Primary testicular tumours among White, Black and Indian patients. A review of all testicular tumours examined in the Department of Pathology, University of Natal, over the past 25 years has revealed a very low incidence in the Black population. In comparison with White and Indian patients, testicular teratomas are particularly uncommon, a surprising feature in view of the frequency of ovarian teratomas in Blacks.


Hepatitis B surface antigen and primary liver cancer. Sera of 184 patients were examined to determine the incidence of hepatitis B surface antigen (HBsAg). Ninety-two patients had primary liver cancer (PLC) and there were 92 matched controls. Thirty-one of the 92 patients with PLC and 8 of the 92 patients with no clinical evidence of liver disease had radio-immunoassay-positive tests for HBsAg. The difference was significant (P less than 0,01). In 56 of the patients with PLC it was possible to assess the nature of associated liver disease histologically. HBsAg was found in the sera of 66,6% of patients with postcollapse cirrhosis and in 22,2% of patients with chronic Budd-Chiari syndrome. It is likely that the role played by hepatitis B infection in the pathogenesis of PLC varies according to local circumstances in different geographical areas.


Anterior sacral meningoceles.

Anterior sacral meningoceles. Three cases of the extremely rare lesion, anterior sacral meningocele, are reported. Its mode of presentation, pathology and possible methods of treatment are reviewed.


Postpartum veno-occlusive disease treated with ascitic fluid reinfusion. Three patients presenting in the postpartum period with veno-occlusive disease not related to the ingestion of pyrrolizidine alkaloids are described. The patients were treated by intravenous reinfusion of the ascitic fluid. This form of therapy has, to our knowledge, not previously been reported in the management of this condition.


Herpes zoster of the chest wall and gynaecomastia. A case report. Herpes zoster in a young male at puberty, associated with aggravation of gynaecomastia on the same side as the intercostal nerve involvement, is described.


The 1973 CPS-IRS-SSA exact match study.

The 1973 CPS-IRS-SSA exact match study. The 1973 CPS-IRS-SSA Exact Match Study--a joint undertaking of the Social Security Administration and the Bureau of the Census--links survey records for persons in the March 1973 Current Population Survey to their respective earnings and benefit information in SSA administrative records and to selected items from their 1972 Internal Revenue Service individual income tax returns. The resulting set of files provides a very broad base for cross-section and longitudinal analyses of income-distribution questions. This article attempts to provide an overview of the techniques employed in the study. Among the topics discussed are the confidentiality requirements in force during the project. The original study goals are also described and a list of some of the completed research is provided.


Cash benefits for short-term sickness, 1948--76. National income-maintenance programs provide cash benefits when workers become unemployed, retire, are injured on the job, have a long-term disability, or die. For short-term sickness, however, only five States, one other jurisdiction, and a single industry require wage-replacement protection. Voluntary plans cover a substantial number of additional workers, including many whose protection was established through labor-management negotiations. In this annual update of estimates on the extent of protection provided, many of the historical statistics have been revised back to 1967 as a result of new information on the amount of sick-leave benefits paid to employees of the Federal Government. The effects of the new data on the benefit series are examined, as are trends in the provision of sickness benefits for maternity--an issue subject to considerable recent controversy.


Student OASDI beneficiaries: program utilization and educational aspirations. This article describes the past, current, and projected utilization of social security student benefits by children receiving them in December 1972. Of the nearly 2 million children aged 18--21 estimated to eligible in 1972, about one-third were actually receiving benefits at the end of the year. School enrollment rates by age and race for the beneficiary and total populations were remarkably similar. Nearly half the students with benefits in current-payment status had been initially awarded benefits as children 5 or more years earlier. An estimated 68 percent of those in the sample were expected to have fulfilled their undergraduate plans before benefits were terminated because of the age cutoff. Multivariate analysis revealed that the amount of the monthly benefit has a significant nonlinear relationship with the beneficiary's plans to continue in school. The median cumulative benefit received was projected to be just over $5,000 for those intending 4 or more years of college.


Access to social security microdata files for research and statistical purposes. This article focuses on the characteristics of SSA microdata files and on the development of a disclosure policy aimed at serving the public interest while protecting the privacy of individuals and the confidentiality of research and statistical information. Several dimensions of the disclosure question are explored: A description of the persons (both living and dead) and other entities that are the data subjects; the ability of users to associate known data subjects with information about them; the sources of data; expectations as to recontact of data subjects; and the terms and conditions under which microdata are released to users outside SSA. The factors controlling the decision whether or not to release microdata are discussed. The factors range from those intended to protect the data subject--the criteria specified by law for maintaining confidentiality for example and the principles applied by SSA in assessment of disclosure risk--to those more concerned with agency function, such as financial cost to the agency, and interference with its primary mission. Some particular practices are described to illustrate application of present policy principles. Brief attention is given to future implications of certain current developments such as the Privacy Act, the Sunshine Act, and the Tax Reform Act of 1976.


Symptomatic anomalies of the aortic arch. Twenty-eight patients with anomalies of the aortic arch producing compression of the trachea and the esophagus have undergone surgical correction at this hospital since 1949. Of the vascular rings encountered, 15 had a double aortic arch and eight, a right aortic arch with a constricting ligamentum arteriosum. Five had an aberrant right subclavian artery passing posterior to the esophagus producing dysphagia. The patients with the double aortic arch were all infants. Two of the patients with a right arch and constricting ligamentum arteriosum and one patient with a retroesophageal subclavian artery were adults. Stridor from pressure on the trachea was the common symptom in the infants. The diagnosis was confirmed by esophagograms; aortography was less helpful. The surgical approach was the same for all of the anomalies, through a posterolateral incision in the left fourth interspace. For the double arches, the smaller limb, usually the anterior, was divided. Division of the ligament relieved the constriction of the right aortic arches, and the anomalous right subclavian artery was divided near the aorta. There were no hospital deaths, but one infant with a double aortic arch operated upon at the age of two weeks and with a tracheostomy died at home seven months later.


Histopathologic study of subcutaneous mastectomy specimens from patients with carcinoma of the contralateral breast. Fifty subcutaneous mastectomy specimens, each of which were removed from a patient who had previously undergone radical or modified radical mastectomy of the contralateral breast for carcinoma, were age and date matched to a control group of patients with which carcinoma was not associated. The patients were evaluated with regard to specific types of epithelial proliferative lesions and other entities of fibrocystic disease without knowledge of their group membership. The results included a statistically significant dominance of certain epithelial hyperplasias in the study population and a lack of statistical significance in intergroup difference of some previously suspected lesions, such as sclerosing adenosis and gross cystic disease. It is concluded that the recognition of those forms of epitheliosis associated with carcinoma may help in the management of patients at high clinical risk for carcinoma of the breast.


Normothermic hepatic vascular exclusion for extensive hepatectomy. In humans, there is still considerable controversy concerning the tolerance of the liver to warm ischemia. To avoid anoxic hepatocellular damage, chilled intraportal and intra-arterial infusion has been advised as an adjunct to hepatic vascular isolation. Fourteen patients with hepatic tumors underwent extensive hepatic resection, complete hepatic vascular exclusion being used but without the use of refrigeration. This procedure may considerably reduce blood loss during resection of large and hypervascular hepatic tumors and increase the safety of hazardous lobectomies. Careful hemodynamic monitoring including pulmonary artery pressure is necessary. Hepatic tolerance to prolonged warm ischemia up to 65 minutes is surprisingly good, in the absence of preoperative, extensive hepatic dysfunction. The use of this procedure is advised for resection of large hepatic tumors when the technical risks appear to be high. It is suggested that the classical delay of 15 to 20 minutes of normothermic hepatic ischemia may be safely extended to about one hour when necessary.


Hypercalcemia in thyrotoxicosis.

Hypercalcemia in thyrotoxicosis. Hypercalcemia occurs in approximately one of every five patients with thyrotoxicosis, and one of seven patients with hypercalcemia and thyrotoxicosis will have hyperparathyroidism as the cause of the serum calcium elevation. While there are no clinical features which permit easy identification of patients with hyperparathyroidism and thyrotoxicosis, determination of serum parathyroid hormone levels may help. Parathyroid hormone levels may be normal or suppressed if hypercalcemia is due to hyperthyroidism alone, and an elevated parathyroid hormone level suggest coexisting hyperparathyroidism.


The anatomic and metabolic source of lactate in shock. The size of the lactate pool in canine shock was measured directly by determining the lactate concentration of various organs. All organs tested, except skeletal muscle, had lactate concentrations similar to those of arterial blood. Skeletal muscles had much higher concentrations of lactate than did arterial blood. When 14C-labeled glucose was infused intravenously, it was concluded from the relative specific activities of glucose and lactate in blood that about one-third of lactic acid originates from blood glucose in shock. Only skeletal muscle had lower lactate specific activity than did blood. This is a possible indication that skeletal muscle is the site of production of lactate. Low glucose specific activity in muscle indicates massive glycogen breakdown, which probably serves as a metabolic precursor of lactate. Lactate production from amino acids produced by proteolysis could also play a role.


Cephalothin-tobramycin as a preventive antibiotic combination. Antimicrobial therapy should never be used indiscriminately, nor can it take the place of meticulous surgical technique. Appropriate antimicrobial agents administered within the critical time period and in the recommended dosage to achieve adequate serum concentrations effectively reduce the incidence of postoperative wound and other systemic infections. The low incidence of infection and virtual absence of adverse effects strongly suggest that cephalothin-tobramycine combination therapy is a valuable adjunct in emergency surgical procedures.


Perioperative suppression of the leukocyte migration inhibition assay in patients undergoing elective operations. The effect of anesthesia and operation on immunity measured by leukocyte migration inhibition using streptokinase-streptodornase is reported in normal patients undergoing elective surgical procedures. Eight-five per cent of the patients exhibited postoperative immunosuppression, and this persisted for 60 days or longer in more than half of them. Despite this, no complication was encountered relating to wound healing or sepsis.


Protection of organs during experimental ischemia. Cell death complicating ischemia has profound local or systematic effects on the organism. We have tried to protect the small intestine and severed extremities from the effects of ischemia by using various drugs and techniques. Occlusion of the superior mesenteric artery for 1.5 hours in anesthesized, fed rats had a 97 per cent mortality. This was improved by pretreatment with methylprednisolone and amplicillin given together. Histologic preservation was seen in treated survivors. Chlorpheniramine, diphenylhydantion and methylprednisolone or amplicillin given alone had little, if any, effect. In dogs, reimplantation of severed extremities subjected to a 1.5 to two hour warm ischemic period resulted in toxic systemic picture, and 100 per cent mortality. This was improved by perfusion with Collins solution and postoperative injection of methylprednisolone. The incidence of gangrene was decreased. The judicious use of some drugs and preservation techniques may protect organs and the organism from the consequence of ischemia.


Comparison of expanded polytetrafluroethylene and autologous saphenous vein grafts in high risk arterial reconstructions for limb salvage. Polytetrafluoroethylene bypasses were used in a series of 56 reconstructions, to the popliteal artery in 45 instances or below in 11 instances. These were performed in high risk situations in patients who usually did not have a suitable saphenous vein. Autologous saphenous vein bypass grafts were performed in a comparable series of 56 high risk situations. The polytetrafluoroethylene reconstruction was patent at four to 14 months in 43 of 45 patients having femoropopliteal bypasses, with limb salvage in 39 of the 45. The saphenous vein bypass was patent at eight to 14 months in 39 of 45 patients having femoropopliteal reconstructions, with limb salvage in 36 of the 45. Distal--small vessel--bypass patency rates were similar for reconstructions with polytetrafluoroethylene and saphenous vein. No increase in the number of deaths or complications was observed in the polytetrafluoroethylene group, rather, a general reduction was noted in the operating time and in the incidence of wound complications. These results justify the continued use of polytetrafluoroethylene grafts in patients without saphenous veins who require arterial reconstructions of the lower extremity for limb salvage. The exact place of polytetrafluorethylene grafts in reconstructive surgery of arteries in the lower extremity awaits definition based upon longer periods of observation.


A modification in the technique of making the Koch ileostomy pouch. This minor modification in the original technique assures greater security and permanence of the nipple, yet takes no longer to perform than the original procedure. The steps have been defined in a manner calculated to simplify the technique for the surgeon who is not already familiar with the operation.


A technique for vaginal oophorectomy.

A technique for vaginal oophorectomy. If retention or removal of the postmenopausal ovary is to receive similar attention at vaginal hysterectomy as at abdominal hysterectomy, more consideration must be given to the development of safe and secure techniques for vaginal oophorectomy. Technical problems relating to exposure and accessibility are obviously more pronounced with a transvaginal surgical approach. When salpingo-oophorectomy is surgically inaccessible, oophorectomy may often be performed. A stitch embodying a single penetration of the mesovarium is described for suture ligation.


Results and merit of estrogen receptor data derived from metastatic tumors of the breast. It is clear that a variety of metastatic deposits can successfully be assayed and found to contain estrogen receptor protein even up to 13 years following the initial tumor surgical procedure. Whether or not the patient has received previous treatment, estrogen receptor status does not appear to be influenced, and biopsies of the 23 metastatic lesions were found to contain estrogen receptors. Fourteen of nineteen patients with metastatic tumors containing estrogen receptors who were treated and evaluated demonstrated remission after hormonal manipulation. Only one patient with a tumor with no estrogen receptors demonstrated tumor regression after hypophysectomy and suggests that a previous response to hormone manipulation may warrant a further trial even when estrogen receptors are not found. The results of estrogen receptor values on metastatic disease of the breasts are extremely valuable in the therapeutic decision making process and should be routinely obtained.


Experience in selective operations in the management of penetrating wounds of the neck. Experience with 100 patients demonstrated that a selective approach to penetrating injuries of the neck can be accomplished without increasing morbidity and mortality. However, this selective approach must be done in a setting in which there are adequate nursing and house staffs. Facilities and personnel to perform arteriography and other diagnostic tests must also be available. Otherwise, observation would be unsafe, and it would be in the best interest of the patient to choose immediate operative intervention.


Transcatheter embolization of autologous clot in the management of bleeding associated with fractures of the pelvis. Extraperitoneal hemorrhage, associated with a fracture of the pelvis, is a major cause of death in pedestrian accidents. Transfusion alone may be unsatisfactory. Direct control of bleeding may be required. Surgically, this may be technically difficult or inadequate. Transcatheter embolization of autologous clot was used to control hemorrhage in three patients with such a fracture. If laparotomy is required immediately, arteriography of the pelvic area may be done postoperatively, If laparotomy is not performed, arteriography may define pelvic bleeding sites. Transcatheter embolization of autologous clot controls hemorrhage from branches of the hypogastric artery.


Evaluation of intraoperative arteriography as a routine for vascular reconstructions. A retrospective analysis of 391 intraoperative arteriograms performed after reconstruction operations on the carotid, aorta and lower extremity vasculature showed the value of incorporating this procedure as a routine only for the last mentioned site. Identification and correction of inadequacies due to technique are possible. Revisions in technique based upon these experiences have significantly diminished their incidence. Routine intraoperative arteriography for revascularization procedures of the lower extremity has further enabled us to classify reliably the runoff and correlate these findings with subsequent graft patency. Late graft closure, predominantly due to progressive or accelerated obliterating atherosclerosis in the distal circulation, occurred almost exclusively within the first year following reconstruction in those patients identified as having poor runoff by intraoperative arteriography. This group, in particular, should be closely monitored by noninvasive physiologic means and even post-operative arteriography to enable either prophylactic or therapeutic correction. In some instances, based upon intraoperative arteriography or subsequent studies, fruitless and potentially harmful reoperative vascular procedures may be obviated.


The use of heparin bonded shunts for perfusion of the renal artery during resection of complex abdominal aortic aneurysms. During resection of certain complicated aortic abdominal aneurysms, the circulation of the renal artery may require separate perfusion. To achieve this in a simplified manner, a heparin bonded shunt has been used for continuous perfusion of the kidney. This has been used in patients with a horseshoe kidney undergoing aortic aneurysmectomy; for intraoperative perfusion of a previously inserted saphenous vein to renal artery graft for renovascular hypertension and in simultaneous correction of an aortic aneurysm and insertion of a renal artery graft for hypertension. In each situation, the technique worked well with minimal heparinization and excellent results.


Microsurgical techniques in experimental lymphedema of the rabbit ear. One of the main obstacles to the study of changes occurring in lymphedema and the effects of various therapeutic modalities has been the lack of a reproducible inexpensive experimental model. We believe that the rabbit ear model satisfies this requirement permitting both evaluation of changes which lead to development of lymphedema as well as evaluation of the efficacy of microsurgical techniques.


A comparison of the open and closed methods of anastomosis for colostomy closure. A transverse colostomy was performed in dogs and, later, closed by resection and anastomosis. Half the anastomoses were done by the open and half by the closed method. The anastomoses were evaluated by barium enema series and by gross and microscopic examination. All anastomoses functioned well, but barium enema series showed great variation in the lumina diameter. Results of histologic studies revealed evidence of more inflammation and reaction about the open method.


A review of one hundred and fifty thyroidectomies following prior irradiation to the head, neck and upper part of the chest. The records of 150 patients who had operations on the thyroid following prior irradiation to the head, neck and chest regions were analyzed. The over-all incidence of carcinoma of the thyroid in these patients was 32 per cent; however, 8.6 per cent of these were occult microscopic tumors. The technetium scan was found to be a reliable method of identifying nodules of the thyroid, while physical examination proved to be a less accurate method of nodule detection. The multifocal nature of the disease was confirmed in this series in which a 68 per cent incidence of residual carcinoma was detected in patients in whom reoperation was required.


Colposcopy in anorectal disease.

Colposcopy in anorectal disease. If used properly, colposcopy will increase the scope of anorectal examination. It will allow for more precise diagnosis and early diagnosis of rectal, anal and perianal neoplasis during dysplastic phase. It is accepted today that, in its natural course, neoplastic lesions progress from dysplasia through intraepithelial neoplasia to invasive cancer as an interrelated function of time and immunologic status. If dysplasia and intraepithelial neoplasia is present for ten years prior to invasion, as has been suggested, the use of colposcopy in the younger aged patients could help reduce the incidence of invasive disease later.


The necessity of increased doses of amikacin in burn patients. Extended periods (6 to 9 hours) of subtherapeutic serum amikacin levels were observed in five burn patients receiving the recommended intravenous dose of 7.5 mg/kg every 12 hours. Kinetic studies revealed an unusually short half-life, especially in younger patients. This more rapid elimination necessitated a shorter dosing interval (every 6 hours), resulting in an increased daily dose (30 mg/kg/day). In this study of 10 patients with normal renal function, an intravenous dosage regimen of 7.5 mg/kg every 6 hours resulted in therapeutic peak concentrations and shortened intervals of subtherapeutic serum concentrations. A transient episode of tinnitus without cochlear damage occurred in one patient after the first dose. Neither ototoxicity nor nephrotoxicity occurred in any of the patients. Because of interpatient variability in amikacin elimination, frequent monitoring of serum levels with necessary dosage changes is imperative to provide optimal serum concentrations. However, it must be emphasized that these increased dosage regimens of amikacin are not suggested for routine use without previously measuring serum levels.


Effects of lysolecithin on isolated gastric mucosa. The effects of lysolecithin, a normal constituent of duodenal juice, on gastric mucosa were measured under isolated conditions. In a relatively low concentration (0.5 mg/ml), lysolecithin, added to the luminal side, caused liberation of organic acids without altering the spontaneous rate of mineral (i.e., HCl) acid secretion by fundic mucosa. The low concentration of lysolecithin also did not appear to affect other active ion transport processes or permeability of either fundic or antral mucosa. However, at a higher concentration (1 mg/ml) lysolecithin  inhibited spontaneous mineral acid secretion by fundus, altered active transport of other ions, and increased mucosal permeability of both fundic and antral mucosa. The results suggest that intraluminal lysolecithin in concentrations found in vivo may contribute to gastric mucosal damage.


The choleretic action of cholecystokinin and cholecystokinin octapeptide in dogs. Mongrel dogs were prepared by cholecystectomy, ligation of the lesser pancreatic duct, and insertion of gastric and duodenal cannulas. The common bile duct was cannulated through the duodenal fistula for bile collection while the enterohepatic circulation of bile salts was maintained by intravenous infusion of sodium taurocholate. Cholecystokinin (CCK) and cholecystokinin octapeptide (CCK-OP) caused increased bile flow and had no influence on the biliary clearance of erythritol. The results indicate that the predominant mechanism of CCK and CCK-OP choleresis is due to ductular stimulation.


The determination of lymph shed by colloidal gold scanning in patients with malignant melanoma: a preliminary study. Colloidal gold radionucleotide 198Au scanning can demonstrate the direction of regional lymphatic drainage in patients with primary malignant melanoma. Each of 32 patients with primary melanoma of the trunk received an intradermal injection of 0.1 mCi of 198Au colloid around the primary melanoma site. Imaging was accomplished with a tomographic scanner 24 hours following the injection. Twenty-seven of these patients underwent 36 regional lymph node dissections; nine had nodal metastases histologically demonstrated in the area (s) of nucleotide uptake. In clinical evaluation of up to 55 weeks, no patients demonstrated regional lymph node metastases in node groups which did not show preoperative gold uptake. Early evidence shows excellent correlation between the route of regional lymph node metastases and the direction of lymphatic flow to regional node groups, as demonstrated by gold colloid scanning. This procedure may be useful for evaluating patients with histologically defined high risk melanomas situated on the trunk in areas which drain to one or more lymph node regions.


Physical training of patients with intermittent claudication: indications, methods, and results. Supervised dynamic physical training for 4 to 6 months as a treatment of intermittent claudication was studied in 148 patients who had clearcut symptoms for more than 6 months. Nineteen patients could not complete the planned training program because of cardiac complications, rapid progress of the disease, intercurrent disease, or social reasons. Before the training was started, walking tolerance and calf blood flow were determined. The intensity of each training session (three times per week) was adjusted to the patient's cardiac tolerance as predicted by the cardiac tolerance test. The walking ability increased in 88% of the patients and the average increase was 234%, while the calf blood flow remained unchanged. After the training period, more than 40% of the patients could walk 1,000 m or more. The increase in walking ability was independent of the location of the atherosclerotic lesion or the presence of diabetes. It is concluded that physical training is a good alternative to reconstructive surgery in the treatment of patients with intermittent claudication. It does not interfere with the surgical possibility if operation becomes necessary in the immediate or later course of the disease.


Replacement of the inferior vena cava and iliac veins with heterologous grafts in animal tests. The use of a modified bovine collagen graft as a low-pressure conduit was investigated by implantation into the iliocaval system of dogs. In the 210 day observation period, a patency rate of 87.5% was achieved. Nearly all graft failures occured within the first 14 days following implantation; failure after that time did not seem to be dependent upon length of time of implantation. Progressive organization of the neointima was seen histologically. New smooth muscle fibers were observed in the neointima with electron microscopic evidence of reconstitution of the subendothelial membrane. Continuing resorption of graft collagen coincided with its replacement by newly developed collagen type III fibers in a surface-parallel orientation.


Occult splenic abscess: an unrecognized complication of heroin abuse. Despite increased recognition of surgical problems related to narcotic addiction, splenic abscess has not been commonly recognized as such a complication. Seven male patients with splenic abscess secondary to heroin abuse have been treated. Six had bacterial endocarditis. Symptoms were nonspecific. Splenomegaly in two patients was the only useful physical finding. Five patients had left pleural effusion, of which three were proven to be empyemas. Staphylococcus aureus was the predominant pathogen of of bacterial endocarditis and splenic abscess. The splenic scan was diagnostic. All patients recovered following curative splenectomy.


Evaluation of surgical response in renovascular hypertension using angiotensin II blockade. The mechanisms involved in residual or recurrent hypertension following operation to correct renal artery stenosis were studied in 10 patients by performing angiotensin II blockade with Saralasin (Sarcosine, alanine, angiotensin II) before and after operation. Peripheral renin and renal vein renin determinations, angiography, and renography were done as well. The limitations of renin determinations are cited and the application of angiotensin II blockade as a specific method of detecting renin-dependent hypertension before and after operation are presented. Saralasin infusion under the controlled conditions of our study proved to be a sensitive method for detection of renin-dependent hypertension. The results of Saralasin infusion correlated closely with peripheral and renal vein renin determinations. Thus angiotensin II blockade before and after operation may supercede more invasive and less specific diagnostic methods.


Pharmacological vs. mechanical reduction in portal pressure: a comparative study. Previous studies have shown that decreasing blood flow in the superior mesenteric artery (SMA) by the infusion of intra-arterial vasopressin into or partial mechanical obstruction of the SMA by a balloon catheter (partial balloon obstruction) causes similar alterations in splanchnic hemodynamics, but divergent changes in systemic hemodynamics. The effects of these two methods of reducing SMA blood flow were compared in each of six anesthetized normal dogs. Vasopressin and partial balloon obstruction induce similar reductions in portal pressure (-54 +/- 12% vs. -46 +/- 11%), wedge hepatic vein pressure (-54 +/- 13% vs. -53 +/- 18%), and portal venous flow (-34 +/- 7% vs. -37 +/- 7%). Significantly different effects between intra-arterial vasopressin and partial balloon obstruction were observed, however, in cardiac output (a decrease of -24 +/- 5% vs. an increase of +12 +/- 4%) (P less than 0.001), heart rate (-8 +/- 3% vs. 0) (P less than 0.05), and systemic vascular resistance (+36 +/- 8% vs. -2 +/- 2%) (P less than 0.005), respectively. These results indicate that the two procedures are equally effective in reducing portal venous pressure and blood flow. Partial balloon obstruction, however, does not induce the potentially deleterious systemic hemodynamic effects seen with vasopressin infusion. In fact, some of the changes observed with partial balloon obstruction, especially the increase in cardiac output, are considered to be beneficial. In an additional five dogs, partial balloon obstruction was maintained for 5 hours. Throughout, the reduction in portal venous pressure (hepatic venous wedge minus hepatic venous free pressure) was maintained at less than half of the baseline levels (4.75 +/- 0.43 vs. 2.25 +/- 0.32 mm Hg), and the mean arterial pressure at baseline values. All of the dogs survived and were well at 1 week after the prolonged partial obstruction. No abnormalities were observed in the anatomical or histological studies of the small intestine. This study suggests that partial balloon obstruction of the SMA has theoretical therapeutic advantages over intra-arterial vasopressin for reducing portal venous pressure.


Preduodenal portal vein: its surgical significance. Preduodenal portal vein is a rare anatomical variant which may be one of many anomalies in the neonate with duodenal "atresia." Preduodenal portal vein also may be an occasional finding in an adult undergoing biliary, gastric, or pancreatic surgery. Awareness and recognition of the anomaly are essential for the avoidance of injury during such operations. We report here a symptomless patient whose preduodenal portal vein was discovered at cholecystectomy.


Comparison of techniques of autotransfusion. At least nine different autotransfusion devices have been evaluated experimentally or clinically. Each has its advantages and disadvantages. The major problems involve concepts of extracorporeal anticoagulation and the logistics of operating the equipment.


Vascular surgery--is it different?

Vascular surgery--is it different? In 1972 the Society for Vascular Surgery and the North American Chapter of the International Cardiovascular Society recommended that the American Board of Surgery establish a method for the certification of special competence in vascular surgery. The American Board of Surgery in 1974 judged that, for the present, vascular surgery training best could be upgraded by certifying training programs and not individuals. The Residency Review Committee for Surgery now has approved guidelines which define acceptable vascular surgery training programs. These guidelines require approval of the American Medical Association and the governing bodies of the Liaison Committee for Graduate Medical Education before accreditation procedures can be implemented. It is proposed that vascular surgery is different enough from general surgery and cardiothoracic surgery so that special training programs are needed. Vascular surgeons require a fund of knowledge and surgical skills beyond that learned in most surgical programs as well as a special experience with vascular operations if they are to provide optimal patient care. Acceptance of the principle of the accreditation of surgeons caring for vascular surgical problems is an important step in the upgrading of vascular surgery.


Rational approach to the differentiation of vascular and neurogenic claudication. Lower extremity pain caused by exercise but relieved by rest is usually a reliable symptom of chronic arterial insufficiency. However, similar discomfort often occurs in patients with neurospinal compression. Furthermore, arterial occlusive disease and demonstrable spinal stenosis may be present simultaneously. Fifty-two patients with symptoms suggesting intermittent claudication comprised the study group. All were proven to have a nonarterial cause of their complaint. The study consists of a retrospective analysis of the diagnostic methods used in confirming the proper diagnosis. Conclusions reached suggest a rational approach to solution of individual patient problems. The nonvascular origin of the symptoms was suggested initially by clinical evaluation in 19 patients, and by noninvasive arterial evaluation in an additional 22. The neurospinal origin of symptoms was obscured in 11 patients because of the presence of significant arterial occlusive disease, as demonstrated by nominvasive arterial testing. Seven of the 11 patients underwent arterial reconstruction, which failed to relieve their symptoms. Subsequently, the neurospinal origin of these symptoms was proven by appropriate treatment. This experience has shown that the errors in diagnosis and treatment could have been avoided by using a combined diagnostic approach, correlating results of an accurate clinical evaluation with noninvasive arterial testing as well as the findings shown on lumbosacral spine films.


Extended profundoplasty for limb salvage. Extended profundoplasty was performed in 50 limbs of 39 patients for relief of rest pain or gangrene. This operation was effective in 95% of the limbs operated on because of rest pain, and in 54.5% of the limbs operated on because of gangrene. In 32 limbs the popliteal artery was patent. Profundoplasty was successful in relieving ischemic symptoms in all but two limbs. Postoperative ankle pressures were increased consistently in the improved limbs. In 18 limbs the popliteal artery was occluded. Profundoplasty abolished the ischemic symptoms in 13 limbs. Ankle pressures did not increase consistently in limbs that were clinically improved in this group. The authors believe that restoring blood flow and pressure to the profunda femoris artery and its branches, by means of open endarterectomy and patch graft, can salvage limbs which otherwise would be fated for amputation. As such, it represents a reasonable alternative to bypass grafting, and in some cases it is the procedure of choice for the patient with threatened tissue loss.


New approaches to limb salvage by extended extra-anatomic bypasses and prosthetic reconstructions to foot arteries. Because our femoropopliteal reconstructions with expanded polytetrafluorethylene (PTFE) and saphenous vein have comparable patency rates up to 22 months, we used this prosthetic for longer, more complex bypasses for limb salvage. Fourteen axillopopliteal or cross-over axillopopliteal bypasses were performed largely because groin infection or deep femoral artery disease precluded standard procedures; 12 are patent up to 14 months. Five patients required a bypass from one femoral artery to an opposite leg artery; four are patent up to 17 months. Because of progressive necrosis, eight patients required a secondary extension from a femoropopliteal bypass to a distal artery; five are patent up to 12 months. Three patients required extra-anatomic bypass for leg or popliteal space infections; all achieved limb salvage up to 12 months. Twenty patients without other suitable proximal arteries required a bypass to the dorsalis pedis or anterior tibial artery at the ankle; 10 are patent up to 14 months. Eleven patients required posterior tibial bypass at or below the ankle; seven are patent up to 18 months. One postoperative death followed these 61 procedures. Thus these operaions with long PTFE grafts that cross multiple joints can salvage limbs for important periods of time with low risk.


Complications and treatment of popliteal aneurysms. Because arteriosclerotic popliteal aneurysms so often present with complications, treatment results are less than optimal in contrast to aneurysms oat other sites. From 1963 to 1977, 40 surgically treated aneurysms in 30 patients were studied. Seventeen limbs presented as asymptomatic aneurysms (42.5%), four with pressure symptoms (10%), one with rupture and ischemia (2.5%), nine with acute thromboses and ischemia (22.5%), and nine with chronic ischemia and claudication (22.5%). Seventeen aneurysms were thrombosed (42.5%). Diameters of all aneurysms measured at operation ranged from 1.0 to 10 cm. It was of interest to note that, generally, larger aneurysms were patent, and thromboses were common in the smaller aneurysms, with an average diameter of 2.5 cm. Saphenous vein grafts were used most frequently for interpolation grafts (65%) and bypass grafts (12.5(). Prosthesis were used in 7.5%, endarterectomy and aneurysmorraphy in 5%. Popliteal reconstruction was accomplished initially in 40 limbs, with two early failures and 10 late failures with loss of two limbs. Cumulative patency rates for 40 limbs at risk at 5 and 10 years were 75.9%, at 14 years, 62.6%. Diagnosis is the most difficult aspect of this problem, as physical limitations impede early diagnosis. Thromboses being the natural history of popliteal aneurysms, early recognition and treatment are important to improve limb salvage rates.


Role of staging in bilateral carotid endarterectomy. Staging of bilateral carotid endarterectomies 1 to 6 weeks apart has been recommended because of presumed excessive morbidity chiefly related to respiratory problems, hypertension, and neurological deficits. Since data regarding the timing of the second procedure are lacking, an analysis of 79 consecutive patients undergoing bilateral endarterectomies staged from 6 days to 34 months apart (median interval, 52 days) was performed. In addition to postoperative neurological deficits, however, transient perioperative mean systolic and diastolic blood pressures (SBP and DBP) were compared after each side and were correlated with the time interval between the two procedures. No significant difference existed between the two sides in terms of preoperative hypertension, administration of steroids prior to clamping, intraoperative clamp time, the use of shunts, and the duration of operation (P greater than 0.05). Seven temporary neurological deficits occurred after operation, six after the first and one after the second endarterectomy. One permanent deficit following operation on the second side led to the only death (0.6%) in this series. Both neurological deficits (one temporary and one permanent) following the second endarterectomy occurred after procedures staged more than 60 days apart. No differences in mean SBP and DBP existed between patients with and without neurological deficits. Statistical analysis of SBP and DBP recordings during and 6, 12, 24, and 36 hours after operation when the two were staged 7 days (nine patients), 8 to 14 days (five patients), 15 to 30 days (10 patients), 30 to 60 days (17 patients), and more than 60 days (38 patients) apart revealed significantly higher readings after the second procedure, only in patients staged greater than 60 days (P less than 0.05). Therefore, in our experience, neurological deficits were less common after the second endarterectomy, and, although postoperative blood pressures were higher after the second side, these were significant only in patients staged more than 60 days apart. We find no evidence to suggest that increasing the waiting period between bilateral procedures will lower the incidence of undesirable neurological sequelae.


Hemodynamic assessment and surgical correction of kinking of the internal carotid artery. Although kinking of the internal carotid artery has been recognized for many years, the surgical significance of this lesion has remained controversial. The present study was designed to identify hemodynamic significance of kinking of the internal carotid artery using a positional testing technique with preoperative and postoperative noninvasive data that were correlated with intraoperative electromagnetic flow measurements to establish operative criteria. A fluid-filled oculoplethysmograph (OPG) was used to assess carotid artery flow in 26 patients with cerebral ischemic symptoms who had angiographic documentation of kinking of the internal carotid artery. OPG testing was done with the patient's head positioned first in the neutral, then in the right and left rotations, and then in extension-flexion positions. Sixteen patients underwent angioplasty. At operation electromagnetic flow measurements of the internal carotid artery were determined in these 16 patients with similar positional maneuvers. A reduction of flow from 30% to 80% was found on positional testing during operation in 14 of these 16, and all 14 of these patients also had abnormal preoperative OPG testing. After angioplasty, effects of position on internal carotid artery flow were eliminated, as proved by electromagnetic flowmeter measurements and by follow-up OPG studies in all 14 patients. The other two patients who had been subjected to surgical correction had no positional effects as documented by electromagnetic flowmeter testing. A high correlation between noninvasive data and operative flow measurements suggests that positional OPG testing is helpful in identifying hemodynamically significant kinking. Symptomatic patients with kinking of the internal carotid artery and abnormal OPG testing may be candidates for corrective surgery.


Staged and combined surgical approach to simultaneous carotid and coronary vascular disease. Between 1969 and 1976, 174 patients were treated surgically for simultaneous carotid and coronary atherosclerosis. In 59 patients, staged carotid endarterectomy was performed a few days to 6 months prior to myocardial revascularization. Severe (more than 60% stenosis) coronary atherosclerosis affected a single vessel in 11 patients (19%), two vessels in 20 patients (34%), and three vessels in 28 patients (47%). Left ventricular contraction was impaired in 30 patients (51%). Nine patients (15%) had previous neurological symptoms, and 50 patients (85%) had asymptomatic carotid stenosis. One patient (1.5%) had a permanent stroke after carotid endarterectomy. There were no permanent strokes after staged myocardial revascularization, and the early mortality rate was 1.7%. Combined carotid endarterectomy and myocardial revascularization were performed in 115 patients with severe cardiac disease. Coronary atherosclerosis affected a single vessel in 10 patients (9%), two vessels in 39 patients (34%), and three vessels in 66 patients (57%). Left ventricular impairment was present in 72 patients (63%). Thirty-five patients (30%) had previous neurological symptoms, and 80 patients (70%) had asymptomatic carotid stenosis. Five patients (4.3%) had permanent strokes after combined revascularization, and four of these patients had occlusion or severe stenosis of the contralateral internal carotid artery. The early mortality rate was 4.3%, but no deaths could be attributed to carotid repair. The results suggest that significant simultaneous carotid and coronary atherosclerosis should be corrected in selected patients by staged operations when feasible. In the presence of severe cardiac disease, a combined precedure may be performed in face of higher risk of intraoperative stroke.


Management of acute lower extremity arterial ischemia due to embolism and thrombosis. Despite a general impression to the contrary, a recent survey showed that the current mortality rate for acute arterial ischemia approximates 25%. Much of this apparently relates to toxins and procoagulants released from the dying limb, a tendency which may be enhanced further by attempts at revascularization. Based on these observations, we have utilized selective management of acute arterial ischemia in an attempt to minimize deaths and to salvage the maximum number of limbs. If the patient presents within 6 to 8 hours of the onset of acute arterial occlusion and if paralysis or anesthesia is present, then ultimate limb loss is likely. The therapeutic choices are high-dose heparin therapy, operative removal of the clot, or amputation of the limb--the ultimate choice being dependent upon the particular status of the patient. But if sensation and motor function are present, viability of the limb is not threatened, and good results can be obtained by utilizing anticoagulation and delayed elective revascularization, if the latter is indicated. But revascularization attempts after 10 to 12 hours of severe ischemia often are unsuccessful, and ischemia is followed by either recurrent thrombosis and ultimate limb loss, or by death from the systemic effects of reperfusion of ischemic tissue. This type of limb is managed best by using high-dose heparin therapy if viable, or by amputation if it is not. Employing the above criteria, 54 patients with acute arterial ischemia averaging 59 years of age, were treated. Seventeen had immediate thrombectomy, yielding two deaths and four subsequent amputations. Twenty-nine received anticoagulation treatment, resulting in one death and five amputations, and six had immediate amputation, yielding one death. Three had no specific treatment, with one poor result. There were four deaths in the entire series--a mortality rate of 7.5%--and two thirds of the limbs were salvaged. We have concluded that selective management, as prescribed above, was responsible for a significant decrease in mortality rate with no corresponding increase in limb loss, and that high-dose heparin therapy ultimately may prove the initial treatment of choice in all cases of acute arterial ischemia.


The importance of combined multisegmental pressure and Doppler flow velocity studies in the diagnosis of peripheral arterial occlusive disease. The value of combined multisegmental pressures and quantitative Doppler flow velocity determinations in the preoperative vascular laboratory evaluation was analyzed in 100 consecutive patients with angiographically documented peripheral arterial occlusive disease. Several new observations were made: (1) erroneously normal or even high segmental pressure  readings appear to be caused by increased arterial wall stiffness and may produce falsely elevated or erroneously normal pressure, suggesting less disease than exists, especially when only ankle pressure screening is used. (2) The addition of quantitative flow velocity determinations significantly improved the reliability of diagnostic decision making. The diagnosis of proximal arterial occlusive disease based on combined pressure-velocity measurements was confirmed angiographically in 143 of 148 limb studies (96.6%), including several with normal pressures and reduced velocity values--a pressure-velocity dissociation. (3) A decrease of the leg segment:arm pressure ratio combined with only a slight reduction of velocity indices suggests a stenosis with good local collateral flow and vessel patency at the site of measurement--a reversed pressure-velocity dissociation. (4) A decreased lower limb segment/arm pressure ratio combined with a significant reduction of velocity indices is evidence of arterial stenosis with poor local collateral flow. The combined multisegmental pressure and velocity evaluation of patients suspected of arterial occlusive disease substantially increases the reliability of noninvasive diagnosis and offers a new level of differential diagnostic interpretation.


The application of thermography in the study of coronary blood flow. The technique presented in this paper is based on the authors' previous observations in which they found that artificial decrease of blood flow to a portion of the heart muscle leads to an immediate and proportional drop in the regional myocardial temperature. It appeared to the authors as a logical next step to apply the thermographic camera to a monitor and to record such changes in the human patient during coronary surgery and to use the data to draw conclusions applicable to regional blood supply and to blood flow through surgically inserted vein grafts. They found that, on the normothermic heart, there were well-identifiable "cold" patches corresponding with areas of impaired coronary circulation. By infusion of blood to the ischemic myocardium through individual release of the bypass grafts, the thermogram responded by immediate appearance of "warm" spots corresponding with the areas supplied by the grafts. Even more dramatic demonstration of graft patency and outline of the area supplied by the graft could be performed by injecting cold saline solution into the grafted saphenous veins. In the author's experience this most interesting new method proved to be a useful tool in coronary surgery both as an adjunct in delineating ischemic areas and in proving the patency and efficiency of the grafts inserted.


The morphogenesis of beta-aminopropionitrile-induced rib malformation in fetal golden Syrian hamsters. In order to provide information on the mechanism of beta-aminopropionitrile (betaapn) induced teratogenesis, the pathogenesis of a fetal rib abnormality was studied at relatively short time intervals following maternal treatment with 2,500 mg/kg aqueous betaapn on day 11 of gestation. Histochemical tests of ribs from betaapn-exposed fetuses indicated a slight decrease in the level of glycosaminoglycans but at a time when the defect was already morphologically established. Ultrastructural observations on the chondrocytes of ribs from betaapn-exposed fetuses revealed alterations in mitochondrial structure indicative of a slight cytotoxic effect for the teratogen. The mitochondrial changes were transient, occurring initially at three hours after treatment and lasting for nine hours. Alterations in the size of collagen fibres in the cartilage of the fetal rib were also observed in the offspring of betaapn treated females. The mean diameter of collagen fibres in the ribs of control fetuses increased throughout the course of the study. The mean diameter of fibres in the fetuses of betaapn-exposed females failed to show any increase and was found to be significantly less than controls as early as three hours following maternal administration. The results suggested that the principal factor in the production of the fetal rib deformity was fundamentally the same as that known to affect the adult; namely a defect in the extracellular maturation of collagen.


The effect of trypan blue on the development of the ferret and rat. The teratogenic effects of trypan blue given to pregnant rats and ferrets at equivalent stages of embryonic development are described. In the rat the well known teratogenicity of the dye at 8.5 days of gestation and the surprising cessation of teratogenic effect at 11.5 days (20+ somites) is confirmed. In the ferret the drug is teratogenic both at 13  and 18 days of gestation though the principal abnormalities seen are different to those described in the rat. It has been suggested that the teratogenic action of trypan blue in rats is due to an interference in the function of the yolk sac which is an organ of histiotrophic nutrition and provides the principal source of nutrition for the 8.5-day embryo that is largely replaced by a functional chorio-allantoic placenta after 11.5 days of gestation. In ferrets histiotrophic nutrition does not involve an inverted yolk sac placental system. In this species endometrial symplasma provides histiotroph which is ingested by the invading trophoblast.  Histiotrophic nutrition is still of great importance at 18 days and morphological evidence indicates that chorio-allantoic placentation becomes important by about 20 days (35+ somites).


Early changes in the mouse neuroepithelium preceding exencephaly induced by hypervitaminosis A. Excess vitamin A orally administered to pregnant mice during neurulation causes most of the embryos to become exencephalic. The study presents light and electron microscopic observations that trace the origin and course of the early cellular and tissue alterations associated with the malformation. The main effects of the teratogen are seen in the neuroepithelial cells of the cephalic region of the presumptive nervous system. The degree to which each embryo is malformed varies but no matter how extensive the abnormalities in each embryo, the neuroepithelium is always affected and the lesions are similar. Mesodermal abnormalities appear only in the most seriously affected embryos. With the electron microscope, changes are apparent in the neuroepithelial cells within a few hours after maternal treatment. These changes include the formation of abnormally shaped nuclei with swollen nuclear envelopes, dilation of the rough endoplasmic reticulum, and formation of cytoplasmic inclusions that contain DNA and/or RNA. The inclusions are thought to arise as an autophagocytic response of the cells to the sub-lethal injury induced by the teratogen. In addition, a number of cells are more severely affected and degenerate. Light microscopic examination of serial sections reveals that by 20 hours after treatment, the neuroepithelium becomes disorganized: the cells are round and misaligned and intercellular connections are lost. We postulate that the early cellular alterations lead to a disruption of the architecture of the early neuroepithelium so that the neural folds fail to meet and close. The tissue may survive the initial insult, but continues to grow in the everted manner characteristic of exencephaly.


Use of dose-response relationships to discriminate between the mechanisms of cleft-palate induction by different teratogens: an argument for discussion. The examples of 6-AN- and cortisone-induced cleft palate in the mouse suggest that dose-response studies can be used to discriminate whether mechanisms of action are different for different teratogens. Evidence for differences in the mechanisms of teratogenic action can be found in terms of the parameters of the response without reliance on other consequences of teratogen treatment. It is argued that the application of established biometrical models or, possibly, the development of new ones is critical to consolidate enumerative data. With practical methods, genetic variation can be sought, interpreted and put to experimental use, structure-function studies can be made intelligible, and safety evaluation programs might begin to make sense.


Cell ploidy in molar placental disease.

Cell ploidy in molar placental disease. Molar diseases of the placenta is associated with cystic change in the villi. The cysts may be from 5-20+ mm in diameter. This disease has been described in association with triploid and diploid cell lines and with and without an accompanying embryo or fetus. It may be followed by malignant change and invasive chorio-carcinoma. In order to investigate the association between cell ploidy, embryonic development and subsequent malignancy, a detailed study of 30 conceptuses with molar disease was made, with the accompanying maternal history and follow-up. The cell ploidy was determined by measurement of nuclei by a cytoscan light microscope connected to a computer program as has been previously described. Diploid cell lines were not found with embryonic or fetal development. Triploid cell lines were always associated with an embryo or fetus. Triploidy is not associated with hyperplastic changes in the trophoblast. These results are presented and discussed.


Teratogenic effect of N-methyl-N'-nitro-N-nitrosoguanidine in mice. The teratogenic effect on the mouse fetus of a potently mutagenic and carcinogenic agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), was studied. Pregnant mice were injected on one of gestation days 7-12 with an intraperitoneal dose of 40, 60 or 80 mg/kg of MNNG, and fetuses were examined on day 18 of gestation. Various malformations affecting the brain, face, vertebra, rib and limb appeared in high frequency. Brain malformations were the most predominant; hydrocephalus, hydromicrocephaly and microcephaly appeared in sequence with developmental stages of treatment, although exencephaly occurred infrequently. Cleft palate, sometimes associated with microglossia and micrognathia, and vertebral anomalies including tail defect were observed following almost every gestation-day treatment. Long-bone defects of fore- and hindlimbs were also predominant. Polydactyly, ectrodactyly and microdactyly frequently occurred together in the fore- or hindlimbs or both in sequence with treatment stages. Ectrodactyly and microdactyly appeared with greater frequency on the left than on the right in both fore- and hindlimbs, but polydactyly and long-bone defects appeared bilaterally.


[Inflammatory and tumorous metastases of the thoracic spine: operative management and results (author's transl)]. 133 patients with inflammatory or tumorous metastases of the thoracic spine were operated upon within the last 11 years. Radical removal of inflammatory lesions with consecutive corticalis-spongiosa-plasty, taken from the christa pelvis, and chemotherapy are a therapeutical unit. Excision of the tumor with supplement bone grafting or "Pallacosplombe" and stabilization according to the principals of osteosynthesis are rewarding in individual cases. Four out of nine tumor patients survived two years after surgery.


[The influence of postischemic reperfusion on the recovery of ischemic lesions of the left ventricle (author's transl)]. In an isolated dog heart preparation the influence of normothermic ischemic arrest and recovery of the ventricular function during the period of post-ischemic reperfusion were investigated. If ischemic arrest has caused a depression of ventricular function, the functional recovery of the myocardium cannot be improved significantly by a prolonged reperfusion of the empty beating heart.


[The value of enzyme-determination after cardiac surgery (author's transl)]. In 342 patients undergoing open heart surgery we determined the serum enzyme levels of GOT, GPT, LDH, alpha-HBDH, LAP, CK and CK-MB from the beginning of the operation up to the 14 th postoperative day. There was an elevation of serum enzymes depending on the type of operation, the duration of extracorporal circulation and the postoperative course. A pattern of enzyme changes for uncomplicated cases is described. The investigations demonstrate a statistically significant correlation between the elevation of "liver specific enzymes" and right heart failure on one hand and of "heart specific enzymes" and myocardial ischemia on the other hand. It is concluded that only repeated determinations beginning with the operation enable to evaluate serum enzyme levels.


[Is creatine kinase isoenzyme CK-MB a diagnostic tool for perioperative myocardial infarctions? (author's transl)]. There is still controversy of the validity of elevated CK-MB serum activity in the diagnosis of perioperative myocardial infarction after open heart surgery. CK-MB activity was investigated using myocardial and skeletal muscle biopsies and in sera postoperatively in 192 patients. In biopsies CK-MB fraction of total myocardial CPK was 37%, the total-CPK activity of human skeletal muscles still shows a 5% fraction of CK-MB. There has to be more than 8% CK-MB fraction of total CPK-serum-activity to take this as evidence of myocardial damage. 3 h postoperatively enzymatic-immunologic CK-MB test is no longer interfered by enzymes derived from hemolyzed erythrocytes. In patients without signs of myocardial lesions postoperatively mean CK-MB-activity is 11 to 27 U/1 depending on the operative procedure performed. Activity levels exceeding 50 U/1 are almost evident of myocardial infarction. Elevated CK-MB-serum activity is a sensitive parameter for myocardial lesions overestimating an event of infarction. It is a helpful tool diagnosing perioperative myocardial infarction.


[Monitoring myocardial performance after open heart surgery by calculation of diastolic and systolic pressure time index (author's transl)]. In order to determine the incidence of subendocardial ischemia after open heart surgery, subendocardial blood flow was monitored in 171 patients subjected to mitral and/or aortic valve replacement or coronary revascularization by on-line calculation of Diastolic (DPTI) and Systolic Pressure Time Index (TTI). Body hypothermia with an esophageal temperature of 25 degrees C and magnesium-aspartate-procaine cardioplegia were applied for myocardial protection. Ten patients developed low cardiac output state with two early deaths. In the two patients with fatal low cardiac output DPTI/TTI remained below 0.8. In the remaining 8 patients DPTI/TTI rose to 1.4 after a mean recovery time of 36 hours. In 161 patients (94%) no low cardiac output state evolved and DPTI/TTI rose to 1.3 within 60 min. after termination of cardiopulmonary bypass. Our results indicate that body hypothermia of 25 degrees C combined with magnesium-aspartate-procaine cardioplegia can reduce the incidence of subendocardial ischemia, but does not prevent this complication completely after anoxic times beyond 60-70 minutes.


[Clinical application of paracorporeal artificial ventricles (author's transl)]. A pneumatically driven artificial heart with tubular silicone rubber membrane and disc valves was used in four patients with intractable postoperative cardiac failure. The operation was performed through a median sternotomy: large cannulas were placed in both atria and blood was returned to aorta and pulmonary artery. In three patients the natural heart recovered and the artificial ventricles were removed. One patient died 6 weeks after the operation, the other two left the hospital in good condition. Profound postoperative heart failure can be reversed by the use of the paracorporeal artificial heart; the advantage of the system lies in the simplicity of its implantation and removal.


[Hemodynamic results of surgery for congenital supravalvular aortic stenoses (author's transl)]. Supravalvular aortic stenosis is either a syndrome combined with typical face characteristics mental retardation and peripheral pulmonary artery stenosis or it occurs as an isolated congenital heart defect. The diagnosis was confirmed in 137 patients by means of catheterization and angiocardiography; 35 pediatric and 10 adult patients were considered to be candidates for corrective surgery because of the severity of their disease. Age varied from 3 to 32 years. 7 patients (15,5%) died. Recatheterization was performed in 12 children 5,6 +/- 4,1 years after surgery. Left ventricular pressures were decreased from 184,1 +/- 28,4 to 155,5 +/- 32,1 mm Hg, and the pressure gradients between left ventricle and the aorta fell from 101,2 +/- 19,7 to 29,1 +/- 23,1 mm Hg. The postoperative values varied between 0 and 80 mm Hg. Operative results are discussed in relation to the anatomical type malformation and the operative technique.


[EMCO for acute respiratory failure: clinical outcome and technique of aortic root perfusion (author's transl)]. A 15-year-old female was treated with ECMO for acute respiratory insufficiency after severe aspiration. During 81 hours perfusion in V-A-technique even distribution of the artificially oxygenated blood was achieved by supravalvular position of the aortic cannula, which had been advanced to this position with a Ducor-Angiographycatheter. Without any improvement of the lung disease the treatment was terminated after cerebral damage due to toxic edema became evident.


[Peripheral nerve injuries complicating extracranial vascular surgery (author's transl)]. Peripheral nerve injuries may complicate extracranial vascular surgery. Pareses of the recurrent and hypoglossal nerves are clinically important. The nervus laryngeus superior, the ramus marginalis mandibulae of the facial nerve and the brachial plexus may be involved. Horner's syndrom indicating damage of sympathetic fibers may also appear. Lesions of the glossopharyngeal, vagus and phrenic nerves are rather seldom.


[Pulmonary artery arrosion due to parietal endocarditis--a late complication of a haemodynamically ineffective VSD (author's transl)]. A case of late complication after operative correction of a valvular pulmonary stenosis is reported. Chronic pulmonary embolism secondary to bacterial endocarditis situated opposite to an uncorrected small ventricular septal defect in the right ventricle caused arrosion of the pulmonary artery and subsequent severe fatal bronchial hemorrhage. The relation between VSD and bacterial endocarditis and the surgical consequences are discussed.


Composition of acidic glycoconjugates (glycosaminoglycans and glycoprotein) in myometrium of rabbit uterus under estrogenic condition. Acidic glycoconjugates (glycosaminoglycans and glycoprotein) were obtained, from myometrium of ovariectomized rabbit under estrogenic condition, by pronase digestion, fractionation with cetylpyridinium chloride and Dowex I column chromatography, in succession. Composition of acidic glycoconjugates was determined enzymatically, employing Streptomyces hyaluronidase, chondroitinase AC II, chondroitinase ABC and crude heparinase. Each glycoconjugate was distributed in 3 approximately 8 fractions obtained by Dowex I column chromatography, indicating its charge and/or molecular heterogeneity. Acidic glycoconjugates consisted of hyaluronic acid (13.4%), chondroitin sulfates A plus C (39.4%), dermatan sulfate (24.6%), heparan sulfate (18.7%) and acidic glycoprotein (most probably sialoglycoprotein) (3.9%). Composition of acidic glycoconjugates in myometrium differed remarkably from that in whole uterus. Myometrium was abundant in chondroitin sulfate isomers (chondroitin sulfates A plus C plus dermatan sulfate), but lacked sulfated glycoprotein. The present results suggested that myometrium and endometrium of uterus may play quite different roles in reproduction.


Avoidance behavior in folate--deficient rats. The effects of folate deficiency in post-weanling male rats in an active avoidance learning test were studied. Ingestion of a folate-free diet for 3 weeks markedly decreased serum and erythrocyte folate concentrations but had only a slight effect on growth rate. The decrease in blood folates was correlated with an increase in the number of trials necessary to reach criterion in the learning test. There was no motor impairment since the mean escape latency was the same in control and folate-deficient animals. These results suggest that folic acid deficiency started at weaning could be responsible for learning impairment.


Intracranial saccular aneurysms--surgical results of 1,000 consecutive cases. The results of our surgical treatment of 1,000 patients with intracranial saccular aneurysm were analyzed with special consideration for age, site of aneurysm, preoperative condition and operative timing. The results on discharge were as follows: 543 cases, excellent; 186, good; 117, fair; 93, poor; and 61, dead. About three-fourths of the cases except for 23 cases of vertebrobasilar aneurysm showed either excellent or good result. The mortality rate became worse with aging. The results fairly correlated with the preoperative grades by Hunt and Hess (1968), but the cases of Grade Ia were unexpectedly worse. The timing of operation influenced the mortality rate; especially, the cases operated within 3 to 7 days following the last subarachnoid hemorrhage bore poor results. Follow-up studies revealed that excellent and good cases increased and poor cases decreased. The mortality rate for each year decreased annually to 2% in 1975. This improvement may be attributed to the advancement in the operative management with supplementary procedures and in the treatment for cerebral angiospasms and general condition.


Distribution of intracranial aneurysm.

Distribution of intracranial aneurysm. The 1,080 cases of intracranial saccular aneurysms, which were seen at our clinic during the period from June 1961 to September 1975, were subjected to the analysis on the location of the aneurysms, age distribution and sex incidence.


Changes in free amino acids of cerebrospinal fluid and plasma in various neurological diseases. By means of liquid chromatography we investigated free amino acids in cerebrospinal fluid (CSF) (161 subjects) and in plasma (138 subjects) in various neurological diseases and in controls. A general increase in CSF amino acids was found in Group C (samples exhibiting both pleocytosis and increasing CSF protein concentration) and in "spinal canal block" and "neuro-Behçet's syndrome". Also, some abnormalities were detected in these groups with regard to changes in CSF cells, protein or IgG%. In the case of "Guillain-Barré syndrome" we noted an increase in CSF alanine, glycine, methionine, arginine and the branched-chain group. In "multiple sclerosis" an increase was evident in CSF alanine, in plasma alanine and arginine, and in the plasma: CSF ratio of tyrosine. In patients of "motor neuron diseases (MND)" CSF glutamic acid, alanine, histidine and arginine all indicated an increase, along with the plasma: CSF ratio of tyrosine. In Group C and in "neuro-Behçet's syndrome" glycine, methionine and lysine were lowered in the plasma: CSF ratio. Also, the ratio of valine in the former and histidine in the latter indicated a decrease. These results can be supposed to reflect either biochemical abnormalities of plasma and/or the CNS, or changes in the transport systems of the blood-brain barrier.


Lymphocyte cytotoxicity to cultured rat liver cells in patients with chronic liver diseases. Microcytotoxicity assay revealed that peripheral bloof lymphocytes from patients with chronic active hepatitis were cytotoxic against cultured rat liver cells established by Coon in 1968. Non E-rosette forming cells were cytotoxic in 26 of 28 patients (93%) with chronic active hepatitis, whereas E-rosette forming cells were cytotoxic in only 1 of them. Either an addition of 10 microgram/well of aggregated IgG to non E-rosette forming cell culture or a preincubation of non E-rosette forming cells with 100 microgram/ml of aggregated IgG significantly reduced the cytotoxicity from 62.9 +/- 12.8% to 32.8 +/- 11.6% or to 25.6 +/- 11.3% (p less than 0.001). An addition of antihuman IgG/Fc also reduced the cytotoxicity to 37.4 +/- 17.2%. Significant cytotoxicity of positively selected EA-rosette forming cells was observed in 4 of 10 patients with chronic active hepatitis and that of positively selected EAC-rosette forming cells was demonstrated in 3, whereas in any of these patients neither non EA-rosette forming cells nor non EAC-rosette forming cells were cytotoxic. Cultured liver cells used in this study were seen to possess insoluble liver specific antigen on their surface membranes, but not soluble liver specific lipoprotein of Meyer zum Büschenfelde, by using an indirect immunofluorescence technique. These results suggested that effector cells are Fc-receptor-bearing cells and that the mechanism of the reaction may be mediated in an antibody-dependent cell-mediated reaction directed against insoluble liver specific membrane antigen(s) rather than soluble one.


Systemic candidiasis produced by oral Candida administration in mice. Systemic Candida infection from the gastrointestinal tract was examined in mice. Candida albicans was undetectable in the blood, lungs, spleen, liver or kidneys of mice 24 hr after oral Candida administration even under condition of severe damage to the host defence system, but became detectable in the liver and kidneys of mice when they received combined treatment of antibiotics, x-ray irradiation and dexamethasone 3 and 5 days after oral Candida administration.


Electron microscopic changes of keratohyalin granules during the freezing and thawing procedure. After 3-day-old rat skins were treated by freezing and thawing procedures, small empty spaces were formed both in keratohyalin granules and in the cytoplasm of the granular cells. When the skin specimens thus treated were further incubated in 50 mM Tris-HCl buffer, pH 8.6, for 15 min, keratohyalin granules were solubilized, leaving electron dense rims. Small electron dense or less dense particles were detaching from these rims. Cell membranes were also disrupted at various regions. Desmosomal structures in the stratum granulosum cells were all preserved.


The diagnostic accuracy of combined colposcopy, cytology, and target biopsy of carcinoma in situ of the uterine cervix. The results of cytology, colposcopy and target biopsy in 91 cases diagnosed by conization as uterine cervical carcinoma in situ and 39 cases diagnosed as microinvasive carcinoma were compared. Lesions limited to the ectocervix could be identified by colposcopy, and those identified as carcinoma in situ by cytology or target biopsy were all included in the group diagnosed as carcinoma in situ by conization. Among the 29 cases of carcinoma in situ limited to the ectocervix, 19 (66%) were similarly diagnosed by both cytology and target biopsy, allowing for us to avoid conization. For cases diagnosed as microinvasive carcinoma using target biopsy, conization must also be performed in order to determine the depth of invasion. Even in cases diagnosed as dysplasia or carcinoma in situ by target biopsy, when it is thought that the lesion may extend into the cervical canal or in cases where agreement with the cytological results is not found, conization is necessary.


Distribution of antibodies against swine and Hong Kong influenza viruses among pigs in 1977. The distribution of antibodies against swine and Hong Kong influenza viruses among hogs in Miyagi Prefecture was examined. Of 456 serum specimens collected since July 1977, 12 were found to be positive against swine influenza virus and 6 against Hong Kong influenza virus. Such serological results reveal that swine and Hong Kong influenza viruses coexist in Japanese hogs and suggest that swine influenza virus reappeared in mid-1977.


Interference with fluorimetric assay of catecholamine by labetalol. Influence of labetalol and 5-(1-hydroxy-2-aminoethyl)salicylamide (SA), a part of the chemical structure of labetalol, on the fluorimetric assay of catecholamine (CA) was studied. Both labetalol and SA have a weak but significant fluorescence which is indistinguishable from that of CA with peaks of excitation/emission wavelengths at 410/490. It is thus concluded that an apparent increase in urinary CA observed in patients receiving labetalol is caused by the contamination of labetalol and/or its metabolite, and that the evaluation of urinary CA in hypertensive patients must be done prior to the use of labetalol to avoid any confusion in diagnosis of pheochromocytoma.


Kinetic properties of galactose influx across the mucosal border of guinea pig ileum. By using everted sac preparations of guinea pig ileum, properties of galactose influx across the mucosal border were studied under various ionic conditions of the media. Mannitol was used as a marker of the extracellular space on the mucosal surface. In the absence of Na+ in the mucosal medium, the "galactose space" was almost the same as mannitol space, indicating the lack of uptake of galactose through the specific carrier mechanism. Galactose influx obeyed Michaelis-Menten kinetics at any Na+ concentration and it was also a Michaelis-Menten type function of Na+ concentration in the medium when examined at a constant galactose concentration. The observed kinetic properties were well explained on the basis of the kinetic model in which galactose was assumed to be transported only in the form of galactose-Na-carrier complex. The increase in Na+ influx associated with galactose influx was not significantly different from galactose influx. Na+ concentration of the serosal medium had no effect on galactose influx across the mucosal border. Choline and Tris, as well as mannitol, had no stimulating or inhibitory effect on galactose influx.


Effects of zirconium and aluminum salts on the alveolar macrophages. Alveolar macrophages from the rabbit were exposed in the culture medium to zirconium and aluminum salts. The specific activities of the lysosomal hydrolases, that is acid phosphatase, beta-N-acetylglucosaminidase and beta-glucuronidase, were measured in the medium, whole cell homogenate, mitochondrial fraction, and in the supernatant fraction. A highly significant increase of these hydrolases was observed in the mitochondrial fraction from cells exposed to zirconium and aluminum salts as compared with those from control cell cultures. However, release of these enzymes into the medium was not much. The phenomenon of macrophage phagocytosis was observed morphologically in the cell cultures exposed in vitro to these metal compounds.


Effect of urinary bladder distension on renal blood flow, blood pressure and plasma renin activity. The effects of urinary bladder distension on renal blood flow, blood pressure and plasma renin activity (PRA) were studied in 50 mongrel dogs anesthetized with chloralose. The dogs were divided into three groups. Group I was composed of dogs intact except for having undergone the surgical procedure for measurement and instillation of 0.9% saline to the bladders. Group II was composed of dogs whose bilateral ureters had been cut. Group III was composed of anephric dogs. Renal blood flow showed reduction during bladder distension in Group I and Group II. This reduction was produced not only by hydraulic mechanisms through the ureters during bladder distension, because the reduction was also observed in the dogs whose ureters had been cut. The rise in blood pressure and increase in PRA were observed in Group I and Group II, while the anephric dogs showed the rise in blood pressure during bladder distension despite the absence of PRA. Therefore, it appeared that the renin-angiotensin system did not directly relate to the rise in blood pressure during bladder distension.


Electron microscopic studies on pulmonary alveolar microlithiasis. The lung tissue of pulmonary alveolar microlithiasis was studied morphologically. Scanning electron microscopy revealed that the microliths were globular or irregular in shape or lobulated and in some loci were coalesced. The outer surface was granular or rough accompanied with deposits. The internal structures consisted of concentric laminar deposits. Frequently, two or more laminar structures were found on one cut surface. These findings may imply that the microliths grow by surface deposition and may coalesce during early stages of formation. In a high power view, granules were seen on the surface. Numerous scale-like structures and elongated electron-dense bodies inside the microliths were other peculiar findings of scanning and transmission electron microscopic studies, respectively. Elastosis in the alveolar interstitium and deposition of abundant glycogen granules in the bronchiolar epithelial cells were the notable findings of transmission electron microscopy.


Cineventriculographic analysis of the ventricular septal motion during stimulation of various pacemaker sites. By means of cineventriculography, contraction pattern of the ventricular septum was studied during electrical stimulation of the right atrium (RA), outflow tract (RVO) and apex (RVA) of the right ventricle and apex (LVA) and lateral wall (LVL) of the left ventricle. RA pacing produced a monophasic shortening of the septal hemiaxes after initial lengthening for about 40 msec from R wave of ECG. In contrast, ventricular stimulation near the septum (i.e. RVO, RVA and LVA) resulted in a biphasic and decreased contraction of the septal wall, in which an early preejection shortening was followed by a brief lengthening and second shortening. LVL pacing showed a monophasic and increased contraction of the septal wall. The biphasic motion of the septal wall was likely to be related to the abnormal mechanical contraction caused by the abnormal conduction sequence of ventricular depolarization. On the other hand, the lateral wall demonstrated a biphasic and decreased contraction during LVL pacing, and a monophasic and increased contraction during RVO, RVA and LVA pacing. Thus, the biphasic and diminished contraction at the site of electrical stimulation was compensated by the monophasic and forceful contraction of the contralateral wall. It is considered that the ventricular septum plays an important functional role in regulation of cardiac performance.


Effect of physical exercise on the activity of GOT isozyme in human plasma. Untrained healthy male volunteers were subjected to the study on the effects of exercise (bicycle ergometer, 920 kpm/min for 30 min) upon GOT isozyme (supernatant GOT, s-GOT and mitochondrial GOT, m-GOT) activities in plasma. Significant increases in the levels of both s-GOT and m-GOT activity were observed after the exercise (p less than 0.001). After 30 min of rest m-GOT activity almost returned to its preexercise value. However, s-GOT activity did not return to its preexercise activity. The changes in the activity of GOT isozyme after physical exercise are discussed.


Roentgeno-histological studies on serial alveolography. Using the lung obtained from a 22-year-old female at autopsy, roentgeno-histological studies were carried out on serial alveolography. The pulmonary lymphatics were shown to play an important role in the wash-out of the contrast media. The contrast media injected into the alveolus was gradually transferred on and into the alveolar wall and finally entered the subpleural space. Inflow of the contrast media was further noted into the portion probably representing the "juxta-alveolar lymphatic capillary" according to Lauweryns. Since local edema occurs artificially in serial alveolography, the functional aspects of fluid clearance may also be studied simultaneously unlike the conventional alveolography with its emphasis on morphological diagnosis.


Low incubation temperature favors detection of depolarization-induced coated vesicles in motor axon endings in frog nerve-muscle preparations. Depolarization-induced coated vesicles were detected in motor axon endings in frog nerve-muscle preparations stimulated at 10 degrees C but hardly in those activated at 25 degrees C.


The absorption by human volunteers of glutamic acid from monosodium glutamate and from a partial enzymic hydrolysate of casein. Peripheral plasma concentrations of glutamic and aspartic acids and alanine were measured after ingestion of monosodium glutamate or a pancreatic hydrolysate of casein by human volunteers. The doses of each material were such that they contained similar amounts of glutamic acid. Plasma glutamic acid concentrations rose promptly after the monosodium glutamate but mean peak concentrations were well below those likely to cause neurological damage. Plasma aspartic acid concentrations also rose after the monosodium glutamate but the behaviour of plasma alanine concentrations suggested that intestinal transamination of glutamic acid was insufficient to cause an appreciable rise in alanine concentration in the peripheral plasma. Significant increments in plasma glutamic acid concentrations did not occur after the pancreatic hydrolysate of casein and it is probable that competition for absorptive mechanisms by other amino acids, both free and peptide-bound, causes absorption of glutamic acid to be slower from mixtures of peptides and amino acids than from monosodium glutamate itself.


Toxicity of free fatty acids for cultured rat heart muscle and endothelioid cells. I. Saturated long-chain fatty acids. Capric (C10:0), lauric (C12:0), myristic (C14:0), palmitic (C16:0), stearic (C18:0) and arachidic (C20:0) acids were compared for their toxic effects upon cultured rat heart muscle and endothelioid cells. The free fatty acids (FFA) were found to albumin (6:1) and tested at 5 x 10(-5)M. Reduction of cell viability (51Cr release) and in situ mitochondrial and lysosomal labilization were used as indices of injury. Reduction in viability of both cell types was produced by palmitic, stearic or arachidic acids, but only after exposures of from 12 to 36 h. These FFA also produced needle-like cytoplasmic inclusions. Mitochondria and lysosomes were labilized after shorter exposures. Capric, lauric and myristic acids, were relatively non-toxic, and protected endothelioid cell lysosomes from labilization.


Toxicity of free fatty acids for cultured rat heart muscle and endothelioid cells. II. Unsaturated long-chain fatty acids. Oleic (C18:1), linoleic (C18:2), linolenic (C18:3) and arachidonic (C20:4) acids were compared for their toxic effects upon cultured rat heart muscle and endothelioid cells. The free fatty acids (FFA) were bound to albumin (6:1) and tested at concentrations from 5 x 10(-5)M to 5 x 10(-4)M. Reduction of cell viability (51Cr release) and in situ mitochondrial and lysosomal labilization were used as indices of injury. Oleic acids was non-toxic at all times and concentrations tested while linoleic acid increased cell death only in muscle cells after 32 h. Arachidonic acid, by contrast, demonstrated significant toxicity as early as 2 h while both linolenic and arachidonic acids produced major injury at longer durations. A detergent effect was excluded as the injury mechanism because of marked differences in the toxicities of the individual FFA. The similarity in the effects of linolenic and arachidonic acids would appear to exclude prostaglandins as responsible toxic products.


Effects of exposure to furfural vapour in hamsters simultaneously treated with benzo[alpha] pyrene or diethylnitrosamine. Syrian golden hamsters were exposed to 0 or 250/400 ppm furfural vapour, 7 h/day, 5 days/week for a period of 52 weeks. Simultaneously, a proportion of the animals were given either intratracheal inslillations of benzo [alpha] pyrene (BP) or subcutaneous injections of diethylnitrosamine (DENA). All treatments were stopped after 52 weeks. The study was terminated after 81 weeks. Furfural exposure caused yellowish discolouration of the animals' coat, irritation of the nasal mucosa, growth retardation, atrophy and downward growth of sensory cells of the olfactory epithelium, degenerative changes in Bowman's glands, and the occurrence of cyst-like structures in the lamina propria beneath the olfactory epithelium. There was no evidence of furfural possessing carcinogenic activity. In a previous instillation experiment with furfural, slight indications had been obtained of furfural potentiating the carcinogenic effect of BP, but in the present study the carcinogenic effect of BP or DENA on the respiratory tract did not appear to be influenced by furfural exposure. It was concluded that little if any, significance can be attached to furfural as a co-factor in respiratory tract carcinogenesis.


Tissue distribution and binding of radioactivity in mouse after intravenous administration of [14C]3-chloro-p-toluidine. The avicide [14C]3-chloro-p-toluidine (CPT) HCL, ring labeled, was injected intravenously to mice. The radioactivity associated with this compound was found to be unevenly distributed in different parts of the body. It leaves the plasma, as well as many tissues, with 2 elimination rate constants, the fast and the slow. The faster component of the [14C]CPT decay curve of the plasma was similar to the faster components of the decay curves of brain, lung, heart, intestine, testicle and kidney. The retention half-life of the radioactivity for the slower component of the decay curve varied a great deal from tissue to tissue, being shortest (14.55 h) in the intestine and longest (326 h) in the adipose tissue. Of the 10 tissues examined, a substantial amount of [14C]CPT radioactivity was found to be covalently bound only to liver, kidney, lung and RBC protein. There was no cause and effect relationship between the covalent binding of radioactivity and the tissue pathology, since no remarkable histopathological lesions were found in the liver and kidney of treated mice. The tissue retention of [14C]CPT radioactivity did not parrallel the covalent binding of the compound to tissue protein. The covalent binding of [14C]CPT radioactivity to RBC was suggestive of the conversion of the parent compound into a reactive metabolite responsible for the generation of methemoglobin in mice. The percent distribution of radioactivity in subcellular fractions of liver and kidney correlated with the amount of protein associated with subcellular fractions. The 102 000 g supernatant fraction of the liver contained the highest proportion of radioactivity, both in terms of absolute percent radioactivity as well as specific activity (dpm/mg of protein). This was also true for the 102 000 g supernatant fraction of the kidney. The majority of radioactivity in the 102 000 g supernatant fraction of liver appears to be bound to one or more polypeptide sized proteins with a mol. wt. of approx. 1000--2000.


[Toxicity by relay. III. Safety for the human consumer of the use of Carbadox, a feed additive for swine, as estimated by a 7 years relay toxicity on dogs]. To check the possible toxicity risks of the meat from swine fed with a residue producing feed additive: Carbadox, a new methodology was used. It is the "Relay Toxicity". Swine were fed with a high dose of the additive and sacrificed without any withdrawal. In such conditions meat contains a high level of residues. The frozen meat was given daily--after thawing--at 100 g or 200 g/dog to 12 beagle dogs, 6 females and 6 males, sacrificed when 87.5 months old (85 months on experiment). On these animals, no anomaly was found: on weight gain and health; on fertility and reproductive performances; on hematology and biochemical values of blood and urine; and after careful macroscopic or microscopic examinations of the animals at safrice. We were able to obtain a safety factor above 9000 when Carbadox is used at the maximum level approved 50 ppm, and the withdrawal 4 weeks before slaughtering. To conclude, the absence of anomaly allows us to confirm the safety for the human consumer when Carbadox is used as a feed additive for swine.


Di(4-aminophenyl)-methane (MDA): 4-7 year dog feeding study. 9 pure bred female beagles ingested purified or crude MDA (in 70 mg doses on 3 days of the week) over periods ranging from 3 years, 11 months to 7 years, 2 months. Total quantities of MDA ingested ranged from 39.98 g to 66.92 g/dog, or from approx. 4.0 to 6.26 g/kg body wt. Purified and crude MDA in the doses administered produced similar effects: (a)occasional loss of body weight followed by rather prompt recovery while treatment was interrupted; (b) no specific effect on blood sugar, BUN, creatinine, uric acid, total protein, albumin and a questionable effect on alkaline phosphatase activity; (c) from moderate to severe gross and micropathological changes in the liver, less severe effects in the kidneys and spleen, and occassionally gross or micropathological changes in other organs. Purified and crude MDA did not produce tumors of the urinary bladder or liver.


Short-term toxicity study of Chocolate Brown HT in pigs. Chocolate Brown HT was given in the diet to groups of 3 male and 3 female pigs at dose levels of 0 (control), 5, 20 or 100 mg/kg/day for 13 weeks. No adverse effects were seen on body weight gain, urine composition of the incidence of histopathological lesions. The haemoglobin levels in all 3 treatment groups of male pigs at week 13 were significantly below the control values, but this effect was not considered to be attributable to treatment with Chocolate Brown HT. The no-untoward-effect level in this study was at least 100 mg/kg/day.


Effect of methylmercury on some constituents of serum and urine. To evaluate some of the early effects of methymercury chloride (MMC) male rats were given 10, 20 or 30 mg MMC/kg intraperitoneally. Urine was analysed for vanilmandelic acid (VMA), leucine aminopeptidase (LAP), alkaline phosphatase (AP), and creatinine, blood for glucose-6-phosphatase (G-6-P) and glucose, serum for glutamate-oxalate-transaminase (GOT) and urea. Except for LAP and AP excretion there is no effect of MMC on the parameters investigated. However, the effects on these 2 renal enzymes are to variable to permit their use as a test for MMC toxicity.


[Therapy and prognosis of testicular tumors: the seminoma, results from radiation therapy in 100 patients (author's transl)]. Hundred patients with seminoma were irradiated in our clinic between 1963 and 1975. The 5-year survival rate corresponds to the rate of freedom from disease. It amounts to 97% for Stage I, 84% for Stage II, 55% for Stage III, O for Stage IV, and to 85% for all stages. These results are obtained by means of consequent radiation therapy. It is not cleared up wether general prophylactic irradiation improves the prognosis of mediastinal and supraclavicular affections. No complications may be expected on account of therapeutic doses, as the sensitivity to radiation is high. It is possible, on these grounds, in generalized stages, to take into consideration the total-body irradiation with low doses as an alternative to chemotherapy.


[Therapy and prognosis of testicular tumors: the teratocarcinoma, results from 52 patients (author's transl)]. In this retrospective study, the course of the disease was investigated in 52 patients having been irradiated because of malignant teratoma between 1963 and 1975. The patients were ranged as follows: four cases Stage I, thirty cases Stage II, six cases Stage III, twelve cases Stage IV. All histological preparations were graded once more, using the classification of Pugh and Collins. The 5-year survival recovery rates amounted to 100% in Stage I, to 64% in Stage II, to zero in Stage III and IV, and to 47% for all stages. A remarkable difference of the recovery rates in relation to histological findings was observed: MTIA Stage II=83%, all stages=40%; MTIB Stage II=57%, all stages=33%.


[Results of radiation therapy of tonsillar cancer in 161 patients treated between 1950 and 1976 (author's transl)]. 161 cases with cancer of the tonsil from 1950 to 1976 are reported. Cure rates in early cases after radiotherapy are about 60%, cure rate in all patients is 26%. Analysis of radiation dose and effect demonstrates, that doses about 1950-2000 ret are necessary for optimal results in cases, in which radiotherapy is planned as sole treatment. Importance of optimal simulator technique, head fixation and verification films is stressed. Using the own results and published data, the indications for radiotherapy and surgery of tonsillar cancer are discussed. In early cases, radiotherapy alone should result in a cure rate about 80%. In all the patients, the cure rate should amount to 40%.


[Generic symptoms of Hodgkin's disease in relation to other prognostic criteries (author's transl)]. In 1967-1973, 74 patients with histologic classified Hodgkin's disease were treated in Marburg. We proved the incidence of the most important prognostic criteries: stage, histologic type and clinical symptoms. These criteries are evaluated as equally significant and independent. The B-symptoms, fever, weight loss and night sweats we found in 24 patients, 18 (75%) of them were in stage IV. In the remaining 6 patients in stage II and III, the B-symptoms were followed by relapse or generalisation. We think that the good correlation to the stage means, that clinical symptoms as prognostic signs are not independent.