Stochastic studies of aging and mortality in multicellular organisms. II. The finite theory. We extend the development of a quantitative phenomenological theory of aging rooted in order theory. An organism is represented abstractly by a chain with a finite number of links. Each link corresponds to a possible rate-limiting event or process in senescence. A link is said to break when the corresponding event occurs or the corresponding process goes to completion. The chain is said to break, and the organism subsequently to perish, when the first link breaks, whichever link that might be. Two models are introduced to describe the failure of an arbitrary link. The first requires that a link break only after sustaining a fixed amount of deterioration; the second associates a non-zero probability of failure with each level of wear. The net deterioration of an intact chain is taken, crudely, to correspond to the decline in physiological vitality sustained by an organism during senescence. Failure of an arbitrary link is described in both models by a Markov process. The corresponding mortality rate derived in each instance describes aspects of available empirical data which cannot be accounted for by either the Gompertz or power-law relations. The decline in vitality is shown in both cases to be linear over time intervals of practical interest. The influence of temperature on the senescence of poikilotherms is briefly examined. We describe the effect of temperature both on longevity and the decline in vitality; indicate how substantial discrepancies can arise in the calculation of a macroscopic, effective, activation enthalpy; and lend theoretical support to the existence of temperature--memory effects in senescence.


Hydrocortisone: a specific modulator of in vitro cell proliferation and aging. The effects of hydrocortisone on the proliferative activity of various vertebrate fibroblast-like cell lines have been measured. The proliferative activity of human fetal lung-derived cell lines, such as WI-38, and those of human fetal foreskin origin were always enhanced by the hormone. The addition of hydrocortisone to a number of other vertebrate cell lines grown under identical conditions showed growth inhibition. We also determined that the stimulation of WI-38 cell growth by hydrocortisone was a specific steroid-cell interaction by testing the growth promoting activity of several steroids with molecular structures similar to that of hydrocortisone. This observation was further supported by the presence of high effinity glucocorticoid binding sites in WI-38 cells whose concentration per cell was found to decrease with increased in vitro age. The results suggest that the proliferative response to hydrocortisone shows a cell-type specificity as well as a steroid-molecular structure specificity. The response appears to be mediated by high affinity glucocorticoid binding sites.


Age-dependent gene induction in quail oviduct. VII. Alteration of DNA polymerase activities in response to progesterone treatment. The changes of DNA synthesis as well as the alterations of DNA polymerase alpha and beta have been determined in oviducts from immature (35 days old), mature (about 300 days old) and senescent (about 3 years old) quails in response to diethylstilbestrol (DES). The DNA synthesis in oviducts from immature quails is strongly stimulated by DES; after 12 days, values equivalent to those determined in mature and senescent animals are reached. The DNA synthesis in immature oviducts can be reversibly blocked by progesterone administration; no influence is observed in the case of DNA synthesis in mature as well as senescent animals. During DNA synthesis in immature oviducts, stimulated with DES, DNA polymerase alpha is strongly induced. Co-administration of progesterone blocks this enzyme induction in a reversible and strong way. The activity of DNA polymerase alpha is identical in mature and in immature animals (after DES treatment for 15 days); the activity of the same enzyme in senescent animals is about 40% lower than the values found in the younger quails. The activity of DNA polymerase beta is not altered if the animals are treated with DES or with DES and progersterone; however, the basic level of the enzyme in senescent animals in 50% lower than in immature or in mature animals.


Developmental restrictions on transcription: determinants of the developmental program and their role in aging. A developing plant system, the soybean hypocotyl has been used to investigate early transcription events which restrict auxin induced cellular proliferation to the appropriate developmental stage. Auxin treatment of 4-day old seedlings resulted in an early (6 hour) activation of chromatin-bound RNA polymerase activity wihich approached 200% of control values by 18 hours. This occurred without a detectable alteration in chromatin template capacity (assayed with exogenous RNA polymerase) and resulted in the synthesis of "induced RNA transcripts" as determined in vitro by nearest neighbor analysis. In contrast, auxin treatment of unresponsive 8-day old seedlings did not alter the chromatin-bound RNA polymerase activity. Hormonal activation did, however, result in the exposure of "induced template" regions in chromatin which could only be transcribed in vitro if exogenous RNA polymerase was included in the transcription reaction. Isoelectric focusing of the endogenous chromatin-bound and soluble RNA polymerase enzymes from successive developmental stages revealed that the chromatin-bound enzymes at the 2-day stage were first released from the chromatin complex and could be recovered in the soluble pool (4-day stage). This was followed by a gradual disappearance of these subspecies (6-day stage) until only a limited ensemble of RNA polymerase subspecies remained bound to chromatin and free in the soluble pool (8-day stage). Similar analyses of both the bound and free enzymes at the 4 and 8-day stages following auxin treatment revealed that the 4-day soluble enzymes could be induced to rebind to the chromatin complex in a defined sequence after hormone treatment while those of the 8-day hypocotyl were unable to do so. These developmental events indicate that the select loss of certain RNA polymerase subspecies serves to restrict the hormone responsivness of this tissue to the early developmental stages. Such restrictions could thus commit the constituent hypocotyl cells to their terminal post-mitotic phase of development.


Factors influencing styles of medical practice: the use of psychiatric referrals by non-psychiatric physicians. There is substantial variation between physicians in the extent to which they employ psychiatric referral as a mechanism for dealing with their patients who have psychiatric problems. A variety of factors, including personal characteristics, professional attitudes, training and practice characteristics, were hypothesized to influence styles of practice in this area of medicine. A regression equation with a multiple R of .71 indicated that personal characteristics and attitudes were particularly strongly related, but that practice and patient characteristics as well as training also play some role in influencing a physician's behavior.


Physician awareness of economic factors in clinical decision-making. Physicians' awareness of economic factors in clinical decision-making at one large urban university medical center was studied by a 50-item questionnaire. Their dollar estimates were considered correct if within +/- 20 per cent of the true October 1976 figure. Eighty-one per cent of the house staff and all of the attendings correctly estimated the daily semi-private room rate, but only 15 per cent of each group correctly estimated the charge for a serum potassium. Roughly half of the questions concerning various third-party benefit plans were answered correctly. These results are consistent with those of the few previous studies. If the findings are generally applicable, they may suggest that a directed teaching program in simple economic facts and principles may be useful at all levels of physician training.


Patient race and physician performances: quality of medical care, hospital admissions and hospital stays. The study has attempted to determine the extent of the relationship between patient race and physicians' performances in patient care. The sample of the study consisted of 3175 hospital episode of patients discharged from 22 short-term general hospitals in the state of Hawaii. The episodes were derived from 15 major diagnostic categories. Physicians performances were measured on the basis of the quality of medical care provided, the appropriateness of hospital admissions, and the appropriateness of hospital stays, including understays and overstays. The study has found: 1) that patient race had very limited influence on physicians' performances: the quality of medical care, the appropriateness of hospital admissions, and the appropriateness of hospital stays; 2) that Asian-Americans receive medical care equal to that of the white Americans (once they had access to the health care systems), at least in the state of Hawaii; 3) that among Asian-Americans, there was no distinct difference in medical care received by Japanese, Chinese, and Filipino; 4) that there was clear evidence of racial mutual selection between patients and physicians; and 5) that patients treated by the physicians with the same racial/ethnic backgrounds received care neither superior nor inferior to the care received by patients from the physicians with different backgrounds.


Care process and patient outcome in diabetes mellitus. The relationship between the process of medical care and patient outcome is a central issue in health services research. We examined this relationship in 244 patients with adult-onset diabetes mellitus, who were under the care of private internists and family physicians. Process measures included physician awareness of patients' concerns, communication of information from physician to patient, medication-taking behavior, physician adherence to minimum care criteria, and extent of patient utilization of services. Outcomes measured during and after a 6-month follow-up period, included diabetic control status and patient satisfaction with medical care. Potentially confounding variables included practice and physician characteristics, patient demographic characteristics, and measures of disease severity. There was a small statistically significant correlation between physician awareness and control status, but the association was not maintained when controlling for other variables. Communication of information from physician to patient was significantly (p less than .005) associated with satisfaction in the multiple regression analysis but explained only 4 per cent of the variance in patient satisfaction. Thus, in patients under treatment for diabetes, there was little association between certain measures of care process and patient outcome. We suggest that process and outcome assessments are distinct but complementary aspects of quality of care.


A new intermediate dental outcome measure: amalgam replacement rate. The length of time amalgam restorations last before replacement was investigated for use as an intermediate outcome measure in utilization review and quality assurance studies. Based on record data from 37 general dental practices, a determination was made of the average percentage of two- or three-surface amalgams receiving another service at 6, 12, and 24 months from the date of insertion. After 2 years, approximately 13 per cent of the amalgams were replaced, and the estimated median life time for amalgams was between 10 and 14 years. The variation in replacement rates among practices was substantial but was not explained by the technical quality of restorations or several practice characteristics.


[Giant cells arteritis. A disease previously reported as various syndromes (author's transl)]. Thirteen cases of giant cell arteritis admitted to a Department of Internal Medicine between 1962 and 1977 are reviewed. Giant cell arteritis exhibited different clinical forms, including: temporal arteritis, rheumatic polymyalgia, syndrome of the supra-aortic trunks, cranial arteritis in its ophthalmic and neurologic forms, and generalized arteritis. On the basis of the clinical data, overall examinations, laboratory tests, X-rays, angiograms and histopathologic findings the authors conclude that a single disease is involved. The fact that various of the symptoms occur simultaneously in different patients and that all of the clinical forms have a common pathologic basis points toward giant cell arteritis with different clinical manifestations.


[Carcinomatous lymphangitis of the lung. Report of 21 cases (author's transl)]. Twenty-one cases of carcinomatous lymphangitis of the lung are reported. In diagnosing them clinical, roentgenologic, and histopathologic criteria were used and the clinical, roentgenologic and evolutive findins were considered in order to emphasize the origin of the primitive neoplasm. From this point of view the principal ones turned out to be carcinomas of the breast, stomach, and lung. The absence of carcinoma of the thyroid gland as a source of pulmonary lymphangitis carcinomatosa must be pointed out. The higher incidence of this condition in older people and the clear predominance in the female sex are stressed. From a clinical standpoint the most important data were the existence of cough and dyspnea, which are often associated with the commom presence of enlarged left supraclavicular or axillary lymph nodes. There was a predominant pure interstitial pattern (the most common feature was the presence of Kerley's A or B lines), sometimes coexisting with alveolar impairment and very often with accompanying pleural effusion. The mean survival rate was 2 months, with a maximum of 7 months and a minimum of 3 days. The results of the present series were compared with those of the literature and the most significant and constant fact in both instances was that two thirds of the cases of pulmonary lymphangitis carcinomatosa had their origin in neoplasms of the breast, stomach, and lung.


[Early prognosis of acute pancreatitis (author's transl)]. One hundred patients with acute pancreatitis are studied. The results in 90 cases were "favorable or very favorable", in ten cases "unfavorable or death". Various different characterisitics were analyzed statistically in relationship to the two types of outcome: sex, clinical histories, and results of physical examination. Furthermore, the individual relationships between age, main initial analytic parameters, and later development were determined. In our experience neither age nor sex, considered individually, showed a significant relationship to the seriousness of the disease. Having had pancreatitis previously proved to be a favorable factor (p less than 0.005). None of the other factors in the case histories showed any bearing of the later course of the condition. Findings in physical examination which were signs of unfavorable prognosis included jaundice (p less than 0.001), low blood pressure (p less than 0.001), tachycardia (p less than 0.005), intestinal paresia (p less than 0.001), pain following decompression (p less than 0.025), and abdominal tenderness (p less than 0.05). Abnormalities in ECG (p less than 0.005), marked leukocytosis (p less than 0.0005), hyperglycemia (p less than 0.02), hypocalcemia (p less than 0.05), and high values for the coefficient of amilase/creatinine clearance (p less than 0.01) also suggested an unfavorable course.


[Study of the causes of death in a hemodialysis unit (author's transl)]. A review is made of the deaths which occurred in a hemodialysis unit between 1969 and 1977. Sixty-two patients were treated during this period, 18 of whom died. The actuarial percentages of survival are also established. The mortality rate was 15.5 percent during the initial period and 31.5 percent after the fourth year. Deaths in the first monts were caused by cardiac and infectious complications. Those occurring at a later period resulted from the lack of good vascular access which is necessary to maintain a good quality of dialysis.


[Chronic lymphoid leukemia. Survival in relation to clinical stages. Statistical analysis of 95 cases (author's transl)]. The prognosis of patients with chronic lymphocytic leukemia is very difficult to evaluate. The classification system by stages, which at the present time is the most simple and useful method for the prognosis of this disease, recognizes five degrees of involvement: stage 0 (medullary and peripheral lymphocytosis); stage I (lymphocytosis + enlarged lymph nodes); stage II (lymphocyosis + hepato-and/or splenomegaly); stage III (lymphocytosis + anemia), and stage IV (lymphocytosis + thrombocytopenia). In the present report 95 controlled patients at the Farreras Valentí School of Hematology are analyzed using the classification by stages; there were 19 cases in stage 0; 16 in stage I; 30 in stage II; 21 in stage III, and 9 in stage IV. The mean survival rate in the global series was 63 months and the average 90.9 months. As in other series, it was observed that patients in stages 0 and I have a much better prognosis than those in stages III and IV. Stage II occupies an intermediate position in relation to prognosis, since the actuarial survival figure for this stage can practically be superimposed on that of the global series. The classification of chronic lymphocytic leukemia by stages permits the specification of the therapeutic indications for this condition; it also encourages the search for new modalities of treatment for stages with poor prognosis, since in these cases chronic lymphocytic leukemia behaves in the manner of an acute or subacute hemopathy.


[Granulomatous hepatitis. Etiologic study of 107 cases (author's transl)]. An etiologic study was made of 107 cases of granulomatous hepatitis which were observed in a Department of Internal Medicine between January, 1971 and December, 1977 (excluding the hepatobiliary diseases). The most common etiology was tuberculosis (30 cases, 28 percent) followed by sarcoidosis (19 cases, 17.7 percent), Mediterranean exanthematous fever (13 cases, 12.1 percent), brucellosis (8 cases, 7.4 percent) typhoid fever (7 cases, 6.5 percent) and the idiopathic forms (8 cases, 7.4 percent). A lower rate of incidence was among Hodgkin's disease, toxoplasmosis, adenocarcinomas, leprosy, and those of unknown etiology, classified in this way because the study and follow-up of the patients could not be completed. There were, moreover, individual cases caused by mononucleosis, BCG reaction, hypogammaglobulinemia, celiac disease, and temporal arteritis. From a clinical point of view 50 percent of the patients had hepatomegaly and moderate disturbance of the liver enzymes. The most important enzymatic increases were detected in the cases caused by brucellosis; in the cases which were secondary to sarcoidosis the liver enzymes were normal. A comparison is established between the etiologic incidence of the present series and of others published in the literature. The causes and diagnostic problems of this type of lesion are discussed.


[Hemodialysis and complement (author's transl)]. After observing alterations in the activity of the serum complement in patients undergoing periodic hemodialysis, the authors performed a preliminary study to determine repeatedly the activity of C3, C4, and CH50 in 44 patients. They discovered a consistent drop in C3 and CH50 while C4 remained normal. An attempt to explain these findings with information from the literature offered no more than a hypothesis for further study. While the possibility of a decline in the synthesis of the complement factors cannot be disregarded, the authors believe it is much more probable that they are consumed at a rate higher than normal. Since the C4 factor does not appear to be involved, activation is probably along the alternative pathway. Defective synthesis cannot be attributed to liver disease because the latter is not always present and because there is no relationship between C3 levels and levels of albumin or the presence of hepatopathy. The literature was reviewed for data that might support the idea that the complements in these patients are activated continuously by some process in connection with dialysis, by chemical products employed for to clean the machines, by commonly administered drugs, etc. Because so few data could be found on the subject, the authors consider that is necessary to study these mechanisms and their repercussions over a longer period of time.


[Roentgenologic characteristics of Gaucher's disease (author's transl)]. Gaucher's disease is a rare metabolic disorder in which there is an abnormal accumulation of cerebrosides in the reticuloendothelial system due to a deficit of beta-glucuronidase. Three patients with this disease, 8, 14, and 23 years old, were studied. The purpose of this paper is to point out some of the roentgenologic findings, such as areas of femoral osteolysis, renal venous thrombosis, and in one patient, sclerosis of the sacroiliac joint. Splenomegaly and alteration of the tubular bony structure of the distal end of the femur were present in all three cases. The roentgenologic images of the disease are discussed. The osteoarticular system is the most often affected. Osteolysis is the basic lesion with expansion of the bone marrow and sclerosis. The earliest symptom and sometimes the only one is the Erlenmeyer flask deformity or widening of the distal portion of the femur. Sometimes there is a high degree of deossification without definite osteolytic lesions. Pathologic fractures and fractures caused by pressure of the vertebral bodies are common. Aseptic femoral necrosis are often present. Other less frequent sites of osteoarticular pathology are the skull, jaws, ribs, and sacroiliac joints. Splenomegaly is the most frequent visceral lesion. Other organs sometimes affected are the liver, kidneys, heart, lymphatic system, and lungs, with nodular or basal reticular infiltrations.


[Liver disease associated with hypernephroma. A case report (author's transl)]. The observation of a non-metastatic reactive hepatopathy associated with a hypernephroma in a 39-year-old man who had had fever for 4 months led to a review of the literature and an analysis of basically three aspects of the disorder: a) The various manifestations of carcinoma of the kidney, which include a large number of paraneoplastic clinical symptoms (polycythemia, anemia, prolonged fever, hypercalcemia, hypertension, nefropathy, loss of salt, peripheral neuropathy, and amyloidosis); b) an alteracion of hepatic function known since 1961 which is characterized by an abnormal retention of sulfobromophthalein, increase of alkaline phosphatase, prothrombin decrease, dysproteinemia with hypoalbuminemia, and alpha2-globulin increase. It may or may not be accompanied by enlargement of the liver. c) Criteria of operability of the primary tumor.


[Bile acids. I. Nature, physiology, and functions (author's transl)]. Bile acids play a fundamental role in the degradation and absorption of intestinal lipids. The primary ones are cholic acid and chenodeoxycholic acid which are synthesized from cholesterol in the liver and conjugate with taurine and glycine amino acids. The secondary bile acids are derived from the primary ones by the enzyme action of intestinal bacteria through a process of deconjugation and dehydroxylation. Their detergent property is based on the molecular configuration of these compounds, which present a hydrophilic and a hydrotion of these compounds, which present a hydrophilic and a hydrophobic surface. The different enzymes in the liver cells that intervene in the process of synthesis of bile acids are now known. A basic element in their physiology is the enterohepatic circulation, enabling the organism to take maximum advantage of these compounds. The dynamics of the cycle are maintained and regulated by the system of uptake and secretion of the cells, cholecystokinin, intestinal peristalsis, active transport across the ileal membrane, and by portal venous flow. Much of our knowledge about the biogenesis and functions of the bile acids has been acquired quite recently. Research over the past three decades has contributed to a great advance in our understanding of their physiology.


[Platelet function in systemic lupus erythematosus (author's transl)]. The platelet function was studied in 23 patients with systemic lupus erythematosus, all of whom met the diagnostic creteria established by the American Rheumatism Association. They were not under any treatment, especially with any drug that might interfere with platelet function. The same study was performed on a control group composed of volunteers donors at a blood bank. The platelet count was definitely lower in the patients with lupus than in the control subjects (p less than 0.0005), although a clear thrombopenia was observed in only two indivduals (8.7 percent). Anti-platelet antibodies were found in only six cases (26 percent). There was a linear correlation between thrombopenia and the presence of hemorrhagic diathesis and low levels of C4 and CH50 components. Plateler adhesiveness was clearly lower in the lupus group than in the control group (p less than 0.0005). The presence of kidney disease determined a greater impairment of the platelet adhesiveness (p less than 0.0025). A notable defect on platelet aggregation was induced by ADP, adrenaline and collagen. This was more apparent in the group of patients exhibiting a higher degree of clinical activity and in those who showed a serum complement decrease. The mechanism responsible for this thrombopathy appears to be an interference in the platelet function due to the presence of circulating immunocomplexes. They adhere to the platelet membrane blocking its function and inhibiting the release of the necessary thrombocytic components for the second phase of the aggregation. This platelet alteration is not usually manifested clinically; for this reason no relationship was found between this platelet defect and the presence of hemorrhagic symptoms in our patients. The condition is reversible and may disappear after therapy with steroids and/or immunosuppresive agents.


[Epidemiologic data on bronchogenic carcinoma (author's transl)]. The Bronchogenic Carcinoma Co-operative Group analyzed the epidemiologic data of 240 cases of bronchogenic carcinoma in a prospective study. When risk factors (exposure to potencial pathogenic substances) were studied, a relationship was noted between the incidence at an early age and the presence of nondifferentiated small cell carcinoma. The number of years of exposure to tobacco had a direct effect on the curative value of the thoracotomy and the survival rate. Forty years of smoking appeared to be borderline for a poor prognosis. Localization of the tumor by bronchoscopy showed a frequency in the left main bronchus (18 percent) more than twice than in the right (8 percent). In 25 percent of the cases the tumor was more peripheral than the subsegmental situation according to the bronchofiberoptic examination. Evaluation of clinical data only showed a lack of correlation between the different symptoms and the various means of evaluation and the prognosis of the disease. For example, a patient with hemoptysis has a statistically higher probability of having an epidermoid tumor and a greater possibility of a successful curative thoracotomy (23 percent as opposed to 17 percent for the rest). The group of incidental cases (9 percent of the total) was analyzed. The degree of resectability was higher as compared with the rest (62 percent against 34 percent) as well as the absence of nondifferentiated small cell type carcinomas.


[Role of secondary hyperaldosteronism in the pathomecanism of hydropic decompensation in the cirrhotic patient (author's transl)]. Plasma aldosterone levels before and after walking were compared in a series of 10 controls and 41 patients with cirrhosis of the liver. The latter were distributed in the following way: 8 had compensated cirrhosis, the remaining 33 were in a situación of hydropic decompensation, 10 with associated renal insufficiency, and 23 without. Basal aldosterone levels in compensated cirrhotics were similar to those of the controls, but these values increased significantly more than the controls following postural stimulation. Decompensated cirrhotics without renal insufficiency had significantly higher values than the controls, both in basal conditions and after stimulation. The highest values corresponded to the decompensated cirrhotic patients with renal insufficiency who were in advanced stages of liver disease. On the basis of the present findings and those of other authors, it is suggested that a certain reduction in the metabolic clearance of aldosterone appears to exist in hepatic cirrhosis. However, hormonal hyperproduction is the dominant factor in the pathogenic mechanism of secondary hyperaldosteronism. The pathogenesis of the excessive production of hormone is discussed. In conclusion, it appears that the scant affluence of sodium to the macula densa may be the primary factor in explaining this common situation in patients with cirrhosis of the liver.


[Non-secretory myeloma. Report of a case with negative immunofluorescence in the tumor cells (author's transl)]. A 39-year-old patient with bilateral paralysis of the VI cranial nerve was studied. Numerous foci of intracranial osteolysis were discovered as well as on the right calvicle and several ribs. Two bone marrow aspirates gave results within normal limits. A biopsy of the lesion on the right calvicle led to the diagnosis of myelomatosis. Immunoelectrophoresis showed that paraprotein was not present in serum and urine. Immunofluorescence with antisera marked with fluorescein was negative in the diseased bone marrow. Treatment with melphalan and prednisone given alternately produced an improvement in all of the lytic lesions within several months; 20 months after treatment was started no new destructive bony lesions have appeared. There have been very few reported cases of non-secretory myeloma. In most of these cases the presence of immunoglobulins in the tumoral cells has been shown by immunofluorescence. The absence of the immunoglobulins, as described in our case, is extremely rare. Unlike most cases of non-secretory myeloma published to date, our patient has a favorable clinical course after treatment was administered.


[Sarcoidosis, toxic thyroid adenoma, and De Quervain's thyroiditis. Association or coincidence (author's transl)]. The case of an association of three well-differentiated pathologies is reported. A 40-year-old woman with a toxic thyroid adenoma developed acute polyarthritis during the course of the disease. The articular symptoms together with chest X-rays and a consistently negative PPD (1:100) were suggestive of sarcoidosis. This was later confirmed by the discovery of non-caseating granulomas in the liver and superficial lymph nodes, and by a positive Kveim's test. Histopathologic examination of the thyroid gland confirmed the existence of the adenoma. Sarcoid infiltration was not observed, but on the other hand the typical images of subacute granulomatous thyroiditis (De Quervain's thyroiditis) were discovered.


[Viral etiology of insulin-dependent diabetes (author's transl)]. Data are collected here that may support the hypothesis that there is an infectious component in the genesis of insulin-dependent diabetes mellitus. The clinical and experimental data on which that hypothesis is based referring to viruses such as: mumps virus, rubella virus, encephalomyocarditis virus, and Coxsackie B viruses, are presented. The authors mention the pathogenic mechanism, which extends over the existence of diabetogenic genes linked to the major complex of the histocompatibility HLA system, as well as the existence of an autoimmune reaction induced by the infecting virus. This review shows up the large gaps that exist in the accurate knowledge we have about the possible infectious etiology of diabetes. However, it also offers different pathogenic possibilities for further experimental investigations on bases that are reasonably scientifically consistent.


A simple data-processing system for the monitoring of cross-infection in a district general hospital. A year's trail has demonstrated the effectiveness of a simple data processing system in the early identification of cross-infection problems at their source. The system has particular advantanges for small and scattered surgical units where cross-infection monitoring is particularly difficult because patients are transferred before their treatment is complete. A simple extension of the system could audit the efficiency of preventive antiseptic measures, particularly aseptic techniques, and provide antibiotic profiles.


History and future of the MUMPS in medical computing. MUMPS is an integrated language and operating system. It was originally developed in the mid 60s, primarily for the interactive manipulation of text-like, hierachical data found so pervasively in medicine. This paper traces the growth in use of MUMPS. Some of the many medical application for which MUMPS is used are discussed, as are the achievements and goals of the MUMPS Users' Group, particularly in facilitating application transfer. The influence of federal funding upon the growth and use of MUMPS is noted. Of particular importance is the federal support of the MUMPS Development Committee in the standardization of MUMPS, and the MUMPS User's Group in promoting MUMPS information and application exchange.


Analysis of the oxygen supply to porous implants in bone. A mathematical model of cylindrical porous surgical implant for orthopaedic prosthesis is presented. The model allows calculation of the net oxygen consumption as a function of porosity and pore diameter from 0 to 500 microM. In addition, limitations on implant size and pore diameter due to the length of the arteriole 'tree' have been considered. Literature data have been used to evaluate the model of the implant when infiltrated with bone in the steady-state. The model suggests that minimum pore diameter of 75 microM is necessary for bone ingrowth. Further, the limiting relationship between pellet diameter and pore diameter due to arterial tree length has been found to be a nearly linear function, with slope dependent on the tortuosity of the pores of the implant.


MUMPS applications in doctor's office systems. As basic elements of an information network in ambulatory care, doctor's office computers are currently being tested in various hardward and software configurations. MUMPS has proved to be most effective in developing complex text-oriented application packages on small-scale computers. Separation of program and text modules increased the flexibiltiy necessary to serve different medical specialities. The final goal of the project is improved economic and organizational efficiency in the management of ambulatory care. The field test is supported by the German government (DOMINIG DVM 404).


[Symptomatology and treatment of malformations of the inferior vena cava (author's transl)]. A review of the embryology, pathophysiology semiotics and surgical treatment of malformations of the inferior vena cava is given based on 3 clinical histories. The cases consisted of a typical membrane occlusion, an atresia of the infrarenal segment and of a hitherto not described combination of several malformations of the inferior vena cava: membrane occlusion, aplasia of the infrarenal segment of the vena cava inferior and multiple aneurysms of the iliac vein. The symptomatology of malformations of the vena cava inferior depends on the compensation by the collateral or the persisting embryonic veins, respectively, and on the localization and the degree of the obliteration. The varying hemodynamic reactions are described. The following surgical methods for the treatment of inferior vena cava occlusions in the hepatic segment are available: The so called conservative interventions for the creation of collaterals, the direct or indirect recanalization and the bypass operation. Congenital infrarenal atresias of the vena cava are corrected by homologous or prosthetic interposition. The venous replacement with a bovine heterograft presented here, has not yet been described in the literature.


[Experiences in 130 operations of carotid elongation (author's transl)]. A report on 130 operations of carotid elongation is presented. Indications for reconstruction are based on angiography, neurologic symptoms, and recently, on ultrasonography (Doppler's). Several surgical methods have been performed: 25 resections of the internal carotid artery, 5 resections of the common carotid artery, 3 resections of loop aneurysms. The main operative techniques were resection and neoimplantation, the latter with patch-plastic surgery. Usually, a shunt was used. Mortality was 0%, lethality, 2%. During a follow-up period of 6 weeks to 2 years, 86% of the patients were found to be free of complaints, and 14% were without change of the neurologic symptoms. The good neurologic results are convincing.


[Surgery of bronchus carcinoma (author's transl)]. The results of surgery for bronchial carcinoma can be improved by further stressing of early diagnosis, by operative methods adapted to oncological needs and assessment of techniques which increase operability as well as by adequate and general additional therapy. Based on our material of 8,423 patients of which 2,773 (i.e. 23%) have been operated the results of the operation in relation to type of operation, histology, Feinstein's classification, TNM stages and other are demonstrated.


[Reconstructive procedure in aortoiliofemoral occlusive disease (author's transl)]. Based on experience with about 1,000 patients with operable aortoiliofemoral occlusive disease, the factors influencing the operative procedure are discussed. These include the angiographic picture, the severity of ischemia, general risks, accessibility of the operating field, and availability of reconstructive material. It is concluded that, in discussing the operative procedure in aortoiliofemoral occlusive disease, the central question must be, which procedure is best for this patient, in view of his special circumstances, and not, which procedure is technically possible.


[The distal spleno-renal anastomosis of Warren (author's transl)]. This is a report on 28 Warren-Shunts, 17 of these patients had undergone clinical, hematological and angiographic controls 2--46 (mean 10) months after the operation. The critical evaluation of the results shows that the Warren derivation, which is selective at the moment of operation, develops in the following time some hepatofugal circulation. This is a more radical effect than the intended drainage of the gastro-esophageal venous bed alone.


[Cumulometry with fast components of nystagmus (author's transl)]. The cumulogram of slow nystagmus phases has proved as a useful method for the analysis of vestibular nystagmus. However, its computation depends on the availability of special apparatuses. Therefore, the relations are studied between the cumulogram of slow phases and the cumulogram of fast phases that can be determined more easily. The analysis of 57 pendular tests shows the close correlation (r = 0,98) of the respective values for vestibular gain. Considering the statistical connection the comparison of these two methods and their results, resp., is well practicable.


[Malignant fly-grub infection (myiasis) of the ear (author's transl)]. On the basis of an own observation of a malignant fly-grub infection of the ear and by means of a detailed checking of the literature a benignant and a malignant shape of this disease are distinguished. The peculiarities of the mode of infection in relation to the fly-species are described, some apparent typical characteristics of the Muscidae-Larva infection are put out and directions for treatment are given. The disease nearly wrotten in Europe to-day was not a seldom event especially in the eastern parts of Germany.


[Sarcoidosis of the larynx (author's transl)]. The isolated case of sarcoidosis of the larynx is very rare. We are referred to a case of histologically confirmed by the kweim-test of sarcoidosis of the false vocal cord. The problems of the case are discussed.


Malignant melanoma of the scalp.

Malignant melanoma of the scalp. Malignant melanoma of the scalp has a significantly worse prognosis than cutaneous melanoma arising in other head and neck sites. In this series, 125 patients were treated for Stage I invasive melanoma of the scalp and followed 3 to 19 years. Survival rates for these patients were calculated on the basis of several factors. Survival after treatment was not affected by the age and sex of the patient, size and site of the primary, or treatment of the primary lesion, although local failure was higher among those treated by primary excision and closure. Patients undergoing elective neck dissection with histologically negative nodes had significantly better survival rates than those with histologically positive nodes or patients in whom a neck dissection was not performed.


Long-term follow-up of tympanic neurectomy for sialorrhea. Thirty-one patients who had undergone a bilateral tympanic neurectomy (sectioning of both Jacobson's nerve and the chorda tympani) for sialorrhea are evaluated after two years (ranging from 24--45 months). Drooling control improved in 74%. There was a significant difference of improvement in the group where a diligent search was made to sever all branches of the tympanic plexus. A 50% improvement was attained in two failures of a tympanic neurectomy who underwent transposition of Stenson's ducts into the tonsillar fossa.


Amyloidosis presenting as a mass in the neck. A 54-year-old white male presented with a large suprahyoid midline mass. On thorough history and physical examination, he had features which characterize amyloidosis, including congestive heart failure and carpal tunnel syndrome. The classification, clinical findings, and associated syndromes are reviewed. A striking feature of the amyloid deposit is its rapid growth. Amyloidosis should now be considered in a differential diagnosis of a neck mass.


Diatrizoate meglumine (Hypaque) treatment for sudden hearing loss. During the 24 month period ending in December 1978, 31 patients with sudden idiopathic sensorineural hearing loss were treated with vasodilators and Hypaque. Fifteen patients met the treatment criteria of being treated within the first month following onset, no vertigo, and the hearing loss was not complete. Twelve patients (80%) had complete return of their hearing. Two patients (13%) had partial return of their hearing, and 1 patient (6%) had no response to treatment. Of the 16 patients treated who did not meet the criteria, 6 patients (38%) had complete return of their hearing. Eight patients (50%) had partial return of their hearing and 2 patients (12%) had no return of their hearing.


Metastatic tumors to the sphenoid sinus. Patients with cranial nerve palsies and roentgenographic evidence of sphenoid sinus destruction present diagnostic problems. Although the presence of local primary neoplasms may be considered first, metastatic disease from distant sites also should be considered. We report on eight patients with metastatic tumors to the sphenoid sinus seen at the Mayo Clinic from 1950 through 1976. Primary sites of the lesions included the breast, thyroid gland, lung, kidney, and prostate (two patients). Metastatic myeloma was seen in two patients. Symptoms resulted from involvement of the structures adjacent to the sphenoid sinus and in all patients included diplopia or decreased visual acuity. In four patients, these ocular symptoms were the first sign of disease, after which a complete general examination disclosed the occult primary sites.


Gunshot injury to the temporal bone: an analysis of thirty-five cases. By retrospective analysis of 35 surviving gunshot injuries to the temporal bone and by presentation of 6 representative cases, the management and reconstructive procedures of these injuries in the Tulane University affiliated hospitals are presented. The most frequent single injury was facial nerve paralysis (16 cases), followed by external canal injury and conductive hearing loss. Anacusis occurred in 12 cases. In conductive hearing loss the intact posterior wall tympanoplasty with mastoidectomy (16 cases), or the modified radical mastoidectomy (5 cases), allowed middle ear reconstruction. Transmastoid facial canal decompression, combined with the above procedures or with a middle fossa craniotomy, was performed in 6 cases. Delayed facial reconstruction (5 cases) utilized microneural anastomosis between facial-facial and hypoglossal-facial nerves and fascia lata slings. Intracranial complications of thrombosis of internal carotid artery, dural venous lacerations, temporal lobe aphasia, bitemporal hemianopsia, cerebral abscesses and meningitis are also discussed.


Alveolar soft part sarcoma of the head and neck. The twelfth case (in 25 years of literature) of alveolar soft part sarcoma of the head and neck is presented. It represents the seventh case to occur in the base of tongue and the second to be associated with pregnancy. The average age of onset is in the second decade with a 2:1 female preponderance and a marked tendency to right-sided occurrence. Treatment with surgery and/or radiotherapy is not curative. Local recurrence is common as are distant metastases, usually to lung, brain or bone. Theoretically, chemotherapy may offer better control of disease but few agents have shown dramatic response. The characteristics of the tumors are discussed and various chemotherapeutic agents are reviewed.


Laryngotracheal trauma: observations on its pathogenesis and its prevention following prolonged orotracheal intubation in the adult. The authors have clinically examined the larynges of 117 patients who were successfully extubated in a Respiratory Care Unit, and have examined the larynges at autopsy from an additional 68 patients who failed to survive in the same Respiratory Care Unit. Based on these observations, our understanding of the pathogenesis of laryngotracheal trauma has allowed us to modify our clinical management in order to minimize such damage. Influence of this study on the management of patients is described.


Biliary cholesterol absorption in normal and L-thyroxin-fed rats. Infusion of bile containing labeled cholesterol into bile fistula rats has permitted an in vivo study of the movements and of the absorption of biliary cholesterol in the digestive tract. The specific activities of cholesterol were similar in the micelles and the sediment of the luminal content after a 6 hr infusion, indicating rapid exchange of cholesterol between these fractions. In animals fed a basal diet, the biliary cholesterol absorption was higher (83%) than that of dietary cholesterol (70%). Bile cholesterol is essentially absorbed in the jejunum while the absorption of cholesterol from the diet takes place all along the small intestine but preferentially in its second and third quarters. Both alimentary cholesterol and bile cholesterol enter the top cells of the villi in preference to those of the crypts. In L-thyroxin-fed rats, a parallel decrease in biliary and dietary cholesterol absorption was observed. The increase in the intestinal transit of cholesterol and epithelium cell renewal of the jejunum accounted for this observation.


Perinatal development of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in rat lung, liver and brain. The developmental pattern of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34), which catalyzes the rate-limiting step of cholesterol biosynthesis, was studied in lung, liver and brain of Sprague-Dawley rats. Each tissue exhibited a distinct pattern. Reductase activity in the fetal lung reached a peak at 19 days of gestation, which corresponds to the onset of active surfactant production. This observation is consistent with the suggestion that the fetal lung synthesizes all surfactant components including cholesterol. In the liver, reductase activity varied in a reciprocal fashion with serum cholesterol levels. The peak of brain reductase activity occurred at 3 days after birth at the onset of rapid brain growth despite rapidly rising serum cholesterol levels.


De novo fatty acid synthesis and fatty acid elongation catalyzed by subcellular fractions from hog and human aorta. De novo synthesis and mitochondrial elongation of fatty acids have been demonstrated in subcellular fractions from hog and human aorta. Microsomal fatty acid elongation has been shown in hog aorta. The activity catalyzing the formation of fatty acids from acetyl and malonyl CoA was associated with a high molecular weight complex in the 6 x 10(6) g x min supernatant fraction. The principal product was palmitic acid. Some myristic and stearic acids were also formed. One elongation system was associated with protein which sedimented between 4500 g x min and 150,000 g x min. It used acetyl CoA but not malonyl CoA, and NADH was the preferred reducing agent. Radioactivity from acetyl CoA was incorporated into many fatty acids. In hog aorta a second elongation system was found associated with protein which sedimented at 6 x 10(6) g x min. It used malonyl CoA preferentially as substrate and either NADH or NADPH as reducing agent.


Age-related changes in glycerolipid formation in lean and obese Zucker rats. Age-related changes in hepatic and adipose glycerolipid formation have been described in Zucker rats. Glycerolipid formation was measured in vitro in the presence of [14C]glycerol-3-phosphate, palmitate, ATP, CoA, and Mg2+ by using liver and adipose tissue homogenates derived from various age groups of animals. Hepatic glycerolipid formation increased after birth to reach a peak value at 1 day of age. This period was followed by a decline in the rates of glycerolipid formation. Hepatic glycerolipid formation increased again at the time of weaning and continued to rise up to 32 days in lean rats and 42-44 days in obese rats. Obesity in rats was recognizable at the age of 32 days and was associated with increased rates of glycerolipid formation in both liver and adipose tissue. As far as the changes in hepatic glycerolipid formation and triglyceride accumulation are concerned, obese rats showed more resemblance to 1-day-old rats than to lean animals of similar age groups. Glycerolipid formation decreased in liver and increased in adipose tissue with age in both lean and obese rats. These studies suggest that hepatic and adipose tissue glycerolipid formation is significantly influenced by age and obesity in Zucker rats.


Effects of diets high in saturated fat and cholesterol on the lipid composition of canine platelets. The phospholipid composition of platelets from dogs on various experimental diets was determined. Thyroidectomized foxhounds were fed a control diet or the control diet supplemented with (1) beef tallow, (2) beef tallow and cholesterol, or (3) beef tallow, cholesterol, and safflower oil for 23 weeks prior to isolation of platelets. Platelets from animals fed the control diet contained 36.7% phosphatidylcholine (PC), 22.8% phosphatidylethanolamine (PE), 18.4% sphingomyelin (Sph), 11.8% phosphatidylserine (PS), 6.3% phosphatidylinositol (PI), and 2.2% lysophosphatidylcholine. The PE was 77.6% in the plasmalogen form. No highly significant changes in the phospholipid class composition resulted from the experimental diets. Cholesterol supplementation of the diets, however, caused consistent alterations in the fatty acid compositions of the platelet phospholipids including increases in the percentages of 18:1 omega 9 (oleic acid), 18:2 omega 6 (linoleic acid), and 20:3 omega 6 (homo-gamma linolenic acid) and a decrease in the percentage of 20:4 omega 6 (arachidonic acid). Addition of safflower oil to the tallow-cholesterol diet partially reversed these effects. These cholesterol-induced alterations in fatty acid composition could be due to exchange with plasma lipids, de novo synthesis, or altered platelet metabolism. The mechanism remains to be determined.


Utilization of various sterols by lecithin-cholesterol acyltransferase as acyl acceptors. Highly purified lecithin-cholesterol acyltransferase of human plasma was used to study the utilization of various sterols as the acyl acceptor. The esterification of sterols was facilitated by the presence of a 3beta-hydroxyl group and the trans configuration of the A/B rings, as was evident from the lack of acceptor activity of all 3 alpha-hydroxy sterols tested and coprostanol. Cholesterol analogs in which the side chain is modified, such as campesterol, beta-sitosterol, desmosterol and stigmasterol, were less effective than cholesterol as acyl acceptors. However, androstan-3 beta-ol, which completely lacks the side chain, was found to be more active than cholesterol. The transfer of the acyl group to all effective sterols required the presence of the cofactor peptide apolipoprotein A-I.


Simultaneous mass spectrometric measurement of prostaglandins E1 (PGE1) and PGE2 with a deuterated internal standard. The use of (3,3,4,4-2H4)PGE2 as internal standard for the quantitative measurement of PGE1 by gas chromatography-mass spectrometry is reported. A method for the simultaneous analysis of PGE1 and PGE2 is also described. The prostaglandins were analyzed by selected ion monitoring as the methyl ester-trimethylsilyl ether (ME-TMS) derivatives of PGB1 and PGB2, respectively. In all cases, a linear response over the range 1 to 70 ng (2.8 to 198 pmoles) was demonstrated. The use of this procedure is exemplified by its application to the PG analysis of sheep seminal vesicles.


Desaturation of eicosa-11,14-dienoic acid in human testes. The metabolism of [1-14C]eicosa-11,14-dienoic acid was investigated in human testes using whole tissue minces and microsomal preparations. Both types of preparations catalyzed the desaturation of the labeled diene to eicosa-8,11,14-trienoic as well as eicosa-5,11,14-trienoic acid. The reported results, therefore, indicate that human testicular tissue, as well as rat testicular tissue (reported previously), is capable of utilizing eicosa-11,14-dienoic acid as a precursor of arachidonic acid. Since it is known that there is no delta 8 desaturase activity in rat liver and brain, these studies support the concept that there is a tissue variation in this enzymatic pathway.


beta-Oxidation of the coenzyme A esters of vaccenic, elaidic, and petroselaidic acids by rat heart mitochondria. Rates of beta-oxidation of the coenzyme A esters of vaccenic, elaidic, and petroselaidic acids as well as their respective cis isomers by rat heart mitochondria were measured and compared. At all concentrations studied, vaccenoyl-CoA was oxidized more rapidly than elaidoyl-CoA, but more slowly than oleoyl-CoA except at high substrate concentrations. All trans octadecenoyl-CoA esters were oxidized at a slower rate than their respective cis or saturated isomers. Oxidation rates decreased as the double bond approached the carboxyl-end.


The formation of phosphatidylinositol by acylation of 2-acyl-sn-glycero-3-phosphorylinositol in rat liver microsomes. The conversion of 2-acyl-sn-glycero-3-phosphorylinositol into phosphatidylinositol via acyl-CoA: 2-acyl-sn-glycero-3-phosphorylinositol acyltransferase activity was found to occur in rat liver microsomes. Over a wide range of conditions, stearic acid was preferred over palmitate by the acyltransferase when these acids were presented in mixtures as acyl-CoA derivatives. The potential importance of this enzyme activity for the entry of stearic acid into the 1-position of hepatic phosphatidylinositol is further supported by its greater preference for stearate relative to the acyl-CoA:2-acyl-sn-glycero-3-phosphorylcholine acyltransferase under certain assay conditions.


The influence of phthalate esters on human plasma lecithin/cholesterol acyltransferase. The effect of various phthalate esters on the lecithin/cholesterol acyltransferase activity in man was studied in vitro. The enzymatic activity was strongly reduced with all phthalates except for the dimethyl phthalate. The inhibition rate depends on the phthalate concentration and also on the carbon number of the alkyl groups of phthalates.


Isoflavones and hypercholesterolemia in rats. Isoflavones isolated from three commonly used pulses such as Bengalgram (Cicer arietinum), greengram (Phaseolus aureus) and blackgram (Phaseolus mungo) and p-coumaric acid were supplemented to hypercholesterolemia-inducing diet of rats. Among isoflavones, Biochanin A and Formononetin showed hypolipidemic activity but diadzein did not; p-coumaric acid also produced a significant reduction in serum cholesterol levels.


Variations in the molecular species of lung phosphatidylglycerol. Approximately 20% of the phosphatidylglycerol of the lung tissue of several animals was found to have both fatty acids saturated. Pulmonary washings from the lung of the rabbit and guinea pig had more saturated phosphatidylglycerol than the washed lung tissue. Lung-saturated phosphatidylglycerol was relatively low in the perinatal period, a time during which saturated phosphatidylcholine accumulated predominantly. This suggests that the metabolism of the saturated species of lung phosphatidylcholine and phosphatidylglycerol, which are considered to be the major pulmonary surfactants, may not be regulated in the same manner, at least in the perinatal lung.


Incorporation of deuterium-labeled cis- and trans-9-octadecenoic acids in humans: plasma, erythrocyte, and platelet phospholipids. The objective of this study was to follow the uptake and distribution of oleic and elaidic acids into human erythrocytes, platelets, and plasma phospholipids. The use of dual and triple labeling methodology permitted a precise comparison of elaidic and oleic acid utilization. Elaidic acid (EI) was selectively concentrated in all the plasma phospholipids except for lysophosphatidylcholine. Three times more elaidic than oleic acid (OI) accumulated in the 1-acyl position of phosphatidylcholine, as determined by hydrolysis with phospholipase A2. Rapid incorporation and removal of elaidate were observed for all samples. These results support the concept that enzymes responsible for acylation of phospholipids are sensitive to double bond configuration and the physical properties of the fatty acid moieties. Labeled fatty acid levels in red cell and platelet phospholipids were much lower than for plasma phospholipids, indicating a relatively slow rate for the in vivo incorporation of fatty acids into blood cell membrane phospholipids. No isotope effect was found when oleic acid labeled with deuterium on the double bond was used.


Uptake of [14C]choline and incorporation into lung phospholipid by the isolated perfused rat lung. We have used the isolated perfused lung (IPL) preparation from the rat to determine whether uptake of choline from the vascular compartment could limit the rate of synthesis of phosphatidyl-choline (PC). The uptake of choline was rapid and did not saturate at a concentration of 10 mM. The rate of incorporation of choline into phospholipid was saturated above 0.1 mM choline. Whereas, uptake and incorporation were depressed at 4 C, uptake was neither dependent on the extracellular sodium concentration nor inhibited by equimolar concentrations of hemicholinium-3 (HC-3). We could find no evidence that uptake might limit synthesis of lung lecithin and conclude that uptake is either by free diffusion, or by a carrier-mediated process with a very high Km.


A simplified procedure for the quantitative extraction of lipids from brain tissue. A method is described for the quantitative extraction of lipid from brain tissue with chloroform/methanol (C/M) that eliminates secondary purification of the lipid extract by dextran-gel chromatography or aqueous washing of the organic extract. Nonlipid substances that generally contaminate C/M lipid extracts are separated by pre-extraction of the tissue with dilute (0.25%) aqueous acetic acid. The residual tissue is extracted twice with 40 volumes of C/M (1:1, v/v). Approximately 97% of the lipid is recovered in these extractions. A third extraction which yields ca. 1% more lipid is performed if the process is discontinued at this stage in a shortened version of the method. The remainder of the lipid is recovered after treatment of the tissue with 1 N HC1 by two additional extractions, the first with 40 volumes of C/M (1:2, v/v) and the second with 40 volumes of methanol. The method, which was demonstrated with pig brain, gave a complete extraction of the lipid, including gangliosides, free of nonlipid substances.


[Thermostat electronic circuit for vital microscopy]. To provide optimal temperature conditions needed for vital microscopy, an electronic circuit for the thermostat has been elaborated. This unit is designed to heat and maintain at a definite temperature level the table for manipulations and the microscope objective. Thermoresistor MMT-4 served as a temperature transducer.


[Evaluation of linear distortions in rheography]. Methods permitting to estimate parameters of hemodynamics through bioimpedance measurements have gained ground in study and diagnosis of the cardiovascular system. The error in bioimpedance measurement depends considerably on dynamic characteristics of the measuring devices being employed. The dynamic characteristics can be investigated by the method evaluating linear distortions. A relation can be established between these characteristics and errors of measuring major informative parameters of a rheographic signal.


[Reading device for the blind based on the transformation of the optical image into a vibrotactile one]. The article describes a device in which the printed text letters after their photo-transforming are presented as a matrix of bimorphous piezoelements in the vibrotactile form. The operation of a bimorph as an element of a tactile matrix has been studied experimentally and requirements to parameters of excitation signals were settled. Consideration is given to the phototactile transformation principle and to some circuits for its practical embodiment.


[Effect of the filler and liquid medium on the surface quality in the vibration treatment of medical equipment products]. The surface quality of products made from stainless steel 40--13 are determined mainly by methods and parameters used for their final processing. Investigation of technological characteristics of different fillers used in vibration processing and, as well, the influence of polyvinyl emulsion-water solution has shown that T-trihedral granules (made at the Moscow Plant of Abrasive Articles) can be the choice for the vibration processing of details of stainless steel 40 X 13. The polymeric component in the liquid technological medium, instead of Na2CO3 water-solution, permits a threefold increase in the metal removal, improves the surface roughness by 1.5 times, and considerably improves the surface reflectivity.


[Methodological bases for designing multipurpose laboratories]. A well-grounded selection of the necessary minimum of measuring facilities is of paramount importance in projecting multipurpose laboratories. These facilities should ensure the required accuracy of analyses to be carried out, and measurements covering the whole dynamic range of the values variations. It was suggested to organise new multipurpose laboratories in accordance with technical and economical reasoning and with the calculated generalized index which shows a compliance of technical characteristics of the measuring equipment chosen with the methodical demands.


[Definition of the nomenclature for quality indices for medical equipment products]. The qualimetric approach to the definition of qualitative indices for the medical engineering products allows to propose five initial levels of the "index-tree" with the use of the indices nomenclature comprised in GOST--22.851-77. Due to the proposed method of the expert opinions' formal processing, classification structure of qualitative properties for these products has been revealed.


[Improvement in the methods of performing the work in assuring the operating characteristics of medical equipment]. Improvement of operation methods that ensure reliability, climatic and mechanical stability, strength and other service qualities of medical equipment is now accomplished under conditions of intimate cooperation between constructors and manufactures, introduction of progressive norms and approaches for the provision and verification of the equipment operation qualities, building and employment of common test facilities.


[Blood heat exchangers for the artificial heart using a radioisotope power source]. A design of a vascular heat exchanger enabling it to establish in experiments with animals the degree of the possible specific-capacity thermal loads has been devised. The performance results may be taken account of in designing implantable appliances of assistive circulation and artificial heart.


[New model of laboratory contact microscope]. A new model of a laboratory contact microscope is described that keeps the ocular and the photocamera motionless during their focusing. The latter is performed by means of a moving positive lens placed between the objective and the opaque illuminator. The new focusing approach allows different attachements to be used, such as photometric, binocular etc. The microscope enables one to reach the stereoscopic effect that can be intensified diaphragms located at exit pupils. The opaque illuminator of a new type incorporated into the microscope gives a considerable gain in light brightness.


[Loco-regional anesthesia in remote medical units. I. - Basis (author's transl)]. This paper is a foreword to a series of articles about anesthesia in small medical units in tropical areas. When general anesthesia must be discarded in regard to the patient's condition or the poor level of facilities, loco-regional anesthesia proves to be of great value. The authors review the main drugs available, their dosages, accidents, counter-indications and pre-anesthetic cares.


[Histo-pathological features of African mycetomas (author's transl)]. From a review of 94 original cases of mycetoma, a description of the most important histo-pathological features of these tumors is given. The microscopic diagnosis of mycetoma is easy and so is generally the identification of the responsible agent, either a bacteria or a fungus. In every case and specially in atypic ones a mycological study is necessary to ascertain the aetiological diagnosis.


[Value of radiology for the diagnosis of mycetomas (author's transl)]. Mycetomas have raised a new interest because of cases introduced from tropical areas to non endemic countries, and because of the emergence in these countries of autochthonous cases in immuno-depressed patients. Radiologic diagnosis is no more limited to the description of osseous changes, the basic aspects of which are characteristic: cortical erosion, periosteous condensation and reaction. Using modern radiological technics such as arteriography and lymphography, gives a possibility to appreciate more thoroughly the extension and the potential evolution, so that the radiological approach may be similar to that of carcinology.


[Tactic for treatment of African mycetomas (author's transl)]. The authors report their own experience from 200 cases and they consider the matter from the point of a surgeon operating in a small medical unit in Africa. The clinical and biological aspects are described; the importance and the difficulties of appreciating the real spreading of infection are emphasized. Conventional radiology is of major value. The biological diagnosis may give way to a medical treatment with DDS and sulfamethoxypyridazine in cases due to actinomycetes with red or yellow granules; but in fungic cases fungicid drugs proved to be inefficient. Surgery is still an important component of the treatment. Its tactics are discussed according to the germ, the localization, the extension and also to the social and psychological status, but it is hoped that more sanitary education will reduce its preponderence in making possible earlier diagnosis and treatment.


[A controlled experience with a thermostabile measles vaccine in Cameroon (author's transl)]. Rimevax, a thermostabile measles vaccine, has been stored, before reconstitution, during seven days at temperature from 23 degrees C to 25 degrees C. This vaccine has given seroconversion in 87 per 100 of the babies vaccinated and aged from 9 to 24 months. This percentage assesses the value of Rimevax for field campaigns.


[Some new cases of congenital human African trypanosomiasis (T. gambiense) (author's transl)]. The authors report three cases of congenital transmission of T. gambiense. In two cases, the parasite has been found in the blood of the umbilical cord. In the third case, it has been found twenty hours after birth in the peripherical blood of a new born child whose mother was affected by trypanosomiasis. They report also two cases of pregnant mothers with sleeping sickness, whose children were born-unaffected by the disease. The authors believe that the placental transmission of the human african trypanosomiasis is more frequent than thought.


[Agents of mycetomas: a bacteriological and parasitological study (author's transl)]. Microscopic agents responsible of Mycetomas are reviewed. They may be bacteria belonging to the Actinomycetalae order (Nocardia, Actinomadura, Streptomyces) or very various fungi belonging to the classes of Adelomycetes or Ascomycetes (Madurella, Leptosphaeria, Neotestudina, etc.). Though the procedures for collecting and transporting samples are the same, direct microscopic examination gives possibility to choose among the selective culture media the most appropriate ones to isolate either fungi or Actinomycetalae. Technics of identification for the most important bacterial agents are given, but fungi can be identified in only very specialized laboratories. Immunological methods may bring valuable indications for helping diagnosis or treatment supervision.


[Paralysis of the opposition of the thumb in leprosy: value of the transplantation of the extensor indicis (author's transl)]. The transplantation of the extensor indicis to restore the opposition of thumb has been realized by two techniques: -- transplantation through the 2nd interosseous space with suture on the abductor pollicis brevis but the result was poor for the guide pulley resulting did not work well. -- transplantation with reflexion on the cubital side of the wrist which in 5 cases proved to be satisfactory. In medico cubital paralysis one must also cure the "cubital claw of the thumb". The surgical procedure, using a dispensable tendon, could be directly associated to the sutures of the proximal injuries of the cubital nerve as a temporary palliative.


[Late aspects of palpebral anthrax (author's transl)]. Report of 5 cases of palpebral anthrax treated after the acute phase, in a cicatricial or precicatricial stade. The authors recommend to delay plastic surgery up to three months and to select total skin graft for upper eye-lid and pediculed skin flap for lower eye-lid.


[Trachoma prevalence in the Sahel: report of a 1978 survey in Gourma area (Mali) (author's transl)]. Report of a survey conducted in 1978 in the Niger sweep on a population consisting for one third of adults and for two thirds of children and adolescents. 2.571 persons have been controlled, giving evidence of 441 cases of trachoma (17,15 p. 100), 327 of which were evolutive and 114 cicatricial; 30,4 p. 100 of the cases were severe and 10 p. 100 suffered of a loss of visual acuity.


Endotoxic glycolipid as a potent depressor of the hepatic drug-metabolizing enzyme systems in mice. Inhibitory effects of the endotoxic glycolipid from Salmonella minnesota R595 on hepatic drug-metabolizing enzyme activities in mice were investigated, and the depressor activity of the glycolipid in the enzyme systems was confirmed. Among degradation products of lipopolysaccharides tested, lipid A preparations derived from the mild acetic acid hydrolysates of lipopolysaccharides were the most active, but the lipid A fractions prepared from the hydrolysates with 1 N-HCl were almost inactive. A degraded polysaccharide fraction from E. coli lipopolysaccharide was inactive. The activities of the glycolipid and the lipid A preparation were markedly reduced by treatment with alkaline-hydroxylamine, mild alkali or hydrazine. The data showed that the lipid A moiety of the glycolipid may be responsible for the inhibitory activity on the hepatic drug-metabolizing enzyme systems.


Glycolysis-dependent antimetabolities: possible improvement in antineoplastic selectivity. The increased rate of glycolysis in neoplastic cells may be used to design tentatively antimetabolites whose detoxification would be faster in normal cells. Pyruvo-substituted nucleotides are examined in this respect and their expected differential metabolism outlined.


The cause of cancer: biochemical defects in the cancer cell demonstrated by the effects of electromagnetic radiation, glucose and oxygen. The responses of a person carrying a cancer to 434 MHz electromagnetic radiation are such that they demonstrate that each human cell contains at least two separate respiratory pathways which can convert glucose to energy. The first pathway produces energy by an anaerobic mechanism and it can be demonstrated that this energy is used for the purpose of cell replication. The second pathway(s) produces energy from glucose by aerobic oxidative processes which can be shown to energise other cellular functions. One of these functions is that of controlling its own cell division. Other demonstrable functions of this aerobic energy producing mechanism are concerned with individual cellular repair processes, multicellular organisation and repair and the preservation of gross anatomical perfection. Release of the first or anaerobic system from supervisory control by the second or aerobic sytem(s) permits the unlimited cell division which is the phenomenon known as cancer. The available circumstantial evidence suggests that this is not the result of nuclear or chromosomal defects or mutations but is due to direct irreversible sublethal damage to the cellular aerobic glucose metabolic system whilst the anaerobic system remains intact.


Gastric cancer etiology: a biochemical hypothesis. We have proposed a two-stage biochemical model for the etiology of "intestinal" gastric cancer. The model postulates that the gastric mucosal barrier is biochemically pierced as a result of chemical interactions between the mucoproteins and mucopolysaccharides of the barrier and ingested polysaccharrides (starches). This would allow the growth of gastric flora which could produce carcinogenic nitrosamines and/or nitrosamides. Observational and experimental evidence in favor of the model is provided. The model suggests various research initiatives, the results of which might provide the basis for biochemical and physiological methods for the prevention and/or treatment of gastric cancer. Various ways in which the model may be tested are also noted.


Childhood cancer and the SBLA syndrome.

Childhood cancer and the SBLA syndrome. Two nuclear families showing characteristics of the SBLA syndrome are described wherein progeny of breast cancer-affected mothers manifested early childhood malignant neoplasms. These observations have led us to postulate a novel type genetic-environmental interactive model which incorporates Knudsen's "two-hit" hypothesis as a partial explanation for the exceedingly early onset of cancer in the subject progeny. Given the assumption that the first hit was germinal with transfer of the deleterious SBLA gene at conception, we postulate that the second or somatic-hit occurred early on in utero. This may have involved a complex mechanism of one or more factors including tumor cell products, tumor specific antigens, immunosuppression, de-repressed oncogene, or an activated oncogenic virus via a transplacental communicable phenomenon. The testing of this new hypothesis dealing with carcinogenesis in the SBLA syndrome should employ immunologicalgenetic parameters concurrently in fetuses and mothers.


Solar cycles and malignant melanoma.

Solar cycles and malignant melanoma. There has been a sixfold increase in the incidence of malignant melanoma in the State of Connecticut during the past forty years. Superimposed on a steady incidence rise are cycles of markedly increased incidence rates which follow periods of maximum sunspot activity. We propose that the effect of sunspot cycles on human melanoma occurrence is mediated by modulation of stratospheric ozone and thus indirectly affects UV flux at the earth's surface. This hypothesis would predict a time lag in melanoma incidence cycles, relative to sunspot activity, with increasing distance from polar caps. This appears to be the case. The increase in melanoma incidence related to a given reduction in ozone depletion in this hypothesis, is in great excess of existing models relating anthropogenic ozone depletion and skin cancer.


Proliferon: the functional unit of rapidly proliferating organs. Continuously replicating organs are generally composed of several cell population types. These may be divided according to their function into two classes: 1. parenchyma: cells destined to perform a certain metabolic function peculiar to the organ under study, 2. supporting cell populations, consisting of fibroblasts and vascular supply always accompanied by nerve fibers. The kinetics of all the cells are highly coordinated. They all share one progenitor region. It is postulated that in this common progenitor region the two cell population classes are assembled into complex units denominated as proliferons. The proliferon starts its existence as a whole, matures as a whole and disintegrates at the organ periphery. It consists of four basic elements: parenchyma, connective tissue, blood vessels and nerve fibers. This model has been previously called upon to describe the kinetics of the rodent incisor tooth and the intestinal mucosa. It is assumed to be the elementary functional unit of all rapidly proliferating organs such as: skin, hair, endometrium, bone marrow, intestinal mucosa and rodent incisor.


Selectivity and rejectivity in cancer metastasis. In cancer metastasis, "selectivity" denotes the formation of secondary tumor in an organ in such a manner that its localization pattern is peculiar. The opposite phenomenon should be recognized and called "rejectivity". In man, carcinomas appear to spread selectively to the umbilicus, whereas lymphomas seem to reject that site. In all probability, recognition of the twin theory of selectivity and rejectivity will stimulate research on cancer dissemination.


Is the role of the environment in carcinogenesis overestimated? The dominant role of the physical and chemical environment in the development of cancer is challenged. Analyses of the etiology of skin, bladder, respiratory and gastric cancers are presented which demonstrate the considerable extent to which one's health status may modify the initiation and promotion of environmentally associated cancers. It is concluded that although environmental factors may initiate and/or promote 85 to 90 percent of all cancers this is misleading since it neglects the critical role of the individual's health status as a factor modifying carcinogenesis.


On the aging of organisms and their cells. An explanation of organismic ageing based on a limited division capacity of dividing cells is difficult to reconcile with much of the available data. The physiology of cells in ageing organisms tends, on the contrary, to suggest that organisms age as a result of degeneration in their non-dividing cell populations. Senescence in these non-mitotic cells resmebles the ageing of the non-dividing fraction of cell cultures clonally senescing, or maintained in long-term quiescence in vitro. As cultures of diploid human fibroblasts senesce there is an accumulation of non-dividing cells. Alterations in these post-mitotic cells can explain the senescent properties of late passage cultures. It is proposed that during the in vitro senescence of fibroblast cultures, cell ageing results from, as opposed to causes, the absence of mitosis. Cell ageing may primarily result from changes in the chromatin induced by the non-mitotic state.


Intracellular hyperthermia. A biophysical approach to cancer treatment via intracellular temperature and biophysical alterations. This paper introduces a new multi-disciplinary "intracellular" biophysical treatment of cancer. The basic concept uses locally induced heat energy after tumor phagocytosis of submicron particles whose composition permits magnetic excitation. The key to this process is the utilization of the cancer cell membrane to contain the energy within the cancer cell. Any magnetic or electric dipole contained within or introduced into the cell, or that is capable of being produced by an external field, can be used. Submicron particles are colloidally suspended, injected intravenously and are phagocytized by cancer cells. Application of an external high frequency or pulsed electromagnetic field then raises the particles' temperature thus generating intracellular heat in precise increments. This results in selective thermal destruction of cancer cells with little effect on normal cells. Experimental evidence is presented showing tumor cell destruction in spontaneous mammary tumors in Sprague Dawley rats. In addition, we suggest that certain biophysical properties are altered within the cancer cells and could be used to enhance this effect. Specific radioisotopes or tumor specific antibodies bound to particles or chemotherapeutic microspheres increase cancer cell sensitivity and affinity for these particles. This "intracellular" treatment of cancer has a wide potential range of applications.


The influence of ambient ozone on the incidence of bone fractures especially among the elderly. Elevated levels of breatheable ozone will reduce the amount of UV radiation in the range of 280-305 nm reaching the surface of earth. This range of UV converts the provitamin 7-dehydrocholesterol to vitamin D, within the human. Since most typical diets contain low levels of vitamin D, the role of UV related vitamin D synthesis in the skin is considered to provide very important contributions to the total vitamin D content of the blood. Thus, elevated levels of ambient ozone should result in a decreased level of vitamin D synthesis which may be expressed as an increase in the incidence of histological osteomalacia and ultimately bone fractures, especially among the elderly.


Ischaemic heart disease-an hypothesis to integrate the role of insulin, fibre and sucrose. The theory that a high dietary cholesterol and saturated fat intake has an aetiological role in coronary artery disease is inadequate. So are those theories based upon insulin, upon refined carbohydrate and upon dietary sucrose. An alternate hypothesis is presented. Central to it is prolonged hyperinsulin-aemia. This, acting synergistically with the changes in lipide metabolism secondary to the effects of dietary fibre and sucrose, is crucial to atherogenesis. There is abundant evidence for an association of insulin and vascular changes, both in vitro and in epidemiological studies. Laboratory and epidemiological evidence also exists for an effect of fibre and soluble carbohydrate on cholesterol synthesis and excretion, both as itself and as bile acid. A scheme is presented to demonstrate these complex inter-relationships and their role in vascular diseases.


Toward establishing scientific credibility in acupuncture research. While the effectiveness of acupuncture has been established clinically, research methods and tools which are basic for establishing objective scientific credibility in medicine have been a problem in acupuncture research. Research methods developed in other areas and reported in the literature are presented which could, if applied to acupuncture research, contribute toward establishing scientific credibility in medicine.


Psychosomatic disease and acupuncture.

Psychosomatic disease and acupuncture. The medical philosophy implied by a "mind-body unity" hypothesis is outlined and the type of therapy appropriate to the stage of development of disease is discussed; special reference is made to the place of acupuncture within a modern medical program. Starting from the premise that mind is the primary causal force determining neural states, it is concluded that the highest level medical art would be "psychosomatic psychoanalysis." The next highest form of therapy would deal directly with nerve impulses (acupuncture, etc.), followed by drug therapies directed at intra- and extracellular fluid composition, hormone macromolecule manipulation, and finally minor and major surgery.


Limitation of resistance as a parameter by which to characterize epithelia that actively transport ions. It is theoretically inappropriate to characterize an actively transporting epithelim by "resistance" alone which is correctly applied only to passive circuit elements. Rather, such epithelia (if they actively transport sodium) required, as a minimum, characterization by an active circuit element parameter such as voltage (E Na), current (I Na) or power (WNa) in some configuration with resistances. Recent experimental studies of epithelia which actively transport sodium have omitted consideration of the active circuit element and attributed all measured changes observed to "resistance" changes in the epithelium as the transepithelial sodium gradient is altered. It is suggested that the observed changes in voltage/current ratio could be consequences of changes in the electrical behavior of the active circuit element of such epithelia. It may be biologically impossible to suppress all electromotive forces in epithelia to measure the truly passive characteristics of the epithelim without destroying tissue viability. The actual methods used to date for measurement of "resistance" in epithelia consist of perturbing signals which might alter the electrical behavior of an active element such as an "ion pump"; the observed changes in voltage to current ratio observed in such experiments can be better explained by a change in the active ion pump rather than by changes in passive epithelial "resistance".


Potential for therapeutic gain similar to pions by daily combinations of neutrons and low-LET radiations. Biological studies with negative pi mesons (pions) at the Los Alamos Meson Physics Facility (LAMPF) have shown a relatively constant reduction of shoulder of the survival curve for single cell cultures and relatively constant reduction in the no response region for multicellular tumor spheroids (MTS) with little change in sensitivity (or slope), in both single dose and fractionated experiments. In clinical studies, a trend toward therapeutic gain for pions has been demonstrated in patients treated at LAMPF, with marked, rapid turmor regression for relatively mild acute normal tissue injury and no untoward effects observed over 7 to 24 months. Since the pion beams used therapeutically at LAMPF are characterized by a small amount of high-linear-energy-transfer (LET) radiation (in the range 10 to 20%), it is hypothesized that pion radiation as compared to x-rays increased the differential tolerance to sublethal injury in favor of normal tissues, resulting in therapeutic gain. It is further proposed that the near simultaneous application of high-LET radiation (such as neutrons) and low-LET radiation (such as x-rays) might create a bilogical situation similar to that of pion treatment, potentially resulting in therapeutic gain, although without the added benefit of dose localization obtainable with pions.


Etiology of neural tube defect in man--Do teratogens play any part? Evidence from sex ratios. Neural tube defect (NTD) is more common among spontaneously aborted fetuses than in infants born in the third trimester, but there is no direct evidence that NTD-affected conceptuses, presenting at these two different gestational ages, are components of a single disease process. Evidence for homology is here presented in an analysis of the sex ratios of spontaneously and therapeutically aborted NTD-affected fetuses, and of sex ratios differing with variations in prevalence of NTD-affected infants. If it could be shown conclusively that NTD is a single disease process, with an inverse relationship between components expressed early and late in gestation, there would be implications for the ascertainment of families at risk for NTD, and for the search for environmental factors potentially involved in the causation of NTD.


Pathogenesis of cystic fibrosis: possible importance of alteration in epithelial surface topography. As the pathogenesis in cystic fibrosis (CF) has been considered to lie in a disturbance in the behavior of secretions, particularly mucins, from exocrine glands, it has been proposed that an alteration in surface topography (form, number or distribution of microvilli or blebs) of epithelial cells lining ducts could impair distribution leading to retention of mucus leading to the clinical phenotype. Scanning electronmicroscopy of human epithelial suspension cultures now offers an opportunity to evaluate the role of plasmalemma topography in CF.


Is kernicterus due to inhibition of brain hexose-monophosphate shunt activity by bilirubin? Degradation of biogenic amines in the central nervous system is accomplished by the monoamine oxidase system. The by-products of this reaction, hydrogen peroxide and amino aldehydes, are toxic to neurones. Detoxification of these by-products is normally mediated by generation of NADPH via the hexosemonophosphate (HMP) shunt. It is proposed that inhibition of the HMP shunt by unconjugated bilirubin leads to the toxic accumulation of hydrogen peroxide and aldehydes.


The therapeutic effect of hemodialysis on schizophrenia: comments and further possibilities. Intermittent hemodialysis was recently found to have a therapeutic effect on schizophrenia, pointing to biochemical disturbances and possibly to renal malfunction as the cause of some forms of mental disorder. This paper points out that intermittent hemodialysis is not equally effective for the elimination of all solutes in the plasma. It can dispose of significant quantities of substances for which the normal urine/plasma concentration ratio is small, not of substances which the kidney concentrates in the urine by a large factor. It is further pointed out that for substances with a small urine/plasma concentration ratio thermogenic sweating could also constitute an effective means of disposal and its use is suggested as possible alternative to hemodialysis.


Change and stability in cellular organisms. The living cell is characterized by both its potential for change and its tendency towards a stable state. The interaction between the DNA information system and the metabolic steady state is described. A model based on this interaction leads to the conclusions that change can only be initiated from the environment but that the direction of any change is determined by the cell.


Hyperhidrosis and the sympatho-adrenal system. Some disorders in which excessive sweating, hyperhidrosis, is a symptom are also characterized by increased sympatho-adrenal activity. Such disorders are hypotension, hypoglycemia, pheochromocytoma and hyperthyroidism. Sweat glands are controlled by a cholinergic innervation but can also be stimulated by adrenergic agents whose effects can be blocked by both alpha- and beta-receptor blocking drugs. An adrenergic innervation has also been demonstrated. There is evidence that the adrenergic component of sweating particularly secretion of the adrenal medulla, is responsible for the enhancement of sweating during exercise but not for the hyperhidrosis present in these disorders since sweating in these circumstances can be effectively blocked by cholinergic blocking compounds. Cutaneous vasoconstriction due to elevated plasma catecholamines reduces the rate of evaporation of sweat and allows sweat to accumulate on the skin. It is suggested that in the case of hypotension and insulin hypoglycemia sweating results from general sympathetic stimulation and that adrenal medullary hormones are not an essential component of the response. Hyperhidrosis in pheochromocytoma may be due to central activation of heat loss mechanisms resulting from the passage of plasma catecholamines across the blood-brain barrier combined with increased thermogenesis and cutaneous vasoconstriction. The hyperhidrosis of hyperthyroidism is probably due to increased thermogenesis.


Heart disease, cancer and vehicle travel. A new concept as to the cause of heart disease, cancers and diabetes is put forward in this paper. It is established that there is a mathematical relationship between motor vehicle use, from 1920 to 1975, and deaths due to the abovementioned diseases. This relationship has been established by an extensive statistical study of vehicle usage and deaths due to these diseases.


"Fatigue on rest" and associated symptoms (headache, vertigo, blurred vision, nausea, tension and irritability) due to locally asymptomatic, unerupted, impacted teeth. "Fatigue on Rest", headache, vertigo and the feeling of loss of balance, blurred vision, nausea, tension and irritability, were found to be prevalent amongst patients who had locally asymptomatic, unerupted impacted teeth. A comparative pressure sign was developed, which, when positive, confirmed the relationship between the impacted teeth and the medical symptoms. Removal of the impactions resulted in the alleviation of the symptoms. Stress and psychogenic factors are considered as trigger mechanisms, rather than as basic causes of the symptoms.


Metastasis as a beneficial process.

Metastasis as a beneficial process. The most important message to be found in the "Fourth report on end results in cancer" in the U.S., states that with the progression of cancer, its force of mortality declines. This has been reexamined in the present study. The declining force of mortality implies that as the disease advances the chances of the average patient to survive, improve. Since in the cancer patient all vital functions gradually deteriorate, and the only process gaining with time is his tumor load, one has to consider the possibility that the improving chances of the cancer patient could be linked with the amount of tumor mass in his body. These ideas are illustrated by the following example. Cancer could result from a gradual loss of a vital tissue product 'A', to be replaced by an analogous tissue product 'B' which is of embryonal origin. In the adult, 'B' is produced by stem cells which gradually adapt to the loss of the primary product and increase in number. 'B' is less efficient than 'A' to meet the necessary vital functions. Its deficiency in quality is however augmented by quantity. In order to keep up with the increasing demand, the stem cells proliferate and spread throughout the organism where each metastasis continues to secrete 'B'. The penalty inflicted by this compensatory mechanism is relatively high. Some metastases hit vital functions, and the increasing tumor load depletes the available energy sources. The net effect however is beneficial since without metastasis the organism would have succumbed to the disease in its earliest stage.


Behavioral effects of cyclic changes in serotonin during the human menstrual cycle. Many cyclic changes during the menstrual cycle (temperature, depression, motor activity, pain sensitivity, etc.) are closely paralleled by changes in brain serotonin level. These changes, in turn, are associated with peripheral hormone levels which are comparatively regular and easily measured. Their measurement may be useful both in predicting behavior and in accounting for atypical menstrual-related behavior.


Basic principles of cellular organization. The hypothesis is put forward that the division of the animal body into three germ layers represents not only histological, but also functional specialization, the ectoderm taking over functions through which the animal is in contact with, acted upon or reacts to the external world, the entoderm metabolism and the mesoderm architectural and mechanical organization. This is assumed to mean that the tasks of life have been divided into three large function domains at an early stage of multicellular evolution, each germ layer taking over one domain and developing largely independently of the other two in the further course of phylogeny. The germ layers are autonomous in their own spheres, giving the body, in effect, a tripartite government. The potentiality of conceptual thought is inherent in all germ layers, reaching a high state of development in the entoderm and mesoderm at a much earlier stage of development than in the ectoderm. The animal body, as a whole, is in control of all its biologic activities; it is a self-designing, self-developing and self-perpetuating entity. The control of cellular organization is a mesodermal task.


The mechanism of coronary artery spasm: roles of oxygen, prostaglandins, sex hormones and smoking. A reduced oxygen supply to the heart causes coronary vasodilatation in the first instance. But if the hypoxia is severe or prolonged, the dilatation passes off and coronary vasospasm develops leading to a vicious circle with a further reduction of myocardial oxygenation. The spasm is associated with increased outflow of prostaglandin (PG)-like material and can be prevented or reversed by inhibitors of PG synthesis such as indomethacin or antagonists of PG action such as chloroquine. The spasm does not appear to be caused by thromboxane (TX) A2 since selective inhibitors of TXA2 synthesis enhance the hypoxic spasm and by themselves can cause spasm even in oxygenated hearts. The mechanism may be related to loss of negative feedback control of the PG pathway by TXA2. Oxygen may enhance TXA2 production and reduce formation of vasoconstrictor PGs, while smoking, because of the formation of carboxyhaemoglobin, may have the opposite effect. Oestradiol and testosterone do not influence the hypoxic spasm but progesterone at physiological concentrations blocks it completely. Progesterone may be the protective female hormone and the increased susceptibility to myocardial infarction in women on oral contraceptives may be related to reduced formation of endogenous progesterone.