Control of membrane morphogenesis in bacteriophage PM2. The regulation of membrane formation in bacteriophage PM2 serves as a simple model for changes in membrane structure in eukaryotic cells. Prior to Pseudomonas host lysis, wild-type virions mature to an icosahedral morphology at the inner face of the cytoplasmic membrane. The preliminary characterization of two temperature-sensitive mutants of PM2 is described. In cells infected at the restrictive temperature with ts 1, an abundance of "empty" virus-size membrane vesicles are seen. Synthesis of DNA is also reduced in ts 1 infected cells. The preponderance of vesicles is not seen in cells infected with wild-type virus or with ts 1 at the permissive temperature. The "empty" appearance of the viral membranes suggests that viral DNA is not encapsulated. The major viral capsid protein (MW 26,000) is located just outside the viral membrane and normally sidiments with host and virus membranes. This protein made by mutant ts 5 does not pellet with these membranes; instead, large amounts of capsid protein can be precipitated from the supernatant with TCA. Compared to cells infected with wild type virus, cells infected with ts 5 at the restrictive temperature produced inside the cell an abundance of virus-size membrane vesicles. Taken together, these results with viral mutants suggest that formation of a viral membrane of the proper size does not require a DNA core around which to form, or an outer scaffolding of coat protein against which to form a spherical bilayer.


Improved liquid cholesterol ester crystal thermography of the breast. The infrated detection apparatus used in breast thermography is relatively costly and therefore is not widely available to less populated areas in the country. The use of liquid cholesterol crystals, applied to the breast (applied over a water-base black dye) has already been described in the literature as an effective substitute for infrared instrument thermography. This method, however, has been hampered by the time and troublesome effort necessary for removal of the substances upon completion of the study. The object of this study was to devise a feasible method of cutaneous breast thermography using liquid cholesterol esters, as in prior studies, but by applying them to an easily removable black base. As a result the length of the examination has been shortened, and patients have found the examination to be aesthetically more acceptable. With this improved method, liquid crystal thermography of the breast (and other areas) should become more widely applicable.


Radiation-induced peritoneal mesothelioma. A case report of a patient who developed peritoneal mesothelioma 7 years after internal and external irradiation for carcinoma of the cervix is reported. No previous reports of induction of this tumor by irradiation have been found. The subject of radiation-induced tumors and peritoneal mesothelioma is briefly discussed.


Adenocarcinoma-associated antigen: enhancement of tumor growth with serum from animals bearing adenocarcinoma. Why do tumors continue to grow in the presence of cell-mediated immune reactions? When inoculated subcutaneously, 10(5) viable spontaneous mammary adenocarcinoma cells produced solid tumors that progressively proliferated and eventually killed all the recipient mice. During the first 10 days after inoculation, the mice developed antibody titers, and the serum acquired toxic activity against the tumor cells. As the tumor gained in size these two activities ceased. Serum of normal mice had no effect on the tumor; the serum of mice immunized with an adenocarcinoma-associated antigen (a glycoprotein) inhibited growth, but that of mice with progressive tumors enhanced proliferation of the tumors.


The influence of facial-nerve sacrifice in surgery of malignant parotid tumors. Malignant parotid tumors in 224 patients were dealth with surgically at the Mayo Clinic between 1940 and 1969. The clinical histories, including follow-up of 5 years or more in every case, were reviewed with particular attention to sacrifice of the facial nerve in conjunction with the excision of tumor. This was done in 65 cases. High-grade malignancy necessitated nerve sacrifice; other frequent indications were preoperative facial-nerve paralysis, pain, and rapid growth of the tumor. Over the 30-year review period, the trend was toward more radical surgery, often including nerve sacrifice, and away from local excision and radiotherapy. Nerve grafting or anastomosis of a sacrificed nerve was seldom performed in an attempt to lessen the cosmetic defect of facial paralysis. Later reconstructive procedures are favored.


The lip-splitting approach to resection of oropharyngeal cancer. Adequate margins are of primary importance in a composite resection of oropharyngeal carcinomas. Secondary considerations include the functional status and cosmetic result of the patient after the operation. A series of 6 patients demonstrate that, in selected cases, a lip-splitting approach to increase exposure while ensuring adequate margins may be undertaken without undue fear of functional impairment or cosmetic deformity. The ultimate result will depend on proper placement of the incisions and careful reapproximation of tissue.


Screening random asymptomatic women under 50 by annual mammographies: does it make sense? The effectiveness of screening random asymptomatic women for breast cancer using mammography has been analyzed using a new mathematical-computer technology. The technology is based on a general mathematical theory of screening recently developed by Blumenson combined with a mathematical model for breast cancer developed by Blumenson and Bross over the past decade. The technology makes it relatively simple to try alternative strategies for age at onset of screening, screening interval, etc. and to calculate the relative effectiveness of the strategy. When the benefits of alternative strategies with periodic screening beginning at different ages were compared with the increasing risk of iatrogenic disease from multiple exposure to low levels of radiation, it was concluded that screening of asymptomatic women should begin no earlier than age 50.


Combination chemotherapy in the treatment of advanced breast cancer. Seventy-two women with metastatic breast cancer were treated with multiple-agent chemotherapy. Fifty women were treated with 5 drugs in combination: 5-FU, methotrexate, vincristine, cytoxan, and prednisone; 22 were treated with the combination of 3 drugs: 5-fu, cytoxan, and prednisone. In 14 patients receiving 5 drugs and in 22 receiving 3 drugs, the multiple chemotherapy was the primary palliative treatment of extensive visceral metastases unsuitable for adrenalectomy. Results were similar with 6 responders in 14 (0.43) receiving 5 drugs, and 10 responders in 22 (0.45) receiving 3 drugs. The remaining 36 patients who were given 5-drug therapy all had previous adrenalectomy, and there were 16 responders (0.44). Toxicities from 3-drug treatment were substantially less severe than those from the 5-drug combination therapy. Whereas treatment-related death occurred in 6 of 50 patients receiving the 5-drug combination, no such incidence occurred in those receiving 3-drug combination therapy.


Kidney total fatty acids in renal cell carcinoma and infection. Lipids extracted from the kidneys of adults with renal cell carcinoma or infection after careful dissection of lesions and from organs showing minimal alterations were saponified and the fatty acids converted to the methyl esters. Gas chromatographic criteria were applied to the esters as such and to hydrogenated aliquots, and the relative percentages of the component acids were ascertained. The various lipid classes were well represented in the total fatty acid mixtures. The unsaturated acids ranged higher than the saturated homologs. Comparisons of the fatty acids were carried out on the basis of age, sex, kidney position, mode of ascquisition (surgery and autopsy), and pathology. Several small but statistically significant differences were discerned according to the categories but with few exceptions, these involved acids occurring at low levels and with wide variance.


Breast cancer arising in surgical scars. Twelve women who developed breast cancer at the site of old surgical scars in the breast are presented. Six had had former breast biopsies, 3 drainage of breast abscesses, and 3 developed breast cancer in old thoracotomy scars transversing the breast. The combination of trauma as an oncogen and scar tissue as a functional and immunological locus minoris resistentia seems to play a major role in the development of breast cancer in this group of patients. The associaton of breast cancer, scar, and trauma would not be coincidental. Increased attention drawn to this entity may lead to a rise in the number of cases diagnosed among patients with breast scars after biopsies, abscesses, trauma, or foreign body implantation.


Serum ribonuclease in patients with lung carcinoma. Fifty-one previously untreated cases of lung carcinoma and 7 normal healthy controls were evaluated with respect to serum ribonuclease (S-RNase) levels. Cellular immunity was tested in 22 of these 51 cases by leukocyte migration inhibition test (MIT) using extract of culture cell line of lung carcinoma. S-RNase levels in lung carcinomas were significantly elevated. There appeared to be no difference in S-RNase levels by histological classification. More striking was high S-RNase level in disseminated versus localized cases. MIT results indicated impairment of cellular immunity in those cases of more elevated S-RNase. S-RNase may be implicated in blocking phenomenon associated with neoplastic disease.


Plasma CEA, tumor CEA, and tumor histology. Carcinoembryonic antigen (CEA) has been thought to be a diagnostic and prognostic indicator of colorectal cancer. Initial descriptions of CEA as a tumor specific antigen suggests a relationship between tumor CEA and circulating plasma CEA. To define the relationship between CEA and colorectal carcinoma, we have studied the CEA concentration of preoperative plasma, tumor tissue, and normal bowel distant from tumor in 35 patients who had clinically curative resections. Tumor histology was evaluated for Dukes class, histologic grade, necrosis, and vessel invasion. Regression analysis yielded no evidence of correlation between tumor CEA and plasma CEA. No correlation could be shown between tumor concentration of CEA and the histological parameters previously noted. CEA was found in all specimens of normal bowel. Furthermore, in 34% of the cases studied, the tumor CEA was not significantly higher than in normal bowel. No significant difference was shown when histopathological findings were compared to normal and abnormal plasma CEA values. These findings suggest the following conclusions: CEA is not tumor specific. Increased levels of CEA in tumor tissue are not a constant finding in colorectal carcinoma. Tumor levels of CEA do not appear to correlate with histologic degree of tumor differentiation. Elevated plasma levels of CEA do not necessarily connote elevated tumor tissue levels of CEA, and conversely, normal plasma levels of CEA do not necessarily mean low levels of tumor CEA.


Transsphenoidal hypophysectomy: a laboratory approach and commentary. A laboratory technique for learning and practicing the transsphenoidal approach to hypophysectomy is described. The procedure utilizes a sphenoid block with the sella turcica at its center taken from a cadaver skull. The laboratory approach stimulates the operative technique, including the use of standard instruments designed for transsphenoidal hypophysectomy. Commentary on the historical background and applications of the transsphenoidal approach to the sella turcica is presented.


Patterns of serial CEA assays and their clinical use in management of colorectal cancer. Through persistent clinical research efforts, the CEA test has developed into a useful although complex disease monitor for colorectal cancer. Although improved or prolonged survival from its use has not been demonstrated, CEA monitoring may allow more knowledgeable patient management. Several reports indicate that postoperative serial CEA assays may identify patients with early recurrence, especially when assays are done frequently. Patients with elevated pretreatment CEA levels usually showed progressively rising titers before other objective evidence of recurrence was apparent. A progressively rising CEA titer correlated well with recurrent cancer, but a normal CEA could not be used as proof of its absence. Persistently elevated CEA titers post-treatment was caused either by persistent disease or by nontumor-related factors. The CEA assay was not a substitute for clinical follow-up but was an adjunct in the diagnosis of eary recurrence. Patients with elevated CEA levels caused by localized disease treated by radiation therapy demonstrated a marked fall in serial CEA levels if all CEA-producing tumor was localized within the radiation portal. The use of pretreatment CEA values plus the pattern of CEA reponse to irradiation may help in the selection of fulguration versus abdominoperineal resection as primary treatment for rectal cancer. Persistently low serial CEA titers after irradiation therapy correlated with disease control. The use of frequent serial CEA assays in patients treated with chemotherapy compared well with other parameters as a monitor of disease progression or regression. When used with other clinical parameters, serial CEA trends appeared to be a useful adjunct in assessing the effectiveness of chemotherapy. A fall in circulating CEA or the stabilization of a rising titer after starting chemotherapy usually indicated an effective regimen, whereas a rising CEA titer may signal may signal the need to initiate or to change chemotherapy.


Enhancement of hepatic and renal tumorigenesis with thyroidectomized NZR/Gd rats treated with dimethylnitrosamine. Endocrine modulation of DMN carcinogenesis was studied in NZR/Gd rats preconditioned by starving 48 hr and then injected i.p. once with 20 mg DMN/kg. Intact rats developed kidney tumors (44% TBA), most of tubular epithelial type resembling human tumors rather than mesenchymal. Thyroidectomy (Tx) 45 days before DMN significantly enhanced DMN carcinogenesis, renal carcinoma incidence increasing to 69%. Renal carcinomas showed more signs of malignancy in Tx rats. Other neoplastic responses useful for further studies including tumors in nasal epithelium (13%), liver (18%, increased to 59% in Tx rats), and lung (40%): these tumors were rare or not previously reported in single-dose experiments in other rat strains. A sex difference in lung tumor incidence (male 70%, female 16%) was statistically significant and thyroidectomy reduced the sex-differential (to 54% and 39% respectively). The increased incidence of kidney and liver tumors could be due to altered metabolism of DMN in tissues of Tx rats.


Efforts in cancer diagnosis: national task forces--large bowel cancer. Current information from the National Large Bowel Cancer Project and other sources is given concerning new leads and avenues of research that may be used in early diagnosis or possibly in monitoring therapy. The search for biological markers has developed in two general directions: (1) to identify by genetic studies patients with a high probability of developing cancer who will provide insight into biochemical changes as premalignant lesions develop into frankly developed cancer, and (2) to fine differences between tissue and body fluid constituents in normal subjects and patients with cancer. Screening for colon cancer is discussed with a selective diagnostic approach and with emphasis on this approach in early diagnosis of asymptomatic high risk patients.


Management of concomitant occlusive disease of the carotid and coronary arteries. With the advent of direct coronary artery revascularization, the high mortality rate from cardiac disease associated with carotid endarterectomy can be favorably altered by simultaneous or staged revascularization for combined lesions. The choice for combined or sequential procedures is determined by the severity of the disease both clinically and anatomically in each system. Review of 32 patients with both severe coronary and carotid occlusive disease established that selective surgical intervention has been successful, with no deaths and only minimal morbidity. Simultaneous revascularization was carried out in 8 patients with preinfarctional angina, significant left main lesion or triple vessel disease producing a functional lesion of the left main coronary artery, and tight carotid lesion. Staged operations were performed in the remaining 24 patients. Priority of staging was determined by the extent of disease in each system.


Use of the augmented ejection fraction to select patients with left ventricular dysfunction for coronary revascularization. Thirty-three patients with angina (31 men and 2 women, age 33 to 68 years, 52), as well as signs and symptoms of severe left ventricular dysfunction, were evaluated for coronary revascularization surgery. All had multiple vessel coronary artery disease and at least one prior myocardial infarction. Cardiac catheterization demonstrated abnormally elevated left ventricular end-diastolic pressure (LUEDP), low cardiac output, and depressed resting biplane systolic ejection fraction (SEF) ranging from 18 to 45 per cent (31 per cent). To evaluate potential myocardial function, a premature ventricular contraction was introduced during the ventriculogram and the SEF of the postextrasystolic potentiated (PESP) beat calculated and compared to a sinus beat SEF. Patients were separated into two groups based on the increase in SEF: those with greater than 0.10 augmentation (24 patients) and those with less than 0.10 augmentation (9 patients). Coronary revascularization was carried out with at least two bypass grafts in each patient. The operative mortality in those with more than 0.1 SEF augmentation was 9 per cent (2/24), late mortality rate 5 per cent (1/22), and 20/21 became Class I or II in the follow-up period of 11 to 57 months (25). Operative mortality in those with SEF augmentation of less than 0.1 3/9 33 per cent), late mortality rate 1/6, and only 1/5 achieved Class 1 status during the follow-up period of 10 to 35 months (22) postoperatively. These data suggest that significant augmentation of SEF by a premature ventricular contraction is a simple and useful indicator to aid in selection of patients with left ventricular dysfunction for coronary revascularization.


The "bad" left ventricle. Results of coronary surgery and effect on late survival. Between 1968 and 1971, 252 patients with severe ventricular malfunction underwent revascularization surgery. By means of single-plane ventriculography, the ventricle was divided into six segments, three anteriorly and three inferiorly, and ejection fractions were calculated. Patients were classified into four groups according to these observations. Results were assessed in regard to relief of angina, graft patency status, surgical mortality rate, and survival as determined by actuarial life-table analysis. These results were then compared to over-all medical and surgical experience contained in the Milwaukee Cardiovascular Data Registry as well as to other reported series of medical treatment for similar degrees of coronary artery disease and impairment of left ventricular function. Comparison between the surgical and medical series suggests improved survival and improved quality of life in the surgically treated patients. Thus many patients with severe ventricular malfunction, especially if associated with angina, can be reasonably considered candidates for surgery.


Experience with fifty repeat procedures for myocardial revascularization. Fifty coronary reoperations were performed in 49 patients. The reasons for the operations were occluded or stenotic grafts in 23 patients, an inadequate first operation in 13, progression of coronary atherosclerosis in 3, and combinations of these reasons in 11. Mediastinal adhesions made the operations difficult and produced hazards. Six patients died from the operation. Seven surgical mishaps occurred, including damage to five functioning grafts from the previous operation and laceration of two ventricles. Nine patients had less than complete operations because angiographically demonstrated targets could not be found. Repeat angiography was performed on 9 of the surviving patients. Ten of the 14 new or revised grafts were found to be functioning. Although a repeat operation is more difficult technically and carries additional risks as compared with a first operation, the indications are thought to be the same for both first and secondary revascularization procedures. The increased risks of the repeat operations are compelling arguments to strive for complete revascularization at an initial operation in order to avoid the necessity of the second one.


Congenital malformations of the mitral valve in children. Pathology and surgical treatment. A systematic study of congenital mitral valve malformations was undertaken on a surgical basis in an attempt to develop techniques of valvular reconstruction adapted to the various lesions. Forty-seven children between the ages of 4 months and 12 years (average 6 years, 4 months) have been operated upon between January, 1970, and March, 1976. Valvular lesions were classified into four group: Group I, mitral insufficiency owing to valvular lesions: Group II mitral insufficiency with subvalvular lesions; Group III, mitral insufficiency and stenosis; Group IV, stenosis. Associated lesions (ventricular or atrial septal defects, coarctation, or aortic valve stenosis) were present in 31 patients (65 per cent) and were corrected during the same operation. Valve reconsruction was possible in 38 patients whereas valve replacement was necessary in 9 patients. In the valve repair group there were three operative deaths (8 per cent), no late deaths, one reoperation for residual ventricular septal defect, and one myocardial infarction. In the valve replacement group of 9 patients, there were three operative deaths, three late deaths, and one case of repeated embolization. Thirty-one of 38 patients in the valve repair group were classified into Functional Class I after the operation (86 per cent), 2 were in Class II, and one in Class III. Minimal or moderate regurgitation and cardiomegaly persisted in the majority of the patients. Pulmonary artery pressure significantly decreased, however, as demonstrated by postoperative catheterization in 17 patients.


Individual responses to heparinization for extracorporeal circulation. It has been proposed that wide variations in individual response to heparin lead to deficiencies in popular heparinization protocols for extracorporeal circulation (ECC). Thirty-nine patients undergoing open cardiac operations with ECC were anticoagulated with the heparinization protocol in use at St. Thomas' Hospital. The coagulation state was monitored with the blood activated recalcification time (BART) test. Wide variations in heparin dose-response and heparin activity-decay curves were observed. No patient was underheparinized, but many had markedly prolonged BART's. The total dose of heparin declined because BART monitoring allowed elimination of incremental heparin doses up to 180 minutes of ECC. Adequate reversal with protamine was achieved in all patients regardless of response to herparin. Alternative approaches for heparinization for ECC can be developed with the aid of rapid tests of the intraoperative coagulation state.


Myocardial protection during bypass and arrest. A possible hazard with lactate-containing infusates. Severe myocardial tissue damage may results from the use of prolonged ischemic arrest during cardiac surgery. A number of experimental and clinical studies have been reported in which various protective agents have been infused into the coronary vessels before the onset of ischemia in an attempt to reduce or delay this damage. Although these agents are undoubtedly able to protect the ischemic myocardium, their efficacy may be considerably reduced or enhanced by the composition of the medium in which these agents are dissolved. In experiments with a rat heart model of bypass and ischemic arrest, we found that lactate-based media are detrimental to optimal tissue protection.


Prolonged epicardial mapping in myocardial infarction: the effects of propranolol and intra-aortic balloon pumping following coronary artery occlusion. A methods of prolonged epicardial surface mapping of myocardial infarction by serial epicardial ECG's is described. The progression of infarction following coronary artery ligation in dogs was monitored over a 4 day period and the early and late changes in the configuration of the epicardial ECG's associated with the underlying myocardial injury were defined. The determination of the infarct size by surface mapping in vivo correlated accurately with the final infarct size determined by dehydrogenase staining in vitro. Treatment with propranolol resulted in a significant reduction in the infarct size. Treatment with intra-aortic balloon pumping did not alter the size of the myocardial infarction induced in this experimental model.


Late follow-up of ball-valve prostheses in the descending thoracic aorta. Clincal and hemodynamic observations are reported in a group of five patients with free aortic regurgitation treated with insertion of a ball valve prosthesis in the descending aorta. Long-term follow-up ranging from 13 to 23 years illustrates the durability and biocompatibility of the valve and the validity of the concept that a moving prosthesis can function for indefinitely long periods of time. The prolonged survival of these patients at a normal level of activity without congestive failure is strong evidence of the efficacy of the prosthesis even though it did not entirely control all of the aortic insufficiency. All patients showed remarkable improvement of their symptoms from 11 to 21 years after surgery. Four of them have required complete correction of the aortic insufficiency with one postoperative death due to low output syndrome. The valves which have remained in place after insertion of a subcoronary valve are functioning well for 3 to 6 years. There was no evidence of hemolysis, valve malfunction, ball variance, or thrombbosis in any of these patients. The evolution of the technique made it possible to minimize complications which, it should be pointed out, were usually associated with faulty methods of insertion. These patients would appear to represent the longest period of insertion of any valvular prosthesis.


Ebstein's malformation. Surgical experience at the Mayo Clinic. At the Mayo Clinic, 13 patients with Ebstein's malformation have undergone surgical repair since 1963. Their ages ranged from 18 months to 51 years (median 13 years). Ten patients were in Functional Class III or IV. Marked cardiomegaly, cyanosis, paradoxic emboli, and dysrhythmias secondary to Wolff-Parkinson-White syndrome were indications for operation in the remaining 3 patients. A wide range of anatomic variations was encountered. All 5 patients who underwent tricuspid annuloplasty with plication of the atrialized segment of the right ventricle survived operation. Of 5 patients who underwent prosthetic valve replacement, only one survived. Other procedures included atrial septal defect closure alone in one patient, atrial septal defect closure and relief of pulmonary stenosis in one patient, and tricuspid annuloplasty alone in one patient. One patient had concomitant mapping and division of anomalous conduction pathways. Functional classification improved in 8 of 10 operative survivors. There were two late sudden deaths; both patients had had preoperative dysrhythmias. The data suggest that results are improved when the atrialized segment of the right ventricle is dealt with during repair of the tricuspid valve. A combined ventricular plication and tricuspid annuloplasty yielded better early and late results than did valve replacement.


Congenitally cleft atrioventricular valves associated with secundum atrial septal defects. Three patients with the rare association of secundum ASD and congenital clefts of A-V valves are reported. These three patients illustrate the predictive valve of vectoracardiographic analysis in precisely determining the anatomic location of the valvular pathology. The embryologic origins of the lesion are briefly discussed. A review of the literature supports the use of vector analysis in the evaluation of the patients with this type of heart disease.


Prolonged survival following cerebral metastasis from pulmonary cancer. A case is reported of prolonged survival after pneumonectomy for anaplastic carcinoma of the left lung and excision of metastatic anaplastic carcinoma of the brain. The patient has survived for 8 years, 6 months after the lung surgery and 7 years after the brain surgery.


Bypass surgery for vascular disease of the carotid system. A series of 58 operations on 56 patients, in whom a branch of the superficial temporal artery was anastomosed to a branch of the middle cerebral artery (STA-MCA bypass or Yasargil procedure), is reviewed. These operations were performed chiefly for occlussions or for inaccessible stenotic lesions of the internal carotid or middle cerebral arteries. Patency in eight patients operated on from April 1971 through November 1973 was low (25%). Patency in patients operated on since July 1974 has been high (95%). There have been no deaths and no major ischemic strokes attributable to the surgery. The rationale for this procedure is considered in relationship to the anatomy and physiology of the cerebral circulation and the pathogenesis of syndromes of cerebral ischemia. The operation appears to have a low morbidity in good-risk patients. The role of this operation in managing common manifestations of cerebral vascular disease such as focal transient cerebral ischemic attacks (TIAs) and amaurosis fugax, although not fully established, appears encouraging. The procedure seems useful for orthostatic cerebral ischemia caused by multiple occlusions of major extracranial (and intracranial) vessels and, occasionally, for progressing strokes related to internal carotid artery occlusion, both of which are relatively uncommon manifestations of cerebral vascular occlusive disease. It may have application in the rare "slow stroke." The procedure is probably of limited value, if any, in the management of large completed infarcts but may be indicated in selected patients with small infarctions who have preserved most of their cerebral function and who have had evidence of subsequent focal ischemic events. The procedure is useful for bypassing giant aneurysms or basofrontal tumors invading major vessels. It may have a role in the management of fibromuscular disease of the internal carotid artery.


Endomyocardiopathy with eosinophilia.

Endomyocardiopathy with eosinophilia. Five patients were seen at the Mayo Clinic over an 8-year period with the following complex of clinical and morphologic features; striking eosinophilia, cardiomyopathy, hepatosplenomegaly, and either a rapidly fatal or a prolonged, debilitating illness. In recent years, controversy has raged over the precise designation of this syndrome, with proposals ranging from eosinophilic leukemia to hypereosinophilic syndromes. To focus on the major target organ of the disease, we have favored the term endomyocardiopathy with eosinophilia. Experience with these five patients showed that (1) eosinophilia can persist for many years before symptoms appear; (2) progressive restrictive cardiac disease was the major cause of death and debility; (3) osmiophilic cytoplasmic inclusions are present in eosinophils of these patients and also in cells from other patients with marked eosinophilia; and (4) echocardiography may prove to be a useful noninvasive tool to diagnose and follow the progress of cardiac involvement. Although none of these patients was thought to have leukemia, intensive therapy with steroids or cytotoxic agents, or both, is considered necessary to control the progression of the disease.


Autologous blood transfusion.

Autologous blood transfusion. Autologous blood transfusion is a procedure in which blood is removed from a donor and returned to his circulation at some later time. Autologous transfusion can be performed in three ways: (1) preoperative blood collection, storage, and retransfusion during surgery; (2) immediate preoperative phlebotomy with subsequent artificial hemodilution and later return of the phlebotomized blood; and (3) intraoperative blood salvage and retransfusion. All three methods of autologous transfusion offer a potentially superior method of blood transfusion which eliminates many of the problems and complications associated with the banking and administration of homologous donor blood.


Development of radioimmunoassays for prednisone and prednisolone. Application to studies of hepatic metabolism of prednisone. Radioimmunoassays for measuring prednisone and prednisolone (delta1 corticosteroids) in serum have been developed. By using 6,7-3H-delta1 corticosteroids as tracer, rabbit antibodies against delta1 corticosteroid-21-hemisuccinate in bovine serum albumin, and ammonium sulfate precipitation, the assays detected less than 0.8 ng/ml of delta1 corticosteroid and interassay coefficients of variation were less than 8.5 %. The specificity of antibodies, tested against all drug metabolites and major endogenous steroids, showed that only 21-glucuronic acid esters of delta1 corticosteroids had cross-reactivity of possible clinical importance. Assays were validated by measuring levels in samples of fastingstate sera with or without adding known amounts of prednisolone. Measurements of serum concentrations of both prednisone and prednisolone in normal dogs and in those with hepatic vascular exclusion were made after intravenous administration of prednisone. Although high levels of prednisolone appeared rapidly in normal dogs, only slight amounts were measured in dogs with hepatic vascular exclusion, which emphasized the importance of the liver in the conversion of prednisone to prednisolone, its active metabolite.


Hepatic lipids in Reye-Johnson syndrome and in acute encephalopathy without fatty liver. The relationship between Reye-Johnson syndrome and acute encephalopathy without fatty liver was investigated by comparing the lipid composition of liver samples obtained from five patients with Reye-Johnson syndrome, two patients with acute encephalopathy, and five controls. The mean total hepatic triglyceride concentration was increased nearly sevenfold in Reye-Johnson syndrome and slightly decreased in acute encephalopathy when compared with the mean control value. The mean total hepatic free fatty acid concentration was increased nearly threefold in acute encephalopathy when compared with the mean value in Reye-Johnson syndrome. Total phospholipid content was decreased in the liver in Reye-Johnson syndrome, and this difference was caused mainly by a diminution of the hepatic lecithin fraction. The ratio of palmitic acid to oleic acid and hepatic free fatty acids was 2.5 in Reye-Johnson syndrome, 0.7 in acute encephalopathy, and 0.8 in controls. These results suggest that, despite clinical similarities and laboratory evidence of hepatic dysfunction in both Reye-Johnson syndrome and acute encephalopathy, different pathogenic mechanisms may be responsible for the liver abnormalities found in the two syndromes.


Wegener's granulomatosis. Anatomic correlates, a proposed classification. Based on a 10-year experience with 50 patients who had Wegener's granulomatosis, a new classification is proposed based on anatomic site of involvement: upper airway or ear, nose, and throat (designated E), lung (L), and kidney (K). All combinations of ELK were seen. The system is offered as a unifying concept to embrace the terms midline granuloma, generalized or classic Wegener's granulomatosis, and limited Wegener's granulomatosis. Fourteen patients have died despite the use of corticosteroids and immunosuppressant therapy. Thirteen patients with renal involvement have survived for periods as long as 114 months; all were taking immunosuppressive agents.


A significant interaction between metronidazole and warfarin. Interaction between metronidazole (Flagyl) and warfarin had been suggested based on the disulfiram-like effect of metronidazole and the known interaction of warfarin and disulfiram. This case report confirms that this interaction is clinically significant in man.


Ultrastructure of ischemic contracture of the left ventricle ("stone heart"). Myocardial biopsies from two patients who had developed "stone heart" (myocardial rigor mortis; ischemic contracture of the left ventricle) were studied by electron microscopy. The ultrastructure of tissue in stone heart, though ischemic in nature, differed from that of classic myocardial infarction in some respects. Apart from depletion of glycogen and distension of the sarcoplasmic reticulum and T-tubules, myofibrillar degeneration was much more widespread. Mitochondrial degeneration with active lysosomal autodigestion, disruption of the microcirculation, and lymphedema were prominent changes also observed. In the light of known clinical and experimental observations, our findings suggest that stone heart is an accelerated form of ischemic injury occurring in vulnerable (hypertrophied) hearts and is probably related to ischemia-triggered release of endogenous catecholamines.


Lysosomal enzyme activities in parenchymal and nonparenchymal liver cells isolated from young, adult and old rats. Parenchymal and nonparenchymal cells were isolated from the livers of female BN/BiRij rats, aged 3, 12, 24 and 30-35 months, by means of enzymatic techniques. About 70% of the cells in the nonparenchymal cell suspensions were endothelial cells and 25% were Kupffer cells. More than 90% of the isolated parenchymal, Kupffer and endothelial cells were viable as judged by trypan blue exclusion and ultrastructural appearance. The age-related changes in the specific activities of the lysosomal enzymes acid phosphatase, beta-galactosidase, cathepsin D and arylsulphatase B in parenchymal and nonparenchymal cells showed no correlated behavior. The most prominent change was observed for the cathepsin D activity in parenchymal cells, which nearly triples during the lifespan of the rat. A comparison of the activities obtained with homogenates of the whole liver and with parenchymal and nonparenchymal cells revealed that aging changes in lysosomal enzyme activities in homogenates should be carefully interpreted, since opposite patterns of change were often observed in the activities in parenchymal cells and in nonparenchymal cells.


Altered protein metabolism in arrested populations of aging human diploid fibroblasts. Protein synthesis and turnover were measured in human diploid fibroblasts which were arrested in an essentially nonmitotic state by reducing the serum concentration in the incubation medium to 0.5%. Through the first 4 days of the arrested period both early and late passage cells lost about 20% of their cellular protein. There was a reduction in the rate of protein synthesis at both passage levels during this period, but there was no significant age-related difference in the synthetic rate or the rate of protein turnover. After day 4 both early and late passage cells maintained a constant protein content, but late passage cells did this while processing more protein through faster rates of both synthesis and turnover than did early passage cells. These results support those theories of cellular senescence which predict altered protein metabolism as a major consequence of the aging process.


Changes in immunological potential between juvenile and presenile in rabbit. To investigate the relationship between immunological potential and advance of age, patterns of humoral immune response in different aged rabbits were compared. In the primary response, the appearance of total antibody and the arrival to its peak level were retarded by advance of age. On the other hand, the appearance of IgG antibody was the earliest in young and young adult rabbits though the arrival to its peak level was the latest. The disappearance of total and IgG antibodies was earlier in older and immature animals. In the secondary response, the reincrease of total antibody occurred on the same day regardless of the age, but the older were the rabbits, the earlier was the reincrease of IgG antibody and also the arrival to the peak level of both antibodies. In the primary and the secondary responses, the maximal titers of both antibodies were the highest in young and young adult groups. From these results, the exact comparison of immunological potentials in rabbits of different age is possible only by the comparison of patterns of immune responses together with their intensity.


Relationship of senescence of corn (Zea mays L.) stalk pith, cob parenchyma and first developed leaf tissues to RNA content and synthesis. In stalk parenchyma tissue of WF9 X 38-11 single corn (Zea mays L.), there was a per cell increase in RNA synthesis and a slight increase in total RNA as cells became older. In cob parenchyma tissue of WF9 X 38-11 single cross corn, both total RNA content and RNA synthesis per cell decreased with the age of cells. In first developed leaf tissue of FR43 X FR14A single cross corn, RNA synthesis increased steadily but only slightly over its life span. The pattern of RNA synthesis and destruction in senescing leaf tissue of seedlings and two sources of parenchyma tissue of maturing plants appeared to differ.


Aging and the interstitial content of loose connective tissue. A brief note. The concentration of hyaluronic acid which is the fixed loose connective tissue component determining water and other potentials in the interstitium remains constant with age. Since the collagen fiber network in the native tissue state is unstressed, changes in collagen fiber morphology and in collagen content with age have no influence.


The age-dependent decrease in creatine kinase and aldolase activities in human striated muscle is not caused by an accumulation of faulty proteins. In human striated muscle obtained in surgery, an age-dependent decrease in aldolase and creatine kinase specific activities and an increase in DNA content per wet weight was found. In the group of the elderly (64-84 years), the enzymes decreased by 40-60% when compared with a group between 24 and 47 years old, while DNA content rose by a factor of 1.53 indicating loss of tissue water. Titration of aldolase and creatine kinase molecules by specific antibodies against aldolase A and creatine kinase MM isozymes, respectively, revealed very little accumulation of aldolase cross-reacting materials in the old age group (1.13 fold), and no accumulation of inactive creatine kinase molecules. Similar conclusions can be drawn from thermostability analyses of these two enzymes. The data do not support the view that accumulation of modified proteins due to random errors or to post-translational alternations is a general or causative phenomenon of aging in human muscle tissue.


Unscheduled DNA synthesis in lymphocytes of rheumatoid arthritis patients and spleen cells of rats with experimentally induced arthritis. DNA repair is an important factor in the abolition or manifestation of mutations. Since intrinsic somatic mutations may be related to the occurrence of autoimmunity, DNA repair was investigated by measuring unscheduled DNA synthesis in lymphocytes of rheumatoid arthritis patients by autoradiography. Likewise, unscheduled DNA synthesis was investigated in mycoplasma- and Freund's adjuvant-induced arthritis in rats. Both in human rheumatoid arthritis and experimentally-induced arthritis the capacity for repairing lesions in DNA induced by gamma-irradiation of cells was reduced, while an increased rate of thymidine-incorporation into DNA was found after UV-irradiation. The results are discussed in relation to endonucleases of viral or mycoplasmal origin.


Fractionation studies on human leucocyte dialyzates. Demonstration of three components with transfer factor activity. Fractionation of dialyzates of human leucocyte lysates on a Sephadex G-10 column yielded seven fractions. Oidiomycin sensitivity could be induced with fractions I, III and VI in those recipients whose skin tests had previously been negative. Uraemic patients, who were skin test negative to 100 TU of PPD, regained their in vivo reactivity to PPD after receiving 5 mug of fraction VI, while no alteration in their blast transformation responses to the antigen was observed. We suggest that the active components at least in fractions III and VI, and perhaps also in fraction I, act nonspecifically by stimulating weak immune reactivity or by supporting reactions leading to the expression of this reactivity.


[Neurosurgical treatment of trigeminal neuralgia (author's transl)]. Follow-up studies of 210 cases treated by electrocoagulation and of 146 cases treated by temporal subtotal resection of the posterior root (Frazier) and descriptions of a further 1946 cases in a cooperative study in which different surgical treatments were applied are used as a basis for discussion advantages and disadvantages of the different surgical methods. Selective elimination of pain fibers with protection of tactile sensibility seems the most desirable objective. With this in mind, the new percutaneous method developed by Sweet receives particular attention.


[Problems in operative treatment of portal hypertension by intrahepatic block (author's transl)]. Besides the high risk of surgery for bleeding esophageal varices, this therapy can involve an unacceptable rate of late complications following portacaval shunt (PCS). High mortality (liver failure) and morbidity (encephalopathy) can only be diminished by strict selection of patients. Alternative procedures have not yet been proved preferable in the long term. This is also true for the PCS with arterialization of the hepatic part of the portal vein. On the grounds of their own results, the author and his colleagues prefer the distal splenorenal anastomosis (Warren shunt).


[Results of veno-venous shunt with arterialization of the liver (author's transl)]. Since 1968, arterialization of the liver with a portacaval shunt has been carried out in 82 patients for the treatment of portal hypertension caused by cirrhosis. Lethality in the first 4 weeks after operation was 19%. In 35 patients it is now over 5 years since the operation, 5 years survival being 46%. The general condition of these patients is remarkably good. The liver's detoxifying function has been preserved. Encephalopathy is rare. In cases of existing portacaval shunt arterialization can still be performed by way of the V. umbilicalis. The detoxifying function will improve after this.


[The Warren sunt (author's transl)].

[The Warren sunt (author's transl)]. The fundamental principles of the distal splenorenal shunt are three-fold (1) selective decompression of gastroesophageal varices; (2) simulation of a spontaneous and sometimes effective gastro-spleno-suprarenal shunt; and (3) maintenance of the portal-venous perfusion of the liver. The cirrhotic patient with hemorrhagic episodes who is free of ascites and in whom angiography reveals either good or poor portal flow to the liver is a suitable subject for this procedure. The essential stages and difficulties of the surgical technique are discussed.


[Splenorenal anastomoses].

[Splenorenal anastomoses]. Of the operative procedures that can be used to relieve the pressure in portal hypertension, the authors prefer the terminolateral splenorenal anastomosis if the assessment of relative anatomical positions and the patient's hemodynamic situation has shown that these are adequate for the procedure. In contrast to portacaval shunting, after splenorenal anastomosis portal blood supply to the liver is partially maintained. Therefore less patients suffer from hepatic failure or encephalopathy. In addition a lower short-and long-term postoperative mortality has been observed. The risk of thrombosis and recurrent bleeding are the drawback of the method, occurring in about 15% of the patients. A meticulous technique can reduce this percentage.


[Reoperations in cancer surgery (author's transl)]. Early detection of local recurrences and metastases is the most important condition for the success of reoperation in cancer surgery. A strict long-term follow-up, with standardized documentation, of patients operated on for malignancies is therefore necessary. While reoperations in cancer of the esophagus, the stomach or the lung are not very effective, surgery for recurrent carcinoma of the female breast, the colon and the rectum is more successful. The results of reoperation improve with increasing lapse of time since initial surgery, if radical resection of the local recurrences and the solitary metastases is possible. Treatment by an interdisciplinary team is considered to be the best.


[Postoperative care of cancer patients: an interdisciplinary responsibility (author's transl)]. Postoperative care of cancer patients is the joint interdisciplinary responsibility of surgeons, general practitioners (GP'S) and registered specialists. The necessary centralization in hosptal is ensured through cooperation on the part of the general practitioners. By means of a standardized follow-up programme, the organizational model described guarantees 9 postoperative check-ups at predetermined intervals within a period of 5 years. Clinical cancer registers are a mark of quality for hospitals and ensure detection and analysis of the pathography of cancer patients. Surgeons must also acquire the knowledge necessary for their use.


[Reoperation in carcinoma of the thyroid (author's transl)]. From 1960 to 1975 a total of 82 reoperations were performed in patients with malignant goiter in the Surgical Clinic of the University of Munich. In reoperation as in primary surgery, the criteria for operative management and prognosis are dependent on histology (differentiated-undifferentiated carcinomas), extension of tumor, and age and sex of the patient. The need for early and radical reoperation increases with declining age, and also with limitation and differentiation of the carcinoma. Early results are presented: an accurate statement about late prognosis is not yet possible.


[Surgery in recurrences of breast carcinoma (author's transl)]. Local recurrences of a tumor generally indicate a poor prognosis, because they are often associated with metastasis. The guidelines for treatment suggested by the author are: radiotherapy should be used first, and surgery as a rule only when radiotherapy has been exhausted or it is not possible. If radiation ulcers occur, extensive palliative resection of the chest wall should be performed. The resulting defect should be covered by means of sliding flaps or Kiricuta sieve grafts rather than direct transfer flaps.


[Reoperation in bronchial carcinoma (author's transl)]. After lung resections in bronchial carcinoma, reoperation for recurrences, metastases, or secondary primary tumors is rarely possible. The possibility depneds on the extent of the primary resection, the physiological state of the patient, and the spread of the primary or secondary tumor. From 1950 to 1975 1628 lung resections were performed in Düsseldorf, with reoperation in 26 cases (1.6%). n Bremen (1964-1974) 915 lung resections were performed, with 20 reoperations (2.2%). Survival times recorded in Bremen and Düsseldorf and in the literature justify reoperation in individual cases.


[Reoperation in recurrence of carcinoma of the esophagus, Cardia and stomach (author's transl)]. Reoperative surgery is performed with the object of restoring gastrointestinal passage or of pain relief and only rarely, for example in recurrence of an early carcinoma, with the object of curative resection. Out of 31 reoperations for such a purpose, a second resection (total or extended gastrectomy) was possible in 9 cases, gastric bypass or some other palliative operation in 12; in 10 cases, only a laparotomy was possible. The interval between the 1st and 2nd operations was 29 months in the resectable group and 17 months in the nonresectable group, the survival times 11 and 3.3 months respectively. Indications have to be considered separately for each patient.


[Reintervention in recurrent carcinoma of the large bowel (author's transl)]. Reintervention has a good change of success in recurrent of carcinoma of the sigma and colon. Early detection is essential for reintervention to be  successful, and meticulous follow-up is therefore necessary in all patients operated on for tumors: follow-up examinations can best be carried out at a special tumor clinic. Since 1964,-42 patients have undergone reintervention for recurrences. In 50% of them the condition was found to be inoperable. On the other hand, 14 of 21 patients in whom reintervention was successful are still alive. Adjuvant therapy such as radio therapy or cytostatics is rarely administered, but should be employed more in the future.


[The use of CEA radioimmunoassay for the detection of recurrence of carcinoma of the large bowel (author's transl)]. Carcinoembryonic antigen (CEA) is a tumor marker defined by specific heterologous antisera. Elevated levels of circulating CEA can be detected by radioimmunoassay in most cases of colorectal carcinoma, depending on the degree of tumor spread. The fact that elevation of CEA level can also be observed in other types of carcinomas and in several nonmalignant conditions greatly limits the value of the CEA test for the early diagnosis of colorectal carcinomas. Repeated CEA measurements and their critical interpretation, however, appear to be of importance after tumor resection for the detection of tumor recurrence during the postoperative follow-up period.


[Reoperation in rectal cancer (author's transl)]. Carcinoma of the rectum is reported to have a local recurrence rate of 3-48 percent. In 80 percent of cases, recurrence appears within 2 years after the first operation. The possible causes of its occurrence and its localization are discussed. Early diagnosis is important. Follow-up examinations are therefore necessary every 3 months in the first 2 years. Curative secondary operations are rare. In pelvic, perineal, and genital recurrence, radiation therapy is usually considered to be the treatment of choice.


[Some structural and functional peculiaritis of the growing skeleton and their significance in fracture healing (author's transl)]. The following properties of the growing skeleton are discussed in relation to fracture healing: (1) The pronounced reaction of periosteum and endosteum and their part in the correction of deformities, and the vascular pattern of cortical bone; (2) the microscopical structure and the vascular supply of the growth plate, with reference to their significance in injuries; (3) the involvement of growth plate and growing articular cartilage in the modeling of the end of long bones and in the correction of angular deformitis.


[Clinical and radiographic diagnosis of fractures in childhood (author's transl)]. The diagnostic procedure followed in cases of childhood fractures consists of positive identification of the fracture type (greenstick, complete, or open fracture) and also determination of the degree and age-specific tolerance limit of axis deviations. This diagnostic procedure also includes decisions concerning indications for operative or conservative therapy, and lays great emphasis on the identification of epiphysial injuries. If function is to be fully restored, the extent of injuries must be rapidly determined. Long-term injuries are identified at follow-up examinations and can then be corrected surgically.


[Treatment of juvenile fractures: general introduction (author's transl)]. As fractures sustained during childhood are "different", the treatment for them is also different than that for fractures in adults. In general the treatment is conservative. A childhood fracture has in its favor the enormous potential of the growing skeleton for healing and correction, while against it is the possibility of impaired growth following certain injuries in growth areas. There are quite specific indications for operative treatment; in other words, some fractures require internal fixation, e.g. genuine epiphyseal fracture, fracture of the neck of the femur, displacement of the head of the radius.


[Conservative management of juvenile fractures (author's transl)]. The preliminary conservative management of juvenile fractures by closed reduction must be performed with due regard for the pressure of epiphyseal plates, the more rapid bone healing and the increased stimulation of growth. Malunited fractures are realigned by the normal process of bone remodeling, and results are better in young children. The management of shaft. metaphyseal and joint fractures by closed reduction is outlined. Late sequelae such as a diminished range of motion of the affected limb are rare, so that intensive physical therapy is not required.


[Internal fixation of juvenile fracture (author's transl)]. There is a great difference in the internal fixation of infant and adult fractures. Biological and anatomical pecularities in childhood make it possible for lingitudinal growth to be impaired by the implanted material, its size, its topographic relationship to the growth organ and the duration of implantation. Internal fixation in children should therefore be limited to a few cases and should not be undertaken. Without excellent operative techniques and special aseptic operating rooms. Various ASIF techniques, such as Kirschner wiring, screwing, and fixation with plates, are suitable. Medullary nailing (Küntscher) should not be used in children.


[Pseudarthrosis, growth deformity and malpostioning after fractures in childhood (author's transl)]. Malpositioning of head fractures in children can carrect itself spontaneously, depending on various parameters. Tolerance thresholds, the consequences of noncorrected malpositioning and the indications for operative correction are reported. Growth disturbances following healing of fractures are most frequent in the elbow, knee and ankle joints. Occasionally operative correction in necessary, sometimes repeatedly. Pseudarthrosis, although rare in growing bones because of the high capacity for regeneration, is treated according to the established principles of pseudarthrosis therapy.


[Compound fractures in childhood (author's transl)]. The incidence of compound fractures increases with the age of children. The importance of emergency care at the site of the accident, with sterile coverage of wounds and preliminary fixation, and of fast and careful transportation to hospital, is gaining recognition. Final management should comprise meticulous mechanical cleansing under sterile conditions, treatment of any additional injury, and stabilization. Compound fractures call for more generous application of internal fixation. Tetanus prophylaxis and routine monitoring of wounds are essential when there is any danger of gas gangrene.


[Infected fractures during the period of growth (author's transl)]. The stabilization of the injured and infected region is the most important condition for the bone structuring and the healing of infection. The author recommends the use of external fixation clamps, by means of which it is possible to achieve stability during movement while avoiding implantation of the metal in the infected region and the epiphyseal zone. The indications for autogenous cancellous-bone and skin grafts are mentioned. The results of follow-up examinations make it clear that the treatment should be started as early as possible.


[Spontaneous fractures and tumors (author's transl)]. During childhood, pathologic fractures are found in systemic diseases of the skeleton (e.g. osteogenesis imperfecta or rachitis), but especially when bone tumors or tumorlike changes are present. Conservative measures such as continuous traction and application of a plaster cast lead to healing of the fracture only in a limited number of cases. Treatment of benign and potentially malignant and tumors and of tumorlike growths by excochleation and by resection and subsequent filling of the defect with autologous spongiosa and in some cases metallic fixation respectively has proved useful. The surgical treatment of malignant tumors depends on the king of tumor and its localization.


[Physiotherapy of fractures in childhood (author's transl)]. Fractures in Children need physio-and ergotherapy as much as fractures in adults. Before the seventh year monitoring is of prime importance, because malpositioning of fractures is frequent. In children between 7 and 12 years of age physio- and ergotherapy are essential factors in rehabilitation. Massage and irradiation are noxious. Passive exercise of the elbow joint is not successful but causes new injuries. Fractures of the vertebral column or injuries of the spinal cord should receive only functional treatment. Later consequences cannot be assessed until growth has ceased.


[Fracture in polytraumatized children (author's transl)]. The appropriateness of surgical therapy in polytraumatized children is influenced by a series of facts, such as severe additional injuries, the age of the child, type and localization of the fracture etc. Fractures of the neck of the femur and fractures involving extensive injuries of soft tissue are an indication for immediate operative treatment. Transepiphyseal fractures and fractures in cases of additional cerebral contusion are an indication for early treatment. Fractures of the forearm or the lower leg are treated conservatively after the stabilization of circulation (wiring, plaster cast).


[Cardiorespiratory problems in intensive care (author's transl)]. Prompt and aggressive support of lung and hemodynamic function are required if the incidence of recovery from acute respiratory insufficiency is to be improved. Prophylactic ventilator and inotropic therapy are required to prevent progressive deterioration of blood gas exchange and maintain myocardial function in the face of an acutely elevated right ventricular afterload. Methods for early diagnosis are now readily available; the criteria for therapeutic intervention are discussed.


[Specific probelms in the intensive care of patients with multiple injuries (author's transl)]. Respiratory problems such as throacic injuries, shock lung, fat embolism aspiration are predominant in a specialized intensive care unit for patients with multiple trauma. The most important pulmonary complications are tension pneumothorax (in which case an immediate diagnosis is essential), atelectasis, lesions of the trachea, and pulmonary infections (12 percent of the patients). With severe head injuries it is often difficult to decide whether intensive care is justified. Unfortunately, there are no clear criteria for an early assessment of the prognosis in many of these cases.


[Postoperative acute renal failure (author's transl)]. Despite progress in intensive therapy and dialysis the lethality of postoperative acute renal failure (ARF) remains very high. Between 1958 and 1976, 374 out of 11474 patients treated in the intensive care unit developed ARF. By conservative treatment that is described in detail, the mortality was reduced from 80 percent (up to 1972) to 50 percent. The mortality rate of dialysis was 86 percent (85 of 98 patients). ARF reflects the severity of the illness of these patients. The prognosis depends besides further complications on the administration of optimal intensive care and early dialysis.


[Problems in intensive care for burns (author's transl)]. Severe burns are followed by a shock period of more than 48 h. Insufficient fluid replacement may lead to serious organic damage. Protein losses are high. Cardio-respiratory complications are frequent. Infection and sepsis are still frequent causes of death. Skin damage requires extensive operations for debridement and skin replacement, and blood losses must be replaced simultaneously.


[Hospital infection during postoperative intensive care (author's transl)]. Since 1970 all postoperative bacteriological findings recorded in surgical patients have been analyzed and compared with the postoperative course. There are also regular checks of bacterial invasion in the operating suites and in the intensive care units. By such means as systems of double lock for personnel and equipment, regular surface disinfection, frequent hand disinfection, cleaning of the respirators with antiseptics, etc., the authors have been able to reduce the incidence of hospital infection very drastically. These measures also almost eliminated cross-infections in patients on long-term ventilation and complications with long-term indwelling catheters.


[Pain, a human and a medical problem (author's transl)]. Physiological, psychological and also psychiatric aspects of pain are of great importance for the surgical treatment of pain. The inhibition of pain conduction of physical and psychic stimuli makes it difficult to evaluate therapeutic procedures and forces us to apply adequate treatment in each single case.


[Pathologic-anatomic aspects of the formation and complications of diverticula (author's transl)]. Diverticulosis is favored by general (erect posture), diatetic (low-roughage diet) and anatomic factors (discontinuity and particularly spiral arrangement of the musculature). A pouch of mucous membrane passes through the bowel wall in some cases, which makes comparison to the false diverticula of the so-called trabecular urinary bladder understandable. An important feature of the pathogenesis is the displaceable layer between mucosa and musculature. Diverticulosis is the basis of a disease, i.e. diverticulitis: this begins with stercoraceous pressure ulcers, and causes granulation tissue local peridiverticulitis. In peridiverticulitis, confluated inflammation sometimes involves all the sigmoid ensheathing it, with pernicious fomation of scars, i.e. perisigmoiditis. In this way, a disease of the intestinal wall becomes a disease of the intestine. The symptoms of perisigmoiditis are similar to those of carcinoma of the sigma.


[Abnormality of the muscular structure of the colon: a possible cause of diverticulosis (author's transl)]. Diverticula of the colon result from myostatic contracture. In each case an asymmetric contracture leads to the formation of a gap in the wall of the bowel, through which the muscularis mucosae with the contents of the bowel slip out. Diverticulitis is compared with appendicitis.


[Internal aspects of diverticulosis (author's transl)]. Diverticular disease of the colon is, apart from the irritable colon syndrome, by now probably the commonest disorder of the large intestine. The incidence of the disease seems to be increasing, which might be due to fundamental dietary changes during the last 60-80 years. It has been suggested that the condition may be a dietary deficiency disorder caused by an inadequate intake of fiber in the diet. Undiagnosed diverticulosis can suddenly progress to painful diverticular disease or diverticulitis with no warning. Complications are sometimes life-threatening, and they demand immediately surgical intervention. The optimal medical and surgical management of diverticular disease and diverticulitis is not well defined as no controlled clinical trials are available.


[Myotomy: a surgical treatment for diverticulitis (author's transl)]. Since 1973 myotomy after Reilly has been performed on 30 patients with sigmoid diverticulosis or diverticulitis. The operation is most suitable for patients with moderate stenosis and clinically recurring symptom that no longer respond to conservative treatment. When widespread inflammation is present the risk involved in the operation should not be underestimated: separation of the intestinal wall layers is more difficult and the danger of perforation is increased. The operation cannot be used successfully to remove an early carcinoma developing between the diverticula.


[Continuity and change in medical ethos (author's transl)]. The report develops first of all a general concept of ethos and categories for comprehending its structure [2]. Classical hippocratic ethos then emerges as a "modell" which medical treatment standardizes as a matter of "practical" science-oriented values in the service of the "private" welfare of the patient [3]. The will, under changing conditions of medical practice, to permanently engage the substance of the ethos, demands a) consciousness of the "practical" character of the misunderstanding of medicine as a theoretical physical science, b) recognition of the importance of the "private" doctor-patient relationship vs. the widening of a purely social objective, c) orientation to the whole needs of the patient in opposition to a technologically created "depersonalization".


[Septic complications in vascular surgery: a review (author's transl)]. The importance of vascular infection is determined by localization and extension, by the type of graft, by the type of bacteria and by subsequent complications. Prophylactic measures are: strict selection of patients (in obesity, diabetes), unyielding attention to hygiene and asepsis in the operating theater, use of adhesive plastic skin coverings, instrument preparation, short operation time, meticulous blood coagulation, intraoperative control of the hemodynamic result and adequate wound drainage. Antibiotics can be given preoperatively; their usefulness in the prevention of wound infection is not generally accepted. The use of a prosthesis in the perforating vascular trauma should be avoided; extra-anatomic reconstruction may be performed as the primary procedure. When the graft is removed and extra-anatomic reconstruction performed definitive healing cannot always be expected.


[Diagnostic and clinical aspects of septic complications in vascular surgery (author's transl)]. The clinical symptoms of wound infection depend on the location and the tissue layer of the infectious process. The classic signs of inflammation are usually present if the subcutaneous tissue is involved. The diagnosis is based mainly on clinical signs. Deep wound infections, e.g. in the retroperitoneal space can progress unnoticed for days or even weeks, to be suddenly unmasked by a vascular complication (bleeding; aorto-enteric fistula). An early daignosis is essential for an aggressive surgical approach, i.e. early elimination of the septic focus in combination with an aseptic bypass procedure.


[Septic complications in vascular surgery: operative treatment and results (author's transl)]. The treatment of infection after vascular operations depends on the severity and extent of this complication. In infections of low virulence an attempt to prevent progression of the infectious involvement should be made with the help of antibiotics and immobilization. Suppurating infection involving a vascular graft but not yet causing bleeding can be treated successfully by drainage and antibiotic irrigation. In case of bleeding at the site of an infected anastomosis it is sometimes possible to prevent further bleeding and to cure the infection by wrapping omentum round the anastomactic lines. Severe infection and repeated hemorrhage require sacrifice of the reconstructed vessel to prevent loss of limb and even life: arteries reconstructed with the use of autogenous material must be ligated; any implanted synthetic material has to be removed. In these cases limb salvage can be accomplished using a remote bypass (axillo-femoral bypass, obturator-bypass, crossed bypass, etc.).


[Surgical treatment of malignant melanoma (author's transl)]. The primary lesion is widely excised under a general anesthetic. The resulting defect is covered by a free graft. Prophylactic lymph-node dissection seems to be reasonable for stage-I melanoma with deep invasion (microstage III-V) according to recent investigations. Stage II is an absolute indication. Stage III patients received an individual palliative therapy. The value of additional measures is not yet clearly defined.


[Immunology of malignant melanoma (author's transl)]. Melanoma cells carry membrane-bound antigens that induced both antibody production and cellular immunity. However, these antigens appear not to be tumor-specific, as the activity of human antisera can be absorbed out by fetal antigens. Nonetheless, the phenomenon of spontaneous regression, though mostly affecting only parts of a lesion, indicates that effective attack mechanisms do exist. Simultaneous tumor progression is due to heterogeneity of tumor cells, which vary widely in antigen expression. Cells that are not recognizable sneak through defense mechanisms and produce metastases.


[Chemotherapy of malignant melanoma (author's transl)]. Chemotherapy of malignant melanoma is indicated in advanced disease when local treatment is no longer possible. The results of single-agent chemotherapy, including alkylating agents, antimetabolites and several antibiotics as well as vinca alkaloids and recently the nitrosoureas, are critically reviewed. The overall response rates do not reach levels about 15 percent. The imidazole carboxamide compound (DTIC) has been most extensively studied, And increases the response rate to about 25 percent. The influence of pretreatment and the preponderance of certain localizations, and also the survival rates of responders, partial responders and nonresponders are discussed. Combination chemotherapy seems not to be superior to single-agent therapy. Various factors, including biochemical, pharmacological, cytokinetic and immunologic parameters that differentiate responders from nonresponders, still require examination.


Transmeatal labyrinthectomy with and without cochleovestibular neurectomy. 1. The surgical anatomy and approach to the internal audiotory canal through the transmeatal route is presented. 2. The results of 22 patients undergoing transmeatal labyrinthectomy with cochleovestibular neurectomy indicated that 15 of 20, or 75 percent, had vertigo cured or markedly improved. The best results were found in patients with Ménière's disease (10/10). 3. Similar results were found regarding the symptoms of tinnitus. Fifteen of 22 patients, or 68 percent, had tinnitus cured or markedly improved in a six-month to 36-month follow-up. The best results, again, were found in patients with Ménière's disease (8/10). 4. Patients undergoing transmeatal labyrinthectomy without cochleovestibular neurectomy showed only one of six cases with improvement of tinnitus and three of six cases with vertigo cured or markedly improved. 5. Transmeatal labyrinthectomy with cochleovestibular neurectomy appears to have the following advantages over transmeatal labyrinthectomy or translabyrinthine section of the VIIIth nerve: a. The surgical time is shortened by the direct route to the internal auditory canal. b. A second procedure is avoided by not having to obtain abdominal adipose tissue for obliteration of the mastoid cavity. c. Complete unilateral ablation of vestibular function is assured. d. Best chance of alleviation or improving tinnitus. e. The internal auditory canal is routinely inspected to be sure no acoustic neuroma or other pathology is found. f. Skill is obtained in transecting the "singular nerve."


Ossicular discontinuity.

Ossicular discontinuity. Because of the numerous and varied surgical approaches to ear pathology devised and expanded in the past two decades, we are destined to be confronted with increasingly frequent cases of ossicular defects behind an intact eardrum. Using a technique which is the converse of the established "patch" test a simple office procedure is described which may help establish the diagnosis of ossicular discontinuity in the adult with an intact eardrum. An audiogram is obtained and then a myringotomy performed with insertion of a large ventilation tube. A second audiogram is then done. A rise in the air conduction level, in the absence of fluid, is suggestive of ossicular discontinuity.


Proplast chin augmentation.

Proplast chin augmentation. A method of chin augmentation employing a newer synthetic material (Proplast) is presented. The characteristics and biocompatibility of Proplast are detailed. Technical considerations and results of short term clinical trials in 20 patients are discussed. One implant necessitated removal secondary to trauma four months after surgery. All other implants including over 30 additional cases have been without incident.


Effective stimulus for the Xenopus laevis lateral-line hair-cell system. An in vitro preparation of the lateral-line organ of the African clawed toad Xenopus laevis was used to evaluate the properties of the physiological stimuli which are most effective in evoking neural responses in this simple hair-cell system. Changes in the mean firing rate and the amount of modulation of the neural activity in the fibers innervating the hair cells were determined during the presentation of well-controlled pressure or water-movement stimuli in a specially designed chamber that prevented movement and deformation of the organ during stimulation. It was shown that the most effective stimulus for the preparation was a varying flow of fluid past the organ. Sinusoidally varying water movements over a frequency range of 1 to 100 Hz were effective in evoking neural responses at stimulus amplitudes less than 10 mu peak-to-peak; in addition, a small response to a constant-velocity flow was found. Since no movement or deformation of the organ was present during the water-movement stimuli, it was concluded that these aspects of normal physiological stimuli were not necessary to evoke neural responses. Finally, it was demonstrated that the preparation was sensitive to neither constant nor varying-pressure stimuli.


Calcifying odontogenic cyst (Gorlin's cyst) of the maxillary sinus. Occasionally the maxillary sinus is invaded by a cyst or tumor of odontogenic origin. Though usually benign, these lesions may be locally aggressive. A recent case involving bone destruction and sinus opacification is presented.


The inferior thyroid veins--the ultimate guardians of the trachea. The inferior thyroid veins and their multiple tributaries are the ultimate guardians of the cervical trachea. Deeply embedded in the pretracheal fat pad, this plexus of veins is consistently encountered during low tracheostomy that accompanies conservation laryngral procedures as well as in tracheal reconstruction. In a high tracheotomy, the handling of the thyroid isthmus is simplified by an appreciation of these veins. Even cricothyrotomy is potentially complicated by hemorrhage sebsequent to a tear in a tributary of the inferior thyroid venous system. A cadaver study, employing 10 embalmed head and neck specimens, was performed to elucidate the tributary patterns of these veins. In every dissection there was at least one and as many as five veins overlying the trachea just below the thyroid isthmus. In 7 of 10 dissections a confluence of right and left inferior thyroid veins formed a large thyroid ima vein draining into the left innominate vein, and in 1 of 10 cases the thyroid ima vein drained into the right innominate. This confluence was present at a level which would be encountered in low tracheostomy or tracheal repair procedures. Six of 10 dissections presented large tributaries of the inferior thyroid veins overlying the cricothyroid membrane. An awareness of such anatomical considerations should result in safer surgical procedure performed in a dry operative field.


An unusual thyroid tumor in a child.

An unusual thyroid tumor in a child. Malignant neoplasms of the thyroid gland are quite rare in children. Winship, in his classic article, could find only 562 cases in the literature. The histopathological patterns resemble those of the adult tumors. Despite early cervical metastasis, the prognosis in general is favorable, with many long-term survivals. Prior exposure to radiation of the head and neck is a definite pre-disposing factor. Teratomas of the neck are a medical curiosity--less than 100 cases are described in the literature. The vast majority of these are found during the neonatal period, and are benign histologically. These are usually large, cystic, bulky masses which produce mechanical obstruction of the upper airway and digestive tract. Only one of these tumors, described by Pupovac in 1896, has been considered malignant. A six-year-old child was examined with a right thyroid mass of three months' duration. The thyroid scan showed a "cold nodule." At surgery, a well-encapsulated mass was found. The pathology showed a predominance of malignant spindle cells, with areas of papillary carcinoma; however, there were well-defined mucous glands present in the tumor. Clinically the child has remained well and asymptomatic. The slides have been extensively reviewed. To my knowledge no such tumor has been previously described. The tumor is considered to be a malignant thyroid tumor growing out of teratomatous tissue.


Effect of bovine serum albumin on monoacyl- and diacylglycerol 3-phosphate formation in mitochondrial and microsomal fractions of rabbit hearts. The formation of monoacyl- and diacylglycerol 3-phosphate (P) by rabbit heart mitochondrial and microsomal fractions was studied by varying the concentration of acyl-CoA and that of bovine serum albumin in the assay system. The two subcellular fractions were prepared by the conventional differential centrifugation technique. The optimal concentration of acyl-CoA for both mitochondrial and microsomal acylation of glycerol 3-P was shifted to a higher range of acyl-CoA concentrations by greater amounts of albumin. A similar shift in the acyl-CoA concentration-enzyme activity relationship was observed in the acylation reaction of 1-palmitoylglycerol 3-P by the heart microsomes. The addition of albumin increased slightly the rate of diacylglycerol 3-P accumulation but increased greatly the rate of monoacylglycerol 3-P accumulation at any concentration of acyl-CoA; the effect was observed with mitochondrial or microsomal fraction as the crude enzyme source. Moreover, palmitoyl-CoA and linoleoyl-CoA served equally well as the acyl donor for the acylation reaction. However, relatively more monoacyl- than diacylglycerol 3-P was accumulated in the assays with rabbit heart mitochondrial fraction in the presence of albumin, whereas more diacyl- than monoacylglycerol 3-P was formed by the microsomal fraction. As a result, the microsomal diacyl:monoacyl-glycerol 3-P ratio was invariably greater than the mitochondrial ratio at a given concentration of acyl-CoA and albumin.


Inhibition of acid esterase in rat liver by 4,4'-diethylamino-ethoxyhexestrol. The effect of 4,4'-diethylamino-ethoxyhexestrol (DH) on acid esterase in rat liver was studied in vivo and in vitro. The acid esterase activity in the livers of rats treated with 0.125% DH for 1 week was found to decrease more than 60% as compared with that in untreated rats. The addition of DH to the incubation medium caused considerable inhibition of the acid esterase activity in lysosome from untreated rat liver, and the inhibition type appears to be noncompetitive. The acid lipase activity in rat liver lysosome was also inhibited by DH. Some antihistamic agents and chloroquine also inhibited the acid esterase activity in rat liver lysosome.


Effect of dietary fats on pentobarbitone-induced sleeping times and hepatic microsomal cytochrome P-450 in rats. Female Wistar-derived rats were fed diets containing either sunflowerseed oil or tallow for 4 weeks. Rats fed the sunflowerseed oil diet had longer pentobarbitone-induced sleeping times and lower concentrations of hepatic microsomal cytochrome P-450 than rats fed the tallow diet. The addition of pentobarbitone to the drinking water of rats caused approximately 2-fold increases in the concentrations of hepatic microsomal cytochrome P-450 but did not alter the relative effect of the diets.


Lipid content and fatty acid composition of heart and muscle of the BIO 82.62 cardiomyopathic hamster. Microscopic and analytical studies of the lipids in the heart and muscle of the BIO 82.62 myopathic hamsters and age-matched normal animals at the average ages of 33, 67, and 108 days were performed. Microscopic examinations did not show increased lipid depositions in the hearts of the diseased animals as was found in the BIO 14.6 strain. No consistent differences in the lipid content of the cardiomyopathic hamsters (BIO 82.62) and age-matched controls were observed in the three age groups except in the cholesterol content of muscle. Cholesterol increased significantly (P less than 0.01) in the 67 and 108 day old animals. This increase elevated the cholesterol/phospholipid ratio. Analysis of the fatty acid composition of triglycerides showed that the cardiomyopathic hamsters store more saturated fatty acids in both heart and muscle than do their normal counterparts. The abundance of more saturated fatty acids may imply that either the desaturation mechanism is altered in the diseased animals or that unsaturated fatty acids are preferentially utilized in other processes.


Determination of background serum density for lipoprotein ultracentrifugation. It is necessary to know the density of serum exclusive of its macromolecules (background density) prior to density adjustment with solid potassium bromide for ultra-centrifugal separation of lipoprotein fractions. To evaluate this, we compared the densities of the corresponding ultrafiltrates or dialysates of both human and equine sera produced by ultrafiltration and equilibrium dialysis method for macromolecule removal. Excellent correlation is found between background densities determined following ultrafiltration or equilibrium dialysis. These data validate the use of ultrafiltration as a simple, direct method for determination of background serum densities but reveal equilibrium dialysis to be more time consuming and less precise. Using ultrafiltration, we find the background density for equine serum to be 1.004 g/ml, and initial investigation suggests this value may be altered by freezing, prolonged refrigeration (3 months), or heating to inactivate lecithin: cholesterol acyltransferase.


Structure-function activity of azasterols and nitrogen-containing steroids. Thirty-nine nitrogen-containing steroids were tested against two gram-negative, five gram-positive, and two yeast organisms. Many of these steroids have been previously reported to inhibit various metabolic processes involving sterol metabolism. While low minimal inhibitory concentration (MIC) values were recorded for sterol producing yeast, growth of bacteria which contain no sterols was also inhibited. Structure-function studies provided no relationship between biological activity and hypocholesteremic effects of these azasteroids. A hypothesis put forward is that amino and azasteroids are effectors of membrane which, in the case of mitochondria, lead to changes in adenosine triphosphate levels and/or dehydrogenase activity. Their effects on sterol metabolism, therefore, may be of secondary consideration.


Nutrition and metabolic studies of methyl esters of dimeric fatty acids in the rat. Methyl esters of dimeric fatty acids were prepared by fractionating a mixture of conjugated linoleic and oleic acids that was heated for 24 hr at 300 C in the absence of air. Rats fed diets containing less than 1% dimers showed no significant difference (P less than 0.05) in the growth rate, feed efficiency, liver:body weight ratio, and lipid:liver weight ratio from those fed normal diets. A lymph cannulation study using 14C labeled dimers showed that ca. 0.4% of the dimers fed were absorbed within 12 hr and were transported as free acids in the lymph. Within a 28 hr period, 2% of the labeled dimers fed by gastric intubation were oxidized to 14CO2, and 1% radioactivity was recovered from the urine. The metabolism of methyl oleate appeared normal for rats prefed diets containing dimers.


Inhibition of hepatic sterol and squalene biosynthesis in rats fed di-i-ethylhexyl phthalate. Di-2-ethylhexyl phthalate (DEHP), a commonly used plasticizer, was found to be an inhibitor of the biosynthesis of hepatic nonsaponifiable lipids in the art. The addition of DEHP at levels of 0.5% or 1.0% to a stock diet of rats resulted in a decreased conversion of acetate-1-14C and mevalonate-5-3H into squalene, C30 sterols, and C27 sterols by liver minces or slices, in vitro. In studies conducted with 0.5% DEHP feeding from 2 to 11 days, the degree of inhibition was found to increase with the duration of DEHP feeding; the inhibition of 3H-mevalonate conversion to squalene and sterols developed more slowly, being reduced to ca. 70% control values in 11 days, whereas 14C-acetate conversion was reduced to ca. 35% of control values during the same period. 3H-mevalonate conversion to sterols and squalene was, however, found to be suppressable to the same extent as 14C-acetate conversion when diets containing 1.0% DEHP were fed for 18 days. The inhibitory effect of dietary DEHP on sterol and squalene biosynthesis from 14C-acetate and 3H-mevalonate by rat liver preparations is unlikely to be accounted for by the negative feedback of cholesterol secondary to hepatic sterol accumulation since, in these studies, hepatic total lipid and hepatic total sterol levels were similar in control and DEHP-fed rats.


Modulation by ketone bodies of the rate of fatty acid synthesis in mammary gland slices from lactating rats. The absolute rate of fatty acid synthesis was measured in slices of mammary gland from lactating rats by incubation in [3H]2O-labeled medium containing 10 mM D-3-hydroxybutyrate or acetoacetate alone and paired in combination with 10 mM glucose, lactate, or pyruvate. When compared with our previous studies, the ketone bodies alone supported significant fatty acid synthesis; the rate of synthesis from either ketone body and lactate was higher than that from pyruvate and lactate, and that from pyruvate and glucose; the rate of synthesis from D-3-hydroxybutyrate and lactate was the highest we have observed in the absence of an exogenous substrate for the hexose monophosphate pathway. This study confirms our previous contention that, in rat mammary gland, substrates formed in the mitochondria can be utilized in the cytosol to provide some of the NADPH necessary for fatty acid synthesis.


Further studies of the saturated methyl branched fatty acids of vernix caseosa lipid. By the method of capillary gas chromatography-mass spectrometry, we have identified 35 monomethyl and 46 dimethyl branched acids in the saturated acids of vernix caseosa lipid with chain lengths ranging from C11 to C18. Many other mono-, di-, and trimethyl  branched acids have been partially identified. All methyl branches were found to be on the even numbered C-atoms except for some terminal iso methyl groups. Three types of dimethyl branched acids were found: those with a terminal iso structure, those with a terminal anteiso structure, and those with neither iso nor anteiso structures. The 4-methyl branch predominated for all types of branched acids. Equivalent chain length data for di- and trimethyl branched acids were determined on a Pentasil (nonpopolar) wall coated capillary column and checked by calculation from monomethyl branched acid data. Mass spectral identification was performed with and without the aid of a data system. A possible mode of formation of these acids is discussed.


Lipid accumulation cells derived from porcine aorta and grown under anaerobic conditions. Fibroblast-like cells, derived from porcine aorta, were cultured under aerobic and anaerobic conditions. Light and electron microscopic examinations, lipid composition measurements, and incorporation of radioactive precursors into lipids of these cells were performed. Anaerobically grown cells accumulated oil red O stainable droplets and within 6 hr the triacylglycerol content increased to 4 times the level determined in cells grown under aerobic conditions. This ratio remained constant throughout an additional 12 hr of growth. The fatty acid composition of the triacylglycerols which accumulated under anaerobic conditions differed from the composition of fatty acids in the triacylglycerols present in the growth medium. The cellular unesterified fatty acids of the anaerobically grown cells differed only slightly in composition from the fatty acids in the growth medium, while the unesterfied fatty acids of aerobically grown cells differed to a greater extent from those of the growth medium.


Changes in the cholesterol and phospholipid content of mouse spleen after Raucscher leukemia virus infection. The effect of Rauscher Leukemia Virus (MuLV-R) infection on the lipid composition of mouse spleen from BALB/c mice was investigated. Drastic changes in the lipid composition of the spleen as a result of tumor growth induced by the virus could be demonstrated at 21 days after infection. The molar ratio of cholesterol to phospholipids was found to be low, while a shift within the choline containing phospholipid classes resulted into a lower sphingomyelin and a higher phosphatidyl choline content of the MuLV-R infected spleen. The cholesterol ester content increased more than two-fold during tumor growth, and shifts in the fatty acid patterns of the lipids were demonstrated.


High pressure reverse phase liquid chromatography of fatty acid p-bromophenacyl esters. High pressure reverse phase liquid chromatography has been employed to rapidly separate saturated and unsaturated fatty acids as the corresponding p-bromophenacyl esters. Through  the use of a highly efficient C18 reverse phase column packing, it has also been possible to distinguish among geometrical and positional isomers of the unsaturated acids. The use of ultroviolet-sensitive esters has permitted the detection of low (nanogram range) concentrations of fatty acids. The time required for analysis has been further reduced by employing a novel and rapid method for the preparation of the esters.


Diester waxes containing 2-hydroxy fatty acids from the uropygial gland secretion of the white stork (Ciconia ciconia). The uropygial gland of the white stork secrets mono- and diester waxes as well as triglycerides, all of which contain unbranched medium chain fatty acids. n-Decanol and n-dodecanol have been the only alcohols detected in both types of waxes. The diester waxes contain 2-hydroxy fatty acids.


Blood sampling techniques for studying rapidly turning over metabolic fuels in mice. Experiments were carried out in control and Ehrlich ascites carcinomatous mice to determine whether orbital venous sinus blood could be used to reflect blood in the systemic circulation (decapitation blood) in the case of a rapidly turning over metabolic fuel such as free fatty acids. The early time course of intravenously injected, labeled free fatty acids was measured using (9, 10-(3)H) palmitic acid and (1-(14)C) linoleate complexed to mouse serum. No significant differences between decapitation and orbital sinus blood were found at early times in either group of mice. The orbital sinus clearly contains blood that is not stagnant and is replaced so rapidly that it is suitable for studying very rapidly turning over, circulating metabolites.


Binding of squalene, lanosterol, desmosterol, and cholesterol to proteins in brain and liver 105,000 g supernatant fractions: evidence for specific binding sites. The binding of squalene, lanosterol, desmosterol, and cholesterol to proteins in 105,000 g supernatant fraction (S105) from brain and liver of rats was investigated. The S105 fractions from both tissues contain specific binding sites for sterols, which are sensitive to trypsin. The dissociation constants for squalene and sterol protein complexes were in the range of 10(-6) M and were not appreciably different for proteins in brain and liver S105. Competition studies revealed that both brain and liver S105 contain one receptor protein which binds lanosterol and is specific for methyl sterols, and a second receptor which binds both desmosterol and cholesterol. Binding of 7-dehydrocholesterol reported by others must occur at a third independent site since this compound does not interfere with the binding of lanosterol, desmosterol, or cholesterol. Although binding of squalene to proteins in brain and liver S105 does occur, we were unable to show the specificity of squalene binding. The concentration of desmosterol and cholesterol binding sites, which ranged from 6 to 10 nmol/mg protein, was 3- to 5-fold higher than the concentration of squalene and lanosterol binding sites (1.6-2.3 nmol/mg protein). The brain S105 from suckling rats contained fewer binding sites for desmosterol and cholesterol than the brain S105 from weaned rats. However, the concentration of lanosterol binding sites in brain S105 did not show an age-dependent change. The receptor proteins in brain and liver appear to be identical.


Lipid absorption in the young of protein-deficient rats. The effect of reduced protein in the diet during pregnancy on the subsequent absorption of triolein and of oleic acid which were infused into the intestine of the young was studied. Pregnant rats were fed diets containing either 24% or 4% casein as the sole source of protein. Control and prenatally protein-deprived (PPD) young were studied at birth before and after suckling, and at 4, 8, and 12 days. Both body weight and the weight and length of intestine were reduced in PPD young. Uptake of triolein from the lumen and retention in enterocytes increased on suckling in newborn control pups, but the amount transferred from or metabolized by the cells did not change. In suckled PPD young, transfer of triolein increased through the enterocyte as well. Unsuckled PPD pups had reduced absorption and retention per enterocyte, per g body weight, per cm gut, and in total. In intestines of control and PPD suckled newborn and postnatal pups, absorption per cell did not differ. Blood lipid levels were increased markedly between 0 and 14 days and tended to decrease to newborn levels by 12 days in both diet groups. Oleic acid absorption in newborn and 12-day PPD pups were reduced in total, per g body weight and per cm of gut. The individual enterocytes were shown to be equally capable of absorption and transfer of triolein and oleic acid. Differences in absorption are related primarily to the numbers of absorptive cells.