Granulomatous lesions of the cervix uteri in Black patients.

The incidence of tuberculous, bilharzial and amoebic cervicitis in Black patients at Baragwanath Hospital for the past 5 years is presented. The clinical presentation and the macroscopic and microscopic features of each type of cervicitis are discussed. The treatment of each condition is described, and the importance of differentiating cervical carcinoma from granulomatous cervicitis is stressed.


Stapedectomy in the deafness of Paget's disease.

The causes of deafness in osteitis deformans are various.  One of these, stapediovestibular ankylosis, can be treated by stapedectomy, and hearing can therefore be improved.  Experience with 3 such cases treated by stapedectomy is reported, and the related literature is reviewed.


[Health and sickness as sociological concepts].

Health and illness, as widely used terms in scientific literature, leave a wide scope as to their definition and conceptual interpretation. The medicotechnical perspective refers to health and illness as objective changes in the structure and/or functioning of the human body and mind, as a result of which the bodily and mental integrity of the human organism is affected detrimentally. On the contrary, the social sciences, and especially medical sociology, define health and illness essentially in terms of the social system within which they occur. The main task of medical sociology is to pay attention to those social systemic and sociocultural aspects of health and illness which are sometimes grossly neglected or insufficiently understood by the medical sciences, thereby to contribute to a comprehensive approach to these phenomena.


Maximal rate of fall of left ventricular pressure in cardiomyopathy and constrictive pericarditis.

The maximal rate of fall of left ventricular pressure (peak negative dp/dt) was measured in 4 patients with congestive cardiomyopathy (primary myocardial disease), in 5 patients with constrictive pericarditis and in 3 controls. Measurements were made at rest, with leg raising, after a bolus of 6 mug intravenous isoprenaline, and in patients with constrictive pericarditis during pulsus paradoxus. Peak negative dp/dt was 1810 +/- 234 mmHg/sec in controls; it was reduced in patients with constrictive pericarditis (1337 +/- 514 mmHg/sec) and greatly decreased in patients with congestive cardiomyopathy (812 +/- 190 mmHg/sec). There was close linear correlation between resting peak positive and peak negative dp/dt and there was little change with leg raising. Isoprenaline caused an increase in peak positive dp/dt, but there was only a small change in peak negative dp/dt. In patients with constrictive pericarditis, peak negative dp/dt varied during pulsus paradoxus: the linear relationship to peak positive dp/dt was maintained throughout the respiratory cycle. Peak negative dp/dt may be a useful index of myocardial function.


Rheumatic disorders in the South African Negro. Part I. Rheumatoid arthritis and ankylosing spondylitis.

Epidemiological studies to determine the prevalence of rheumatoid arthritis (RA) have been carried out in two South African Negro populations: one rural people in the north-western Transvaal, and the other an urban community in Johannesburg. Altogether 1352 subjects over the age of 15 years were examined clinically and radiologically; serological tests for rheumatoid factor (RF) were carried out in 920. Rheumatoid arthritis was graded 'definite' or 'probable' on the basis of a modification of the 'Rome criteria' of 1963. A marked difference in the prevalence of RA was encountered in the two populations. Among the rural Blacks only 1 respondent had definite RA and 6 had probable RA, giving a prevalence of 0,87% for combined definite and probable RA. Among the urban group 5 respondents had definite RA and 13 had probable RA, a combined prevalence of 3,3%. This difference is statistically highly significant (P less than 0,01). Moreover, the form and severity of the disorder differed markedly in the two populations. In the rural community such changes as were encountered were invariable mild and no-one had clinical features resembling classical rheumatoid arthritis; by contrast, among the urban Blacks the changes resembled those of rheumatoid disease in White populations. Such marked differences in genetically closely related communities point to the importance of sociological and environmental factors in the pathogenesis of rheumatoid arthritis.


Radiological assessment of the Charnley total hip arthroplasty.

A description is given of the normal radiological appearances of the Charnley total hip arthroplasty. This is followed by a description of the radiological assessment of the complications that may be associated with this operation.


Cystic dilatation of the intrahepatic bile ducts.

Two cases of cystic dilatation of the intrahepatic biliary tree in Black patients are described. Both patients presented with extremely short histories of abdominal pain, and one patient had an associated jaundice. Biliary tree pathology was confirmed by physical examination and biochemical investigation in one patient while in the second patient cystic dilatation of the biliary tree was an incidental finding.


Familial haemophagocytic reticulosis. Report of 2 cases in sibs.

Two cases of familial haemophagocytic reticulosis occurring in sibs are described. The disease is characterised by a widespread proliferation of histocytes showing haemophagocytosis and it usually manifests clinically with haematological abnormalities. The initial presentation may be that of a meningo-encephalitic illness, the result of a lymphohistiocytic infiltration of the meninges and cerebral tissues. The clinical course and pathological features are described and the differential diagnosis is discussed.


Community obstetrics in an urban situation.

The majority of the world's population is of poor economic status, and this is commonly associated with high fertility levels and high infant mortality and morbidity. This population can be divided into two main groups: those in over-populated urban areas and those in scattered rural areas. Both groups have their peculiar problems and comprehensive maternal and child health is a formidable task. This paper is an account of the obstetric services in an urban population in the municipality of Salisbury, Rhodesia, where there is close co-operation between hospital and municipal authorities and all high-risk maternity patients are delivered in hospital and low-risk ones in municipal maternity units. Methods of selection of patients and results obtained are shown.


Benign smooth muscle tumours.

A series of 7748 leiomyomas of the whole body is presented. Ninety-five per cent of lesions occurrred in the female genital tract. Sixty-one of the remaining 371 were rejected because of inadequate histology or uncertainty as to exact site of origin. The 310 cases thus selected were analysed for histology, sex, race, site and age distributions. Comparisons are made between 230 skin lesions, 42 gastric lesions and 5 oral lesions. A further 43 cases of oral lesions were found in an extensive review of the world literature.


Transnasal spehnoidotomy.

This publication describes a relatively simple transnasal and trans-septal surgical approach to the sphenoid sinus, that assists in the diagnosis of pathology in this region and in some circumstances permits the correct treatment. Eight patients on whom this technique was used, are briefly reported. The importance of adequate radiological assessment of this area is illustrated.


Malignant renal arteriovenous fistulae. A cause of reversible cardiac failure.

A patient was investigated for painless haematuria, and a highly vascular renal cell carcinoma was shown on angiography. When this neoplasm was surgically removed, there was a remarkable improvement in the signs and symptoms of heart failure, from which the patient had been suffering for some time.


The need for regional planning of perinatal care.

Regionalisation is urgently needed to provide the best possible maternal, fetal and newborn care. In practice this means organising perinatal care of three specified levels and referring the high-risk problems to the regional centre, preferably before labour and delivery. The programme requires careful planning and constant teamwork.


A biologic comparison of polyglactin 910 and polyglycolic acid synthetic absorbable sutures.

Two synthetic absorbable sutures were implanted in rats for a comparative evaluation of breaking strength, tissue reaction and absorption. Polyglactin 910 suture was stronger than polyglycolic acid suture in both sizes tested and at all time periods from zero to 35 days. Both suture types elicited minimal tissure response. Based upon histologic examination, virtually all remnants of the polyglactin 910 were absorbed by 90 days, while considerable quantities of polyglycolic acid persisted at 120 days. The difference in absorption rates was a highly significant feature of the comparative biologic profiles of the two suture materials.


The observation of myofibroblasts in hypertrophic scars.

Contractile fibroblasts, myofibroblasts, are common cellular components of immature human hypertrophic scars. The contraction of these cells, could play a significant role in the elevation of the scar tissue. The appearance of such cells within granulation tissue suggests that the tissue is pre-disposed to hypertrophy at an early stage of repair.


Hepatic blood flow and oxygen consumption in starvation, sepsis and septic shock.

Total hepatic and portal blood flow as well as hepatic and splanchnic oxygen consumption was measured in pigs in the normal fasted state and in the septic fasted state induced experimentally by cecal ligation. Pigs in the septic state were divided into two groupds, a septic high output state and a septic low output state, according to whether or not a pig showed a higher or lower cardiac output in the septic state than in the normal fasted state. In the septic high output state, the average cardiac output was 155 per cent of that during fasting; hepatic arterial flow increased 96 per cent, while portal flow decreased 19 per cent. Total hepatic blood flow increased slightly, 14 per cent. The ratio of total hepatic blood flow to cardiac output decreased from 42 per cent in the normal fasted state to 30 per cent. The total hepatic oxygen consumption increased 26 per cent because of significantly elevated oxygen transport by hepatic arterial flow. In the low output state, hepatic arterial flow significantly dropped, 74 per cent, while portal flow decreased slightly, 23 per cent, and total hepatic blood flow decreased 38 per cent. The decrease of cardiac output was less, 18 per cent. The ratio of total hepatic blood flow to cardiac output was 31 per cent. Total hepatic oxygen consumption decreased remarkably, 29.1 per cent, due chiefly to the decrease of hepatic arterial flow, and splanchnic oxygen consumption also decreased significantly, 22 per cent. Dissociation of hepatic arterial response to sepsis from the other gastrointestianl vessels caused a great difference in the hepatic oxygen consumption between the septic high output and the septic low output state, contributing in part to the difference in mortality between these two states.


The detection of acute experimental osteomyelitis with 67Ga citrate scannings.

Foci of experimental septic osteomyelitis became radioactive after the intravenous injection of 67Ga citrate. With this method, bone infection can be detected much earlier than with roentgenography. Because of its short half-life, 67Ga may be a suitable isotope for the detection of clinical, primary osteomyelitis in its early stages.


Bone scintiscanning in the initial assessment of carcinoma of the breast.

Bone scans using 99mTc polyphosphate have been obtained in 174 patients with newly diagnosed carcinoma of the breast. This number represents 68 per cent of all patients registered with the disease in northern Alberta during the 12 months of the study. In nine patients, the roentgenograms were abnormal, but in 18, there was scintiscan evidence of metastatic disease involving bone, although one false-negative interpretation is included in this number. In another eight patients with normal or equivocal initial bone scintiscans, metastatic disease involving bone developed during a 12 months' period of observation.


A critical analysis of the cystic duct remnant.

The cystic duct remnant can be an etiologic factor for distress after cholecystectomy, justifying reoperation and excision of the stump. In connection with cholecystectomy, it is not justified to leave any cystic duct stump unless there is a special reason for it. Stones in the cystic duct remnant, overlooked or newly formed, scar tissues and cystic duct syndrome of whatever cause--inflammation and stasis of the bile, a poorly healing stump end and neuroma--can also be factors producing the discomfort. Unresorbable suture material which provokes foreign body granulomas should be avoided in operations upon the biliary tract since, together with even a normal nerve under pressure, it may cause biliary distress. For the same reason, special attention should be devoted to careful trimming of the cystic nerve in cholecystectomy, and ligation or cautery of nerve tissues should be avoided. The cystic duct remnant is more often visualized in peroperative cholangiography than in an intravenous examination but even then not unfailingly. The cholangiographic finding alone does not justify surgical intervention, since in a number of patients troubles deriving from elsewhere in the biliary tract or from adjacent organs persist and not all cystic stumps apparently produce discomfort.


Gardner's syndrome.

The clinical manifestations of Gardner's syndrome were studied in 280 patients from 11 families. Forty-five per cent of the patients at risk inherited the syndrome. Forty-one patients had carcinoma of the intestine develop, with only a 27 per cent survival rate for this type cancer. Eight per cent of the patients with the syndrome showed peritoneal fibrosis and fibrous tumors. They also had carcinomas of the ampulla of Vater, liver, bldder and ovary develop as well as osteogenic sarcoma. The patients without the syndrome had carcinomas of the pancreas and breast develop as well as melanoma and leukemia. Twelve of the 16 patients having had a colectomy and ileoproctostomy showed regression of the remaining polyps of the rectum.


Surgical treatment of malformations of the uterus.

The reproductive history in 13 patients with uterine malformations was reviewed. Following plastic repair, there was a high incidence of pregnancy salvage. Of 19 pregnancies, 14 resulted in term deliveries, four in premature deliveries and one in abortion; there are 14 living children. The surgical repair in two patients with primary sterility was the contributing factor in achieving pregnancies with full term deliveries.


Portacaval shunt as emergency procedure in unselected patients with alcoholic cirrhosis.

A prospective evaluation of emergency portacaval shunt has been conducted during a 12 year period in 138 unselected, consecutive patients with alcoholic cirrhosis and bleeding esophageal varies. An extensive diagnostic evaluation was completed within seven hours of hospital admission, and the shunt operation was undertaken within a mean of 8.5 hours. Follow-up study was conducted in a special clinic, and the current status of 97.1 per cent of the patients had jaundice, ascites or encephalopathy alone or in combination on admission. Systemic intravenous administration of posterior pituitary extract temporarily controlled the hemorrhage in 94 per cent of the patients, and the emergency portacaval shunt promptly and permanently controlled the varix bleeding in 96 per cent of the patients. Contrary to recent proposals, patients with the highest portal perfusion pressure and, presumably, the largest hepatopetal portal flow had the highest survival rate and those who were presumed from pressure measurements to sustain the smallest portal flow diversion from the shunt had the lowest survival rate. The operative survival rate was 51 per cent, the predicted seven year survival rate for those operated upon seven or more years ago was 42.5 per cent. Encephalopathy requiring dietary protein restriction developed at some time in 17 per cent of the survivors. Sixty per cent of the survivors abstained from alcohol, and 53 per cent resumed gainful employment or full time housekeeping. Preoperative factors that adversely influenced survial rate were ingestion of alcohol within one month of bleeding, ascites, severe muscle-wasting and a small liver. Postoperatively, the single most important factor that compromised long term survival was resumption of alcoholism. In comparisons with our previous prospective studies, emergency portacaval shunt resulted in a significantly greater long term survival rate than did either emergency medical therapy or emergency varix ligation, followed by elective shunt. It is concluded that emergency portacaval shunt is the most effective treatment of bleeding esophageal varices in patients with alcoholic cirrhosis. Criteria for exclusion of those patients who are unlikely to derive long term benefits from portacaval shunt remain to be defined by further studies.


A method for reducing the incidence of infusion phlebitis.

A departmental routine has been evolved wherein intravenous infusions are administered for a maximum daily period of 12 hours. Exceptions are made for patients with poor peripheral veins. Results of a prospective study of 376 patients for a period of one year demonstrated a markedly reduced incidence of thrombophlebitis, namely, 4.4 per cent in 297 patients treated by the intermittent method versus 20.3 per cent in 79 patients who received continuous intravenous infusion therapy for more than 24 hours.


Fatty metamorphosis in patients with jejunoileal bypass.

Two-thirds of all preoperative patients had some degree of fatty metamorphosis of the liver; at least 8 to 10 per cent had marked steatosis prior to performance of the jejunoileal shunt. In preoperative patients, marked fatty metamorphosis was seen most prevalently in the heaviest patients, while the incidence of moderate to minimal fatty infiltration was highest in those not as massively obese. Nevertheless, marked degrees of fatty metamorphosis were seen in patients just meeting the minimal weight criterion for operation, and minimal steatosis or normal livers were seen in more massive candidates. Subsequent to the bypass operation 95 per cent of patients had a moderate to severe degree of fatty metamorphosis apparent within the first 300 days. Subsequently, the incidence of fatty infiltration rapidly decreased so that by 1,500 to 2,000 days the incidence of severe steatosis had returned to that seen preoperatively. In fact, only those patients having associated problems late in the course showed a severe degree of fatty metamorphosis after 1,000 days. A screen of liver function studies was not found helpful in detecting minimal to moderate degrees of fatty metamorphosis and showed only inconsistent changes in those patients with severe steatosis. These tests were not helpful in detecting a quiescent cirrhosis of the liver. Cirrhosis of the liver was seen in two patients. In one, it occurred late in the course after the liver had completely cleared of fat. The cause was thought to be acute alcoholism, and steatosis cleared when drinking ceased. A second patient had a degree of cirrhosis at the time of the bypass operation. There has been slight progress in the ensuing seven or eight years that may be unrelated to the presence of the shortened intestine. Liver function studies do not indicate activity. Because the severe degrees of fatty infiltration seen in patients having previously normal or minimally infiltrated livers occurred during the time of rapid weight loss, it is presumed that the extensive mobilization of depot stores of fat to fulfill caloric requirements of the patient results in accumulation of triglyceride in the liver. Steatosis may be further aggravated by the fact that protein absorption  is reduced and, therefore, the formation of low density lipoproteins by the liver is curtailed. In this series, no patients have died as a result of fatty infiltration and liver failure alone.


A sterile technique for adjustment of intra-aortic balloon catheter position after closure of the groin incision.

Following insertion or prolonged pumping, intraaortic balloon position is occasionally found well below the desired site with the concomitant loss of mechanical advantage. Repositioning may mean having to advance a semisterile catheter into the arterial lumen. To alleviate this risk, a new technique of balloon catheter insetion is suggested whereby a 10 inch length of prosthetic material is sewn into the artery. The redundant length is allowed to protrude beyond the skin closure. If prolonged pumping is envisaged, the cuff may be left intact altogether or else it is amputated upon satisfying oneself that the balloon is placed in the desired position.


Use of pedicled omentum as an autogenous pack for control of hemorrhage in major injuries of the liver.

Since massive hemorrhage from the traumatized liver is usually caused by disruption of the deeply situated hepatic veins, repair or resection is seldom practical. Instead, after appropriate debridement has been accomplished, such venous bleeding can rapidly and effectively be controlled by packing autogenous omentum, based on its respective gastroepiploic vessels, into the hepatic fracture crease. The liver edges are then oversewn, and sump drainage is installed. An experience with the use of this technique in 37 patients has demonstrated its almost uniform success.


An easy and safe technique for nephrostomy.

By an atraumatic technique of nephrostomy, dysfuncti-n of the nephrostomy due to hemorrhage during the early postoperative period can be prevented. The nephrostomy can be changed at any time without difficulty by the use of this technique.


Selective ligation of the hepatic artery for trauma of the liver.

Selective ligation of sundry hepatic arteries in patients with hepatic trauma obviated death from hepatic bleeding in 59 of 60 patients treated with this method of hemostasis.  Hepatic insufficiency did not occur in survivors.  Reconstitution of intrahepatic arterial flow is rapidly accomplished by collateral arteries.  When the source of hemorrhage is perihepatic, that is, hepatic veins and retrohepatic vena cava, hepatic artery ligation is ineffective.  Two patients died from this kind of hemorrhage.


Studies on the healing of anastomoses of small and large intestines.

It is well known that large intestine anastomoses tend to leak much more frequently than do small intestine anastomoses.  These studies were undertaken to elucidate the pathophysioplogic basis of this phenomenom.  Single layer interrupted silk suture anastomoses were performed in both the distal part of the ileum and the distal part of the colon in 29 dogs.  The anastomoses were resected at one through eight days and 19 to 31 days after operations.  Collagen response, vascular response and bursting strength at the site of anastomoses were investigated.  The results demonstrated a statistically significant decrease in the collagen and vascular response of the large versus the small intestine.  This differential response may play a role in the mechanism of the relatively high incidence of suture line separations observed after colonic anastomoses.


Corrosion failure in stainless steel implants.

Two patients in whom corrosion failure of stainless steel implants occurred had the surgically removed implants subjected to metallurgic analysis.  Both implants showed marked pitting corrosion and required removal due to adverse tissue reaction.  Analysis of the failed implants showed them to be fabricated of alloys with a chemical composition that resulted in inferior corrosion resistance.  A simple magnetic test is suggested to indicate this type of stainless steel.


The pathogenesis of intestinal atresia.

The records of 28 patients with duodenal and 31 with jejunoileal intestinal atresia or stenosis were studied. Vomiting and abdominal distention were the most prominent symptoms; an unusual colon may be present in jejunal as well as ileal obstruction and is not pathognomonic for ileal obstruction. Intestinal atresia is associated with a high incidence of preterm babies but with a low incidence of intrauterine growth retardation. Fifty-three infants were operated upon; the overall survival rate was 79 per cent. The high percentage of mortality in duodenal obstruction is due to associated malformations. Theories of the pathogenesis of intestinal atresia do not seem to fit current clinical and experimental evidence in all patients. Possibly, different factors play a role in separate situations.


Differntiation of primary from secondary varicose veins by Doppler ultrasound and strain gauge plethysmography.

The Doppler ultrasonic velocity detector and the strain gauge plethysmograph were used to differentiate qualitatively and quantitatively primary from secondary varicose veins.  Studies were performed in 21 limbs of 14 normal persons, nine limbs of eight patients with varices secondary  to deep venous disease.  The latter group of patients was identified by ultrasonic evidence of venous reflux through imcompetent deep venous valves.  There was no significant difference  in the maximum venous outflow of the limbs of the three groups of persons as determined by plethysmography.  The primary hemodynamic abnormality in patients with varicose veins was significant venous reflux through imcompetent venous valves.  This reflux was obliterated by tourniquet compression of the varices in patients with primary varicose veins.  However, secondary varicose veins are distinguished by persistent abnormal deep venous reflux after compression of the varices.  These diagnostic techniques not only provide accurate noninvasive diagnostic information but also may facilitate determination of prognosis and therapy of patients with varicose veins.


The acute and chronic effects of alcohol on the human immune system.

The immunologic status of 24 male patients admitted for acute alcoholic detoxification was evaluated by in vivo and in vitro parameters.  In vivo reactivity, as measured by skin testing with a denovo antigen, dinitrochlorobenzene, as well as a recall antigen, tuberculin, was inact.  However, both qualitative and quantitative defects were seen in vitro in the thymus-derived lymphocyte population.  These defects were not seen in recovered alcoholics, that is, they appear reversible.  The defects seen in the cell-mediated immunity of alcoholics may, in part, be responsible for the high incidence of head and neck cancer observed in this patient population.


A direct vasoconstrictor effect of mannitol on the renal artery.

The direct effect of mannitol on the renal artery was studied using spiral cut strips of canine renal arteries.  Spiral strips were equilibrated in Krebs-Henseleit bicarbonate buffer at 37 degrees C.  The strips contracted when challenged with increasing doses of mannitol.  The force of contraction was directly proportional to the dose of mannitol used.  Vasoconstriction is a direct effect of mannitol on the renal artery in the dose range of 10 to 70 milligrams per milliliter.  This observation may explain some of the seemingly contradictory data which have accumulated in studies using mannitol.


Response of patients with carcinoma of the breast to hormonal therapy and combination chemotherapy.

Of the 89 patients with disseminated carcinoma of the breast treated with combination or sequential cyclophosphamide, fluorouracil and vincristine, 63 had received evaluable course of endocrine therapy and chemotherapy.  The response to endocrine therapy, regardless of its nature or duration, failed to predict response to subsequent chemotherapy.  Selection of the patients on the basis of pretreatment disease free interval, menopausal status or metastatic pattern showed the groups of patients to be homogeneous in distribution.  In addition, evaluation for a disease free interval greater or less than two years, menopausal status and visceral or nonvisceral metastasis did not allow identification of groups predicting responsiveness to combination chemotherapy.


Bedside evaluation of heart tracking in the postoperative patient.

A device to track and record the motion of the left ventricular border of the heart has been designed and is undergoing validation in human beings.  The system involves the use of track-while-scan-techniques applied to video signals from a fluoroscope image intensifier.  Results of studies obtained from the animal laboratory as well as from human beings indicate good correlation with standardized contractility indexes as well as with systolic time intervals, an alternative noninvasive technique.


Preoperative identification of tumor of the parathyroid by ultrasonotomography.

Parathyroid echograms were carried out in ten patients with clinical hyperparathyroidism.  In seven patients, the preoperative examination was capable of detecting and localizing enlarged parathyroid glands.  The echograms of parathyroid adenomas as well as carcinoma showed a characteristic cystic pattern, for which the term hollow pattern is the most suitable expression.  In preoperatively detected instances using echography, the parathyroid tumors were oval-shaped and larger in size and weight.  This method is a safe, simple and noninvasive technique that produces no discomfort to the patient.  The reliability rate of 70 per cent in our study is acceptable.  Therefore, echography of the parathyroid is applicable as a new diagnostic procedure for preoperative localization of parathyroid tumors.


Effect of partial constriction of the superior mesenteric artery upon absorption of d-xylose, labeled triolein and labeled albumin.

Intestinal adsorption of triolein, Risa and d-xylose was determined before and after reduction of blood flow in the superior mesenteric artery.  Absorption of d-xylose did not change, but absorption of triolein and Risa appeared to be slightly improved after arterial constriction, even if the artery was completely thrombosed.  Enhancement in absorption of Risa and triolein was probably the result of extensive collateral formation around the constricted superior mesenteric artery.


The value of azygography in carcinoma of the esophagus.

A method of azygography has been used in a study of patients with carcinoma of the esophagus prior to thoracotomy.  Total blockage or progressive reduction of venous caliber at the actual level of the lesion with contralateral filling of the azygos vein or back pressure signs on the azygogram indicates that the growth is not resectable at operation.


Nephrectomy in selected patients with severe refractory hypertension receiving dialysis.

The effect of bilateral nephrectomy was examined in ten patients with severe hypertension in whom dialysis and multiple drug therapy had not resulted in blood pressure control and was compared with that in 15 patients undergoing nephrectomy solely in preparation for transplantation. A highly significant, P less than 0.0005, and clinically impressive reduction in mean blood pressure occurred in the first group of patients, permitting discontinuation of all drugs. Although impossible to quantitate, these patients also demonstrated a reversal of a failure-to-thrive syndrome which had seriously compromides prenephrectomy management. Nephrectomy resulted in a reduction in mean hematocrit values of greater than 20 per cent and less than or equal to 20 percent showed a significant fall in the former but not in the latter. No increase in transfusion requirements developed in these patients. Until more potent and reliable medical therapy becomes generally availabe, nephrectomy will remain an important treatment modality in those patients requiring dialysis and having severe unremitting hypertension.


Bovine graft arteriovenous fistulas for maintenance hemodialysis.

Modified bovine carotid artery grafts have been used for maintenance hemodialysis in 44 patients during an 18 month period.  The technique of constructing an arteriovenous fistula in the leg and in the forearm is described.  The common femoral artery and saphenous vein in the leg and the radial artery and basilic vein in the forearm are the preferred vessels.  The complication rate has been low, consisting primarily of thrombosis and false aneurysms at the dialysis needle puncture site.  Oversized grafts should be avoided because of resultant turbulent flow and the tendency of thrombosis.  Bleeding after withdrawal of the hemodialysis needle must be properly controlled to minimize complications.  Eighty-two percent have various problems and 18 per cent have failed.  Bovine graft arteriovenous fistulas provide excellent vascular access in patients undergoing chronic hemodialysis.


Moyamoya disease.

A case of Moyamoya disease is discussed, presenting in a young adult with subarachnoid hemorrhage. Moyamoya is a rare form of crebro-vascular occlusive disease, characterized by specific arteriographic findings. The etiology of the disorder is unknown.


Ventriculo-venous shunt to the proximal segment of an occluded neck vein. A new method for shunting the cerebrospinal fluid to the venous circulation.

During the past four years, 36 hydrocephalic patients were treated by  shunting the cerebrospinal fluid (CSF) to the proximal segment of an occluded neck vein. When the CSF is shunted in this fashion it takes a complex pathway back to the heart. During its flow to the venous circulation, the CSF washes the blood away from the vein and converts it into an extension of the shunting catheter. The CSF that continuoussly fills the vein forms a barrier which separates the shunting tube from the circulating blood and prevents blood clotting around the end of the tube. Observations revealed that the intraventricualr pressure was maintained within normal limits, no siphonage effect developed when the patient assumed a sitting position, and reflux of blood into the shunting catheter did not occur. Valveless catheters were used in the first 29 patients; in the last seven patients, specially designed valved catheters were used.


Teratomas in the suprasellar region: report of five cases.

Five cases of suprasellar teratoma are presented. The characteristic clinical symptoms consist of diabetes insipidus, visual distrubance, hypopituitarism, and occasionally increased intracranial pressure accompanied by mild erosion of the sella turcica and separation of cranial sutures. A suprasellar mass lesion was demonstrated in all four cases examined by carotid angiography, and fine vascularization was found in three. Removal of the tumor is the treatment of choice, but if carcinoma, choriocarcinoma, or germinoma tissues are contained in the tumor, irradiation therapy should follow surgical treatment.


Subdural effusion and brain tumor: case report and survey of the literature.

Optic glioma associated with bilateral subdural effusion in a four-month-old male infant is reported. Review of the cases with subdural effusion or hematoma and brain tumor in the world literature was made. When subdural effusion is found in a newborn or an older infant, the possibility of an associated brain tumor must be considered. Care also should be taken to search for an underlying brain tumor and to exclude dural metastasis when we deal with chronic subdural hematoma in an adult.


The neuronal theory of experimental traumatic spinal cord dysfunction.

Previous studies by the author have demonstrated a hyperemia in the lateral funiculus of the Rhesus spinal cord following experimental traumatic spinal cord injury which has sufficient to render the animals permanently paraplegic. This absence of ischemia in the lateral funiculus, coupled with a reappraisal of available data from other investigators, has prompted the author to formulate a theory of primary neuronal dysfunction to explain the observed pathophysiology. It is suggested that the initial injury causes a pathologic biomolecular rearrangemant within the neuronal membrane which interferes with its ability to restrict sodium conductance at rest,nd in effect, makes the membrane nonexcitable.


Bowel perforation due to peritoneal shunt. A report of seven cases and a review of the literature.

Seven patients with bowel perforations secondary to ventriculo- or lumbo- peritoneal shunts are described. Five additional patients histories were found reported in the literature making a total of 12 cases. The shunt tubing presented in the anus in seven of 12 patients. Clinical peritonitis was present initially in two patients but developed in four others. Gram negative ventriculitis was present in five of 12 patients. Suggestions for diagnosis and treatment of this complication are made based on analysis of these 12 patients.


Results and complications in 55 shunted patients with normal pressure hydrocephalus.

This retrospective study of 55 shunted patients with "normal pressure" hydrocephalus evaluates the surgical results. Sixty percent of these patients had objective improvement following cerebrospinal fluid diversion but 44% had shunt-related complications of which 9% were fatal. Those patients who received a single theco-peritoneal shunt had a higher improvement rate and a lower incidence of postoperative complications. Successfully treated complications did not preclude postoperative improvement.


Intraoperative prebleeding in man: effect of colloid hemodilution on blood volume, lung water, hemodynamics, and oxygen transport.

The effects of acute normovolemic hemodilution on lung water, blood volume, hemodynamics, and oxygen transport were studied. The subjects were six patients undergoing major operations, with prebleeding and hemodilution under fluoroxene and nitrous oxide anesthesia. The menatocrit was reduced form 43 to 25 percent in one step, with simultaneous infusion of Plamanate and lactated Ringer's solution. Blood volume was expanded by 5 percent by the hemodilution. The major compensation was a striking rise in cardiac output to 161 percent. Systemic oxygen transport (CO times arterial O2 content) increased despite the marked fall in oxygen-carrying capacity, and the arteriovenous O2 content difference decreased. Lung water the aveolararterial (A-a) oxygen differences were reduced. The procedure was well tolerated by this group of selected patients and homologous blood utilization was reduced.


Simplified control of upper abdominal hemorrhage from the vena cava.

Serious upper abdominal hemorrhage can be both frustrating and frightening. Most major vessels in the upper abdomen can be readily dealt with within the abdomen. The upper end of the inferior vena cava is an exception. Control above the liver, below the diaphragm, is difficult and hazardous. The maneuver described here for temporary occlusion within the pericardium is simple and safe. By its use and with control of the lower end at the appropriate level, the main vessel and/or its intrahepatic tributaries then can be approached under direct vision in a relatively bloodless field for safe, accurate ligation and/or reconstruction.


Multiple-plane angiography for more precise evaluation of aortoiliac disease.

In 14 patients an oblique view of the aotoiliac region was obtained in addition to the conventional anteroposterior view. Angiograms in oblique projections are indicated in the following situations: (1) where the symptoms cannot be explained by the findings on the conventional anteroposterior view (2) where the patient has had previous anoroiliac grafts and has redeveloped ischmic symptoms, and (3) where patients with unilateral limb ischemia due to unilateral aotoiliac occlusive disease are being considered for a femororfemoral bypass graft procedure. In six patients appreciation of the true significance of the suspected occlusive lesion was of great value in planning the proper surgical procedure. In the remaining eight, angiographic corroboraion of the absence of significant occlusive disease was equally helpful in managing the patient's condition. Examples of each group are presented.


Delayed cutaneous hypersensitivity reactions to melanoma antigen.

Soluble melanoma antigens were prepared by 3M KCl extraction. These antigens were tested by delayed cutaneous hypersensitivity reactions (DCHR) in 52 patients. Maximum reactivity was noted at 24 hours. DCHR was greater than or equal to 10 mm. of induration in 20 of 34 melanoma patients whereas only three reacted to an autologous muscle extract. Five of 18 patients with other tumors reacted to this antigen. The availability of soluble tumor antigens now permits further purification, chemical characterization, and clinical evaluation of these antigens.


Oxygen tensions in healing anastomosis of rabbit aorta.

Tissue oxygen tensions in healing anastomoses of rabbit abdominal aortas were measured with ultramicro-oxygen cathodes with 1 to 3 mum tips. Two days after constructing the anastomosis, the over-all profile of intramural oxygen tension was different markedly from that of normal aortic wall, showing a progressive fall of Po2 from adventitia to media and no increasing gradient from media to intima. One week after operation to intimal Po2 increased and the oxygen gradient due to diffusion from the lumen was re-established.  By the end of the second week adventitial and medial oxygen tensions reached their minimum. Six weeks after operation the oxygen tensions in the anastomosis resembled those of an intact aortic wall, suggesting that the availability of oxygen to the injured area had been re-established fully.


The relative merits of the heparin-bonded shunt vs. femerofemoral bypass for aortic arch injury.

Six patients with traumatic aortic arch injuries have been repaired with distal aortic perfusion maintained with femerofemoral bypass (three patients) and the heparin-bonded ascending aorta-to-femoral artery shunt (three patients). The two groups are compared regarding pre- and postoperative changes in blood urea nitrogen, creatinine and platelet counts, as well as required blood replacement, days in the hospital, and rapidity of setting up the technique of distal aortic perfusion. No significant difference in the two techniques was demonstrated regarding the above parameters. Both the heparin-bounded shunt and femoral vein-to-femoral artery bypass with the pump oxygenator provide acceptable spinal cord and renal protection. The two techniques should be equally rapid and safe for the larger institution employing cardiopulmonary bypass procedures on a routine basis. The heparin-bounded shunt, however, may provide a more rapid and reliable means of lower aortic perfusion for the smaller institution with less available means of cardiopulmonary bypass support.


Accumulation of mononuclear cells in tumors with growth slowing and elevation in host splenic histidine decarboxylase activity following repeated tumor injections with bradykinin.

Repeated intratumor injections of SV-40 virus-induced and transplaned syngenic fibrosarcomsa in hamsters with bradykinin (BK) has produced markded slowing of tumor growth in comparison with control saline injections. Growth slowing was greatest when the injections were daily, with a decrease in growth slowing as injections became less frequent. The growth slowing also was dose dependent (greater with 250 mug BK injections than with 50 mug BK injections). BK-injected tumors, on histological study, were found to have marked infiltration with mononuclear cells. This was not encountered in noninjected or saline-injected tumors. Significant mononuclear cell infiltration of noninjected tumors was found in two tumor animals which had had one tumor injectecd with BK. Splenic histidine decarboxylase (HDC) activity was higher in BK tumor-injected animals than in saline tumor-injected animals. Splenic HDC activity was higher when studed nearer the period of daily intratumor injections. The findings of this study suggest a potential role of inportance for inter-related vasoactive substances which act as mediators of inflammation in the study and therapy of neoplasia.


A practical approach to the diagnosis of abdominal aortic aneurysms.

In this study 217 patients with proved abdominal aortic aneurysm were reviewed and the diagnostic accuracy of ultrasonography was assessed in comparison with physical examination, plain abdominal roentgenography, and aortography for the evaluation of patients with a suspected abdominal aortic aneurysm. Ultrasonography is most accurate in detecting an aneurysm and in defining the size of the aneurysm. Routine aortography to evaluate the renal and iliac artery is not justified in the preoperative evaluation of patients with an abdominal aneurysm since the renal artery infrequently is involved by the aneurysmal process (3.7 percent) and the surgical results are consistently successful in those patients with renal and/or iliac artery involvement. If preoperatively needed, the renal status can be evaluated accurately with an isotope renogram combined with photoscan of the kidney. A practical approach to the diagnosis of pulsatile abdominal masses is proposed.


Effects of drugs and parenteral solutions on vascular fibrinolytic activity.

The effects of saline, D5W, D10W, dextran, penicillin, cephalothin, and the Renografin "dyes" on vascular fibrinolytic activity were evaluated in in vitro experiments and in caninne preparations. Saline, D5W, D10W, and dextran did not affect fibrinolytic activity. High concentrations of the Renografin "dyes" and penicillin decreased fibrinolytic activity in vitro. Cephalothin, with an increased association of postinfusion in vitro studies but demonstrated minimal effect during the in vivo studies during which sufficiently high local concentrations of drug may not have been obtained. It is concluded that, although intimal damage, stasis, and/or hypercoagulability are responsible for the development of post infusion thromboses, local hypofibrinolytic activity is induced by some infusions and might contribute to the persistence and propagation of the thromboses.


Adenomyomatosis of the gallbladder.

Adenomyomatosis of the gallbladder is an entity that is being recognized increasingly, chiefly by radiologists. The pathogenesis, pathology, and indications for surgery are not well understood. This report is a study of 27 patients seen in the last 6 years, all of whom had proved histologic features. Patients ranged from 21 to 72 years of age, with a preponderance of women. Thirteen patients had no gallstones. The disease was confined to the fundus in 15 patients, to the neck in one patient, and was generalized in 11 patients. Bile cultures were obtained in the last six consecutive patients and all were negative. Histologically there was evidence of thickening of the gallbladder wall, glandular elements in the mucosa, and invagination of glands into the muscularis. The clinical, radiological, and pathologic features supported a hyperplastic and degenerative disorder which should be distinguished from cholecystitis. Associated with these morphologic changes is a dyskinesia similar to that seen in diverticular disease of the colon. Follow-up studies after cholecystectomy have shown that over 90 percent of all patients were completely relieved of symptoms. Adenomyomatosis should be identified as a distinct entity, probably of a degenerative nature. Cholecystectomy is indicated and beneficial when the symptoms suggest biliary tract diseases.


Periepicardial fibrinolytic activity: relation to cardiac bleeding.

The effects of various combinations of streptokinase-induced hyperfibrinolysis, electric shock, myocardial ischemia, and ventricular fibrillation on cat pericardial and epcardial fibrinolytic activity were studied. Streptokinase alone or electric shock alone slightly increased the periepicardial fibrinolytic activity but epicardial rebleeding did not occur. However, streptokinase infusions followed by electric shock and/or myocardial ischemia and/or ventricular fibrillation significantly incrased the periepicardial fibrinolytic activity and rebleeding of the epicardium occurred. Topical application of the fibrinolytic inhibitor epsilonaminocaproic acid (EACA) prevented the epicardial rebleeding.


A disposable in vivo oxygen electrode for the continuous measurement of arterial oxygen tension.

An evaluation of the accuracy, perdision, and clinical safety of the IBC indwellling catheter electrode for the continuous monitoring of arterial oxygen tension during and after general anesthesia was made in a total of 62 patients. A comparison of the standard bench-type electrode (Radiometer) with the International Biophysics Corporation (IBC) electrode for the measurement of oxygen tension in tonometered blood also was performed. Three hundred and fifty comparisons in 51 patients were made of the indwelling electrode with a standard Radiometer unit and, while there was good correlation, there also was ome scatter. An additional small series of 44 comparisons in 11 patients was performed, the primary difference being that the electrode was maintained intr-arterially for approximately 1 day. In both in vivo studies there was excellent correlation but questionable precidion. Four IBC electrodes and eight Radiometer Pao2 electrodes in an additional study were compared at 11 different tonometered oxygen tensions in blood. The IBC electrodes measured oxyygen tension more accurately than did the Radiometer, and standard deviations were consistently smaller at all of 11 different oxygen tensions for the IBC unit. The authors believe that the poor precision within both in vivo studies might be due to the fact that the IBC probe, which was of unknown accuracy and precision, was compared to a standard device (the Radiometer) which in the in vitro investigation proved to be less accurate and less precise. No complications due to the insertion and maintance of this in vivo electrode were encountered. The authors suggest that the IBC method for measuring Pao2 continuously in vivo be considered as an alternative to intermittent gas analysis of oxygen tension.


Adenocarcinoma of the jejunum in an 18-year-old patient: a case report.

The clinical history and surgical findings of an adenocarcinoma of the jejunum in an 18-year-old black man are recorded. The world literature on this subject has been reviewed, revealing a total of six cases of adenocarcinoma of the jejunum and ileum in patients under 20 years of age. This seventh case is recorded for its rarity and the findings which should alert the clinician: cramping abdominal pain, weight loss, and occult blood in the stool.


Cardiac tamponade complicating percutaneous catheterization of subclavian vein.

Cardiac tamponade has not been reported previously as a complication of central venous pressure (CVP) monitoring catheters inserted via the percutaneous subclavian vein approach. In one patient perforation of the vein by the catheter resulted in the catheter lying free in the mediastinum. Deterioration of the patient prompeted increasing infusion of fluids through this catheter with incresing cardiac compression. Relief was obtained after a thoracotomy. Ti is suggested that this complication may be recognized in the future and corrected without thoracotomy if radiopaque dye is infused through the CVP catheter.


Television in the operating room.

Television serves a number of useful purposes in the operating room. For the operating room supervisor, television surveillance provides an easy, economical method of keeping abreast of surgical and turnaround activities in each operating room. For the surgeon it provides an excellent vehicle for teaching, record keeping, remote viewing, and two way communication with the clinical pathology and x-ray departments, as well as with other consultants.


Randomized trial of albumin vs. electrolyte solutions during abdominal aortic operations.

In a prospective randomized trial of 16 patients undergoing abdominal vascular reconstructive procedures, changes in plasma volume, serum oncotic pressure (pis), serum albumin and total protein concentration, alveolar to arterial oxygen tension differences (AaDO2, FIO2 = 1.0), creatinine clearance, body weight, and fluid and sodium intake were examined. By random assignment patients received either an albumin- or a sodium-rich intraoperative fluid regimen. Pulmonary arteriovenous admixture was significantly less in the albumin group (n = 7) than in the electrolyte group (n = 9) on the first postoperative day. The change in AaDO2 correlated positively with the total sodium intake in the electrolyte group. Despite the larger fluid load and significantly greater gain of body weight, patients in the electrolyte group had a postoperative plasma volume significantly lower than the preoperative value. Postoperative values of albumin concentration, circulating albumin mass and pis were significantly greater in the albumin group in comparison to the electrolyte group. Creatinine clearance values were not different between the two groups. The change in pis correlated significantly with sodium intake and circulating albumin mass. Pulmonary shunting and expansion of the extracellular fluid volume may be minimized without adverse effects on renal function by administration of fluids rich in albumin in preference to sodium.


Cellular glucose utilization during hemorrhagic shock in the pig.

To clarify the changes in glucose homeostasis which occur following injury, pigs were subjected to hemorrhagic shock. During shock increased levels of free glucose occurred in red blood cells and muscle tissue, suggesting that inhibition of glucose phosphorylation was occurring. Simultaneously systemic plasma glucose levels were noted to be higher than portal plasma glucose levels while levels of free glucose within the liver fell, indicating that the liver was mobilizing glucose. Plasma insulin and phosphate levels were observed to rise throughout the experiment. From this study it was concluded that the hyperglycemia of injury in these animals was caused by a combination of decreased cellular glucose utilization due to diminished phosphorylation and increased mobilization of glucose by the liver.


Gastrojejunostomy inhibits postshunt siderosis.

Thirteen of fourteen dogs developed marked increases in hepatic hemosiderin (postshunt siderosis) after construction of portacaval shunt, whereas only three of 12 dogs developed such siderosis after construction of a portacaval shunt and end-to-side gastrojejunostomy with duodenal exclusion. Splenic hemosiderin was increased markedly in dogs with portacaval shunt but increased minimally in dogs with portacaval shunt and gastrojejunostomy. Rib marrow fat increased slightly in dogs with portacaval shunt and decreased slightly in dogs with portacaval shunt and gastrojejunostomy. Thus continued iron absorption appears to account for the development of postshunt siderosis and the addition of gastrojejunostomy ameliorates postshunt siderosis by diminishing iron absorption.


The association of carcinoembryonic antigen and peripheral lymphocytes.

A significant association between carcinoembryonic antigen (CEA) assay titers and peripheral lymphocyte counts was observed in 148 simultaneous determinations. The association was present in a high cancer risk study group of patients with myasthenia gravis and in a control group of patients with granulomatous disease of the bowel, ulcerative colitis, and colonic neoplasms. A highly significant difference in the percentage of positive CEA assays in relation to lymphocyte counts was noted both in the study and control groups. In the study group CEA was positive in seven of 41 patients (17 percent) with counts above 2,000 per cubic millimeter, and in 26 of 56 (43 percent) of those with lower counts (X2 = 9.06, p smaller than 0.005). The corresponding percentages in the control group were 20 and 61 percent (X2 = 5.60, p smaller than 0.025). A significant difference between the means of lymphocytes in groups with different CEA titers also was found (F = 6.77, p smaller than 0.05). The finding of lower peripheral lymphocytes and/or higher titers of CEA in groups with increased risk of cancer, i.e., severe myasthenia gravis, patients with thymomas and patients with long history of granulomatous disease of the bowel, suggests on association between the results of the two tests and cancer risk. The observations indicate that the yield of CEA assay in cancer detection may be higher in patients with lwo lymphocytes, and that these determinations used in conjunction may serve better as diagnostic and prognostic aids in patients with known neoplasms or in high cancer risk groups.


Observations on the functioning of committees.

Basic defects in performance of committees are described and guidelines for more effective committee functioning are suggested. To date most experiences with management technology have been with industry. Hopefully, the principles used will be found to be partly applicable to medical schools.


Revascularization of the profunda femoris artery in aortoiliac occlusive disease.

We have presented both early and late results in 236 extremities revascularized by aortofemoral, axillofemoral, or femorofemoral bypass grafts for severe atherosclerotic disease. The superficial femoral artery was occluded in all patients and initial outflow was provided solely through the profunda femoris system. Five different categories have been defined based on the procedure utilized to insure patency of the proximal profunda system. Subsequent patency rates are determined for each category. In reviewing our total experience the profunda femoris system was adequate to maintain both graft patency and limb viability in 90.3 percent of extremities in the early postoperative period. This declined to 78.5 percent at 5 year follow-up. Femoropopliteal bypass was required in 16 patients within the first postoperative month to maintain graft patency or relieve persistent ischemia. It is suggested that the addition of femoropopliteal bypass may improve inmediate and long-term patency rates and offer greater assurance that ischemia will be relieved.


Spontaneous pleural effusion in a human fetus.

Left sided pleural effusion was found in a human fetus spontaneously aborted at 20 weeks postmenstrual. Pulmonary hypoplasia associated with the effusion suggested that the fluid had been present for some time before delivery. Absence of other anomalies supports the view that the effusion was due to maldevelopment of the thoracic lymph channels.


Cysts in cultured fetal rat kidneys.

The formation of cysts has been studied in kidneys removed from day-15 and day-18 rat fetuses and cultured in a mixture of medium 199 (Morgan et al., '50) for periods of up to 15 days. Gas phases of 95% O2 and 5% CO2, and 95% air and 5% CO2, were employed, the latter being considered more satisfactory. In day-15 kidneys cysts formed from the ampullary portions of the collecting tubules after 2 days whereas cysts derived from nephrons were not seen until 9 days of culturing. The latter arose from developing juxtamedullary nephrons. In day-18 kidneys cysts from collecting tubules and nephrons were both present after 3 days of culturing. The latter, in this instance, originated mostly in immature midcortical nephrons, the juxtamedullary mephrons having undergone rapid degeneration. The tubular portion of the nephron seemed to be the primary site of dilatation. Under culture conditions cysts of nephrons thus formed from immature actively developing nephrons and not from those that were mature. Cysts associated with collecting tubules arose from the ampullary (terminal) portions of the latter in both day-15 and day-18 cultured kidneys. The study of cultured mammalian fetal kidneys can provide information on the nature and genesis of renal cysts. It is possible that the same technique also may be helpful for examining the effects of teratogens directly on the kidney.


Ultrastructural changes in rat palatal epithelium after beta-aminopropionitrile.

Beta-Aminopropionitrile (BAPN) retarded or suppressed epithelial changes in the medial edge of the palatal process in later stages of gestation in rats. Programmed cell death did not follow the usual pattern, and only a few lysosomes were observed on day 18 of gestation. The sensitivity of the medial epithelium to BAPN appeared to be different in various areas of the palatal epithelium; the epithelium on the anterior region of the palatal process was hypertrophied and keratinized, while posteriorly the medial or neighboring epithelium was very thin and, in neonatal rats, the covering was absent. A basal lamina was distinct in the anterior region and indistinct or fragmented posteriorly. Collagen fibers did not develop adjacent to the basal lamina, and an amorphous material was scattered throughout the mesenchymal tissue. These findings suggest that BAPN decreases the "connecting capacity" between mesenchyme and epithelium, and results in a modification of epithelial changes.


Comparative distribution and embryotoxicity of hydroxyurea in pregnant rats and rhesus monkeys.

Hydroxyurea was given to pregnant rhesus monkeys and pregnant rats in regimens adjusted to produce similar degrees of teratogenicity, for the purpose of comparing the distribution of the drug in the females and their embryos. According, in rats 137 mg/kg/day ip on days 9-12 resulted in a drug half-life in maternal plasma of about 15 min and in embryos about 85 min, after the last injection; and in monkeys 100 mg/kg/days iv on days 23-32 resulted in drug half-life in maternal plasma estimated to be 120 min and in embryos 265 min, after the last injection. Using as a baseline of biological effects the minimal concentration known to inhibit DNA synthesis in rat embryos and cancer cells, namely 10(-4) M, it was calculated that the rat embryos in the present study were exposed to this level or more for approximately 12 h whereas the monkey embryos were exposed for approximately 100 h. Although the teratogenic effects were not identical in the two species, these data are interpreted to mean that rat embryos are teratogenically much more sensitive to hydroxyurea than monkey embryos. These observations have important implications in the selection of appropriate species for tests to estimate human teratogenic risks. The rat, which is currently the most widely used animal for such tests, displays sizeable differences from rhesue monkeys, which is one of the animals thought to be most like man in teratogenic susceptibility.


The teratogenic effects of 6-mercaptopurine on chick embryos in ovo.

Fertilized eggs of single-combed White Leghorn hens were each injected through a shell window directly beneath the embryo at 70 or 96 h of incubation with 2 mg of the sodium salt of 6-MP dissolved in 0.1 M phosphate buffer, and at 11 days of incubation the embryos were examined for gross morphological abnormalities. Various gross malformations and growth retardation were found, the most frequently and severely affected structures being limbs, beak, and eyes. Treatment at 70 h caused more severe abnormalities than at 96 h, but the spectrum of defects was not very different.


Teratologic effects of LSD in explanted early chick embryos.

Chick embryos were explanted at stage; 4-7 and cultured for 20 h with or without LSD. At any stage 10 mug/ml LSD or higher caused abnormalities in axial structures, particularly somites, in over 50% of the embryos. LSD had no apparent effect on morphogenesis of the heart, but significantly lowered the pulse rate. Cellular degeneration occurred in severely affected structures, but LSD at embryotoxic doses caused alterations in neither cell morphology nor mitotic activity. The effects of LSD were not permanent, i.e., the embryos retained the ability to undergo normal morphogenesis when, after 4-5 h of treatment with 10 mug/ml LSD, they were subcultured on plain nutrient medium.


Inhibitory effect of corticoids on the proliferative pattern in mouse palatal processes.

The formation of the secondary palate in mice is accompanied by intensive mitotic activity, which is mainly concentrated at the medial edges of the palatal processes. In control H-Velaz randombred fetuses the mitotic activity culminated approximately 24 h before palatal-shelf horizontalization, so that the period of intensive cell proliferation coincided with the period when cleft palate could be induced by cortisone administration. Effects of teratogenic doses of corticoids, injected directly into amniotic sac of embryos on day 13 (0.3 mg hydrocortisone) or im to pregnant females on day 12 (7.5 mg cortisone acetate), on the proliferative peak in palatal processes were studied using intraamniotic injection of colchicine. Counts of colchicine-blocked mitoses in histological serial sections revealed both a significant decrease in overall mitotic density and a posterior shift of the proliferative peak in the palatal processes of fetuses treated with doses of corticoids producing cleft palate.


Cytotoxic effects of 6-mercaptopurine on the limb-bud blastemal cells of rat embryos.

On day 12 of pregnancy Wistar rats were each given a single ip injection of 5, 8, 16, 25, or 50 mg/kg 6-mercaptopurine. The embryos were removed 1, 2, 3, 5, 6, 10, 24, 48, or 72 h after injection or on day 20 and studied by light and electron microscopy. After 25 or 50 mg/kg all embryos showed no mineralization in the lower extremities. By electron microscopy condensation, shrinking, and fragmentation of cells in the limb bud blastema could be seen after 5 h. The fragments were phagocytosed and broken down by neighboring cells or remained in the extracellular space. After 25 or 50 mg/kg the damage was so extensive that the number of undamaged cells and of cells transforming into phagocytes was not sufficient to remove the debris or to compensate for the defect by mitotic activity. Epithelial cells, nerves, and blood vessels, show no morphological signs of damage. The "critical period" was the time cartilage just starts developing, i.e., when the blastema begins to differentiate.


Teratologic evaluation of imipramine hydrochloride in bonnet (Macaca radiata) and rhesus monkeys (Macaca mulatta).

Imipramine hydrochloride was administered orally twice daily to 18 bonnet and 3 rhesus monkeys between days 23 and 45 of pregnancy for 1-3 or 18-22 days at 1, 2, and 10 times the recommended human dose. No teratologic changes were observed, although signs of maternal toxicity occurred at the high dose level, and the abortion rate was higher than in controls.


Nonteratogenicity of captan in beagles.

Thirty and 60 mg/kg captan, administered in the diet during the entire gestation period or during gestation and an 8-week lactation period, caused no adverse effects in either mothers or progeny, and captan is thus judged to be nonteratogenic in beagles.


Evaluation of the teratogenic potential of a spray adhesive in hamsters.

Pregnant Syrian hamsters were placed in a 100-1 static inhalation chamber for 30 min twice daily on days 5-10 of gestation and exposed to 8.0 +/- 0.13, 11.6 +/- 0.11,or 13.23 +/- 0.49 g of "Foil Art Adhesive" and killed on day 14. Controls were placed in adjacent identical chambers but received no spray. The spray adhesive was toxic but not teratogenic at the doses administered. Maternal alopecia occurred upon exposure to the 2 highest dose levels, and 1 female died during exposure to the highest dose level. Fetal survival was not affected. Mean fetal weight was significantly decreased after exposure to all 3 dose levels, and delayed skeletal development occurred but was not dose related.


Incorporation of a phospholipid precursor into the hemochorionic and yolk sac placentas associated rat embryos.

Pregnant Long-Evans rats were subjected to a teratogenic regimen, i.e., were fed a synthetic diet lacking folic acid and containing 9-methylpteroylglutamic acid on the 11th to 14th days of gestation. Experimental and control pregnant rats injected with 10 muCi of [2-14C] ethanolamine on the 14th day were killed 1 or 2 days later. The total radioactivity and radioactivities of phosphatidylethanolamine (PE), phosphatidylcholine (PC), and lysophosphatidylethanolamine (LPE) were determined in chloroform extracts of homogenates and subcellular fractions prepared from hemochorionic and yolk sac placentas and maternal liver. The distribution of radioisotope into PC and PE of control and experimental yolk sac placentas was similar, and paralleled the distribution in maternal liver. However, the distribution of radioisotope into PC and PE of the hemochorionic placentas did not parallel that of the maternal liver, and radiolabeled PC accumulated faster in experimental placentas than in controls. We suggest that the ability of the hemochorionic placenta to synthesize PC from PE was impaired by the teratogenic regimen, and that the organ took up relatively more PC from the maternal plasma. We propose that this teratogen-induced shift from placental lecithin synthesis to selective lecithin uptake underlies the previous finding of an increased accumulation of radio-labeled PC in embryos from pregnant females subjected to this teratogenic regimen (Chepenik and Waite, '73).


Isolated absence of human carpal bones.

An unusual instance of congenital isolated absence of carpal bones, in a 38-year-old woman, characterized by total lack of the scaphoid, lunate, and pyramidal and a massive fusion of the distal carpal row is reported. This condition is thought to have been the result of an embryonic error exclusively involving the portion of the autopodic blastema from which the carpus originates.


Histological effects of 6-mercaptopurine on the fetal rat central nervous system: a light-microscopic study.

Wistar rats were administered single doses of 16 or 50 mg/kg 6-mercaptopurine (6-MP) on day 12 of pregnancy. Necrosis in the fetal forebrain and spinal cord was studied by light microscope 6, 12, 14, 48, 72, and 81 h and 8 days afterward. The extent of necrosis was dose dependent. The first necroses were seen after 24 h, regardless of location (brain, spinal cord) or dose; but the extent was greatest after 48 h. All necrotic cells had a typical appearance; they were ballooned and often fragmented, their nuclei were darkly colored and frequently pyknotic, and they were often karyorhexic. Necroses appeared almost exclusively at sites of beginning cellular differentiation, i.e., in the intermediate zone. In the spinal cord the ventricular zone was also necrotic and the alar plate (dorsal horn) always affected. Phagocytizing cells (macrophages) appeared in the spinal cord after 48 h and in the brain after 72 h. After 81 h all the necrotic material had been phagocytized, at which time there was a massive congestion of the extra- and intracerebral vessels. Hemorrhages appeared in defined localizations. Eight days after exposure to 16 mg/kg 6-MP fetuses no longer showed any visible deviations. Fetuses exposed to 50 mg/kg showed deviations in the cytoarchitecture of the neopallium: an extremely broadened ventricular zone, few cells in the intermediate zone, and extensive rarefaction cells in the cortical plate with no clear layer structure. In the spinal cord, cleft formations were especially noticeable in the dorsal-horn region. All fetuses showed a hydrocephalus externus after 50 mg/kg. The mechanism leading to necrosis is discussed.


Prenatal ossification in rabbits as indicative of fetal maturity.

During the prenatal period of development of the rabbit skeleton (days 21-30) the successive phases of fetal maturity can be distinguished by reference to the progress of ossification, particularly in the distal limbs and sternum. In the present study absent or incomplete ossification of sternebra 5 occurred in 8% of term fetuses. The incidence of anomalies of prenatal ossification of the axial skeleton was 1.9%. The relevance of delayed and disturbed ossification with regard to teratological tests is discussed.


Association of cleft lip and atrial septal defect in mice: a preliminary report.

Newborn A/J and CL/Fr mice with congenital cleft lip usually have an atrial septal defect of the secundum type, often associated with cyanosis. Their littermates without cleft lip rarely have a septal defect. The atrial septal defect results from a delay in growth of the atrial septum primum.


Action of the phenothiazine derivative methophenazine on prenatal development in rats.

Single doses of 100-400 mg/kg or multiple doses of 10 or 50 mg/kg of the phenothiazine derivative methophenzaine were given per osto Wistar rats at various times on the 7th-14th days fo gestation and the fetuses examined near term. Results indicated that methophenazine was mainly embryolethal when administered on the 8th-11th days, and was teratogenic at later times, producing types of malformations that depended on the day of treatment, the most susceptible period being the 13th and 14th days of gestation. Teratogenicity occurred only when the dosages were highly toxic to the pregnant rats. Ribovlavin given ip on the 14th day significantly reduced the embryolethal but not the teratogenic action of methophenazine.


The possible role of platelet coagulant activities in the pathogenesis of venous thrombosis.

Recent studies of the role of platelets in blood coagulation have shown that platelets can trigger intrinsic coagulation by two alternative pathways, protect platelet-associated active clotting factors from inactivation by plasma inhibitors and catalyze intrinsic coagulation reactions on the platelet surface to form fibrin. These platelet coagulant activities (i.e., contact product forming activity, collagen-induced coagulant activity, intrinsic factor Xa forming activity and platelet factor 3 activity) were found to be increased in patients with deep vein thrombosis developing after hip surgery, in patients with established retinal vein thrombosis and in patients with established deep vein thrombosis. It is suggested that increases in platelet coagulant activities concerned with triggering and catalyzing intrinsic coagulation reactions may play a role in the pathogenesis of venous thrombosis.


The role of blood and platelets in atherosclerosis and the complications of atherosclerosis.

There appear to be at least three ways in which the blood, and particularly  the platelets, may contribute to the development of atherosclerosis and its complications: 1. In the mechanism causing endothelial injury and the response of the smooth muscle cells to vessel injury. 2. Through the formation of persistent mural thrombi which are organized into intimal thickenings. 3. Through the formation of thrombi in association with advanced atherosclerosis that may be either (a) mural thrombi which fragment and shower the distal circulation with platelet emboli or (b) occlusive thrombi.


Changes of coagulation and fat-metabolism following pulmonary microembolism after trauma and hemorrhage.

In 16 of 24 anesthetized mongrel dogs a standardized bone trauma was performed to both hind legs by open osteootmy. During the following 6 hours the most important hemodynamic parameters, total platelet count (GTZ) and its separate fractions (NKF, KF) were continously monitored. Five hours after the trauma 50% of the total blood volume (taken to be 80 ml/kg body weight) was withdrawn from two of the four groups of animals. The trauma caused no direct effect on the pulmonary hemodynamics. In the following hours there was a slight decrease of cardiac output (HZV) in the traumatised animals. Besides a moderate increase in mean pulmonary pressure (MPP), pulmonary vascular resistance (PVR) increased by 72% of the pretraumatic values. The application of intravascular catheters diminished the total platelet count markedly in the injured, as in the uninjured animals. The increase in PVR was caused less by a mechanical obstruction of the pulmonary capillary bed than by vasoactive substances released by the platelets. The following hemorrhage led to a more marked hemodynamic reaction in the injured animals. All these animals died before the end of the calculated hemorrhage. All animals without trauma survived. Irreversible aggregation of platelets developed in the pulmonary capillary bed caused by the marked pulmonary hypocirculation. Histological examination showed a marked disseminated pulmonary microthrombosis in all animals with trauma and hemorrhage. The initial phase of experimental pulmonary microembolism caused by trauma was characterized by pulmonary hypocirculation and an activated coagulation with simultaneously diminished total platelet count.


Platelet and fibrinogen survival with 75Se selenomethionine in acute infectious hepatitis.

Simultaneous platelet and fibrinogen survival with 75Se selenomethionine was determined in eight patients with acute infectious hepatitis of intermediate severity. Fibrinogen survival alone was estimated in another nine patients, seven of whom were receiving heparin treatment. Platelet survival was found to be normal (7-9 days) in seven of the 8 patients; it was reduced 4,6 days) only in one patient, who was also affected by measles. Fibrinogen survival was markedly reduced (1-3.7 days) and fibrinogen turnover sharply increased (0.59-2.80 mg/ml/day) in all but one patient, who had thalassaemia major, with normal fibrinogen survival and fibrinogen turnover. Heparin treatment did not affect either platelet survival or fibrinogen turnover. In all patients the coagulation defect was mild and no sign of disseminated intravascular coagulation or of increased fibrinolytic activity could be demonstrated by routine tests. These results are consistent with the hypothesis that in acute infectious hepatitis the decreased survival and increased turnover of fibrinogen might be due to a pathological pathway of defibrination in dependent of thrombin of plasmin.


A scanning electron microscopic study of platelets of certain animal species.

Comparative morphology of platelets of the dog, cat, cow, horse, sheep, and goat was studied with the scanning electron microscope and was found generally similar. Most of the platelets were slightly biconvex of flat with relatively smooth surface and even contour. Some of these platelets had few short marginal filaments, oriny protuberances on the surface. A small number of platelets exhibited surface irregularity and few long pseudopods which were thought to result from platelet activation during the processing of blood. The number os such irregular platelets increased in stored blood and in blood fixed at 4 degrees C.


Protective effect of pantethine on experimental thrombocytopenia in the rat.

The effects of pantethine on circulating platelet counts and platelet functions were studied in normal and experimentally produced thrombocytopenic rats. Administration of pantethine to normal animals did not cause any alterations in both platelet count and function except for a slight enhancement of intravascular platelet aggregation induced by collagen or neuramindase. Injection of anti-rat platelet rabbit serum into rats resulted in acute thrombocytopenia. Administration of pantethine prior to the antiserum promoted recovery from the thrombocytopenia in a dose dependent manner, but administration of the drug after development of the thrombocytopenia was not effective. A similar result was obtained with a transietnt thrombocytopenia induced by exchange transfusion with platelet poor blood. Regardless of whether animals were treated with pantethine or not, the platelets newly generated during the course of recovery from thrombocytopenia were essentially normal in the function tested in vitro. A more chronic thrombocytopenia induced by repeated injections of the antiserum was prevented, to some significant degree, by daily administration of pantethine throughout the experimental period. In contrast to these, such effect of pantethine was not observed with the thrombocytopenia models produced bynitrogen mustard N-oxide and neuraminidase. These findings were idscussed in relation to mechanism of the action of pantethine and to possible clinical application to the drug to thrombocytopenia.


Performances of an artificial reagent for the one-stage factor IX assay.

A mixture of adsorbed normal human plasma and chicken plasma was prepared as reagent for factor IX measurement using a one-stage method. The substrate was found to be specific for factor IX. Its performances tested on samples displaying factor IX activity ranging from less than 1%-2,000% compared favorably with those obtained when using the plasma of severe haemophilia B patients as substrate.


Further investigations on antithrombin III in the plasmas of patients with the abnormality of antithrombin III Budapest.

Antithrombin III (AT-III) was studied in a thrombophilic family with an abnormal AT-III molecule (antithrombin III Budapest) using a modified crossed immunoelectrophoresis technique, gel filtration, 'rocket' immunoelectrophoresis and a heparin cofactor assay. When agarose was applied in the first phase of the crossed immunoelectrophoresis, the normal and the pathological AT-III revealed identical electrophoretic mobility. However, when heparin was mixed with agarose in the first phase of electrophoresis, the propositus' plasma displayed a different AT-III pattern from normal plasma. His plasma contained the first component of the normal plasma (Immune Antithrombin III1, IAT-III) in a concentration of only 5% of normal, and a protein in high concentration which although immunoreactive to AT-III antisera, had an electrophoretic mobility similar (but not identical to that of IAT-III2. This abnormal protein had no heparin cofactor activity and a molecular size greater than normal plasma AT-III. Unlike AT-III, the addition of heparin did not change the molecular size of the pathogic AT-III molecule significantly. The abnormal protein was present in lower concentrations in the patient's children and at the time of study they had no clinical or laboratory evidence of intravascular coagulation.


Streptokinase stability pattern during storage in various solvents and at different tempertures.

The activity drop of 5 u streptiokinasewas measured in 1 ml each of various solutions (9.9% NaCl solution, 5% glucose solution, 5% levulose solution, 10% dextran solution, gelatin solution, 3% albumin solution, michaelis buffer, glucose (5%)-heparin (750 u/ml) solution) at different incubation temperatures (-20 degrees C, 4 DEGREES C, 20 DEGREES C, 37 DEGREES C), and over different observations periods (15 min, 30 min, 45 min, 60 min, 6 h, 12 h, 24 h, and 48 h). Solution media tested for streptodinase-protecting quality were broken down into three groups. Group I: Solvents displaying excellent stabilizing properties gelatin and albumin solutions). Group II: Solvents displaying medium stabilizing properties (dextran and levulose solutions). Group III: Solvents displaying poor stabilizing properties (NaCl and glucose solutions, Michaelis buffer). In testing streptokinase concentrations as used for therapeutic purposes (1500 u/ml, 50,000 u/ml), no decay was found to take place over observation periods of up to 48 h, and no invluence by different solvents (Group I. II or III) was traceable. Heparin stored with streptokinase at room temperature over a period of 48 h did not alteranisms concerning the stability pattern of striptokinase are discussed. It appears that low streptokinase concentrations need negatively chargedcolloids to keep the protein structure intact. The streptokinase-protecting macro-molecules tested so far were albumin, gelatin, and streptokinase. Obviously, streptokinase by itself was able to preserve its own stability provided its concentration was of a certain order magnitude (1500 u/ml, 50,000 u/ml) .


Serologic evidence of hepatitis B virus infection in patients with hemophilia B. a multicenter study.

Among sera from 160 patients with hemophilia B from 9 centers in Europe and North and South America, 2.5% were positive for hepatitis B surface antigen (HBsAg), 60for antibody to HBsAg, and 31% for antibody to the hepatitis B core antigen. Evidence of exposure to the hepatitis B virus appeared to be related to severity of disease and age rather than the source and method of manufacturer of factor IX concentrate.


Potentially thrombogenic materials in factor IX concentrates.

Factor XI concentrates manufactured from human plasma and intended for therapeutic infsuion in man have been suspected for some time of being potentially thrombogenic. In the current studies, assays were carried out in vitro and in vivo for potentially thrombognic materials. It was possible to rank the various materials tested according to the amount of thromboninic material detected. For concentrates not containing heparin, there was substantial agreement between the in vivo and in vitro assays, with a coefficient of correlation of 0.77. There was no correlation between the assays for thrombogenicity and the antithrombin III content. We conclude that many presently availabel concentrates of Factor IX contain substantial amounts of potentially thrombogenic enzymes, and that this fact must be considered in arriving at the decision whether or not to use them therapeutically.


[Prevention of Teat Injuries in Dairy Cattle by Remodelling of Tying Stalls (author's transl)].

The effects of longer standings and affording adequate freedom of movement by the use of cow trainers were studied on sixteen commercial farms with short standing tying stalls. Comparison with the results obtained in previous studies showed that the incidence of severe teat injuries had decreased by 41.5 per cent. This was also apparent from the reduced average period required for healing of the injuries. Observations were continued on five farms when the cows were turned out to pasture in the summer. The period required for healing as well as the sites and types of teat injury observed in the remodelled tying stalls and during the grazing period were found to be very similar. The incidence of severe teat injuries was 43.5 per cent lower on the pastures than it was in the remodelled tying stalls.


[Distribution of Rifamycin SV in de Bovine Tissues Following Intramammary Administration of Rifamastene (author's transl)].

Depending on the physiological activity of the udder, from 4 to 95 per cent of the rifamycin SV administered by intrammary injection are absorbed from the udder and approximately 95 per cent of the absorbed rifamycin SV are excreted through the liver. The rifamycin SV eliminated in the faeces will lose its microbiological activity more or less rapidly, depending on the temperature and oxygen tension. Accumulation of rifamycin SV in the meat and organs will not occur on intramammary administration of this antibiotic. A balance between absorption and excretion is attained within sixty minutes after intramammary administration of Rifamastene in cattle. The maximum rifamycin SV concentrations determined in the serum, bile and urine were 0.12, 18.2 and 0.32 mug/ml respectively. Van Schothorst's S. lutea kidney test which is required by law in the Netherlands, was negative in every case.


[Psychosedatives in Veterinary Medicine (author's transl)].

In this paper the psychosedatives are reviewed which have found application in veterinary medicine. To reduce to the utmost the negative effects, combinations are used of sedative agents from different groups. Where possible, neuroleptic and narcotic analgetics are therefore combined.


[Iron Dextran Administered to Horses (author's transl)].

A description is given of three cases in which horses died very shortly after being given an intramuscular injection of iron dextran. The use of iron dextran in the case of horses is inadvisable.


[What is your diagnosis].

A case of craniomandibular osteopathy with a rather successful therapy is reported.


[Results obtained in the surgical treatment of right-sided abomasal displacement and torsion of the abomasum in cattle (author's transl)].

The results obtained by a modified method of surgical treatment in right-sided abomasal displacement and torsion of the abomasum in cattle are discussed. The usual surgical procedure is extended by pyloromyotomy, the technique of which is described. In addition, postoperative drug therapy is discussed and the importance of examination of the blood at regular intervals is stressed. Sixty-five animals took part in these studies pyloromyotomy being performed in twenty-five cases. The results show that pyloromyotomy has a beneficial effect on the prognosis of surgery. Moreover, the present study showed that the use of fixation of the abomasum by omentopexy is open to doubt in these cases.


[Parturient hypocalcaemia prevention in parturient cows prone to milk fever by dietary measures (author's transl)].

Dietary measures designed to prevent low postparturient plasma calcium concentrations were tested in dry dairy cows in Hoorn during a number of weeks before and after calving for a period of five years (1967-1972). Approximately 170 cows prone to milk fever took part in these trials. The effects of various concentration of calcium and phosphorus in the rations, a day's fasting, feeding below energy and protein requirements as well as those of intravenous and intramuscular infusion of EDTA (ethylenediamine-tetra-acetate) on the calcium, phosphorus and magnesium plasma levels and on the haematocrit value of the blood were studied in these trials. Dietary measures by which the postparturient plasma calcium levels were kept within normal limits in a trial with forty-five calving cows prone to milk fever, were based on the results obtained. These forty-five cows were fed a diet low in calcium (33.1-43.9 g. of calcium daily) during the dry period. After calving, they were given a diet high in calcium (148.3-196.3 g. of calcium daily). The diet was adequate as regards energy, protein, phosphorus, magnesium and vitamin D requirements. Milk fever did not occur in these cows and only four animals showed a decrease in plasma calcium to less than 7.5 mg/100 ml.  The following dietary measures are recommended to prevent parturient hypocalcaemia. (1) During the dry period, cows should be fed rations containing the lowest possible concentrations of calcium (for instance, smaller than 0.50 per cent of calcium in the dry matter of the total ration). Phosphorus and vitamin D intakes should be adequate. (2) The intestinal calcium intake should be increased immediately after calving. This may be achieved by administration of 250 g. of calcium carbonate in the form of an aqueous suspension which is fed orally by bottle. The concentration of calcium in the rations should also be increased (greater than 1.0 per cent of calcium in the dry matter). Phosphorus and vitamin D intakes should again be adequate. (3) Additional administration of 30 g. of magnesium daily before and after calving is advisable to prevent not only low plasma magnesium levels but also grass-tetany-like symptoms after calving.


[Chronic hepatitis in lambs (author's transl)].

When deaths and symptoms of chronic emaciation not due to any apparent cause occurred in weaned lambs, the morphological changes observed suggested that the liver probably was the main organ, the function of which was impaired. This was believed to be so because of the homogenity of the changes in this organ and the disseminated character of the lesions of the liver. These were termed chronic as secondary perilobular reactions occurred in addition to primary degenerative changes of the parenchyma, in which septa appeared in addition to lymphocytic infiltration in the portal triad. In view of the epidemiological findings, this heaptitis was believed to be infectious rather than toxic.


[Prevention of retained placenta and endometritis on cattle farms by hygienic procedures (author's transl)].

Animals showing retained placenta or endometritis are present on a large number of farms. This has become a serious problem, particularly when the animals are housed in cubicles. Effective hygienic procedures at the time of parturition will considerably reduce the incidence of retained placenta or leucorrhoea. Preventive insertion of after-birth capsules into the uterus is inadvisable.


[New Castle disease in imported birds. Cases observed and experimental vaccination (author's transl)].

An acute, highly virulent form of Newcastle disease is frequently observed in imported birds. Particularly parrots and, in some cases, pheasants are a potential source of danger. Diseased birds are imported from Asia as well as from South America. Outbreaks among birds imported from Africa have not so far been observed. The number of shipments in which Newcastle disease was found to be present in the birds is reviewed. Moreover, experimental vaccination is discussed.


[[Mycoplasma synoviae and Infectious Sinusitis in Turkeys (author's transl)].

Studies on two flocks of table turkeys affected with chronic respiratory distress and sinusitis showed that M. gallisepticum infection could be ruled out, whereas it was apparent from serological tests as well as examination by culture that M. synoviae infection was present in these cases.


[Preliminary studies on the incidence of Filaziae in equidae in the Netherlands (author's transl)].

Biopsies of the skin of the umbilical area were taken from ninety-nine horses and one donkey, all reared in the Netherlands. The biopsy specimens were examined for the presence of microfilariae by a recovery procedure. Microfilariae were identified in eight horses. These were microfilariae of the species Onchocerca cervicalis in each case.


[Myocardial fibrosis. A case of falling disease (author's transl)].

A case of chronic progressive heart failure in a bull, resulting from myocardial fibrosis, is reported. In view of the low concentration of copper in the liver, this condition is believed to be similar to that termed falling disease.


On the localization of the Gb locus within the MHS region of chromosome No. 6.

Further data on the Gb - HL-A linkage relationship are presented. All three GBG informative recombinants investigated are Gb - first HL-A recombinants; therefore Gb must be situated on the second HL-A side of the first HL-A locus. Ninety additional apparently Gb - HL-A non-recombinant offspring from 23 matings indicate that the Gb locus is situated in clsoe proximity to the second HL-A locus.


W4(4a) and W6(4b) in diverse human populations. Demonstration of their genetic identity in population and segregation studies.

The status of the W4, W6 system as related to the HL-A system was re-evaluated by means of segregation and mating studies in 200 Dutch families with 755 children. Inclusion analyses were performed on the Fifth Workshop human populations and related to a reference analysis on the main file in Leiden. The results of the mating and segregation analyses showed a good fit for W4 and W6 as a genetic system. The inclusion analyses showed a high degree of concordance. Based on those results, and other cited evidence, it was suggested that W4 and W6 may represent the basic substance of the HL-A antigens in the FOUR series.


Second, third locus and 4a/4b antigen associations in Negroids and Caucasoids.

In Caucasoids the third locus antigen Hu (FJH or T-2) shows a 91% association with W27 and W10. Less than 10% of the Hu positive cells had an unknown antigen at the second locus. In a Negroid population from Zambia studied with 1972 Workshop data W27 was absent and W10 present in low frequency. Hu in contrast was present with twice the frequency seen in Caucasoids. Eighty-six % of positive cells had an unknown antigen at the second locus. Data from the use of platelet complement fixing sera suggests that this unknown allele was Da(6), an antigen present in very low frequency in Caucasoids. Recombination between second and third locus alleles has been proposed as an explanation for these associations. Associations of HL-A12 and Hu with 4a, W5 with 4b in Caucasoids and vice versa in the Negroids was demonstrated, and the possibility that this finding may be an indication of recombination between a separate 4a/4b locus and the second and third loci was discussed.


HL-A8: a genetic link with thyrotoxicosis.

The incidence of HL-A8 was significantly increased in 64 Caucasian patients with thyrotoxicosis compared with 700 Australian blood donors (42% versus 24%). No significant correlation was observed between HL-A8 and autoantibodies to thyroid components in thyrotoxic patients; thus the association of HL-A8 must be either with the disease itself, or possibly with immune responses not tested for this study.


Anti-HL-A7 lymphocyte-dependent antibody.

Target cell specificity of a human cytotoxic lymphocyte-dependent antiserum correlated with the presence of HL-A7 on target cells. Target cells from 10 of 11 HL-A7-positive donors were damaged in vitro by this antiserum together with lymphocytes from normal donors. Target cells from six donors lacking HL-A7 were not damaged. Cytotoxic activity was removed by adsorption of the antiserum with lymphocytes from any one of four HL-A7-positive donors. Adsorption with lymphocytes from any one of three HL-A7-negative donors failed to eliminate cytotoxic activity.


The HL-A7 histocompatibility antigen in sarcoidosis in relation to tuberculin sensitivity.

Eighty cases of sarcoidosis have been investigated. In all except eight patients a histological verification of the diagnosis was obtained by mediastinoscopy or liver biopsy. The HL-A7 antigen was not increased in the entire group. However, in the group of patients with a negative sensitivity to tuberculin after the appearance of the disease there was a significant increase compared with controls. In the patients with a positive reaction, there was a complete absence of HL-A7. The HL-A system therefore does not seem to influence the liability to contract sarcoidosis, but once this condition has developed HL-A7 positives are more likely to lose cellular immunity to tuberculin and to reveal symptoms.


Histochemical studies of pancreatic calculi.

Fourteen pancreatic calculi from the corresponding number of pancreatic lithiasis patients were examined mineralogically and histochemically. The following results were obtained. The main components of calculi were calcium carbonate in 13 of the 14 cases, and calcium phosphate in the remaining one. Calcium carbonate calculi were all so-called intraductal calculi, with acidic glycoprotein apparently enwrapping the component particles. Acidic glycoproteins acted to bridge calcium carbonate particles, as in the cases of gallstone and urinary stone. The calcium phosphate calculus had a histochemical feature of pathologic calcification with degenerated collagen fibrils as the matrix, suggesting the calcification of the fibrotic pancreatic parenchyma after pancreatitis.