mean, 52 mm Hg) was obtained in 2 patients with 60% FIO2, including 1 survivor who was weaned from the membrane lung. The remaining 2 patients had heart failure and insufficient venovenous membrane lung flows to improve systemic oxygenation (mean PaO2, 45 mm Hg on 100% FIO2). Four other patients were placed on venoarterial membrane lung (GE-DuaLung) bypass for 18 to 110 hours. With 40 to 85% of the cardiac output bypassed through the membrane oxygenator, immediate improvement was seen in systemic oxygenation (mean PaO2, 75 mm Hg), effective compliance (mean increase of 75%), and reduction in pulmonary hypertension (mean decrease, 15 mm Hg). These changes during bypass allowed the lungs to be put at rest with a decrease in FIO2 and positive end-expiratory pressures. This clinical experience indicates that venoarterial membrane lung bypass may be both supportive and therapeutic, decompressing the pulmonary circuit and maintaining systemic oxygenation. Membrane lung supported by either mode of perfusion has been shown to be clinically effective in patients suffering acute respiratory failure.


Food-choking and drowning deaths prevented by external subdiaphragmatic compression. Physiological basis. Applying subdiaphragmatic compression has been successful in saving victims of food-choking and drowning by expelling the asphyxiating bolus or aspirated water. Sudden elevation of the diaphragm compresses the lungs, which explosively forces air out through the trachea, ejecting the obstructing object. The flow rate, pressure, and volume of air expelled were determined in 10 subjects and found to be substantial, providing confirmation of the effectiveness of the procedure.


Pulmonary aspergilloma. A report of its occurrence in 2 patients with cyanotic heart disease. This is an account of our experience with 2 patients with congenital cyanotic heart disease who developed pulmonary aspergillomas. Neither patient had a demonstrable cavity in the lung before the appearance of the fungus ball. Both patients had pulmonary artery-to-superior vena cava shunts, but the aspergilloma was in the ipsilateral lung in one and the contralateral lung in the other. Repeated life-threatening hemoptyses made excision of the lung containing the cavity and fungus ball necessary in both patients.


Aortic and mitral valve replacement with cloth-covered Braunwald-Cutter prosthesis. A three-year follow-up. From February, 1971, through February, 1974, heart valves of 510 patients were replaced with cloth-covered Braunwald-Cutter prostheses. The data indicate that cloth encapsulation of the prosthetic cage is associated with a reduction in thromboembolic complications, particularly for mitral valves. Cloth wear on the distal strut, however, is not prevented by use of a Silastic poppet and appears to be a typical finding in aortic valves recovered or inspected after 3 months. Excessive poppet wear has also been noted in the aortic position; poppet embolization has occurred on 2 occasions, and a third patient was found, at the time of reoperation for periprosthetic leak, to have opppet wear sufficient to permit embolization. Although there have been no reports of clinical malfunction of the mitral prosthesis at the time of this writing, further long-term observation of these patients appears warranted.


Late stenosis of Starr-Edwards cloth-covered prostheses. During a two-year period (August, 1971, to July, 1973) 1 Starr-Edwards Model 2400 and 135 Starr-Edwards Model 2320 aortic prostheses were inserted without postoperative antiocagulant therapy. Seven of these valves (including the Model 2400 prosthesis) have been replaced because of substantial transvalvular gradients resulting from fibrous overgrowth of the valve orifice. Symptoms associated with aortic stenosis occurred an average of nine months after  the initial operation. Six patients had severe anemia (packed cell volume less than 30%) and hemolysis (serum lactic dehydrogenase greater than 900 units). Gradients across the prostheses ranged from 66 to 105 mm Hg with a mean of 87 mm Hg. One valve was size 8A, 3 were 10A, and 1 was 12A. Fibrous ingrowth was not observed in an earlier group of 23 patients receiving the Model 2310 or Model 2320 prosthesis who were placed on long-term anticoagulant therapy. These findings, coupled with a 9% incidence of thromboembolism at one year, indicate that patients having these prostheses inserted should receive long-term anticoagulant therapy.


Occluder disruption of Wada-Cutter valve prosthesis. Total detachment and embolization of the hinged, tilting occluder of the Wada-Cutter prosthetic heart valve was the proved cause of death in 2 of 25 patients who had these devices implanted at the University of California, San Francisco, Medical Center in 1969-70. In addition, there were 8 late deaths without postmortem examination, 2 of which were sudden and 4 of which followed rapidly progressive congestive heart failure over a period of hours to days. Prosthetic malfunction appears to be a possible mechanism of death in the majority of these patients. The 2 additional late deaths were unrelated to valve malfunction. Regurgitant murmurs have been identified during follow-up examination in 17 patients. Two patients had prosthetic replacement for hemodynamically significant leaks through the valve mechanism and were found to have no perivalvular leak. Six additional patients had prophylactic replacement of the Wada-Cutter valve. Measurements on 7 available occluders that were removed showed variable degrees of material movement at the hinge. This experience has caused us to recommend elective replacement of remaining Wada-Cutter valves.


Long-term results of "simple" thrombectomy for thrombosed Björk-Shiley aortic valve prostheses. During the past two years 8 patients were seen with thrombosis of their Bjork-Shiley aortic valves. Six patients were from our series, an incidence of 4% and 2 patients had their original valve implanted at another institution. All patients had substantial problems with anticoagulation therapy. Three died prior to operation. Early detection and emergency surgical intervention is mandatory for survival. At operation debridement of all thrombotic material from the valve provided satisfactory immediate hemodynamic improvements as well as freedom from complications for up to two years. Therapeutic levels of anticoagulation with warfarin are the only apparent protection from thrombosis of the Bjork-Shiley aortic valve.


Analysis of homograft valve failure in 311 patients followed up to 10 years. Homograft aortic valve replacement was performed in 311 patients at the tnational Heart thospital, London, between 1964 and 1973. Valve failure has occurred in 61 patients (20%), 32 of whom survived reoperation. From 1963 through 1967, 156 valves were freeze-dried and account for 56 of the valve failures. From 1968 to 1973, 118 fresh or fresh-frozen valves resulted in only 5 failures. Six general types of failure have been identified: calcification (13), dehiscence (15), infective endocarditis (17), prolapse (6), cusp degeneration (5), and tear or perforation (5). Valve failure may be due to surgical technical error resulting in dehiscence or valve incompetence, or it may be related to degenerative changes in the homograft. The clinical results, supported by gross and histological examination and viability testing, enable us to conclude that fresh or fresh-frozen valves are superior to freeze-dried valves, having resulted in only 4% valve failure over the past five years.


Aortic valve replacement in the anephric patient. A 30-year-old anephric patient on a home dialysis program developed bacterial endocarditis, aortic insufficiency, and severe hear failure. After a period of intensive medical management she underwent aortic valve replacement successfully. One year following operation she continues to do well and is again managed by home dialysis without further complication.


An improved statistical method for assessing the results of operation. The advantages of the acturarial method of analyzing postoperative survival are now widely accepted. In evaluating the late results of heart valve replacement operations, however, certain nonfatal complications must also be considered. The use of individual event-free rates does not portray individual risk, since some valves have multiple complications. By using cummulative complication-free rates, however, it is possible to estimate the percentage of valves active and free from certain major complications for each postoperative interval. A series of actuarial curves is used, each of which represents a different major complication. These curves are subtracted progressively from the total of valves at risk, and an acturial representation of complication-free survival results.


Congenital cardiac anomalies: one-stage repair in infancy. A proposed preferred treatment plan consisting of one-stage operative repair of congenital cardiac anomalies whenever complete correction was feasible and operative intervention required was tested during the period February 1, 1972, to September 15, 1974. Experience with 74 patients aged 14 hours to 24 months allows some conclusions to be made regarding the advisability of this approach. For patients with ventricular defect and tetralogy of Fallot, this approach has quite acceptable results and certainly is more direct than palliative operations and second-stage repair. The hypothesis is more difficult to justify in patients with transposition of the great arteries. By avoiding repair in patients under 4 months of age and using a better technique for placement of the intraatrial partition, improved results are anticipated. In the miscellaneous group of anomalies, results depend upon the complexity of the defect and the ability to achieve accurate anatomical correction. After an early mortality of 20% and some late deaths, survival and improvement resulted in 51 of these babies. These results justify persistence in the choice of one-stage correction when operative intervention is required.


Transtelephone pacemaker monitoring: five years later. Six hundred nineteen patients have been followed by remote monitoring of pacemaker function using ECG and rate or rate alone; 278 of 280 have had battery exhaustion or electronic failure demonstrated. Ten percent of exhausted pacemakers failed prior to the average longevity of the particular model, and 32% (89 of 280) exceeded 36 months' longevity; of these, 13% (37 of 280) lasted more than 40 months and 4.6% (13 of 280) exceeded 50 months. The error rate is 0.7% (2 of 280). With pulse generator longevity increasing, monitoring is done less frequently during the first 2 years, then calls are made weekly after 24 months.


Spontaneous closure of a traumatic ventricular septal defect following a penetrating injury. A ventricular septal defect acquired from a penetrating injury to the membranous septum closed spontaneously, as documented by repeat cardiac catheterization. The patient was asymptomatic from the time the lesion was discovered until the present. We advise observation of these lesions for a period of time, provided that no evidence of cardiac decompensation or pulmonary hypertension is noted as determined by hemodynamic studies and clinical observation. Cardiac catheterization is mandatory to confirm the diagnosis, measure the magnitude of the shunt, and rule out associated intracardiac injuries. We believe the lesion should be closed on an elective basis, regardless of the absence of symptoms, if after a reasonable time there is no evidence that the ventricular septal defect is closing and a significant shunt is demonstrated.


A possible hazard with the use of pressurized constant-infusion systems. We have observed small bubbles in lines used to monitor left atrial pressure. The source of these bubbles may be gas from a supersaturated infusate solution. Personnel responsible for the maintenance of atrial pressure lines should be alerted to this possible hazard.


Superior vena cava obstruction: a review of the literature and report of 2 cases due to benign intrathoracic tumors. A review of the literature shows an increaseing number of cases of superior vena cava obstruction associated with malignancy and a marked decrease in the number of patients with caval obstruction of benign origin. In contrast to granulomatous diseases and aneurysms of the ascending thoracic aorta, which have decreased, the incidence of benign tumors is essentially unchanged. Clinical features of superior vena cava obstruction in relation to the anatomical site of obstruction and collateral pathways are correlated. Diagnostic approaches, including angiography and technetium scanning are usually definitive in outlining the site of obstruction. Experimental data and the numerous available techniques for surgical correction indicate that an entirely satisfactory procedure is not available for all patients. Methods include the use of venous bypass or Teflon prostheses and the addition of a small arteriovenous fistula proximally. Two new cases of superior caval obstruction due to benign tumor are reported. In 1 patient, who had intrapericardial bronchogenic cyst with fibrotic caval obstruction and thrombosis, a method for caval reconstruction while maintaining venous return to the right atrium is described. The second patient had an intrathoracic thyroid adenoma and caval obstruction without thrombosis.


[Anti-arrhythmic effects of derivatives of metoclopramide]. The antiarrhythmic effect of Metoclopramide and its analogs, sultopride and thiapride, were studied. In the dog arrhythmias were induced by epinephrine, ouabain and coronary artery ligation. In the guinea-pig the effect of each compound was determined on the ouabain-induced arrhythmias as well as on the refractoriness of the electrically stimulated isolated atria. In the dog sultropide and thiapride were less active than metoclopramide. However, metoclopramide and thiapride depressed auriculo-ventricular conduction. None of these agents exerted a protective antiarrhythmic effect in the guinea-pig. Metoclopramide increased the refractoriness while sultropide and thiapride were almost inactive. Unlike metoclopramide, the two analogs have no local anesthetic activity.


[Blood-brain barrier. II. Kinetics of distribution of 3H-parahydroxyamphetamine in brain structures after intravenous administration in the rat]. Intravenously injected parahydroxyamphetamine hardly penetrates into the Central Nervous System, since, 5 minutes after injection, the tissue to plamsa concentration ratio for brain and cerebrospinal fluid amounts to 0,67 and 0,35 respectively. Its concentration in muscle is 5 times higher than in plasma. In the brain, the molecule is preferentialy taken up by the corpus striatum and the hypothalamus. Thus, parahydroxylation of amphetamine inhibits the penetration of the molecule into the brain and suppresses its cortical fixation. These characteristics could explain why this parahydroxylated amine has no psychotropic action.


Cooperativity in classical receptor theory. Classical receptor-theory presents models of the relation between drug concentration and biological effect, also in the case where more than one binding site on a receptor must be occupied by the agonist to evoke a response. These models have considered only the possibility that none or all of these sites on the receptor are occupied by drug molecules; the possibility that receptors might by only partly occupied was disregarded. The present paper considers the consequences of this last possibility. It is concluded that the relation between concentration and effect, represented in different types of plots, is not determined only by the order of the reaction between the drugs and their receptors, but also by the ratios of the dissociation constants for the different steps of dissociation of the drug-receptor complex. This may make it almost impossible to make statements about the order of the reaction between drugs and receptors based on experimental data, and to discriminate between allosteric and classical receptor-theories.


A comparison of the discriminable CNS effects of ketamine, phencyclidine and pentobarbital. In a shock-escape T-maze task, rats were required to learn drug discriminations involving various doses of pentobarbital, phencyclidine and ketamine. Repeated training sessions were administered. Typically a right turn in the maze was required during drug sessions and a left turn was required during alternate no drug sessions. Results were as follows: 1. Linear dose effect curves relating discriminability (sessions to criterion) to dosage were obtained with all three drugs. 2. Phencyclidine and ketamine produced much more 'response randomization' than did pentobarbital at doses matched for discriminability. 3. Phencyclidine and ketamine tended to mimic each other's discriminable effects, but neither mimicked or was mimicked by pentobarbital. 4. Drug vs drug training demonstrated that phencyclidine and ketamine differed discriminably from each other.


Elevation of amphetamine levels in rat brain after administration of the choline acetyltransferase inhibitor 4-(1-Naphthylvinyl) pyridine (NVP). Following amphetamine administration both NVP and SKF-525A cause elevations in whole brain levels of amphetamine compared with saline treated controls. NVP was found to be about 3 times more active than SKF-525A; significant effects were obtained after doses of 0.625mg/kg and above. NVP also inhibited brain choline acetyltransferase in vitro (I50 of 4.0 x 10-5 M). Following the administration of NVP (20-200 MG/KG, I.P), there was a dose-dependent inhibition of this enzyme in brain. These results suggest that potentiation of the behavioral effects of amphetamine by NVP, which occur after doses of 5 mg/kg of NVP, are probably related to its inhibitory effects on amphetamine metabolism.


Changes in rat brain monoamine metabolism following the acute administration of lithium chloride in combination with antidepressant drugs. The acute administration of lithium chloride resulted in a decrease in the concentration of serotonin, tyrosine, dopamine and noradrenaline in the rat brain. The antidepressant drugs imipramine, amitriptyline and Org GB94 did not reverse or potentiate the effect of lithium chloride on these monoamines or tyrosine. It is concluded that the ability of lithium salts to enhance the effect of antidepressant drugs in the treatment of endogenous depression cannot readily be explained by their synergistic action on brain monoamine metabolism.


Effects of hydroxylamine on the consequences of long-lasting administration of morphine in mice. II. Time course of the hydroxylamine effect on morphine tolerance. Mice injected for 35 days with morphine sulfate in increasing doses did not show tolerance to the analgesic effects of morphine if injected intracranially with 0.3 M hydroxylamine. The excitatory action of morphine was unaffected. The interference with tolerance lasted for at least six weeks following the hydroxylamine injection. There were no apparent histological changes in the brains of treated mice as well as no differences in the composition of water-soluble brain proteins.


Effect of hydroxylamine on the consequences of long-lasting administration of morphine in mice. III. Effect on preferred drinking of morphine solution. C57BL/6J mice were periodically required to drink a morphine solution for one, ten or sixteen weeks and then injected intracranially with the mutagens hydroxylamine or sodium nitrite. Whereas before the injection of the drugs the mice demonstrated a definite preference for morphine, after hydroxylamine this preference disappeared. Sodium nitrite had no such effect on the consumption of morphine solution.


Effect of subpressor infusions of angiotensin on cardiovascular reactivity in the conscious rat. Cardiovascular reactivity before and after 30 minutes and 20 hr Angiotensin infusions (40 ng/kg/min) has been studied in 26 male Wistar rats. Control responses to Tyramine (T) (0.05, 0.1 MG). Angiotensin (A) 10, 40, 160 ng), Norepinephrine (NE)(25, 100, 400 ng) and Renin (R)(0.05 G.U.) were obtained in the conscious animals with chronic cannulas in the aorta and jugular vein. Pressor responses to the same vasoactive agents were obtained immediately after A infusions. Similar 5% dextrose infusions were performed as controls. Results showed that pressor responses to T and A were significantly increased after 30 minutes A infusion and even more after 20 h infusion. Pressor responses to NE increase significantly only at the intermediate dose (100 ng) after 20 hr infusion. Response to R was potentiated by A infusion after 30 minutes and 20 hr. Dextrose infusions did not produce any significant changes in pressor responses.


The negative inotropic effect of secobarbital on the heart of reserpinised newborn and adult guinea pigs. The negative inotropic effect of different concentrations of secobarbital was studied on isolated hearts of reserpinised newborn and adult guinea pigs. This effect was expressed as the percentage reduction of contraction height, from which the sensitivity of the heart was obtained as the reciprocal of the secobarbital concentration X1/2 needed to yield a 50% reduction (i.e. 1/X1/2). It was found that in adults depletion of catecholamines increased this sensitivity, but not in newborns. Possible interpretations are discussed and it is concluded that the age effects are not due to an effect of reserpine on contractility.


Pharmacokinetics and Eigenvector decomposition. Two-compartment open system after rapid intravenous administration. The theroetical background of linear pharmacokinetics is presented in terms of elementary mathematical operations while preserving the important aspects of eigenvector decomposition. The discussion is limited to two-compartment open models with rapid intravenous administration. Eigenvector decomposition allows to extend the theory in a straightforward manner to models of higher order and to other ways of administration. A computational scheme is included that can be carried out on a desk-calculator in a small number of steps.


Pharmacokinetics of secobarbital in rabbit. The pharmacokinetic study of secobarbital in the rabbit utilizing gas chromatography (GC) indicated a correlation between blood levels and brain tissue levels; and that the distribution of the drug appears to be more complex than a first order process is suggested by the compartmental simulation midel. The liver and kidney which eliminate the drug into bile and urine, respectively, tend to follow first order elimination kinetics more closely than those which act as depots for drug storage such as muscle and fat. The two dose levels of secobarbital indicate the same relationship with blood and tissues, therefore an increase or decrease in the dosage has no effect on the pharmacokinetics of secobarbital. The termination of action of secobarbital is due to the combination of rapid uptake by liver and its disposition there and a slower uptake by muscle. Computer simulation of secobarbital distribution has strongly suggested the elimination of this drug in bile and that the rebound rise in liver amy be due to enterohepatic circulation.


Absorption, distribution and excretion of trifluoperazine in rats. In rats receiving a low oral dose (0.35 mg/kg p.o.) of trifluoperazine (TFP), a potent neuroleptic phenothiazine, the parent drug distribution was separate from that of its metabolite trifluoperazine sulfoxide (TFP-SO). This was not seen after intraperitoneal administration (i.p.) of the same or high dose (5mg/kg). TFP-SO was not detected in the brain, wheras TFP was significantly associated with microsomes when its brain level was highest. Absorption, distribution, metabolism, and dose dependent excretion procedded rapidly with 97% of a dose recovered 24 hr after p.o. treatment, only 6% in the urine and the remainder in feces with 87% of this metabolized to compounds other than TFP-SO. TFP and its metabolites arrived in feces via two pathways, largely the bile plus another route. The excretion pattern was unchanges with other drugs or after treatment for 3 wk, although excretion differed on the first day after i.p. and p.o. administration.


Uptake and release of 3H-metaraminol by rat lung. The influence of various drugs. Uptake and release of 3H-metaraminol was measured in vitro incubating rat lung tissue in the presence of ouabain (1.5-45 mug/ml), cocaine (1-30 mug/ml), tyramine (0.1-3 mug/ml, reserpine (0.05-1.5 mug/ml), imipramine (0.1-3 mug/ml) and desipramine (0.3-10 mug/ml. All drugs significantly inhibited uptake and release of 3H-metaraminol from lung tissue. This blockade most probably occurs at membrane levels of both neuronal uptake-1 sites and extraneuronal uptake-2 sites. These results further emphasize the importance of the lung in the fate of drugs and endogenous substances.


Catecholamines and the actions of morphine on the guinea-pig ileum. The effects of catecholamines in modifying the response to some analgesic drugs of the guinea-pig ileum, electrically stimulated in vitro, were studied. Pre-treatment with reserpine reduced the potency of morphine in depressing twitches of the preparation. Noradrenaline and especially dopamine mimicked with stricking similarity the effects of morphine in producing 'chronic tolerance' and stimulating twitch height at high concentrations, and reversed 'acute tolerance' produced by repeated administration of 10 ng/ml of morphine. No phase of the response of the preparation to morphine was affected by phentolamine and propranolol, haloperidol or droperidol. The efflux of catecholamines from the preparations was depressed by morphine but output in the various phases of the response did not differ significantly from each other.


Distribution, metabolism and excretion of etomidate, a short-acting hypnotic drug, in the rat. Comparative study of (R)-(+)-(--)-Etomidate. Tritium-labelled (R)-(+) and (S)-(--)-etomidate was injected intravenously in male Wistar rats at four dose levels. Initial plasma clearance was high and the largest part of etomidate was rapidly distributed over those tissues, that had entered in equilibrium with plasma, such as brain, erythrocytes, heart, spleen, lung, kidney, muscle and intestines. Only in subcutaneous fat, testicles and stomach peak levels appeared after 28 minutes. The levels of etomidate, observed in all these tissues varied proportionally with the dose. Although the contents in brain of thw two isomers were comparable, only (R)-(+)-etomidate possesses hypnotic activity. The concentration in brain of (R)-(+)-etomidate, producing hypnotic activity in rats, was 1.50 +/- 0.35 mug/g tissues. Peak levels in liver appeared shortly after administration. Capacity-limited ester hydrolysis in the liver was the main metabolic pathway, yielding a single amphoteric metabolite. The rate of metabolization of (R)-(+)-etomidate was higher than that of the (S)-(--)-isomer. Excretion of the metabolite was mainly with the urine.


[Pharmacokinetics and action of digitoxin and ouabain in the isolated hearts of guinea pigs and rats]. Isolated guinea pig and rat hearts were perfused with 3H-digitoxin and 3H-ouabain. After varying perfusion periods (3-90 min) the glycoside content in the tissue was determined. With digitoxin the tissue/medium-ratio at equilibrium was found to be 14 in guinea pigs and 8 in rats, with ouabain the corresponding values were 2 and 1. In further experiments the efflux of radioactivity from isolated perfused hearts preloaded with 3H-glycosides was measured in 3 min intervals. A compartmental analysis was carried out. The efflux could be described by the sum of two exponentials indicating the existence of two compartments. The half lives of compartment 1 (2.1-4.0 min) and those of compartment 2 (16.8-20.6 min) were similar with both glycosides and both species. The development and decline of the positive inotropic effect in guinea pig hearts exhibited a time course similar to that of the glycoside content in compartment 1: the time for reaching the half maximum effect was 3-4 min with ouabain and 5-6 min with digitoxin. It is suggested that compartment 1 represents the site of the positive inotropic action of cardiac glycosides.


[Effect of antihypertensive agents on the in vitro biosynthesis of prostaglandin E and F2 alpha in the rabbit kidney medulla]. This report describes the influence of antihypertensive drugs on the biosynthesis of prostaglandins from endogenous precursors in the homogenates of rabbit kidney medulla. Dihydralazine and reserpine inhibited, alpha-methyldopa on the contrary stimulated the in vitro biosynthesis of prostaglandins E and F2alpha. Clonidin was without effect. The effects of noradrenaline and indomethacine as standard substances were determined.


[Electrophysiological analysis of the effects of 4-amino-pyridine in the isolated heart ventricle of the guniea pig]. The effects of 4-aminopyridine (4-AP) on guinea pig myocardial ventricular isolated strips were studied by means of intracellular microelectrodes. 4-AP increased the maximal depolarization velocity and decreased the effects of quinidine. In contrast to adrenaline, 4-AP antagonized the effects of MnCl1, but was ineffective against the alterations induced by a sodium poor solution. These findings support the suggestion that 4-AP modifies the electrophysiological membrane properties probably by increasing the Na+ inward current.


The influence of serotonin on insulin-stimulated gastric secretion, blood glucose and serum electrolyte levels in the unanesthetized rat. The effect of various doses of serotonin (5-HT) on the basal or insulin-stimulated gastric secretion was studied, for 4 hr after the injection, in unanesthetized rats with chronic gastric fistulas. The blood glucose and serum Na, K and Ca ions concentrations were also determined. Insulin produced hypoglycemia and hypokalemia, most pronounced in the first hr, and increased HCl and pepsin output, with a maximum at 2 hr after the injection. 5-HT significantly inhibited both basal and insulin-stimulated gastric secretion. The amine produced transient hyperglycemia, which was less pronounced in rats simultaneously receiving insulin. The inhibition of insulin-stimulated gastric secretion by 5-HT lasted for a longer period than the prevention of the biochemical changes brought about by insulin. The prevention by 5-HT of insulin hypoglycemia and hypokalemia may be of significant importance in the mechanism of the depression of insulin-stimulated gastric secretion.


Inhibition of the sympathetic nervous system by dopamine. If the right postganglionic cardioaccelerator nerves of cats are stimulated (2 Hz), dopamine, in the presence of cocaine, inhibits transmission. This inhibitory response is prevented by low doses of haloperidol. Phentolamine produces some antagonism and phenoxy-benzamine produces no antagonism to the dopamine-induced inhibition. It is postulated that dopamine receptors on the adrenergic nerve terminals modulate norepinephrine release.


The effect of ergotamine and methysergide on serotonin metabolism in the rat brain. Ergotamine tartrate and methysergide maleate each significantly altered serotonin (5-HT) metabolism in the rat brain. Whole brain levels of 5-HT were markedly reduced in a dose-related manner, with peak activity observed 30 minutes after I.P. administration and persisting through four hours after dosing. In addition, turnover rate of 5-HT was significantly increased. Pentylenetetrazol (PTZ)-induced convulsions were not inhibited by either ergotamine or methysergide but each drug interacted with PTZ to induce lethality, which is suggestive evidence of central 5-HT antagonist activity. Moreover, regional distribution of 5-HT in the rat brain was altered by these drugs in such a way to suggest that neihter was a "universally acting" central 5-HT antagonist.


5-Hydroxytryptamine-14C and dexamphetamine-14C uptake by fundal sarcolemma preparations: effect of thermal and chemical alterations as indirect approach to the problem of the common receptor. By submitting a sarcolemma preparation from gastric fundus to thermal (47 degrees C) and chemical (2 M urea) alterations, a significant decrease of the binding of labelled serotonin and dexamphetamine, 40% and 30% respectively, is observed. This finding suggests that the receptors for these two drugs contain a protein moiety, which undergoes a structural and functional modification upon the thermal or chemical procedure employed. The strictly similar behaviour of the binding properties of serotonin and dexamphetamine, in our experimental conditions, gives a strong indirect support to the hypothesis of a common receptor for these two drugs.


Further experimental evidence for a smooth muscle depressant effect of ketamine. The effect of ketamine on the rat uterus in oestrus and the guinea pig ileum was investigated to determine whether the drug has smooth muscle relaxant properties dependent upon beta adrenergic stimulation or an anticholinergic effect. The results with the rat uterus clearly showed that relaxation was not due to action at the beta adrenergic receptors. On this muscle preparation ketamine depressed carbachol-induced contractions. This anticholinergic action of ketamine was investigated on the guinea pig ileum. Dose response curves were obtained for acetylcholine, histamine and barium chloride in the presence of ketamine. The results showed that ketamine effectively reduced contractions elicited by the three agonists. It is concluded that ketamine is not a beta receptor agonist and it is unlikely that the drug is a specific cholinergic antagonist.


Cardiovascular effects and blood concentrations of ajmaline and its 17-monochloroacetate ester in cats. The antiarrhythmic drugs ajmaline and its 17-monochloroacetate ester (MCAA; Rtimos-Elle) were studied in cats. MCAA was less than half as toxic as ajmaline. Non-lethal doses of MCAA decreased blood pressure before heart rate, whereas ajmaline initially decreased heart rate. Both drugs prolonged the PR, QRS and QT intervals of the EKG. Recovery of these effects was within one hr. MCAA (10 mg/kg) and ajmaline (4.05 mg/kg) were studied separately by a one and 10 min infusion in the same cat. The dose of MCAA was ten times the usual dose in man and that of ajmaline four times the usual clinical dose. More marked effects were observed with the one min infusion. Arrhythmias were usually observed with ajmaline, but not with MCAA, even though it was rapidly converted to ajmaline. Maximal cardiovascular effects of MCAA and ajmaline were observed within 3 min of the end of infusion, which was also the time of peak blood levels. The elimination of MCAA resembled the kinetics of a multi-compartment system after a one min infusion. Peak blood levels declined by one-half in 3 min. Ajmaline blood levels declined  linearly, with a half-life of 100 min, after a one min infusion. The peak blood level of MCAA after an intraduodenal dose of 25 mg/kg occurred at 20 min, whereas the peak blood level of the ajmaline formed occurred at 4 hr. In conclusion, MCAA has some different pharmacological properties and different kinetics of elimination than ajmaline.


Lung enzymes in emphysematous rats: effects of progestagens, antiphlogistics and metabolic inhibitors. Chronic exposure of rats to 10% aerosols of papain or trypsin resulted in marked increases in lung weights and lung beta-glucuronidase and arylsulfatase activities. Destruction of alveolar walls was demonstrated microscopically as a decrease in the number of air spaces touching a line of known length. The pregnenes, progesterone and medroxyprogesterone acetate, but not the 19-nortestosterone derivative norethindrone, partially prevented the papain-induced breakdown of alveolar septa and elevation of beta-glucuronidase. The steroidal anti-inflammatory agent, paramethasone, completely inhibited the rise in lung weight and beta-glucuronidase activity, but did not prevent destruction of alveolar walls. The non-steroidal anti-inflammatory agent, indomethacin, afforded little or no protection. Limited prophylaxis against both histological and enzymatic changes was observed in rats treated with the anti-metabolite, cyclophosphamide, and the proteolytic enzyme inhibitor, aprotinin. The various lung abnormalities resulting from papain inhalation may thus be individually influenced by specific pharmacologic agents.


Floctafenine, a new non-narcotic analgesic. Floctafenine has been studied in comparison with acetyl-salicylic acid, indomethacin and d-propoxyphene in a series of tests for analgesic and anti-inflammatory activity. It is very active in the acetic acid-induced writhing test and on the inflamed paw in the Randall and Selitto test. Furthermore, like acetylsalicylic acid and indomethacin, but unlike d-propoxyphene, it has no effect on the non-inflamed paw, and similarly it is inactive in the tail flick and in the hot plate test. Floctafenine is also very effective in some acute inflammations such as naphtoylheparamine-induced oedema or in UV erythema, but it is distinctly less active in carrageenin-induced oedema or in adjuvant arthritis. In rat gastric and intestinal mucosa its tolerance is excellent. It has no action on the central and autonomous nervous systems. The pharmacological profile of this compound thus places it amongst the non-narcotic analgesics. It has an exceptionally high therapeutic index, much higher than that of acetylsalicylic acid and indomethacin.


Autoimmune hemolytic anemia.

Autoimmune hemolytic anemia. Warm-type autoantibodies of autoimmune hemolytic anemia (AIHA) are usually IgG but may be IgM or IgA. They are usual Rh specific. Cold-type antibodies are IgM or IgG  (Donath-Landsteiner [DL] antibody). IgM antibodies are usually anit-l (occasionally anti-i) and DL antibodies anti-P. The warm IgG antibodies do not fix complement (C); they cause red blood cell (RBC) destruction predominantly in the spleen as the result of interaction between fixing; they cause RBC destruction either by intravascular lysis (complement sequence completed) or by interaction between C3-coated RBCs and phagocytes in liver and spleen. Gentic factors, immunoglobulin deficiency, somatic mutation, viral infections and drugs, and failure of T-lymphocyte function, all probably play a part in breaking immunological tolerance and the development of AIHA.


Metabolism of human erythrocytes. Studies in health and disease. Deficiency states have been well established in nine enzymes of anaerobic glycolysis and suggested, but inadequantely confirmed, in others. In additon, hemolytic anemia has been defined in glucose-6-phosphate dehydrogenase deficiency, in certain enzymes glutathione metabolism of importance to the function of the oxidative hexsemonophosphate shunt, and in certain enzymes of nucleotide metabolism. In heterogeneous dyserythropoietic states with ineffective erythropoiesis, enzyme ratios are grossly distorted and differ greatly from those of either normal or reticullocyte-rich blood. Red blood cell (RBC) enzyme deficiencies show noticeable genetic polymorphism, most apparently recessively transmitted anemias actually resulting from inheritance of two different mutant, allelic genes. In addition to causing hemolytic syndromes in selected instances, deficiencies of enzymes more important to other tissues than to the RBC itself are detectable by assay of hemolystates.


Herediatary spherocytosis. A review.

Herediatary spherocytosis. A review. Studies of the clinical features of hereditary spherocytosis since 1871 and laboratory investigation of the cellular abnormalities since 1940 have led to the characterization of hereditary spherocytosis as a prime example of a Mendelian dominant, genetically determined disorder of the erythrocyte membrane. This review of hereditary spherocytosis emphasizes the contributions of Dr. Lawrence Young and many others of out present understanding of the disease and discusses current studies of the protein abnormality in the membrane of hereditary spherocytes.


Hematology and the Derivation of Psychosomatic Concepts. During the past 25 years, Dr. Lawrence Young has played a major role in the evolution of the Medical-Psychatric Liaison Unit at the University of Rochester and in development of new psychsomatic concepts. Investigations of patients with leukemia and lymphoma highlighted the occurrence of separation and loss in the prodromal period of the illness, perphaps serving as precipitating role in its manifest development. Study of these fatally ill patients required scrutiny and clarification of the dying process through the past two decades. Similarly, consideration of accompanying emotional distress in patients' family members necessitated attention to the manifestations of grief.


Multiple expanded roles for nurses in urban emergency rooms. 'Emergency room nurse-practitioner'. The increasing number of patients seeking general medical care in the emergency rooms of urban teaching hospitals creates substantial volume loads, especially in triage and in delivery of primary care. Interns perform these tasks unethusiastically and inefficiently, session physicians indifferently. Selected experienced nurses, after brief but intensive and targeted training, can successfully assume these full responsibilities with a high degree of job satisfaction.


Acute myocardial infarction diagnosed by myoglobinuria. Myoglobin can be found in excess in the urines of some patients with acute myocardial infarction. To test the specificity of this finding, urine specimens were analyzed from 39 patients with provisional diagnosis of myocardial infarction by means of a hemagglutination-inhibition technique with prepared antisera to monkey myoglobin. Of 24 patients with subsequently documented myocardial infarction, 15 had at least one positive determination. None of the 15 patients without infarction had positive tests. Ten of 13 patients with infarction studied within 24 hours of the initial event had positive reactions. The percentage of positive reactions in the infarct group decreased sharply after the first 24 hours. This technique may be of value in rapid screening of patients with possible acute myocardial infarction during early stage of symptoms.


Immunopathologic findings in idiopathic renal hematuria. Eighty patients had idiopathic renal hematuria and normal renal function. Renal biopsy showed minimal changes or focal glomerulonephritis in two thirds of the patients. The remainder exhibited diffuse proliferative glomerulonephritis and included nine patients with segmental glomerular sclerosis. Electron microscopy disclosed alterations of the capillary loop in 23 biopsy specimens and electron-dense deposits in 11. Immunofluorescent microscopy identified glomerular-bound immunoglobulins, C3, or fibrinogen in 58% in a generalized distribution. IgG was the immunoglobulin seen most commonly. IgA and IgM were present in 14 and 13 biopsy specimens, respectively. These findings suggest that idiopathic renal hematuria is a clinical syndrome rather than a single disease with varying underlying renal findings. Both immunologic and nonimmunologic mechanisms may be involved, and the prognosis is favorable even in patients followed up for 11 years.


Immunoglobulin A nephropathy.

Immunoglobulin A nephropathy. Of 475 renal biopsles examined by immunofluorescence, IgA was seen located selectively in the glomerular mesangium of 18 patients. These patients were generally young men and had hematuria, only minimal proteinuria, and normal renal function. Glomerular lesions consisted of focal segmental capillary hypercellularity or sclerosis and mesangial thickening due to an increase in mesangial cells, matrix, and electron-dense deposits. Both IgG and C3 were frequently seen with IgA in the mesangium as was properdin in five of six cases, but C4, a component of the classical pathway of complement activation, was seen only infrequently. Serum IgA levels were elevated in many patients, but serum complement components were normal. These findings suggest a possible unusual immune pathogenesis with local mesangial binding and alternate pathway activation of complement.


Glucagon-blood catecholamine test: use in isolated and familial pheochromocytoma. In 149 cases, blood pressure response to glucagon test did not exceed 20/10 mm Hg more than the response in the cold pressor test control and was considered negative. Plasma catecholamine level increases may be seen in 95% of patients without pheochromocytomas. Among six patients with pheochromocytomas, urinary metanephrine levels were of diagnostic importance in two with isolated pheochromocytoma and in one with the multiple endocrine neoplasia of type 2 (MEN-type 2). Urinary metanephrine determinations yielded false-negative results in three patients with MEN-type 2, while vanilmandelic acid level was normal in one and nephrotomograms were positive in two of these three. These results suggest that the early diagnosis of pheochromocytoma in patients with MEN-type 2 may be difficult and may require multiple biochemical and roentgenographic investigations.


Combined clonidine-chlorthalidone therapy in hypertension. Two years' experience in 30 patients. The efficacy and safety of the antihypertensive drug, clonidine, were tested by open-label trial in 30 ambulatory, hypertensive patients who were concomitantly receiving the diuretic, chlorthalidone. This combined treatment followed several weeks of base line treatment with the diuretic alone. In both the recumbent and the upright position, clonidine potentiated the blood pressure-lowering effect of chlorthalidone to a noticeable degree; with combined treatment, the reductions in systolic and diastolic pressures were from 12.9% to 16.4% greater. Side-effects, consisting mostly of drowsiness and dryness of mouth, were mild and were observed mainly at the beginning of clonidine therapy. Orthostatic hypotension or weakness was experienced by 3 patients, but it subsided after dose adjustment in two of them. The drug combination was well suited for long-term management of patients with hypertension of all degrees of severity.


Plasma cells in urine: occurrence in multiple myeloma. Numerous plasma cells were transiently found in the urine of a patient with multiple myeloma. The patient was in acute renal failure, and she had K-type Bence-Jones proteinemia and proteinuria. A slide of stained urine sediment showed cells with freatures characteristic of plasma cells. Their cytoplasm was highly reactive with anti-K antiserum on immunofluorescence, suggesting that these were myeloma cells.


Metastatic adrenal cortical carcinoma. Documented cure with combined chemotherapy. In 1966, we published the case report of a patient with adrenal carcinoma and wide spread metatasis who, after treatment with mitotane (o,p-DDD) and fluorouracil, developed Addison disease accompanied by a clinical remission. The patient's unexpected death from an unrelated cause now allows us to verify what to our knowledge is the first cure of metastatic adrenal carcinoma by chemotherapy.


Rupture of the spleen in infective endocarditis. A patient had delayed spontaneous rupture of the spleen complicating infective endocarditis. In 20 other cases reported through 1973, the most common presentation was found to be left upper quadrant pain followed by signs of peritoneal irritation and cardiovascular collapse. Abdominal paracentesis consistently yields free blood or pus in the peritoneal cavity; blood replacement and emergency splenectomy may be lifesaving. The basic pathological mechanisms may be (1) rupture of a mycotic aneurysm into the splenic substance (2) rupture of a splenic abscess, and (3) rupture of a suppurating intrasplenic vessel with hematoma formation, subcapsular dissection, and delayed capsular tear.


Reduction of oxidized inorganic nitrogen compounds by a new strain of Thiobacillus denitrificans. Denitrification by Thiobacillus denitrificans "RT" strain was investigated using manometry and gas chromatography. 1. From nitrate, resting cells produced only nitrogen anaerobically with thiosulfate as the electron donor. The data suggest that nitrate was assimilated and dissimilated by the same nitrate reductase, assayed with benzyl-viologen as the electron donor. 2. From nitrite, whole cells produced nitric oxide, nitrous oxide and nitrogen, using thiosulfate as the electron donor; nitrogen was the final product of the reduction. Crude extract reduced nitrite to nitrogen with p-phenylene-diamine and dimethyl-p-phenylene diamine as the electron donors, and produced nitric oxide, nitrous oxide and nitrogen with tetramethyl-p-phenylene-diamine as the electron donor. Nitrite was reduced to nitric oxide and nitrous oxide by crude extract using ascorbate-phenazine methosulfate as the electron donor. 3. From nitric oxide, whole cells produced nitrous oxide and nitrogen using thiosulfate as the electron donor, nitrogen was the final reduction product. Nitric oxide was reduced to nitrous oxide by crude extract with the ascorbate-phenazine methosulfate system. 4. Whole cells reduced nitrous oxide to nitrogen with thiosulfate as the electron donor. It was not possible to detect any nitrous oxide reductase activity in crude extract. 5. A scheme was of denitrification by Thiobacillus denitrificans "RT" strain.


Subcellular distribution of yeast invertase isoenzymes. Homogenates from yeast cells contain 1% or less of sedimentable invertase activity. Sedimentability is equally low in homogenates from cells repressed or derepressed with regard to invertase secretion. Intracellulary, the mannanprotein form of invertase is largely localized in vacuoles whereas the small isoenzyme is largely present in the soluble cell fraction. These findings indicate that vesicles are not involved in the secretion of invertase. A soluble mode of invertase secretion is discussed.


[Ataxia and deafness secondary to meningitis in children: the role of labyrinth diseases]. A study is made of post meningitic ataxia from 9 purulent meningitis observations in children. This ataxia is accompanied by a bilateral vestibular destruction syndrome in 6 of the 7 patients examined. The labyrinthic origin of the ataxia accounts for its pure static aspect, its regressive evolution and the frequency of associated deafness. The study of sightless walking on unstable ground (mattress) gives a clinical sight of the vestibular impairment long after the acute phase. In the same way, the study of post-meningitis deafness shows that, most of the time, it is accompanied by an impairment or the suppression of the vestibular reactions. The frequency of the inner ear impairment, after purulent meningitis is certainly underestimated for two reasons: on the one hand, the ataxia remains unknown most of the time because of the excellent vestibular compensation; on the other hand, the deafness can be slight or localized only on one side. Consequently it seems important to undertake in each purulent meningitis convalescent, a clinical examination of standing and walking positions, together with an examination of the hearing and vestibular functions, as soon as age allows it. Lastly, with regard to a pathogenic theory of purulent meningitis, the role of a possible viral component of the infection in the cochleo-vestibular impairment is called into question.


[Congenital aplastic anemia, type I].

[Congenital aplastic anemia, type I]. Case report of a 7 year old girl, anaemic since birth. The anaemia, of variable intensity, is associated with a moderate reticulocytosis. Bone marrow films, show a marked erythroblastosis with conspicuous morphological abnormalities and internuclear chromatin bridges. The erythrocinetic pattern is that of ineffective erythropoiesis. The morphologic features are those of Heimpel and Wendt's type I congenital dyserythropoiesis. The erythrocytes are lysed by some acidified sera, thus showing a membrane anomaly which is unusual in type I. However the characteristics of the lysis are different from those of type II (HEMPAS) erythrocytes.


[Bartter's disease associated with hypercorticism, phosphate and magnesium deficiencies and familial renal tubular disease]. A new case of Bartter's syndrome is described. There is a context of other cases of familial renal tubular disease with a sex-linked heredity. In this case, the Bartter's syndrome is associated with magnesium deficiency and hypomagnesemia, with a ricket and severe phosphate deficiency, and finally with an hypercorticism. The basal secretion rate of cortisol agree with a Cushing's syndrome. This hypercorticism is corrected by aminogluthetimide. The influence of the hyperreninism on the hypercorticism is discussed.


[Renal vein thrombosis in the newborn infant]. In a child born with traumatism to a diabetic mother, an acute thrombosis of the left renal vein occurred. An arteriography performed at the acute stage, established the diagnosis. The newborn received urokinase and heparin administered through an arterial catheterism. An arteriography, repeated at the 3rd day, showed an improvement in the vascularization of the kidney, which returned to normal functions. The radiological symptons of renal vein thrombosis are reviewed including the arteriography which is never used for the diagnosis in newborns. The interest of the use of urokinase and its efficiency in this disorder are discussed. This therapy harmless and efficient seems of interest. Such a therapy has to be tried because of the failure of isolated heparin-therapy and of the sequellae which may be observed after spontaneous recovery or after anticoagulant treatment.


Rate of learning of the conditioned avoidance reflex in rats with various exploratory activity. Rate of learning of the conditioned avoidance reflex in rats with various spontaneous exploratory activity was studied. Rats with low activity learned more quickly, and the most active rats slowly.


Central action of drugs acting on the cholinergic muscarinic receptor. IV. Influence of cholinomimetics and cholinolytics injected into the lateral cerebral ventricle in the rat on concentrations of 5-HT and 5-HIAA. The influence of cholinomimetics (carbachol--CCh, physostigmine--Pht, pilocarpine--Pil) and cholinolytics (atropine--At, scopolamine--Sc) injected into the lateral ventricle of the brain (ivtr) in rats on metabolism of 5-HT was studied by assaying levels of 5-HT and 5-HIAA. In several comparative experiments cholinomimetics were injected i.p. CCh had no influence on levels of 5-HT and 5-HIAA when injected i.p., but raised levels of 5-HIAA injected ivtr. Pht had no influence on concentrations of both substances by either route of administration. Pil raised levels of 5-HIAA when injected i.p. (and by this route of administration also raised levels of 5-HT) as well as ivtr, Both cholinolytics injected ivtr had no influence on concentrations of 5-HT or 5-HIAA.


Influence of NBTI on metabolism of brain-HT. The influence of NBTI, an agent which stimulated dopamine receptor in the central nervous system, on concentrations of serotonin and its metabolic, 5-hydroxyindoleacetic acid in the brain of rats was studied. Turnover rate of serotonin in the brain after administration of NBTI to normal rats and those pretreated with spiroperidol, a factor which blocks central dopamine receptors, was evaluated. The changes in metabolism of brain serotonin under the influence of NBTI are similar to those produced by another factor which stimulates central dopamine receptors, namely apomorphine. NBTI causes transient increase in exploratory activity of rats and lowers body temperature.


Influence of bovine somatotropin on the liver experimentally damaged with carbon tetrachloride. The influence of bovine somatotropin in acute CCl4 poisoning was studied in rabbits. Somatotropin was injected subcutaneously in doses of 2.5 mg/kg. Liver damage was assessed on the basis of alanine and aspartate aminotransferase and aldolase activities. STH injected during 10 experimental days or 5 days preceding experimental poisoning with CCl4 did not increase the degree of liver damage in comparison with the group of animals injected only with carbon tetrachloride.


Influence of tricyclic antidepressant drugs on experimental arterial hypertension. The tricyclic antidepressant drugs: imipramine, opipramol, amitryptiline and nortryptiline inhibit development of experimental arterial hypertension in rats.


Changes of certain pharmacological and biochemical indices in acute methylglyoxal poisoning. Methylglyoxal in doses over 25 mg/kg injected intravenously in cats and rabbits produces distinct changes in the cardiovascular and respiratory systems, but has no effect on respiration or circulation when injected intraperitoneally even in doses up to 1 g/kg. The effect of MG on blood pressure depends on the species of the animal. The effects of MG are dose-related and dependent on the route of its administration. Biochemical studies showed a significant rise in serum activities of creatine kinase (EC 2-7-3-2), lactate dehydrogenase (EC 1-1-1-27) and aspartate aminotransferase (EC 2-6-1-1-) after intraperitoneal injection of MG in the dose of 200 mg/kg in rabbits and 500 mg/kg in rats. The observed changes probably indicate damage of muscle tissue by MG, presumably as a result of low content of one of the glyoxalases in the muscles of the experimental animals. Elevation of glucose levels by MG was probably an adrenergic effect. These biochemical changes can serve to evaluate toxicity of MG preparations, which exhibit variations probably owing to varying degree of polymerization.


Influence of the vaccine Polyvaccinum mite on the nasal mucosa. The necessity of prolonged administration of the vaccine Polyvaccinum prompted this study on the effect of the preserving agent on the nasal mucosa. Buffered physiologic saline solution containing 0.1--0.4% phenol, and the vaccine containing 0.1--0.4% phenol or 0.01% merthiolate were applied for 12 weeks on the nasal mucosa of rabbits. The nasal mucosa, parenchymal organs and adrenals were studied macroscopically and histologically, and immunologic studies were made. On the basis of the results, preservation of Polyvaccinum mite with 0.4% phenol is suggested.


Central action of 2-amino- and 2-amino-5-aryltetrahydropyrimidinediones-4,6. The influence on the central nervous system of five 2-amino- and 2 amino-5-aryltetrahydropyrimidinedione-4,6 derivatives was studied. The most favorable action was exerted by benzylamine-tetrahydropyrimidinedione, which inhibited spontaneous and amphetamine-induced motility most strongly, acted synergistically with hexobarbital, was the only one of the studied group of compound which delayed convulsions induced with pentamethylenetetrazole and amphetamine, and potentiated most strongly the central action of DOPA in mice with inhibited MAO activity. The weakest effects were produced by methylpiperazinephenyl-tetrahydropyrimidinedione.


Synthesis and preliminary pharmacologic studies on 1-(4-pyridyl)- and 6-methoxy-1-(4-pyridyl)-beta-carboline. 1-(4-pyridyl) and 6-methoxy-1-(4-pyridyl)-beta-carboline were synthesized by dehydrogenation of 1-(4-pyridyl)-1,2-3,4-tetrahydro-beta-carboline and 6-methoxy-1-(4-pyridyl)-1,2,3,4-tetrahydro-beta-carboline, and their central action was studied pharmacologically. In the doses employed neither preparation showed significant sedative, analgesic or antidepressant activity.


Semi-flexible sockets for amputation below the knee. A semi-flexible socket fitted to a series of 47 consecutive below-knee amputees is evaluated, and the problems in assessing prosthetic components and appropriate methodology are discussed. The results suggest that this type of socket deserves wider use and further evaluation in active amputees, where comfort, perspiration control or the condition of the skin is interfering with the patient's function.


Abdominal problems in patients with spinal cord lesions. The physiatrist faces two major difficulties when dealing with abdominal problems in spinal cord-injured patients: (1) realizing when there is a serious problem; and (2) determining the etiology of the problem. Patients are presented which demonstrate these difficulties. One patient with a ruptured appendix and the periappendicial abscess had only mild symptoms whereas another patient with severe abdominal pain, rigidity and rebound tenderness had a viral enteritis. The neurologic innervations of the abdomen and the various signs and symptoms appearing in cord-injured patients with abdominal problems are described. A methodical evaluation procedure for acute problems in paraplegic patients is presented.


Inferior vena cava interruption: a new indication? Propagating illofemoral venous thrombosis that occurs despite adequate anticoagulation can be detected by the serial fibrinogen uptake test. Twenty-three patients who were receiving heparin sodium for confirmed iliofemoral thrombophlebitis underwent the serial fibrinogen uptake test. There was an increasing percentage of isotope uptake at the groin and the upper part of the thigh in eight of these patients, three of whom subsequently developed clinical signs, perfusion, and ventiliation lung scan findings compatible with the occurrence of pulmonary embolism. The remaining 15 patients had decreasing serial fibrinogen uptake during heparin therapy and no sequelas indicative of pulmonary embolism. Progressive thrombosis in adequately heparinized patients indicates failure of anticoagulation therapy and, when this occurs, we believe that interior vena cava interruption should be considered before a first, but potentially lethal, pulmonary embolus develops.


The role of definitive surgery in the management of perforated duodenal ulcer disease. From 1970 to 1973, 147 patients were treated at Wayne State University Affiliated Hospitals for perforated duodenal ulcer disease. One hundred thirteen were observed for at least 18 months and findings showed that (1) mortality was dependent on the condition of the patient rather than on the choice of operation, (2) current indications (previous ulcer history, degree of peritoneal contamination, and time interval between performation and surgery) were not reliable in choosing the initial operation or in predicting the need for subsequent surgery, and (3) morbidity was high following simple closure. Therefore, we recommend vagotomy and pyloroplasty as the procedure of choice for a perforated duodenal ulcer, unless the patient is in septic shock at admission.


Isolation and purification of mediators of cell proliferation. An attempt was made to isolate and purify the important biological mediators that cause an increase in proliferative activity of fibroblasts following tissue injury. DNA synthesis and cellular growth, using cultured WI-38 fibroblasts, and DNA synthesis in an in vitro assay, using purified DNA polymerase, were stimulated by factors extracted from the lysosomal-mitochondrial fraction of normal guinea pig liver. These factors precipitated in 45 percent to 60 percent ethanol. They were insensitive to treatment with RNase, DNase and heating to 56 C for 30 minutes, but were inactivated at 100 C. isoelectric focusing of the active ethanol-precipitate resolved activity into five discrete fractions, one of which has been purified, using ion-exchange chromatography. The presence of these factors in normal tissue may explain the increase in proliferative activity of fibroblasts and other cells in the early stages of wound healing, via release caused by injury.


Hepatic reticuloendothelial host defense failure following surgical trauma. We evaluated potential pituitary-adrenal influences on postoperative reticuloendothelial (RE) function. Male dogs, 13 to 18 kg (28.6 to 39.6 lb), were used and the operative procedure was hemicolectomy. The RE function was evaluated by a colloid clearance technique and circulating opsonin levels were quantified by bioassay. Normal animals manifested RE depression three hours following incision (49 percent decline in the global phagocytic index K and an associated 30 percent decline in the circulating opsonic activity). Dexamethasone sodium phosphate pretreatment over a three-day preoperative period prevented the postoperative RE clearance failure (control K = 0.69; postoperative k = 0.79) however, a slight (18 percent) but not significant decrease in opsonic activity occurred. Cortisone acetate or adrenocorticotropic hormone over a wide-dosage range manifested no depressing effect on in vitro phagocytosis. These studies, in conjunction with our previous findings of Kupffer cell activation following adrenalectomy, as well as the demonstration of opsonin depletion and RE phagocytic depression following surgery in the absence of the adrenal glands suggest that the pituitary-adrenal system modulates postoperative RE phagocytosis.