Neutron diffraction analysis of myoglobin: structure of the carbon monoxide derivative. The locations of hydrogen and deuterium atoms and water molecules have been investigated in carbon monoxide myoglobin using neutron diffraction, and the results are compared with earlier work on metmyoglobin. Parallel real space refinements on the two molecules show relatively few changes, but do show the carbon monoxide molecule with the iron atom moving into the heme plane.


Delayed-type hypersensitivity to sheep red blood cells: inhibition of sensitization by interferon. Interferon, when given or induced 24 hours before contact of mice with sheep red blood cells, prevented sensitization, and no delayed-type hypersensitivity reaction could be elicited 4 days later, after challenge with the antigen, as shown by the absence of footpad swelling in treated animals.


Synthesis of (6-3H)-1alpha-hydroxyvitamin D3 and its metabolism in vivo to (3H)-1alpha,25-dihydroxyvitamin D3. [6-3H]-1alpha-Hydroxyvitamin D3 was chemically synthesized and its full biological activity and radiochemical purity were demonstrated. With the use of this preparation it has been possible to demonstrate in vivo that in rats the [6-3H]-1Alpha-hydroxyvitamin D3 is converted to [6-3H]-1alpha,25-dihydroxyvitamin D3, the natural hormone. In fact, in the intestine and bone of rats given 32 picomoles of [6-3H]-1alpha-hydroxyvitamin D3 each day for 6 days, more than 80 percent of the lipid-soluble radioactivity exists as [6-3H]-1alpha,25-dihydroxyvitamin D3, a finding that suggests that much of the biological effectiveness of 1alpha-hydroxyvitamin D3 is due to its conversion to 1alpha,25-dihydroxyvitamin D3.


Regulation of serum 1alpha,25-dihydroxyvitamin D3 by calcium and phosphate in the rat. A new radioreceptor assay was used to quantify changes in serum concentration of 1alpha,25-dihydroxyvitamin D3 in rats with low calcium or low phosphate diets. Low availability of either ion elicits a fivefold increase in the circulating concentration of 1alpha,25-dihydroxyvitamin D3. The enhancement of 1alpha,25-dihydroxyvitamin D3 concentration in response to calcium deficiency is dependent on the presence of the parathyroid or thyroid glands (or both), suggesting that this effect is mediated by parathyroid hormone. In contrast, the response of phosphate deficiency is independent of these glands and may result from an action of low serum phosphate concentration or some factor associated with phosphate depletion on the renal synthesis of the 1alpha,25-dihydroxyvitamin D3 hormone.


Guanidinium-CsCl density gradients for isopycnic analysis of nucleic acids. The addition of guanidinium chloride to CsCl gradients lowers the apparent density of RNA, DNA, and hybrid polymers in such a way that all three can be banded, fractionated, and analyzed in one gradient with essentially no damage to their chemical integrity or to their biological activity.


Subcutaneous temperatures: a method of noninvasive sensing. A new method of noninvasive sensing of the subsurface temperature distribution in human and animal tissue is described. Thermal radiation emitted from subsurface depths of several centimeters can be detected with microwave receivers. Temperature sensitivity of order 0.1 degree C and spatial resolution of approximately 1 by 2 centimeters have been obtained. Measurements demonstrating the technique, with feline and human tissue, are reported. A potential medical application is the detection of subsurface thermal anomalies such as malignant tumors and regions of vascular insufficiency.


Alpha-lactalbumin production in human mammary carcinoma. Alpha-Lactalbumin was isolated from mature human milk and utilized as an immunogen in rabbits. A radioimmunoassay was developed that was capable of detecting nanogram quantities of the antigen. Alpha-Lactalbumin synthesis was detected in human breast cancer cells (MCF-7) cultivated as a continuous cell line in vitro. Other human carcinoma epithelial cell lines (throat and cervix) failed to react in this assay. The ability to synthesize alpha-lactalbumin by breast carcinoma cells appeared to be independent of the addition of prolactin to the culture medium.


Sensitive period for the development of human binocular vision. Twenty-four subjects with abnormal binocular experience, due to a condition of convergent strabismus that existed during different periods of their lives, were tested. Interocular transfer of the tilt-aftereffect was used to assess binocularity. Individuals between 1 and 3 years of age are most susceptible to abnormal binocular experience.


Apneas during sleep in infants: possible relationship with sudden infant death syndrome. Several types of apnea are described in premature infants and in infants who have survived breathing-stoppage episodes which may be related to the sudden infant death syndrome. Upper airway apnea appears to induce the greatest changes: oxygen desaturation is more pronounced than in a central apnea of similar duration, and secondary cardiac changes are observed earlier and are more severe.


Preferences for sweet and salty in 9- to 15-year-old and adult humans. Preferences for the tastes of sucrose, lactose, and sodium chloride were measured in 618 subjects between 9 and 15 years of age and in 140 adults. The younger subjects preferred greater sweetness and saltiness that did the adults. In the younger groups, there were race and sex differences in preferences, none of which appeared among the adults.


Molluscan gastrin: concentration and molecular forms. Blood and gastrointestinal tissues of the sea hare Aplysia californica and the land snail Otala lactea contain immunoreactive gastrin in heterogeneous forms similar to those of mammals. The observation that blood concentrations in terms of porcine gastrin standard are comparable to those of pig, man, and dog suggests significant homology between the structures of molluscan and mammalian gastrins.


Induction of F1 hybrid antiparent cytotoxic effector cells: an in vitro model for hemopoietic histoincompatibility. An in vitro system has been developed in which F1 spleen cells can generate cytotoxic activity directed specifically against parental cells. The antigenic differences detected are controlled by the H-2D-Hh-1 region of the murine major histocompatibility complex. The parent-F1 combinations demonstrating F1 antiparent activity in vitro are the same as those demonstrating F1 rejection of parental hemopoietic grafts in vivo. Hence, the F1 antiparent cytotoxicity test serves as an in vitro model for the recognition and effector phases of hybrid resistance to parental hemopoietic grafts and may be of value in clinical transplantation.


Prostaglandin F2alpha production by the brain during estrogen-induced secretion of luteinizing hormone. The arteriovenous difference in the concentration of prostaglandin F2alpha (PGF2alpha) across the brain of the anestrous sheep was measured before and during the induction of luteinizing hormone secretion with 17 beta-estradiol. The results indicate that (i) the brain in vivo is a significant source of PGF2alpha, (ii) the release of PGF2alpha from the brain occurs in pulses with a circhoral rhythm, and (iii) the process through which estrogen exerts its negative and positive feedback effects on luteinizing hormone secretion may involve amplitude modulation of PGF2alpha output from the brain.


Orientational anisotropy in infant vision. Infants prefer to look at horizontal and vertical gratings rather than at oblique gratings only when they are at or near threshold spatial frequencies, as would be expected if acuity for oblique edges is lower than that for horizontal and vertical edges. That such a bias exists as early as 6 weeks of age suggests that the orientational asymmetry of the visual system depends on endogenous maturation rathat than exposure to a carpentered world.


Cortical effect of early selective exposure to diagonal lines. Neurons in the visual cortex that respond preferentially to diagonal contours are present only in cats exposed to diagonal lines early in life. In contrast, cells that prefer horizontal or vertical contours are found following exposure to horizontal, to vertical, and to diagonal lines. Such cells do not require a specific visual input for maintenance or for development; neurons responding preferentially to diagonal lines do.


Modification of cortical orientation selectivity in the cat by restricted visual experience: a reexamination. Recent reports have stated that the orientation selectivity of cells in the cat's visual cortex can be biased by limiting the early visual environment to stripes of one orientation. Data obtained from seven kittens using systematic and quantitative sampling of preferred orientation, together with a blind procedure, do not show a bias toward the orientation presented in one type of restricted rearing environment.


Perceived visual motion as effective stimulus to pursuit eye movement system. Human eye tracking of a foveal afterimage during angular head oscillation in the dark produced smooth eye movements exceeding those for normal vestibular nystagmus, and a reduction in the frequency of the fast phase component of nystagmus eye movements. These results may support a closed loop extension of the corollary discharge theory, with oculomotor commands based on perceived object velocity.


Stages in adolescent involvement in drug use. Two longitudinal surveys based on random samples of high school students in New York State indicate four stages in the sequence of involvement with drugs: beer or wine, or both; cigarettes or hard liquor; marihuana; and other illicit drugs. The legal drugs are necessary intermediates between nonuse and marihuana. Whereas 27 percent of high school students who smoke and drink progress to marihuana within a 5- to 6-month follow-up period, only 2 percent of those who have not used any legal substance do so. Marihuana, in turn, is a crucial step on the way to other illicit drugs. While 26 percent of marihuana users progress to LSD, amphetamines, or heroin, only 1 percent of nondrug marihuana users and 4 percent of legal drug users do so. This sequence is found in each of the 4 years in high school and in the year after graduation. The reverse sequence holds for regression in drug use.


Diversity and adaptation in rodent copulatory behavior. Copulatory patterns of muroid rodents provide an ideal locus for comparative behavioral research. Such patterns are highly stereotyped within and between the individuals of a given species, variable across species, readily elicited in the laboratory, and of great biological significance. Detailed behavioral comparisons of a broad range of muroid species have revealed extensive behavioral diversity that was not anticipated from research confined to laboratory rats. Various muroid species display postejaculatory compulations without sperm transfer, locking, thrusting, and other behavioral patterns. This behavioral diversity appears not to be the result of a simple linear pattern of evolutionary history. Rather, patterns appear to have evolved repeatedly in response to particular selective pressures acting on particular species. While understanding of the adaptive significance of these behavioral patterns remains rudimentary, important beginnings have been made.


"Half" membrane enrichment: verification by electron microscopy. Membranes of intact erythrocytes bound to polylysine-treated glass fracture nonrandomly when covered with thin copper and frozen. Electron microscopic examination of the glass side reveals extensive areas of outer "half" membrane (B face) and of the copper side, inner "half" membrane (A face). This technique allows the ultrastructural examination of square-centimeter areas of fractured membrane and the chemical analysis of these membrane "halves".


Soluble protein of the organic matrix of mollusk shells: a potential template for shell formation. A significant proportion of the soluble protein of the organic matrix of mollusk shells is composed of a repeating sequence of aspartic acid separated by either glycine or serine. This regularly spaced, negatively charged aspartic acid may function as a template upon which mineralization occurs.


Goldfish retina: functional polarization of cone horizontal cell dendrites and synapses. In serial electron micrographs we observed that dendrites of goldfish cone horizontal cells are either central or lateral in ribbon synaptic triads, depending on cone and horizontal cell type. The chromatic properties of cone horizontal cell responses may be explained if the cone horizontal cells act as interneurons, receiving from cones through their central processes but acting on cones through their lateral processes.


Prostaglandins in rabbit blastocyst.

Prostaglandins in rabbit blastocyst. Rabbit blastocysts recovered at 144 hours post coitum contained the prostaglandins F and E-A. We suggest that one or more of these prostaglandins act as mediators in blastocyst steroidogenesis. (In another study we have demonstrated steroidogenesis in rabbit blastocysts).


Neuroplasticity in the sparing or deterioration of function after early olfactory tract lesions. Mating behavior in male hamsters depends on the sense of smell. Thus, complete transection of the lateral olfactory tract in adults eliminates mating. If the cut is made early in life, however, mating is spared. Partial section of the tract in adults does not affect mating, but similar cuts in the neonate lead to impaired mating performance later in life. Observed postsurgical rearrangements in the connections of axons in the lateral olfactory tract may explain both the sparing and the deterioration of function.


Chromosome damage in liver cells from low dose rate alpha, beta, and gamma irradiation: derivation of RBE. Relative biological effectiveness (RBE) for chromosome damage in liver cells was determined after low dose rate exposures to alpha, beta, or gamma irradiation. Protracted exposures to beta and gamma irradiation were equally effective, whereas low dose rate exposures to alpha emitters were 15 to 20 times more damaging than exposures to beta or gamma irradiation. These data support the use of the quality factor of 10 recommended by the International Commission on Radiological Protection and the National Council on Radiation Protection for estimating the biological hazard from internally deposited alpha emitters. When the dose rates were low, all types of chromosome damage observed were produced by single-hit processes.


High speed scintillation autoradiography. Impregnation of nuclear track emulsion with liquid scintillator and exposure at -85 degrees C allows rapid autoradiographic labeling. With tritiated thymidine of high specific activity (40 to 60 curies per millimole), exposure time can be shortened to 20 to 60 minutes, allowing complete sample processing within 4 hours. In experiments requiring isotopes with low incorporation rates or low specific activity, exposure time can be shortened from months to several days.


Nongenetic variability in susceptibility to oncogenesis. Genetically homogeneous mice varied in susceptibility to tumor induction by 3-methylcholanthrene. The early appearance of an induced tumor identified an animal of relatively great susceptibility to tumor induction as compared to other animals of the same genotype.


Deoxycorticosterone-adenine interactions in a crystalline complex. Deoxycorticosterone-adenine monohydrate is the first complex involving a steroid and a component of DNA to be successfully crystallized and studied by single crystal x-ray analysis. Hydrogen bonds between O(20) and N(6) as well as O(21) and N(1) connect the corticoid side chain to an adenine molecule. The molecules are also packed such that a second adenine moiety is situated over the delta4-3-one region of the steroid. These observations of the solid state suggest ways in which steroids and nucleic acids may interact in vivo.


5-iododeoxyuridine potentiation of the replication in vitro of several unrelated RNA and DNA viruses. Enhancement of the replication of unrelated viruses (three RNA viruses and one DNA virus), representative of four major virus groups, occurs in human, rodent, or avian cells treated in vitro with 5-iododeoxyuridine (IdU). The results suggest that the potentiation of viral replication by IdU is a widespread phenomenon.


Immunoglobulin E antibodies to pollen allergens account for high percentages of total immunoglobulin E protein. The quantities of immunoglobulin E (IgE) antibodies to grass or ragweed allergens were measured by an immunoabsorption in the serums of patients sensitive to one of these allergens. IgE antibodies to grass or ragweed allergens accounted for means of 30 and 29 percent of the total IgE protein. After the ragweed pollination season, the levels of serum IgE antibodies to ragweed allergens rose dramatically and in postpollination serums they accounted for 39 percent of the total IgE protein with a range from 13 to 50 percent.


Axonal projections of medial preoptic and anterior hypothalamic neurons. Projections from medial preoptic area (mPOA) and medial anterior hypothalamic area (mAHA) neurons were investigated in albino rats with the use of tritiated amino acid autoradiography. Both the mPOA and the mAHA gave long-axon projections to structures in limbic forebrain and midbrain as well as short-axon projections to other hypothalamic regions. Differences between mPOA and mAHA neurons were observed in projections to the mid-septal region, ventromedial hypothalamus, premammillary region, and central gray. Further, while axons from the mPOA traveled within the medial forebrain bundle, those from the mAHA remained in a band ventromedial to the fornix. These anatomical differences may underlie functional differences between the mPOA and mAHA which have been demonstrated with other experimental techniques.


Deficits in binocular depth perception in cats after alternating monocular deprivation. Allowing very young kittens to see with only one eye at a time greatly reduces the proportion of binocular cortical cells. Compared to normal cats these specially reared animals suffer deficits in binocular depth perception while retaining normal activity in the two eyes. Evidently, binocular cells play a crucial role in stereopsis.


Wrist arthrography: review and comparison of normals, rheumatoid arthritis and gout patients. Bilateral wrist arthrograms performed on a randomly selected population of 100 adult males revealed an unexpected high prevalence of communications among the three wrist compartments. These findings warrant reassessment of wrist arthrographic criteris for synovial involvement of rheumatoid arthritis. Midcarpal joint extension correlated with increasing age and occupational trauma, suggesting a degenerative or "wear and tear" mechanism in the breakdown of the delicate interosseous intercarpal ligaments. Such extension was also found to a greater than expected frequency in gout. Radioulnar joint extension correlated with acute trauma secondary to wrist sprains or fractures, presumably through tears in the tough triangular fibrocartilage. Such extension was also found to a greater than expected frequency in RA. While midcarpal extension and inferior radioulnar extension correlate with gout and RA, respectively, their occurrence in a random adult male population is so frequent (as is three compartment communication) as to obviate their diagnostic value. However, synovial corrugation and lymphatic visualization were seen only in the wrists of patients with diagnosed inflammatory arthritic conditions and may have potential diagnostic significance. Selected anthropometric variables were analyzed by age in this randomly selected adult male population and compared with the gouty and RA patient groups. Significant continuously decreasing grip strength and hand mineralization occurred with age, which was opposite to the trend for osteoarthrosis. The hematocrit, erythrocyte sedimentation rate, and serum uric acid were impressively stable until the ninth or older decades, at which time a significant increase in sedimentation rate and decrease in hematocrit were found.


Gonococcal arthritis in pregnancy: a ten-year review. Thirty-two cases of gonococcal arthritis in pregnant women admitted to Jackson Memorial Hospital between 1962 and 1971 are reviewed. Our specific aim is to reinforce awareness of this serious complication in pregnancy. The incidence of gonococcal arthritis is higher in women, but more significantly, it appears that the pregnant patient is at greater risk. The incidence of skin lesions seems to be higher in pregnancy. Penicillin was universally effective, since penicillin-resistant strains appear not to involve joints.


Childhood brain tumors: a 15-year survey. Eighty-seven children with histologically confirmed brain tumors were reviewed. Fifty-nine of the tumors were in the posterior fossa, 19 were cerebral gliomas, and nine were miscellaneous supratentorial tumors, including five craniopharyngiomas and two papillomas of the choroid plexus. In the posterior fossa there were 22 astrocytomas, 11 medulloblastomas, and ten ependymomas, indicating that half of the cerebellar tumors are benign. Of the patients with cerebellar astrocytomas, 15 are alive and 10 are probably cured. The cerebellar ependymomas have a very poor prognosis with only one long-term survivor and an average survival time of 14 months. The medulloblastoma group has only four survivors, and some of these are less than two years postoperative. Of 11 patients having cerebral astrocytoma, only three are leading satisfactory lives, three are dead, and five are handicapped to a significant degree. Of the eight patients with supratentorial ependymoma, all are dead with the longest survival being six years. It is emphasized that a benign cerebellar astrocytoma is the single most likely tumor in childhood, and many of these patients can be cured and survive without significant neurologic deficit.


Tuberculosis of the wrist: a report of ten cases. Ten patients with tuberculosis of the wrist are reported. In three, the disease was limited to the tenosynovium and these patients were treated by synovectomy. Seven patients had disease involving the carpal bones. In six of these an arthrodesis of the wrist was done, and solid fusion was attained in four. In all of the patients the wrist disease became inactive under treatment with isoniazid and para-aminosalicyclic acid.


Leiomyoblastoma of the stomach.

Leiomyoblastoma of the stomach. Two cases of leiomyoblastoma of the stomach are reported. Endoscopic features, ie, submucosal mass with umbilication and apical ulceration, presence of normal peristalsis, and absence of stenosis or irregularity, help differentiate this tumor from carcinoma of the stomach. Case histories are presented and pathologic features are described.


Male pattern baldness: classification and incidence. The need for a widely accepted, accurate, and reproducible standard of classification for male pattern baldness has increased with the advent and increasing popularity of hair transplant surgery. This report establishes such a classification, and reports its use in determining the incidence of male pattern baldness at various ages in 1,000 white adult male subjects. The action of testosterone as an incitant in male pattern baldness is well known, but this study points out the continued effect of time, even in later years. Since most hair transplant surgery is peformed on subjects with male pattern baldness, and because the success of hair transplant surgery is largely dependent on proper patient selection, a complete understanding of male pattern baldness is essential for consistently good results with hair transplantation.


Trauma to the portal venous system.

Trauma to the portal venous system. During a 16-year period, 47 wounds of the portal and/or superior mesenteric veins were encountered. Overall mortality was 57%. Survival was greatest in patients with injury to the superior mesenteric vein, wounds repairable by lateral phleborrhaphy, absence of associated major vascular trauma, and only transient or minimal hypovolemic shock. The majority of deaths were due to uncontrollable bleeding or sequelae of profound hemorrhagic shock. Limited follow-up of survivors has demonstrated a low patency rate at the site of venous repair, suggesting that mere ligation may be all that is necessary when lateral repair is impossible.


Radiologic aids in the diagnosis of appendicitis in children. Chest and abdominal radiograms are most helpful in evaluating acute abdominal pain in children. When basilar pneumonia is found the likelihood of associated appendicitis is slim. Evidence of appendicolithiasis on abdominal films secures the diagnosis of acute appendicitis and should prompt the surgeon to early operative intervention, since the threat of appendiceal perforation is great. Barium enema is safe and informative when obscure clinical presentation or associated illness exists. The likelihood of appendicitis is great when the appendix fails to fill at the time of barium enema. Complete filling of the appendix excludes the possibility of acute appendicitis.


Acute systemic toxicity from bupivacaine during epidural anesthesia in obstetric patients. Convulsions occurred within 30 seconds after the injection of bupivacaine through the epidural catheter in four obstetric patients in labor, and mild excitation without convulsions occurred in three others. Since the time between injection and the reaction was so short and since the dose was so small, the response probably was due to intravenous injection resulting from lodgement of the catheter in a vein, rather than to absorption from the epidural space itself. It is not generally known that the epidural veins become thin-walled and engorged during labor; thus, inadvertent placement of a cathether in a vein can occur readily. Convulsions, therefore, may follow even injection of a test dose of a drug. Other colleagues have had similar though unreported experiences. Physicians performing epidural blocks should be aware that such an occurrence is possible and that the catheter may be within a vein without blood returning on aspiration.


Temporal bone radiography: a screening survey approach. For preliminary evaluation of the temporal bone, a combination of conventional radiographs and hypocycloidal tomography in the frontal projection is advocated. If significant abnormalities are detected in this screening survey, a more in-depth study can then be pursued.


A rational approach to carcinoma of the ovary. Carcinoma of the ovary is the leading cause of death from pelvic gynecologic malignancies in the United States. Factors which may reduce mortality from ovarian cancer include (1) emphasis on early diagnosis by awareness of neoplastic possibility and by an aggressive approach to persistent ovarian enlargement, (2) concentration upon the common epithelial tumors as the primary cause of ovarian cancer, (3) specific histologic classification and staging of the tumors as a guide to clinical management, (4) attention to certain principles of treatment, and (5) postoperative follow-up with radiation therapy and/or chemotherapy.


Innovar as a preoperative medication.

Innovar as a preoperative medication. Innovar, administered intramuscularly 45 minutes preoperatively, provides excellent operative sedation, analgesia, and patient cooperation. Postoperative complications are minimized, and the quantity of postoperative analgesics and antiemetics is drastically reduced when Innovar is used as a preoperative medication.


Repair of vesicovaginal fistulas: simultaneous transvaginal-transvesical approach. The records of 91 patients with vesicovaginal fistulas at the Ochsner Clinic between 1942 and 1974 were reviewed. The fistulas were managed in several ways: spontaneous closure, palliative operation, urinary diversion, transvesical repair, transvaginal repair, and a combined transvaginal-transvesical procedure. The latter had a 100% success rate in the eight patients in whom it was used. The technic of this procedure is described and the indications are expanded to include (1) large fistulas, (2) fistulas near the ureteral orifice, (3) if other abdominal or urologic surgery is being done, (4) if transvesical approach is being used, (5) previous failed attempts at correction, (6) difficulty of access by vaginal approach, and (7) fistulas resulting from transurethral resection of the bladder neck.


Glaucoma with elevated episcleral venous pressure. A chronic elevation of the episcleral venous pressure may occur after venous obstructive disease or arteriovenous fistulas in the orbit, head, neck, or mediastinum. Idiopathic and familial occurrences of elevated episcleral venous pressure have been reported. Association with an increased episcleral venous pressure is a rise in intraocular pressure which, if of sufficient magnitude and duration, may cause cupping of the optic nerve and visual field loss. A case of glaucoma with visual field loss secondary to elevated episcleral venous pressure is presented. Recognition of the etiology of such cases is important, since the management of these patients differs from that of patients having primary open-angle glaucoma.


Reliability of the signs of fetal distress. The outcome of 3 659 consecutive labours, during which no heed was paid to fetal monitoring, is reported. Perinatal morbidity and mortality were neither better nor worse than the rates which have been reported from units which practise intensive intrapartum fetal monitoring.


Rheumatic disorders in the South African Negro. Part II. Osteo-arthrosis. The prevalence of osteo-arthrosis of the hip, the knee, the small joints of the hand and the metatarsophalangeal joint of the big toe, has been studied in a South African Negro population. The pattern of joint involvement differed considerably from that expected in a White population. Interphalangeal osteo-arthrosis was much less common in Black women than in White, and Heberden's nodes were seen in only 3 of 93 respondents who were over 65 years of age. Osteo-arthrosis of the metacarpophalangeal joints also, was less common in Black women than in White, but the Black men showed a much greater involvement than that seen in White men. As in White peoples, osteo-arthrosis of the metatarsophalangeal joint of the big toe was commoner in women than in men, but the over-all prevalence did not reach the high levels in Whites. Osteo-arthrosis of the knee was much commoner in the women than in the men; this was associated with a marked tendency to obesity in the older women. The hip joint which is a common site for osteo-arthrosis in Whites, was seldom affected in this Black population. It is clear from this study that the apparent rarity of certain forms of degenerative arthritis in the South African Negro is not owing to any inherent resistance to the disease, because osteo-arthrosis of certain joints, such as the knee in women and the metacarpophalangeal joints in men, is even more common in Blacks than in Whites. The differences encountered can, in many instances, be attributed to differences in occupation and life style in the two populations; but genetic factors, may also play a part in the sense that certain predisposing disorders, such as congenital subluxation of the hip, appear to be far less common in Blacks than in Whites.


Prazosin in the treatment of hypertension: a preliminary study. This was an open, uncontrolled, comparative study of prazosin carried out in 32 patients, to test the efficacy and toleration of the hypotensive agent. In 8 patients prazosin was combined with a diuretic and in 2 patients prindolol (Visken), and in 1 patient, methyldopa (Aldomet), were added. A satisfactory drop in blood pressure occurred in 30 of the 32 patients. Other effects occurred in 18 patients (56%), but they usually disappeared with continued therapy. In 5 patients therapy was stopped because of these effects. There was no postural hypotension, nor did the males experience sexual problems. The mode of action appears to be an adrenoreceptor blockade without receptor occupancy. Prazosin alone or in a combination of drugs, may be a useful hypotensive agent.


Evaluation of aorto-iliac disease with Doppler ultrasound and isotope clearance techniques. The clearance of 99mTc from the hamstring muscle compartment of patients with aorto-iliac or iliac disease was examined with the patients at rest and after exercise. The values were compared with those obtained in a group of controls and another group with superficial femoral, or femoropopliteal arterial occlusion. A statistically significant difference in the rate of 99mTc clearance was found in patients with proximal vascular disease.


Diagnostic peritoneal lavage in blunt and penetrating abdominal trauma. Peritoneal lavage as a diagnostic aid is described in a small series which includes both blunt and penetrating abdominal trauma. Its value for blunt injuries has been confirmed, and it is recommended for penetrating injuries, when the diagnosis of visceral injury is in doubt.


Pre-operative preparation of the skin with a depilatory. Although the removal of hair as a pre-operative preparation of the skin is desirable, it need only be removed over an area limited to a planned incision, and then only in hirsute patients. The use of a depilatory cream as an alternative to a razor would seem to have the advantages of increasing patient comfort; of avoiding injuries inflicted by even skilful shaving; and perhaps of diminishing the incidence of wound infection, without significant risk of reaction to the depilatory. Routine extensive pre-operative hair removal in all patients is unnecessary.


Visuomotor performance in Blacks.

Visuomotor performance in Blacks. The performance of Black hospital employees in the copying of designs, the drawing of human figures, and the assembling of blocks, is discussed. They performed the latter two tasks poorly. This may be attributable to their culture but it emphasises the unsuitability of these tests for Blacks, in that they are not standardised as a measure of ability for this ethnic group.


Enzymic micromethod for semiquantatative analysis of oxypurines in specimens of skeletal muscle. A rapid and specific micromethod for semiquantitative determination of oxypurines in small specimens of skeletal muscle is described. Normal levels of xanthine plus hypoxanthine and uric acid in human skeletal muscle are in the ranges of 0,07-0,34 mg/100 g and 0,38-0,74 mg/100 g, respectively.


Forced expiratory volume and expiratory flow rate in Black miners and in a control group. The peak expiratory flow rate and the forced expiratory volume and 1 second were measured in 772 Black miners who did not have pneumoconiosis, tuberculosis or chronic bronchitis. The same tests were done in 164 non-mining workers. It was found that exposure to dust associated with the miners' work had no effect on the results of these tests.


Effect of delta-aminolaevulinic acid on the resting membrane potential of frog sartorius muscle. The porphyrin precursor delta-aminolaevulinic acid can significantly decrease the resting membrane potential in a single fibre from the sartorius muscle of the frog Rana angolensis. This effect is dose-dependent and reversible.


Analgesic renal papillary necrosis.

Analgesic renal papillary necrosis. Analgesic nephropathy is well recognised. This is a retrospective review of 19 patients with the disease, who presented at Groote Schuur Hospital over a 4-year period. The diagnosis was made on historical and clinical grounds and on the radiological manifestations of papillary necrosis. The mean age was 49 years (26 - 74) with a sex ratio of 3,8 female : 1 male. The period of abuse varied between 3 and 20 years. Aspirin, phenacetin, codeine, and antipyrine were the compounds mainly ingested. If the abuse is stopped, renal deterioration can be halted. However, factors which lead to dehydration and infection tend to cause further decompensation. As a means of preventing this disease greater control over analgescis is needed.


Irreversible renal failure in acute post-streptococcal glomerulonephritis. Irreversible renal failure in sporadic acute post-streptococcal glomerulonephritis rarely occurs. Most patients have extracapillary proliferation. Complete recovery from the epidemic form is the rule. It is possible that the two conditions are different clinicopathological entities.


Rheumatic disorders in the South African Negro. Part III. Idiopathic necrosis of the femoral head. Idiopathic necrosis of the femoral head, with progressive articular destruction, is a well-recognised disorder in the South African Negro. Twenty-nine cases were studied in detail. In 17 there was evidence of associated iron overload, but it is unlikely that this contributed directly to the occurence of osteonecrosis. The syndrome of siderosis, scurvy and osteoporosis in Johannesburg Blacks is attributed to the ingestion of large quantities of iron in home-brewed beer. Often the beer is mixed with much more potent liquor and it is postulated that this, rather than the iron overload, is the cause of 'idiopathic' femoral head necrosis.


Potassium retention in acute diarrhoeal disease. Most children suffering from severe acute diarrhoeal disease had a low total body potassium (TBK) or admission to hospital. TBK fell even lower during the first 5 - 9 days in hospital, and returned to normal levels during the next 8 - 12 days. There was good correlation between potassium retention and stool weight. An increase in the potassium intake had little effect on the rate of potassium repletion.


Split hands and feet.

Split hands and feet. We present 2 Iranian children, siblings, with the very rare but classical 'lobster-claw' deformities of hands and feet. We could not trace any hereditary influences.


Sulphonylureas and insulin resistance.

Sulphonylureas and insulin resistance. This is a case report of a diabetic who required 750-1000 units of insulin per day when gangrene of the leg developed, whereas previously he had needed no insulin. After amputation of the leg, the patient remained asymptomatic for 9 weeks without insulin. This was clearly related to an increased concentration of circulating antibody-bound insulin. Despite healing at the site of amputation, diabetic symptoms and insulin resistance reappeared. Chlorpropamide treatment reduced the insulin requirement to zero, which was unrelated to a change in insulin antibody concentration.


Pernicious anaemia with hypogamma-globulinaemia. A case report. Auto-immune mechanisms are important in the evolution of pernicious anaemia, but cannot be demonstrated in all cases. Cell-mediated immunity is involved in the pathogenesis, and explains the occurrence of pernicious anaemia in patients with hypogammaglobulinaemia. The pernicious anaemia seen in these patients differs in some respects from the classical form of the disease. The case history of a patient with pernicious anaemia and hypogammaglobulinaemia is presented, and the possible pathological mechanisms are discussed.


Medical ethics and clinical therapeutic trials. Old and modern codes of ethics exist, which can be used as guidelines in human experimentation. Medical researchers should be familiar with the contents of these codes. A four-point proposal, to be used in determining the ethical acceptability of clinical therapeutic trials, is presented.


Fetal tachycardia and maternal pyrexia during labour. Fifty-two cases of fetal tachycardia during labour were investigated. Nine of these cases (17%) were possibly attributable to maternal pyrexia. In most, fetal tachycardia preceded the rise in maternal body temperature. Fetal tachycardia can be an early indication of intra-uterine infection.


Systemic lupus erythematosus and spontaneously arising anticoagulants. Of 36 patients with systemic lupus erythematosus, 3 were demonstrated to have an abnormality in their haemostatic mechanism. In 2 this was believed to be on the basis of an auto-antibody to the phospholipid of platelets in the prothrombin activator complex. In the third an inhibitor was directed against factor VIII.


Congenital atresia of the external iliac artery. A patient with congenital atresia of the external iliac artery is presented. Successful revascularisation was acheived by means of an ileofemoral reversed long saphenous vein graft. The embryology of this malformation is discussed.


Twenty-one years' experience with ruptured abdominal aortic aneurysms. The surgical experience with 107 ruptured abdominal aortic aneurysms at this hospital during the years 1953 to 1975 has been reviewed. The operative mortality rate during the first ten years of this study was 86 per cent, but since 1966, it has fallen to 40 per cent. These improved mortality statistics are related primarily to improved techniques for controlling operative blood loss and minimizing the time of aortic cross clamping. The use of an intra-aortic balloon has been useful in this regard. Twenty-four additional patients died from ruptured aneurysms without undergoing operation, all before 1966. Only seven had a correct diagnosis prior to death, and these seven serve to emphasize the importance of being alert to the diagnosis of ruptured aneurysm which often masquerades as urologic or orthopedic problems because of the frequent symptoms of back, abdominal, flank or groin pain. Since the operative mortality rate for elective resection of the aneurysm has been less than 1 per cent at this institution during the last eight years, we believe we are justified in encouraging prompt resection of aneurysms on an elective basis to eliminate the high mortality rate that still accompanies rupture of the aneurysm.


Portal hepatotrophic factors, diabetes mellitus and acute liver atrophy, hypertrophy and regeneration. The acute influence of portal blood hepatotrophyic factors upon the canine liver and upon hepatic regeneration was studied after surgical operations which provided qualitatively different portal venous perfusion to the right and left liver lobes. With one such procedure called splanchnic division, the nutrient rich venous return from the intestines was directed to the left lobes, whereas the hormone rich blood from the pancreas and other splanchnic organs of the upper part of the abdomen passed to the right lobes. Within three to five days, the rate of cell division on both liver sides was increased as judged by autoradiography, but the hormone influenced right lobes exhibited hypertrophy and hyperplasia relative to the nutrient enriched left lobes. In the latter, the hepatocytes underwent pronounced atrophy, deglycogenation, depletion or distortion of the rough endoplasmic reticulum, fatty vacuolization and other structural changes. When 30 or 60 per cent hepatic resection was carried out at the same time as splanchnic division, the regeneration of the hormone dominated hepatic tissue after three to five days was greater than that of the hepatic tissue receiving the intestinal venous effluent, as judged by multiple criteria, although both liver sides participated in the regeneration process. The advantage enjoyed by the right liver lobes in relation to the left liver lobes both in the resting or in the regeneration state after splanchnic division was reduced or eliminated by pre-existing alloxan-induced diabetes or after concomitant total pancreatectomy. Similar, but less complete, observations about the effect of pancreatectomy were made in dogs submitted to the procedure of partial portacaval transposition, in which all the splanchnic venous blood passed to the right lobes, whereas the left lobes were revascularized with systemic venous blood from the vena cava. These observations have added to the recent torrent of evidence that insulin is the most easily demonstrable and, therefore, probably the most important specific hepatotrophic factor in portal venous blood. At the same time, further subtle support has been added to our previously proposed hypothesis that mutliple other hormonal and possibly nonhormonal factors from the splanchnic viscera and other sources also contribute to the essence of the hepatotrophic effects. These effects were evident and quite advanced within a few days. A prominent hepatotrophic role of glucagon was not identifiable.


The use of bone and brain scans as screening procedures in patients with malignant lesions. A retrospective study to determine the value of bone and brain scans was performed in preoperative patients with melanoma, sarcoma, cancer of the head and neck and carcinoma of the pelvis. No occult metastases were identified in 170 patients in whom brain scan was performed. On late follow-up data, eight patients had neurologic symptoms develop and had brain metastases identified on scan. Of 223 bone scans performed, only one distant metastatic lesion was identified. It is, therefore, suggested that, in these types of patients, bone and brain scans be reserved for those with symptoms referable to the neurologic or skeletal systems.


Behavior of the portal vein system in man after laparotomy. At the end of an abdominal operation, a Teflon catheter was inserted into the portal vein, where it remained for nine days. Thus, blood samples could be withdrawn for analyses, and pressures could be recorded. The investigations were carried out in 41 patients who had a gastric or intestinal operation and had an uncomplicated postoperative course. The pressures in the portal vein and the arterioportal oxygen content difference were constant with 7 to 8 millimeters of mercury and by 2 volume per cent, respectively, during the period of all nine postoperative days. The pressure gradient between portal and central veins was about 6 millimeters of mercury. By infusing 350 to 500 milliliters of dextran 60 on day one or two postoperatively, the cardiac output was elevated about one-third, the central venous pressure increased from 0.9 to 4.9 millimeters of mercury and the portal venous pressure increased from 7.8 to 9.7 millimeters of mercury. This means that the pressure difference between the portal and central veins diminished. Simultaneously, the oxygen content difference between the systemic and pulmonary artery decreased from 4.7 to 3.3 volume per cent and between the systemic artery and portal vein, from 1.8 to 1.3 volume per cent. By assuming a constancy of the oxygen consumption in the region of the mesenteric circulation during infusion, it can be calculated from the behavior of the arterioportal oxygen content difference that the flow increase in the portal vein nearly equals that of cardiac output. The physical transhepatic resistance decreased about 50 per cent.


A urodynamic analysis of micturition symptoms in the female. The presenting symptoms of 570 females with micturition disorders have been studied with particular reference to the urodynamic state of the detrusor in an attempt to define those symptoms and symptom complexes which are associated with the presence of absence of detrusor instability. The results show that patients who complain of recurrent urinary tract infection or stress incontinence in the absence of any other micturition symptoms usually have stable bladders and do not require cystometric confirmation of this fact. When the symptom of urge incontinence is associated with persistent frequency and nocturia, there is a high correlation with detrusor instability, although hypersensitive urethral states which may present with identical symptoms and are usually associated with stable bladders are difficult to differentiate clinically. Groups of patients in whom it was difficult to predict the detrusor state from the symptoms were studied, and the results of a prospective analysis, predicting the detrusor state from the micturition history of 230 incontinent females, have been presented.


The effects of nicotinic acid upon postburn plasma volume loss. The effects of intravenously injected nicotinic acid upon postburn plasma volume loss have been studied in the anesthetized dog. Results of this study have shown that two hours after a third degree flame burn over 40 per cent of the surface area, approximately 12 milliliters per kilogram of plasma are lost to the extravascular spaces. If untreated, this loss will increase to 16 milliliters per kilogram at four hours postburn and 19 milliliters per kilogram at six hours postburn. Treatment of the dogs with nicotinic acid beginning two and one-half hours postburn will reduce the plasma extravasation to 13 milliliters per kilogram four hours postburn and to 11 milliliters per kilogram at six hours postburn. In general, the decrease in cardiac output observed after thermal trauma paralleled the loss of plasma volume. In the untreated dogs, this decrease continued with time postburn, but in the treated dogs, the decrease in cardiac output leveled off during the first two hours after beginning treatment and started what appeared to be a slow return toward control levels in the next two hour period.


The effect of antrectomy on gastric acid and gastrin secretion. In three dogs with denervated fundic pouches, ingestion of beef liver test meal increased H+ output and serum gastrin levels during the first hour of the four hour experiment. H+ and serum gastrin output then slowly decreased but did not reach basal values. After antrectomy and gastroduodenal anastomosis, ingestion of the test meal did not lead to the early increase in H+ output and serum gastrin levels. Although serum gastrin levels did not significantly change throughout the four hour experiment, beginning at 80 minutes H+ output slowly increased. The rise in H+ output did not reach preantrectomy values. These results indicate that antrectomy abolishes the early rise in H+ and gastrin secretion in response to a protein test meal. Since gastrin levels did not significantly change throughout the whole experiment, the late increase in H+ output is due to a mechanism other than gastrin release.


The transcutaneous measurement of the elastic properties of the human saphenous vein femoropopliteal bypass graft. The pressure-strain elastic modulus and compliance of 20 reversed saphenous femoropopliteal vein grafts have been measured by a noninvasive, ultrasonic method. The grafts had been in place for an average of 33.6 months, 11 days to 128 months. In this study no correlation was demonstrated between wall stiffness and duration of implantation. It is concluded that the elastic properties of vein grafts may remain stable for considerable periods of time.


The assets and liabilities of mammography. Anyone using mammography should perform it seriously with one or two radiologists in any group as the primary physicians. It is only by being exposed to a high patient volume day after day and having a thorough knowledge of all the pathologic conditions that one can truly appreciate the subtle mammographic patterns present. In only this way is the diligent radiologist optimally helpful to the surgeon and pathologist, and this best serves patient welfare. Conversely, the part-time mammographer, although not necessarily besmirching his professional competence, will tend to give the examination a bad reputation by unnecessary hedges and reporting uncertainties characterized by long winded reports. Patients undergoing mammography should undergo a physical examination by the radiologist. Thus, accuracy rates for the detection of cancer can approach, 98 per cent. Liabilities consequent to mammography can be minimized by the professional competence of the radiologist, understanding the limitations of the examination and the expertise of the reporting style.


Angiographic spectrum in Crohn's disease of the small intestine and colon. Barium and angiographic examinations of the small intestine and colon were performed in 34 patients with histopathologically verified Crohn's disease. The spectrum of angiographic findings varied from hypervascularity with no morphologic changes of the vasa recta to complete obstruction of the vasa recta resulting in hypovascularity of the diseased intestine. A distinctive angiographic pattern was present in the distal part of the small intestine in those patients with advanced narrowing of the intestinal lumen as demonstrated on barium examination.


Disconnection of the ampulla of Vater.

Disconnection of the ampulla of Vater. A patient with ampullary disconnection during gastrectomy is presented, emphasizing the chronicity and retractile scarring which exposes the bile and pancreatic ducts to simultaneous injury. As wider appreciation of this potentially lethal lesion is gained, greater use of predissection cholangiography or probe identification of the papilla should occur. Steps to detect the lesion and primary repair by duodenal advancement or, in unrecognized instances, the Hepp operation using a Roux-en-Y limb after a suitable waiting period are recommended.


Total proctocolectomy without the lithotomy position. Total proctocolectomy for benign disease can be done entirely from within the abdominal incision, thus, avoiding the extra time and inconvenience of operating with the patient in the lithotomy position. This procedure is quick and simple, and the visibility is excellent even in a narrow adult male pelvis, and the lithotomy position is completely eliminated. Results in six patients have been gratifying.


Interposition of the azygous vein in the Blalock-Taussig procedure. Interposition of the azygous vein between the subclavian and pulmonary artery is helpful in extending the subclavian artery, when additional length is required for a satisfactory anastomosis.


Reconstruction of the male external genitalia. Congenital malformation, infection, lymphatic obstruction, trauma and carcinoma all have common denominator, the loss of tissue. This loss necessitates the surgeon's use of various techniques in reconstructing the male external genitalia. The stretching of remaining skin, split thickness grafts, flaps and pedicle tube grafts are used to cover the denuded area or reconstruct the penis and scrotum. These methods have been used recently in transsexual operations, combining the expertise of the plastic surgeon, urologist, endocrinologist and psychiatrist. Further improvement upon the preceding approaches is sought to maintain sensation, achieve acceptable cosmesis, create a sexual organ as well as a urinary conduit and prevent severe postoperative complications.


Embolization of angiomas of the spinal cord. The treatment of arteriovenous malformations has been one of the most difficult of neurosurgical probelms. A high percentage of these cases can be satisfactorily treated by embolization. A series of such cases is reported here. In many instances this is more satisfactory than direct surgical intervention.


Schistosomiasis (bilharziasis) mansoni of the spinal cord stimulating an intramedullary tumor. A case of involvement of the spinal cord by schistosoma masoni is described. There was a granuloma in the conus medullaris stimulating an intramedullary tumor. Biopsy led to the correct diagnosis. After decompression of the spinal cord and the oral administration of Niridazole (Ambilhar) the patient recovered satisfactorily.


Underwater deceleration curves in relation to injuries from diving. Diving accidents result in more than 1,800 cases of paralysis from injury to the spinal cord each year. Studies have been made of underwater deceleration during diving. The mechanisms involved in spinal injury are discussed.


Simulated acute appendicitis secondary to ventriculoperitoneal shunt. A case of simulated acute appendicitis caused by a ventriculoperitoneal shunt is described. This case presented as a perplexing clinical problem. When the diagnosis was established by laparotomy, it was apparent that another complication should be added to the list of abdominal complications which occurred secondary to insertion of a ventriculoperitoneal shunt.


Post-traumatic ophthalmic vein arterialization. An unusual case of post-traumatic exophthalmos without pulsation, bruit or thrill, due to missile injury is presented. Arterialization of the ophthalmic vein represents one of the very few situations where an eye injury can lead to exsanguination and dealth unless the diagnosis is made early. Prompt carotid arteriography is advised to document the pathologic process and guide appropriate therapy.


Neurinomas of the trigeminal nerve.

Neurinomas of the trigeminal nerve. Neurinomas of the trigeminal nerve are rare tumours. Six cases of a series of 8,894 intracranial tumours operated upon in the Neurosurgical Clinic of Bucharest are reported. The literature is reviewed. One hundred one other cases have been found. The signs and symptoms produced by these tumours, their slow development, the radiological and other diagnostic findings, the treatment and the prognosis are discussed.


Removal of an intracranial glioblastoma in a hemophiliac. A case report of a Factor VIII deficient hemophiliac, who underwent surgery for a glioblastoma, is presented. Emphasis is placed on diagnosing the hemostatic deficiency by the use of four hematological tests: bleeding time, platelet count, partial thromboplastin time, and prothrombin time. With close cooperation of a hematologist during the intraoperative and postoperative period, there should be a low mortality associated with intracranial surgery in a hemophiliac patient.


Unilateral proptosis and intracranial schwannoma. Two cases of unilateral proptosis associated with intracranial schwannomas in children are described. In both cases, tumour occupied both the orbit and middle cranial fossa, where in one case the intracranial component was extradural and in the other intracerebral. Possible sites of tumour origin are discussed.


Rapid closed reduction of cervical fracture dislocations. Indications and a procedure for rapid closed reduction and decompression of cervical fracture dislocations in less than two hours by tong traction are described. Large amounts of weight are utilized. Neurologic damage due either to the large amount of weight or to rapidity of reduction has not been observed. The procedure is advocated in appropriate patients, provided that both sequential neurologic and radiographic monitoring are carried out.


Post-traumatic syringomyelia.

Post-traumatic syringomyelia. Post-traumatic syringomyelia is uncommon. It is seen predominantly after injury to the thoracic or the lumbar spine and rarely after injury to the cervical spine. In this report, three cases of post-traumatic syringomyelia are presented. The injury was limited to the thoracic spine in one case and to the cervical spine in the rest. The symptoms began after two years in two cases and after fifteen years in the third. The diagnosis was suggested by radiographic examination and was confirmed at operation in each case. Following evacuation and drainage of the cyst, significant improvement occurred in two patients.


Non-tumoral stenosis of the aqueduct in adults. Nine cases of non-tumoral stenosis of the aqueduct in adults are described. The deformed aqueducts are displayed diagrammatically. Patients may be divided into three groups, according to their presentation; papilledema with raised intracranila pressure, epilepsy, or intellectual impairment. Those patients in the first category tended to be younger, and to respond more favorably to treatment. A review of the literature is made.


Effects of local hypothermia and of steroids upon recovery from experimental spinal cord compression injury. Canine spinal cords were compressed by a cylindrical balloon placed in the T-13 epidural space and maintained at 160 mm Hg for one hour. Fifteen minutes after deflation, either local hypothermia or parenteral dexamethasone therapy was initiated. Local hypothermia (dorsal dura mater at 6 degrees C for four hours) was achieved with a miniature epidural heat exchanger which kept cooling fluid isolated from tissue. At seven weeks, the treated groups achieved motor ratings which were significantly superior to those of the untreated group. The untreated group were unable to walk, while both treated groups were able to do so.


Observations of pressure waves in stomach, jejunal, and colonic loops used to replace the esophagus. The motility characteristics of the stomach, upper jejunum, and right colon were studied in 25 patients in whom these organs were used to replace the resected esophagus. The pattern of motility in all three replacement organs generally was similar to that recorded in normal individuals by other workers. But the stomach replacement showed a greater percentage of Type 1 waves, and Type II contractions were weaker. Activity in the jejunal replacements was much reduced. A propagated pressure wave was observed on swallowing water in the jejunal replacements. The nature of this wave needs further elucidation. The functional result was good, except in patients with a weak or without an upper esophageal sphincter. Patients experienced no pain during the test and no side effects were observed.


Banding of arteriovenous dialysis fistulas to correct high-output cardiac failure. Three patients with high output cardiac failure from arteriovenous dialysis fistulas are described. All three were treated successfully by banding the appropriate vessel while constantly monitoring flow rates.


Thigh emphysema and hip pain secondary to gastrointestinal perforation. A patient presenting with thigh emphysema and hip pain may suggest intra-abdominal pathology. Three new and 19 previously reported cases of thigh emphysema secondary to bowel disease are reviewed. The thigh and hip manifestations can obscure the primary intra-abdominal process either due to the obvious emphysema or to the obtunded abdominal signs secondary to associated neuropathy. Only one of 22 patients with thigh emphysema secondary to bowel perforation had gas gangrene. Early diagnosis of this clinical association is essential since eight of the 11 deaths occurred within a few days after admission. Right-sided thigh emphysema suggests appendicitis, whereas left-sided emphysema is more likely to be secondary to left colonic diverticulitis or carcinoma.


Benign obstructing papilloma of the ampulla of Vater in infancy. Obstructive jaundice due to benign neoplasms of the extrahepatic bile ducts is rare in all age groups. A case is reported which represents the first obstructing papilloma of the ampulla of Vater found in the pediatric age group and the literature pertaining to benign obstructing neoplasms is reviewed briefly. Differential diagnosis of persistent jaundice past the immediate neonatal period is discussed and the need for operative cholangiogram and open liver biopsy in difficult cases is stressed. Obstructing papillomas and other neoplasms of the extrahepatic bile ducts should be added to the differential diagnosis of jaundice in the pediatric age group.


Sacrococcygeal chordoma: Report of a case and review of the literature. A review of 222 patients with sacrococcygeal chordoma from the English language literature since the first American case in 1913 reveals that men are affected twice as frequently as are women after age 40, but not before. A history of prior trauma can be found in about 20 percent of patients, but no clear etiologic relation can be proved. The evidence for a congenital origin from displaced notochordal tissue is equally inconclusive. Metastasis occurs in only about 10 percent of patients, but recurrence of the primary lesion is almost universal. Of 67 patients followed, 11 survived 10 years or longer after diagnosis of chordoma. Resection of the tumor rarely is complete. Preservation of sacral stability and of sacral nerve pathways to the rectum and the bladder limit the extent of permissable surgery. Repeated local excision of the tumor recurring after initial excision and irradiation remains the treatment of choice.


Peripheral embolism resulting from unsuspected atheromatous aortic plaques. Three cases of peripheral embolism resulting from atheromatous aortic plaques are reported. Although the majority of arterial thromboemboli are believed to have originated from mural thrombi within one of the cardiac chambers, there is reason to believe that embolism from atheromatous material within a major artery may occur more often than is represented in current literature. Successful management of this condition will necessitate (1) clinical awareness, (2) careful scrutinization of material recovered from embolectomy, (3) angiography to demonstrate the embolic source in the aorta or its main braches, and (4) appropriate remedy by either endarterectomy or graft replacement of the diseased artery segment. The pitfalls in the diagnosis of this condition are discussed.


Post-traumatic aneurysms of the thoracic aorta. Nineteen patients with histologically proved post-traumatic aneurysm of the thoracic aorta were reviewed. Only seven aneurysms were detected at the time of hospitalization for trauma. Eight of 12 patients with chronic aneurysms either became symptomatic or showed enlargment during a period of observation. Surgical excision was the recommended method of therapy.


The nature of arterial healing following dextran treatment of experimental small artery trauma. Vascular thrombosis is a major cause of morbidity and death. Because of the many variables involved with thrombosis in patients, major advances in treatment often depend upon design and study of adequate experimental models which provide a degree of control of the variables. Arterial trauma was produced in small femoral arteries 3 mm. or less in diameter by a standardized intimectomy technique. One group of animals was treated with an equal volume of saline and served as controls. Serial sections of blood vessels at graded time intervals from one hour to 90 days were studied. The damaged blood vessels of dextran-treated animals did not thrombose and provided an opportunity for studying the mechanism of healing in traumatized blood vessels which remained patent. The damaged blood vessels of saline-treated animals uniformly thrombosed and eventually healed for scar formation with evidences of attempts at recanalization. The blood vessels of dextran-treated animals remained open for as long as 90 days and were re-endothelialized and healed. What appears to be beginning re-endothelialization of blood vessels of dextran-treated animals was observed as early as 48 hours. In a model experimental setting, dextran has been shown to prevent thrombosis and permit healing in small arteries subjected to a standardized surgical trauma.


Effect of ascorbic acid on rectal polyps of patients with familial polyposis. Evidence for dehydrogenation by fecal bacteria in the genesis of colon cancer suggested that an antioxidant might modify these mechanisms. Ascorbic acid, 3 Gm. daily, was given to five patients who had active rectal adenomatous polyp formation long after ileorectal anastomosis for familial polyposis. During a 4 to 13 month study, rectal polyps disappeared in two, regressed partially in two, and increased in one. Among three additional treated patients with rectal polyps, one had a reduction in polyps and two were unaffected.


Acute mesenteric vascular occlusion: A review of thirty-two patients. High mortality rates associated with mesenteric occlusion are a tremendous challenge. We reviewed 32 patients admitted to Beckley Appalachian Regional Hospital during the years 1965 to 1974. The majority of the patients were men. There was quite a variation in the symptoms and physical signs, with heart disease commonly associated with mesenteric occlusion. Massive gangrene involving the small and large bowels had the worst prognosis. Thrombectomy and anticoagulation did not prove beneficial in our series. Patients who survived massive resection are having intermittent diarrhea, responsive to medical treatment. The mortality rate in this series of 32 patients was 81.3 percent. It is hoped that with increased use of mesenteric angiography, early diagnosis, and prompt management the mortality rate can be brought down to acceptable levels.


The correlation of sequential changes in the distribution of pulmonary blood flow in hemorrhagic shock with the histopathologic anatomy. Histopathologic changes were described and correlated with hemodynamic changes in a series of farm-reared dogs by a preparation and a protocol which were shown to simulate closely physiologic events in clinical hemorrhagic shock; neither anesthesia nor thoracotomy was used and flush solutions for catheters were strictly limited; a series of sham-treated controls was used for comparison. Five different isotopes were used to label microspheres to measure blood flow sequentially at the tissue level at various stages of the shock protocol. At death, multiple tissue sections were taken relative to six parallel segments of the lung arranged according to dependency so that correlations of structure and function might be related to the influence of gravity. The degrees of severity of atelectasis, hemorrhage, edema, congestion, inflammation, and hyperaeration were evaluated by rating scales. Tissues from the most dependent areas had a higher incidence and greater severity of histologic lesions. Tissues with mild histologic rating tended to have lower percentages of flow after hemorrhage, but normal or increased flow after reinfusion. The severely damaged tissue received greater than average flow throughout. Tissues with severe atelectasis paralleled the course of those with a high over-all severe pathologic rating. Tissues with severe inflammation had less blood flow in the control period, increased flow in Stages B1 and B2 and a subsequent return to control values. Those with severe edema had reduced flow in Stages B2 and B3, but high flows after reinfusion.


Results of left gastric vena caval shunt for esophageal varices: Analysis of one hundred clinical cases. A new selective shunt operation, namely left gastric vena caval shunt, has been applied to 100 patients with esophageal varices, including 77 with cirrhosis of the liver and 19 with so-called idiopathic portal hypertension. Early death occurred in 3.0 percent and postoperative rebleeding from esophageal varices in 10.4 percent. The 5 year survival rate was 78.0 percent and the rehabilitation status of the surviving patients has been satisfactory, without any signs of hepatoencephalopathy. The shunt was proved to be patent in about 90 percent of the patients.


Aneurysm of a polar renal artery.

Aneurysm of a polar renal artery. A patient with a saccular aneurysm arising from the left superior polar renal artery is presented together with a review of two further reports from the literature. The importance of selective arteriography and the interpretation of the "naked calyx" sign in the diagnosis of supernumerary renal arteries has been emphasized. We feel that this is the only report of an aneurysm of a polar artery successfully treated by excision and end-to-end arterial anastomosis.


Acute abdomen due to torsion of a pedunculated mesenteric fibroma. A case history of a boy with an acute abdomen due to torsion of a pedunculated mesenteric fibroma is presented. A review of the literature shows that only a relatively small number of mesenteric fibromata have been reported. In these cases the tumor was described as growing between the two leaves of the mesentery. The symptoms these tumors gave usually were due to the size of the tumor and compression of adjacent organs. The present case is unusual because of the pedunculated nature of the fibroma and its presentation as an acute abdomen.


Iatrogenic entrapment of femoropopliteal saphenous vein bypass grafts by the gastrocnemius muscle. Two patients are described in whom saphenous vein grafts placed distal to the knee joint were "entrapped" by the medial gastrocnemius tendon. In one, the superficial position of the graft was detected by postoperative angiography. In the other, a true aneurysm of the vein graft developed over a 3 year period. The similarity between the iatrogenic and congenital forms of the popliteal entrapment syndrome is noted.


Deep inferior epigastric arteriovenous shunt for hemodialysis. The deep inferior epigastric artery and vein may be satisfactorily utilized for chronic hemodialysis in patients who have no extremity vessels available.


Postprandial rest pain and claudication of the lower extremity: A case report. Postprandial rest pain and claudication in the lower extremities may occur in arteriosclerotic aortic occlusion when mesenteric and systemic collateral pathways provide inadequate blood flow to the extremity. The symptoms occur as a result of vasodilation of the distal mesenteric vascular bed with a concomitant increase in mesenteric blood flow which leads to a decrease in mesenteric artery to extremity collateral blood flow. This normal physiologic phenomenon, increase in mesenteric blood flow, causes the extremity pain. Such symptoms indicate a quite significant decrease in blood flow to the extremity, and prompt surgical correction is indicated. Aortofemoral reconstruction yields total reflief of the symptom complex.


Rejection and repair of endothelium in major vessel transplants. Fresh saphenous vein homografts are gaining popularity as conduits for femoral-popliteal or distal bypass grafts. Aside from major blood group compatibility, there is little clinical evidence that rejection is a significant factor in long-term patency. Some have suggested that blood vessels are weakly antigenic and others indicate that rejection does not endanger long-term patency. Transplantation and toxic damage were produced in experimental animals in order to compare healing processes. Both types of injuries produced early significant endothelial cell proliferation detected by H3-thymidine uptake. This response peaked at 5 days in transplants and ever-expanding islands of proliferating endothelium were present in aortas exposed to 20 percent sodium chloride, leading to healing in 3 to 4 months. In the transplanted vessels, total endothelial destruction occurred at 11 to 28 days, and cells of host origin determined by sex chromatin analysis gradually resurfaced those grafts that maintained patency. At 4 months only two of six carotid artery homografts were patent in unmodified dogs, and eight of nine were patent in animals given 1 mg. per kilogram of Imuran. All patent grafts were resurfaced by host cells. We conclude that rejection does play a role in long-term patency; that donor endothelium of living vascular grafts cannot maintain sufficient proliferative capacity to repair immunological damage; that small doses of Imuran significantly alter the rate of destruction leading to more orderly repair and patency; and that clinical trials utilizing one half the dose of Imuran required for kidney graft survival are likely to improve significantly the long-term patency rate of fresh arterial or venous homografts in man.


Unusual problems of venous thrombosis.

Unusual problems of venous thrombosis. Although venous thrombosis (thrombophlebitis) is well known, there are uncommon manifestations which are seen infrequently, discussed rarely, and documented poorly. Experiences with 38 patients in seven categories are discussed in terms of our results and the pertinent reports of others. Pulmonary necrosis after embolic pulmonary infarction (six patients) may require tube thoracotomy and/or lung resection and contraindicate further heparin therapy. Iliac and/or femoral vein thrombosis occasionally fails to recanalize. Long-standing occlusion (18 patients) may be benefited by a cross-over saphenous vein graft. Left iliac venous occlusion secondary to pressure from the crossing right iliac artery (four patients) may indicate repair or bypass. Budd-Chiari syndrome (thrombosis of the hepatic venous outflow) was, in a single patient, carried past a critical period by a long Dacron tube shunt graft from the umbilical vein to the azygos vein. Subclavian and axillary venous thrombosis due to thoracic outlet pressure syndrome (three patients) often responds to heparin but may require thrombectomy; later resection of the first rib is indicated. Phlegmasia cerulea dolens (blue phlebitis) with tissue gangrene (three patients) requires immediate venous thrombectomy and subsequent heparinization. The occluded inferior vena cava (three patients) remains a challenging unsolved problem.


The effectiveness and mechanism of collagen-induced topical hemostasis. Microcrystalline collagen is a recently developed material possessing remarkable topical hemostatic properties. The potential utility of this substance for cardiovascular surgery was evaluated in a canine arterial bleeding model. A hemostatic protocol allowed comparison of initial and final hemostasis rates as well as the time required to accomplish hemostasis. The results of these studies revealed that microcrystalline collagen, or MCC, achieved hemostasis more frequently and rapidly than either pressure alone or oxidized cellulose cloth. MCC also was highly effective initially after large doses of heparin and in the presence of platelets with function rendered deficient by acetyl salicylate. Only in the presence of profound thrombocytopenia was any loss of initial effectiveness observed. Some delayed hemorrhage occurred in the heparin-treated groups leading to a lessened incidence of final hemostasis, a result intimately related to MCC's probable mechanism of action. However, even under the extreme conditions imposed by this severe experimental model, MCC remained effective in greater than 70 percent of the trials. On this basis MCC seems to possess great potential as a useful adjunct during cardiovascular surgical procedures.


The occluded renal artery.

The occluded renal artery. Twenty-seven cases of renal artery occlusion are presented. In 16 patients the duration of occlusion could be determined and only two of 16 became hypertensive or experienced worsening of existing hypertension. Seven of 11 patients in whom the duration was unknown were hypertensive. Twelve patients were not treated and of these, ten are deceased with renal artery occlusion contributory in six deaths. Nine patients underwent nephrectomy and of eight hypertensive patients, five became normotensive. Six underwent revascularization and four were successful at 2 hours, 22 hours, 9 days, and 39 days, respectively, after occlusion. The experience leads us to conclude that viability can be proven only by direct observation and that revascularization with return of function and lowering of blood pressure is possible after prolonged periods of occlusion.


Flow and pressure characteristics of the portal system before and after splenorenal shunts. The technique of percutaneous transhepatic portal vein cannulation provides a valuable means for determining portal pressure, direction of blood flow, and visualization of the entire portal system in the nonanesthetized patient. This technique, along with selective celiac arterial, superior mesenteric arterial, and renal venous catheterization, was used in the evaluation of a series of 17 splenorenal venous shunts [eight nonselective and nine selective (modified) distal splenorenal shunts]. As a result of these studies it is concluded that (1) prograde portal flow is maintained in the majority of patients following nonselective or selective (modified) distal splenorenal shunts; (2) bidirectional flow occurs in various branches of the portal system before and after splenorenal shunts; (3) a significant drop in portal pressure occurs following the establishment of either type of shunt; and (4) esophageal varices are decompressed by the trans-splenic route following either type of procedure used in this study.


Surgical management of penetrating injuries to the coronary arteries. Among 76 patients with heart wounds treated over a 4 year period, nine had penetrating injuries to the coronary arteries with clinical presentations of pericardial tamponade, electrocardiographic abnormalities of bundle branch block or ST and T wave changes, and hemothorax. The right coronary artery was injured in two patients, the left anterior descending coronary artery in six patients, and the left circumflex coronary artery in one patient. All but one of these injured coronary arteries were treated by ligation. One patient with a proximal left anterior descending coronary artery transection presented with cardiac arrest and was managed successfully by emergency cardiopulmonary support and saphenous vein bypass with ligation of the transected ends of the artery. The only death occurred six days postoperatively in a patient with a right coronary artery laceration and was not related to the heart injury. No late symptomatic or hemodynamic sequelae have been noted among any of these patients. Principles of elective cardiac surgery are readily adaptable to the patient with a coronary artery injury.


Repair of truncus arteriosus in patients with prior banding of the pulmonary artery. This is a review of the 25 patients with truncus arteriosus who have undergone corrective repair following prior banding of the pulmonary arteries. The early and late mortality rate was 20 percent, which has fallen to 6 percent for the most recent 17 operations. These results indicate that the probability of a successful repair for truncus arteriosus is not reduced for patients who have undergone prior banding of the pulmonary artery. In view of the current high mortality rate for corrective repair of the truncus arteriosus in the infant with refractory congestive failure, these results suggest that initial banding of the pulmonary artery for such infants, with later elective correction, may be an appropriate method of management at this time.


Clinical experience with nuclear pacemakers. Approximately 1,400 nuclear pacemakers have been implanted in patients since April, 1970, without a single battery failure; 64 of these have been implanted at the Newark Beth Israel Medical Center. All except four of the 64 pulse generators were attached to transvenous electrodes, 39 to pacing wires already in place. Fifty-nine of the 64 units are in service and continue to function normally in a follow-up period of up to 2 years. In the total worldwide experience, 70 pacemakers are out of service, approximately half because of the patient's death, and the rest for infection or lead problems, and only three or four because of difficulties with components. The first 15 ARCO pacemakers implanted 2 years ago continue to function well. Of the 15 control pacemakers implanted at the same time, one unit has failed. We have concluded that a nuclear pacemaker should not be used in a patient with limited life expectancy or in an infant, but for the otherwise healthy young or middle-age individual, it should be the unit of choice.


An evaluation of electroencephalographic monitoring for carotid study. Continuous electroencephalogram (EEG) monitoring was used during 213 carotid endarterectomies in 157 patients to identify cerebral ischemia. General anesthesia was used for all patients. An intraluminal shunt was not used routinely, but was inserted in 23 operations when EEG abnormalities associated with ischemia appeared. EEG changes occurred in 31 operations (14.5 percent). Four patterns of abnormal recordings were identified and are discussed. Six patients developed ischemic EEG changes in association with hypotension during endarterectomy. In two of these patients changes appeared with a blood pressure drop of only 20 mm. Hg below preoperative levels. Four patients with internal carotid artery back pressures of 75 to 100 mm. Hg developed EEG abnormalities which disappeared after shunt insertion. Our experience emphasizes the value of continuous EEG monitoring in detecting inadequate cerebral perfusion.


Intermittent claudication: its natural course. Of more than 600 patients seen for intermittent claudication by this group and not primarily considered for surgery, 104 had angiographic studies and are the basis for this report. The follow-up period varied from 6 months to 8 years, with a mean of 2.5 years. Classification by severity of claudication revealed 33 with less than one block, 36 with two blocks, and 35 with two or more blocks, foot, calf, or thigh claudication. Eighty-two remained stable or improved and 22 worsened. Of the 22 who worsened, 16 had only worsening of claudication (six of them requiring arterial reconstruction) and six progressed to gangrene and required amputations. Of the 82, 66 either had marked improvement of claudication or remained sufficiently stable not to require any operative intervention. Sixteen required arterial reconstruction for persistent, intolerable, or incapacitating claudication. Five of the six amputees were from the less than one half block claudication group. Angiographic studies were significant only in relation to the below-knee runoff in that three of 25 with less than one vessel runoff, two of 23 with one to two vessel runoff, and one of 56 with two to three vessel runoff came to amputation, regardless of the pattern of more proximal arterial occlusions. The study suggests that intermittent claudication is relatively benign, with only 5.8 percent coming to amputation in a 2.5 year mean follow-up. Prognosis is determined by the severity of below-knee arterial involvement and apparent inability to compensate for ischemia via the collateral circulation since only 12.5 percent of those with the most pronounced involvement came to amputation.


Anastomotic aneurysms after vascular reconstruction: problems of incidence, etiology, and treatment. To gain a better understanding of the pathogenesis, natural history, therapeutic response, and the potential of prevention of anastomotic aneurysms in general and those following aortofemoral interventions in particular, we have reviewed 4,214 reconstructive vascular operations performed in the past 15 years during which procedures (prosthetic bypass, autogenous vein graft, and endarteriectomy) of fairly uniform technical details have been used. Among these operations representing 9,561 anastomotic sites, we encountered 205 anastomic aneurysms, a per site incidence of 1.7 percent. By far the most common site of occurrence was the femoral artery following Dacron bypass procedures, with a per site incidence of 3.0 percent. The lowest rate of incidence was observed after endarteriectomies, regardless of anatomic location (0.4 percent). The most frequent causative factor was found to be structural deficiency of the parent artery, which accounted for 30.7 percent of the aneurysmal lesions. Other etiological agents, in order of importance, were arterial hypertension, mechanical stress, defect of the graft material, and noninfective healing complications. The therapeutic approach was an aggressive one and only patients with prohibitive operative risks were treated conservatively. In the elective surgical cases the rate of good results was 81.6 percent, with no operative deaths.


Traumatic arteriovenous fistulas and false aneurysms: a review of 558 lesions. Through the Vietnam Vascular Registry which was established in 1966 at Walter Reed Army Medical Center, copies of medical records of 509 combat casualties with 558 arteriovenous fistulas and false aneurysms have been analyzed. This represents approximately 7 percent of the vascular injuries in American casualties from Southeast Asia, from 1963 to 1972, which are included in the Registry effort. Contributions of several hundred individuals are included in this documentation, however, more than one fourth of the patients, 149 or 29.3 percent, have been evaluated in our clinic. There were 296 false aneurysms and 262 arteriovenous fistulas. Multiple lesions occurred in 7.9 percent of the casualties. Fragment wounds accounted for 487 or 87.3 percent of the lesions with 85.5 percent in extremity vessels. Early recognition and definitive surgical treatment usually were accomplished: 52.8 percent within the first 30 days following injury. Ligation was either accepted or required in about 50 percent of the lesions. The mortality rate was 1.8 percent and the morbidity associated with the vascular injury was 6.3 percent. There were eight amputations for an amputation rate of 1.7 percent. Potential complications of heart failure, proximal arterial dilatation, and endocarditis were essentially absent.


World-wide environmental problems.

World-wide environmental problems. Man and the physical and natural resources necessary to support him in a civilized society are on a collision course. It is simple to say that man cannot continue to grow in number at an ever-increasing rate without a destructive effect upon the environment. Positive scientific proof for this impending calamity is not now available, yet many indications--sometimes physical and sometimes natural--point towards major world-wide environmental troubles in the near future. A number of environmental problems are described, particularly as they relate to the total world system. A computer model simulating future world-wide environmental trends from 1900 to 2100 A.D. is evaluated and suggested as a major tool for data-gathering purposes to determine the extent of world-wide environmental problems. It is suggested that scientists take an active role in the study of the environment, particularly in relation to man's future on earth. The problems for the future are so potentially dangerous that we must not wait for a global catastrophe and then rely on science to rescue us. The article is about human survival.


Some health aspects of high-energy society. The intensive use of inanimate energy in industrialized or high-energy society has subsidized research, development, and higher education and has brought about changes in nutrition and life-style that have led to great advances in public health and medicine. The emergence of high-energy society, however, has brought with it a new set of health problems, within which the direct effects of measurable pollution may turn out to be more easily dealt with than some of the indirect and hard-to-calculate consequences of high energy use. High-energy society is critically dependent on energy-intensive transport systems, and these systems in turn are dependent upon a continual supply of petroleum products. In the short-term, the aorta of any industrialized nation is its petroleum-supply network. In the longer run, high-energy society faces the depletion and exhaustion of all the nonrenewable resources on which it has fed. Even if technology provides adequate substitute energy systems, high-energy society may deteriorate socially from inability to cope with affluence.


Community control of Strongyloides stercoralis by thiabendazole. Mass treatment of a community in Costa Rica with thiabendazole in 1965 reduced the prevalence of S. sterocoralis from 19.2% to 0.3%, and the rates remained low 2 years thereafter. Re-examination of the treated population 7 years after initial treatment showed S. stercoralis prevalence still at a 0.5% level.


Preliminary studies on the metabolism of 3,2'-dimethyl-4-aminobiphenyl in the rat. Distribution of 3,2-dimethyl-4-aminobiphenyl (DMAB) and its metabolites in vivo and the metabolism of DMAB by liver in vitro have been studied in the Wistar rat. DMAB-HCI purified by recrystallization and dissolved in ethanol was injected subcutaneously and extractions made from liver, feces, and urine. Similar technical procedures were used to study in vitro metabolism in rat liver homogenates. Two components were isolated from urine and liver having Rf values (thin-layer chromatography) of 0.13 and 0.59, respectively. Three additional metabolites were found in the hydrolyzed fecal fraction. Rechromatography of the major fecal component yielded 6 fluorescent compounds. Gas-liquid chromatography of the most highly fluorescent of these indicated at least 3 additional metabolites. The evidence presented indicates that the liver transforms DMAB to several metabolites which are rapidly transferred in conjugated form to the intestine via the bile. The urine does not appear to be the major excretory route. We have examined the purity of commercially available DMAB free base and DMAB-HCL and found an impurity that comprises approximately 10-24% of the total samle upon GLC analysis, depending upon the supplier. This contaminant was completely removed by recrystallization of the hydrochloride and the chemical identity of purified compound as DMAB confirmed. Recommendations are presented for the use of this purified compound in a biological system.


Patho-physiological studies on lactic acid-induced pulmonary thrombosis in rat. I. Effect of heparin, acetylsalicylic acid, urokinase and tranexamic acid. The role of platelet aggregation and coagulo-fibrinolytic systems in thrombogenesis of lactic acid-induced pulmonary thrombosis in rat were studied using an anti-coagulant, platelet aggregation inhibitor, fibrinolytic or anti-fibrinolytic agents. In normal rat, heparin (2.5 mg/kg), acetylsalicylic acid (30 mg/kg) and tranexamic acid (100 mg/kg) suppressed specifically coagulation, platelet aggregation induced by collagen or thrombin and fibrinolysis respectively. Urokinase (10,000 units/kg) activated powerfully fibrinolytic system in addition to suppressing slightly platelet aggregation. The pretreatment with heparin, acetylsalicylic acid or urokinase markedly prevented the formation of thrombus initiated by the infusion of lactic acid at the doses used. Additive effect was also obtained by combined administration of these agents. On the other hand, it was interesting to note that tranexamic acid (100 mg/kg) did not affect the thrombus formation at all despite a potent anti-fibrinolytic effect of this agent. These results indicate that both platelet aggregation and enhancement of coagulation activity are important factors responsible for the formation of thrombi in DIC, while the fibrinolytic activity in blood seems not to be involved in it. On the basis of the findings, mechanism for triggering activation of coagulation and platelet aggregation is also discussed here.


The effects of infusion of thrombin or endotoxin in rabbits treated with cortisone. Rabbits treated for 4 days with cortisone to prepare for the generalized Shwartzman reaction (GSR) were infused with thrombin or endotoxin. Whereas endotoxin induced the GSR, infusion of from 120--400 U/kg of thrombin over 1 to 2 1/2 hr failed to induce the GSR. Mean values for fibrinogen consumption after thrombin or endotoxin, calculated from changes in plasma fibrinogen concentration and plasma 125I-fibrinogen radioactivity, were as follows: for rabbits infused with thrombin, from 43 to 61 mg/kg over a 3 hr period; for rabbits infused with endotoxin, 58.5 mg/kg over a 6 hr period. A small peak of non-clottable protein radioactivity, indicative of secondary fibrinolysis, was found in animals infused with thrombin but not in animals infused with endotoxin. A striking late rise in plasma fibrinogen levels was noted in animals infused with endotoxin. It was not noted in animals infused with thrombin. This observation provides further evidence that endotoxin stimulates fibrinogen synthesis by mechanisms independent of intravascular clotting or fibrinolysis. The failure to produce the GSR with thrombin in cortisone-treated rabbits leads us to conclude that depression of reticuloendothelial cell clearance of fibrin can not account for the preparatory effect of cortisone for the GSR after endotoxin.


The influence of beta-adrenergic blockade upon baseline blood coagulation and fibrinolytic activity and upon the responses to venous occlusion. Twenty volunteers were assessed for baseline coagulation (Thrombelastography, Factor VIII and platelet count) and fibrinolytic (Euglobulin Lysis Time and Fibrin(ogen) Degradation Products) activity two hours after ingestion of 60 mgm propranolol or an identical placebo administered on a double blind basis. The responses of these parameters to a fifteen minute period of venous occlusion was also assessed. Beta adrenergic blockade reduced baseline FDP titres but did not affect other parameters, nor the local response to venous occlusion. During occlusion no significant change in coagulation activity could be detected in the non-occluded arm, but a small but statistically significant shortening of ELT was observed. Since this effect was prevented by propranolol it is probably mediated through adrenergic mechanisms. Adrenergic stimuli appear to influence episodes of coagulation and fibrinolysis during everyday activity, but do not contribute to baseline levels of coagulation or fibrinolytic function.


Soluble fibrin monomer complexes demonstrated by agarose gel filtration and by adsorption on insolubilized fibrinogen: a comparative study. Incubation of fibrinogen with small amounts of thrombin resulted in the occurrence of soluble fibrin monomer complexes. These complexes consisted predominantly of a derivative with a higher molecular weight than that of fibrinogen. It was characterized by its relative electrophoretic mobility in 5% PAA gel (0.28 X 10(-5) cm2/V X sec) and its elution position prior to the fibrinogen peak following gel filtration. Using adsorption chromatography on insolubilized fibrinogen the derivative dissociated at a ratio of almost 1 : 1 into one part which was adsorbed and into fibrinogen which was not adsorbed. The part which was adsorbed seemed to be the thrombin mediated fibrin monomer. This study confirms the concept that dissociable dimeric fibrinogen-fibrin monomer complexes occur after limited action of thrombin on fibrinogen.