Home parenteral nutrition in patients with a cancer diagnosis.

The clinical outcome for 1362 patients with active cancer managed on home parenteral nutrition (HPN) is compared with that of 122 patients with radiation enteritis ("cured" cancer) and 416 patients with Crohn's disease. This longitudinal clinical information was reported to the North American Home Parenteral and Enteral Nutrition Registry (Oley Foundation/A.S.P.E.N. joint project) between 1985 and 1989. The data shows that the number of active cancer patients on this therapy is increasing 13% per year. The annual survival rate is 25% for patients with active cancer, as compared with 88% for patients with radiation enteritis and 95% for patients with Crohn's disease. Although 50% of all active cancer patients starting HPN are dead within 6 to 9 months, the prognosis is somewhat better in children, and 20% of these active cancer patients appear to do well, returning to full oral nutrition and experiencing complete rehabilitation. These are presumed to be patients with a potentially curable cancer requiring super-aggressive treatment, which causes temporary severe gastrointestinal dysfunction. Adult active cancer patients have the same rehospitalization rate for HPN complications (once per year) as radiation enteritis and Crohn's disease patients. However, their rehospitalization rate for non-HPN complications is four times higher. This article reviews the factors that may explain the growth of HPN in active cancer patients and discusses some of the unanswered clinical questions that urgently need to be addressed to more effectively determine the appropriateness or inappropriateness of HPN management in the active cancer setting.


[Diagnostic criteria for chronic fatigue syndrome by the CFS Study Group in Japan].

Much interest recently has been given to chronic fatigue syndrome (CFS) in Japan as other countries. The CFS Study Group sponsored by the Ministry of Health and Welfare has been developed since April 1991, A diagnostic criteria for CFS was newly proposed by this group. The criteria is substantially based upon the working case definition, which was made by Holmes and colleagues in 1988. There are some modification from CDC working case definition; the criteria of probable cases of CFS was defined, and postinfectious CFS was also given.


[Chronic fatigue syndrome in school children].

Chronic fatigue syndrome (CFS) is characterized by persistent or relapsing debilitating fatigue for at least 6 months without any apparent medical diagnosis that would explain the clinical presentation. Although, most of the reported patients are over age 30, CFS also affects school children. To better understand CFS, the network of the central nervous-endocrine-immune systems should be considered, and one must be careful to distinct CFS from school absenteeism and other psychosomatic disorders often seen among them.


[Chronic fatigue immune dysfunction syndrome].

Chronic fatigue syndrome (CFS) is characterized by unexplained, debilitating fatigue or easy fatigability lasting longer than six months. While a viral basis of infection is proposed to be the cause of CFS, other viral infections do not generally persist after several weeks. Immunological disorders, including abnormal functions and distributions of T lymphocytes, B lymphocytes, natural killer (NK) cells, and monocyte/macrophages, are described in CFS. NK cells are known to play an important role in host resistance against viral infection as well as in the regulation of the immune systems. Restoration of NK activity resulted in recovery from CFS. Taken together, immunological abnormalities, especially dysfunction of NK cells, may be involved in CFS.


[Neuro-psychiatric aspects of chronic fatigue syndrome].

Chronic fatigue syndrome (CFS) is easily differentiated from various neurological organic disorders by conventional clinical examinations. The most important disease for distinguishment from CFS is fibromyalgia syndrome, in which the prominent and cardinal feature is a deprivation of stage 4 slow wave sleep. Experimentally, the sleep disturbance in controls can induce general myalgia, muscle tender points, severe fatigue and stiffness on awakening. The EEG abnormality is slow alpha wave contaminants on slow wave background, which is identical to EEG of CFS. The results clearly imply that CFS is not a hysterical or psychogenic disease, and that fibromyalgia may be a central fundamental of CFS. Fibromyalgia, however, has distinct features such as no antecedent inflammatory process and no endemics. Therefore, the syndrome has features distinct from, in addition to common features to CFS. It is also very difficult to distinguish CFS from depression. The above-mentioned features can be observed in depression. Now, study of brain blood flow or metabolism by PET or SPECT can be a possible tool for establishment of the CFS identity.


[Overview of our patients with chronic fatigue syndrome (CFS) from the pathoetiological aspects].

We interviewed 285 patients who visited our department claiming with a complaint of chronic fatigue syndrome (CFS) and subsequently diagnosed 55 as having CFS, according to the criteria for CFS of the centers for disease control (CDC). We measured various virus antibody titers, 2-5, adenylate synthetase levels in the serum lymphocyte subset in blood, employing a double staining technique with monoclonal antibodies. In this paper, we pathoetiology of CFS, based on our findings and other researchers' is discussed.


[Chronic fatigue syndrome--51 cases in the Jikei University School of Medicine].

Between April 1991 and August 1992, we diagnosed 51 cases of CFS who met definition of CFS designated by CDC, 1988. They are 41 female and 11 male, and 78% are women. At first visit, their ages are ranged from 16 to 64 years old, and approximately 45% is 20 to 30 years old. In periods of illness from onset, 39.2% of the patients are in period of 6 month to 1 year, 19.6% within 2 years, and 15.6% within 3 years, respectively. The sufferer who have symptoms of CFS over 10 years long are in 6 cases. Most of patients have already been examined by many other clinics and hospitals. They have been told as no abnormal medical condition, or often as neurosis, depressive state and autonomous imbalance etc. Interesting things are trigger of CFS. 77.5% of patients have onset of flu-like symptom, including 5 cases of acute infectious mononucleosis. In many female patients, symptoms of CFS begun after hand work in addition to psychological factors. Specific laboratory results are not shown in CBC, urinalysis, biochemical studies and inflammatory marhers. 6 cases hare positive Rheumatoid factor and positive ANF are shown in 16 cases (31.3%). Specific patterns of anti EBV antibodies are not shown. Lymphocyte subsets used by monoclonal antibodies are not specific. At the present, prognosis is good and 56.8% of CFS patients are generally improved. For severe cases, NSAID, Sulpiride, Amitryptiline and minor tranquilizer are used.


[Therapy of chronic fatigue syndrome].

Chronic fatigue syndrome (CFS) is characterized by unexplained, debilitating fatigue or easy fatigability lasting longer than six months. While a number of clinical trials have been performed in CFS patients, there is currently no established therapy for CFS. Treatment with acyclovir of CFS patients is ineffective. Intravenous immunoglobulin therapy appears to be effective, though the results are controversial. Antidepressants might help the associated depression and anxiety but not other symptoms. Trials with magnesium have improved the well-being of patients. Restoration of NK activity by biological response modifiers, such as sizofirann, resulted in restoration of NK cell activity and recovery from CFS. Taken together, immunological abnormalities may be involved in CFS, and its restoration may produce clinical benefit in CFS.


[Irritable bowel syndrome--criteria, sub-classification, etiology].

The irritable bowel syndrome (IBS) is a very common condition in gastroenterology clinics, but yet it is one of the pooly understood. A international working team in Rome, 1988, proposed that IBS is a functional intestinal disorder with chronic or recurrent gastrointestinal symptoms without structural or biochemical abnormalities. IBS was sub-classified into 3 groups; abdominal pain as the prominent feature with diarrhea, with constipation, with both while painless diarrhea and simple constipation without pain were excluded from IBS. There is a lot of data suggesting that IBS has a gut dysmotility, which is influenced by many stimuli (food, hormone, drug, menses, mechanical dilatation), including psychological stress. Moreover, currently available evidences implicate that IBS is a more generalized disorder of smooth muscle function not only in the intestine but also outside of the intestine.


[Functional abnormality of the digestive tract and the gall bladder in irritable bowel syndrome].

Functional abnormalities of the digestive tract and the gallbladder in irritable bowel syndrome (IBS) are described in this review. In addition to colonic abnormalities, disordered oesophageal motility, abnormal gastric emptying, abnormalities in small intestinal motility and abnormal gall bladder function have been demonstrated in IBS. Urodynamic abnormalities and bronchial hyperreactivity also have been reported in patients with IBS. Such extensive involvement of the organs suggests that IBS can be a generalized abnormality of the smooth muscle of even the whole body as well as the whole digestive tract. Further detailed investigation is needed to clarify this possibility.


[Role of gut hormones in irritable bowel syndrome].

In irritable bowel syndrome (IBS), motility disturbances occur from the upper gastrointestinal tract to the distal colon, where regulatory peptides have a wide-spread distribution. Studies on basal and postprandial plasma levels of different gut hormones show that VIP, CCK, and motilin may be closely related to the symptoms including abdominal pain, diarrhea and constipation. In addition, peptide YY and NPY have effects on absorption in the intestine, and some opioid peptides exert actions on colonic motility in IBS patients. Recent studies revealed that gall bladder in IBS has an abnormal sensitivity to CCK-8, indicating that IBS patients has an generalized abnormality of the smooth muscle of the digestive tract. Gut hormones, which act as hormones, neurotransmitters and neuromodulators depending on their releasing site, may therefore play an important role in IBS patients.


[Concept and differential diagnosis of irritable bowel syndrome].

The exact etiology of irritable bowel syndrome (IBS) is unknown. IBS is probably one of the commonest gastrointestinal disorders, but it has proved to be one of the most difficult conditions to diagnose. A proportion of patients give a strong history of stress-related or stress-evoked symptoms. In the past there has been a paucity of studies of this disorder because of difficulties in patient selection, choice of appropriate marker to be tested and the correlation of findings with the clinical presentation. A clear and precise definition of IBS is of most importance in the understanding of psychopathophysiological markers in this disorders.


[The relation between irritable bowel syndrome and a major depression].

It has been demonstrated that physical or psychological stress induces dysfunction of bowel movement and intestinal transit in rodents and human. There have been several reports concerning the psychiatric factors involved in the onset and clinical course of irritable bowel syndrome (IBS). We investigated patients with IBS who had been markedly disturbed in their daily life, and it was concluded that the most important psychiatric factor related to the onset and the clinical course of severely impaired IBS is a major depression, fulfilling the criteria of the DSM-III-R. Especially, in diarrhea predominant type of IBS, a major depression was considered to be strongly involved in the onset and the clinical course of IBS. Most of IBS patients with a major depression can be effectively treated with antidepressants and brief psychotherapy. Concerning treatment, the psychological background should be carefully considered.


[Irritable bowel syndrome in children].

The irritable bowel syndrome (IBS) is characterized by alteration in bowel habits (i.e., constipation and/or diarrhea) and abdominal pain, and is most common gastrointestinal disorder in adults. The recurrent abdominal pain (RAP) in children is similar to IBS in adults except bowel habits, but there is no settled conception of IBS in children. In our department, diagnosis of pediatric IBS will be made if the child has; #1 functional gastrointestinal disorders without organic diseases, #2 abdominal pain and other gastrointestinal symptoms continuing more than 3 weeks, #3 psychogenic background factors. We experienced 63 cases of IBS (23.5% in all 268 cases) from April 1990 to March 1992 at our pediatric digestive outpatient clinic. They ranged from 4 to 15 years old and about 60% of them were elder than 13 years old. Psychogenic factors were usually related to environment of school life and home. Careful history taking and routine examination were most important for the diagnostic approach. Management of this disease included counseling and drug therapy. Almost all cases reached much better condition 1 to 6 weeks after the therapy started. The combination therapy with psychologist was required in a few cases.


[Therapy by Japanese Oriental medicine (kampo) in irritable bowel syndrome].

Guideline for the treatment of irritable bowel syndrome by Japanese Oriental Medicine (Kampo) is summarized. It is very important to notice that Kampo prescription will show its best efficacy if it is adjusted for the conditions of a patient. To diagnose ill conditions for the patient is called the process of "Sho" clarification. Sho is the ultimate diagnosis, which is the term given to summarization of diagnostic process for a patient. Conceptual criteria used for making up Sho are "Yin/Yang", "Kyo/Jitsu", and "Hot/Cold". A Kampo formula has its own position regarding these concepts. We interpret about these concepts and formulae. Another important method for making Sho diagnosis is abdominal diagnosis, which is relatively easy to learn. Certain signs in abdominal diagnosis correspond to certain formula. We explain some methods in abdominal diagnosis and the related formulae. We also comment on construction process and features of Kampo prescription.


[Psychosomatic treatment of irritable bowel syndrome].

Irritable bowel syndrome (IBS) may be defined as a psychosomatic disease. Most primary care physicians do not want to undertake psychosomatic treatment, but may find it necessary in refractory patients. Brief psychosomatic treatments, providing patients with betterways to cope with stress, reduce the symptoms. The literature on the psychosomatic treatment for IBS is summarized. Supportive therapy and autogenic training that produce relaxation response appear to be effective. Other special psychological therapies that require specialized training, such as hypnosis, biofeedback, cognitive therapy, transactional analysis may be used for IBS but adequately controlled trials are lacking. It is certain that psychosomatic treatment take part in the management of IBS. Additional studies are needed to verify the effectiveness of these treatment for IBS.


[Coagulase-negative staphylococcal infections].

Coagulase-negative staphylococci are resident flora of the human being and not harmful for ordinary patients. However they cause serious infection for the compromised host, especially the patients with prosthetic valve, prosthetic joint, cerebrospinal fluid shunt, or intravascular catheter. Recent progress of medicine has resulted in the increase of compromised hosts. So, coagulase-negative staphylococci became one of the significant pathogens of hospital infections. Moreover, some hospital strains of coagulase-negative staphylococci demonstrate the resistance against most of the antibiotics recently. To prevent the hospital infection caused by those strains, the contamination control of the prosthetic insert is essential. When once the infection is caused on the prosthetic insert, they have to be removed in most cases.


[Panic disorder].

Panic episodes were described as a distinct form of anxiety by Freud almost 100 years ago, and the recent publication of the Diagnostic and Statistical Manual of Mental Disorders, third edition (D.S.M.-III), has provided the basis for the separate diagnostic entity of panic disorder. In this study, we showed the historical review of research and the result of our clinical study of panic disorder in 7 patients. The following results were obtained: 1) Abnormal DSTs were observed in only two of 5 patients. 2) Five of 6 patients showed high concentration of adrenaline and noradrenaline in urine. 3) Anxiety was provoked by caffeine in two of 5 patients. 4) Depression of T-wave was shown in three of 5 patients with orthostatic E.C.G. 5) Sinus tachycardia was gained in one of 3 patients with Holter E.C.G. 6) Abnormal respiratory functions were observed in all two patients with Treadmill. 7) Only one small heart was observed on a chest radiograph. 8) Panic attacks were provoked by sodium lactate infusion in four of 7 patients.


[Molecular biology of glycoconjugates in eukaryotic cells].

Glycoconjugates, such as glycoproteins and glycolipids, are one of the macromolecules composing a living body. Biological roles of carbohydrate moieties in glycoconjugates have recently drawn great attention. Sugar chains of glycoconjugates comprise an enormous diversity of structures which are known to be expressed in a cell specific manner and are regulated with stage specificity during embryogenesis and cell-differentiation. It is generally accepted that genetic expression and regulation of glycosyltransferases which are present in Golgi apparatus determines the structures of sugar chains. For these several years, a number of successes of cDNA cloning of glycosyltransferases have been reported. Recent progress and accumulated molecular cloning evidences of glycosyltransferases are reviewed and future advance using cloned genes as useful tools for glycobiology and glycotechnology is discussed.


[Hybridoma Data Bank (HDB)].

A Hybridoma Data Bank (HDB) has been developed with the collaboration of ATCC (USA), Cerdic (Europe) and RIKEN (Japan). The database holds more than 23000 records of the monoclonal antibodies. HDB is designed to meet diverse research requirements. HDB describes the development, isotype, specificity, applications, availability and literature citations for an individual monoclonal antibody. The World Data Center (WDC) at RIKEN in Japan is currently giving users' access to HDB on INTERNET, packet switching system and telephone line. The procedures for access to WDC and the interactive information retrieval system in WDC are introduced. The extraction of HDB data to create the visual table, showing reactivity patterns of monoclonal antibodies, are also shown, as an example of intelligent usage of HDB.


[Structures and functions of adhesion molecules--involvement of adhesion molecules in the pathogenesis].

Previous studies have revealed that adhesion molecules are involved in immune responses, such as the interaction between T cells and antigen presenting cells. Recent investigations demonstrated that one of these molecules, integrins, which was concerned with cell-cell adhesion and cell-extracellular matrix proteins, was prominently expressed on lymphocytes and neutrophils in inflammatory diseases. In addition, administration of monoclonal antibodies against integrins in vivo abrogated the inflammatory responses completely in rats. These findings suggest that adhesion molecules are involved in not only immune responses but also in the pathogenesis of inflammatory diseases. As shown here, integrins also play an important role in the metastasis of small cell lung cancers.


[Imported parasitic diseases--recent epidemiology and progress in the chemotherapy].

Imported parasitic diseases have been increasingly important in basic and clinical medicine in developed countries, as the number of travellers in developing countries, where numerous kinds of parasitic diseases are highly endemic, have been increasing. Recent epidemiologic investigation demonstrated that malaria, amebiasis, trypanosomiasis, leishmaniasis and cysticercosis seemed important as judged from the number of infected individuals, primarily Japanese travellers. Although these parasitic diseases pose some serious medical problems, establishment of the effective chemotherapeutic strategy is of urgent significance. In this respect, activities of the Research Group of Development of Chemotherapeutic Agents against Tropical Parasitic Diseases supported by the Japanese Ministry of Health and Welfare appear to be important to keep appropriate drugs in Japan.


[Recent trends in estimating energy expenditures in Japan].

Estimating energy expenditures for daily activities has become an important issue in the promotion of individual health. From this point of view, the variety of estimation methods and their characteristics applied in many countries were surveyed. Then the essential bases used to estimate energy expenditures with the relative metabolic rate (RMR) method and the active energy expenditure rate (Ea) method, which were originally developed and used in Japan, were substituted for daily activities recorded by means of time study, and illustrated. Subsequently, a newly introduced method based on heart rate was explained with its variations and problems followed by practical reports on some populations in Japan. Methods using questionnaires or other devices were also described.


[Changes of nutritional factors related to regional differences in the mortality of cardiovascular disease between 1966 and 1985 in Japan].

Cardiovascular disease has been the leading cause of death since 1946 in Japan. In this paper, the relationship between mortality and nutritional factors was analyzed by 12 different regions in Japan during the period 1966-1985. Data in the Reports of the National Nutritional Survey in Japan were used as the nutritional factors, and calculation was made of age-adjusted mortality from ischemic heart disease (IHD), cerebral hemorrhage (CH) and cerebral infarction (CI). The results obtained were as follows: 1. Correlation coefficients were calculated based on the average value of 20 years in each 12 different regions. Correlation coefficients between the mortality from IHD and intake of total fat and n3-polyunsaturated fatty acids were positively significant for both sexes. Between the mortality from CH and vegetable protein and salt, they were positively significant (p < 0.01) while cholesterol was negatively significant (p < 0.01). Between the mortality from CI and vegetable protein, salt and carbohydrate, they were positively significant (p < 0.01). 2. Correlation coefficients between slopes of CH and slopes of nutrients intakes, indicated cholesterol to be negatively significant (p < 0.05) for women from 1966-1970, and salt to be positively significant for men (p < 0.01) and women (p < 0.05) from 1974-1985. In the period 1966-1970, the correlation coefficient between slopes of IHD and those of Keys' factor was positively significant (p < 0.05) for women. 3. To clarify changes in the relationship between mortality and nutrients, correlation coefficients were calculated each year from 1966 to 1985. Significant positive correlation coefficients for IHD were found with animal protein and saturated fat starting from about 1975. Salt was associated with IHD in the 1960s but not following 1970. Those of nutrients for CH and CI did not change markedly during 18 years. 4. Multiple regression analysis with intake of salt and Keys' factor indicated that the influence of salt on cardiovascular disease to decreased and that that of low serum cholesterol on CH declined. Multiple correlation coefficients with salt and Keys' factor decreased for IHD (men) and CH (women).


[Instrumentation of birth weight in obstetric facilities].

An investigation on measurement of birth weight in facilities was made in the northern part of Fukuoka Prefecture from March 1989 to January 1991. The purpose of the investigation was to clarify the reliability of birth weight data in obstetric facilities. The author interviewed the manager of each facility. The data of 112 cases were analyzed. The following results were obtained: 1) Nurses and midwives measured birth weights in many facilities, but doctors rarely did. Birth weights were obtained within an hour after birth in almost all facilities. Tare and zero-adjustment were frequently checked in many facilities, but horizontal-adjustment was not checked in about a half of the facilities. 2) The types of scales were digital scales (48.2%), dial scales (31.3%), table-top platform scales (10.7%) and bathroom scales (9.8%). It was estimated that 70.6% of the all birth weights in these facilities were obtained with digital scales. The renewals of scales in the past 5 years has resulted in the widespread use of digital scales in facilities. 3) The accuracy and precision of each scale were examined with weights of 3000g. Digital scales were superior to the other types of scales in both accuracy and precision. The legal periodical inspection for scales improved accuracy. Procedures for measuring birth weight are not generalized among and within facilities. Digital scales have many merits for handling and reading. The spread of digital scales in facilities may decrease the degree of many kinds of errors in measurement, especially rounding errors, and improve the reliability of the data in the area.


[Work history, health conditions and hearing loss of Ishigaki fishermen].

Based on our previous health survey among Ishigaki fishermen in 1979, this study aimed at clarifying the relations of their work histories to physical characteristics, physiological functions, blood conditions and hearing levels. Medical examination was conducted in 1987 on 118 fishermen inclusive of 33 followed-up fishermen, and in 1989 noise-level and noise-induced temporary threshold shift of hearing was measured for different fishing methods. The results were as follows; 1) Fishing history was not specifically associated with any physical characteristics. 2) High HDL cholesterol, which was observed among divers using diving apparatus, was considered to be a survival effect for divers, since HDL cholesterol is amplified by intensive muscle work. 3) Abnormalities of ECG except for a high R wave were notably observed among the divers, who once changed from unassisted diving to diving with apparatus and then to fishing lines. The main reason for switching jobs was claimed to be caisson disease, and it was suggested that diving with apparatus was related to a high risk of health hazards in the central nervous system and/or respiro-circulatory system. 4) Acoustic acuity greatly declined with aging, and which was commonly observed in groups with different work histories. By way of explanation, exposure to ship engine sounds during daily travelling was the most likely cause. It was also revealed that several hours' exposure to the engine sounds was needed to detect a temporary threshold shift of hearing before and after work.


[A study of the humoral immunity of mice injected with beryllium chloride].

We studied changes of humoral immunity, such as complement pathway activity, C3 contents and contents of immunoglobulin, in mice injected subcutaneously with BeCl2 or CuCl2 once a week for 12 weeks. Mean body weights of JCL: ICR female mice were approximately 30g in control mice (control group; n = 7), in mice injected with Be (Be group; n = 8) and in mice injected with Cu (Cu group; n = 8). Values of classical complement pathway activity (CH50) were 18.8 +/- 1.4 U per ml, 15.3 +/- 1.8 U per ml and 16.7 +/- 1.3 U per ml in the control group, Be group and Cu group, respectively. The CH50 values of Be and Cu groups were significantly lower than that of the control group (P < 0.01). In contrast, values of alternative complement pathway activity (ACH50) and contents of C3 were almost constant in the three groups. The immunoglobulin content in the Be group tended to increase. The activity of alanine aminotransferase in the Be group was markedly higher than that in the control group (P < 0.05), and the aspartate aminotransferase activity was also high. The CH50 value of mice injected with a small amount of Be once a week over a 12-week period decreased markedly, although either the ACH50 value or C3 content was the same as in the control group. The immunoglobulin content somewhat increased in the Be group. These results suggest the possibility that immune complex is induced by Be.


[Conditions for low-intensity voluntary wheel running in rats and its chronic effects on health indexes].

Studies were undertaken to evaluate the fundamental conditions for a low-intensity voluntary wheel running model in rats and its chronic effects on health indexes. Male Fischer rats (SPF) 5 weeks of age were housed in individual sedentary conditions or in individual wheel-cage units which allowed free access to voluntary wheel running for 8 months. Voluntary running averaged 640 +/- 198 m/day, reached a peak (965m) at the 2nd month and waned over time, reaching a plateau after the 6th month (about 400-500m). Exercising rats consumed more food (+23%), but exhibited decreased body weight gains (-9%), suggesting a remarkable lowering of fat. A lowering effect on resting blood pressure (-5%) was also recognized. In addition, preventive effects on oxygen toxicity and effective bactericidal activity of neutrophils and pulmonary alveolar macrophages (PAM) were suggested. Although the amount of exercise in this study was the smallest of the other preceding ones conducted with a voluntary wheel running model, many potential health benefits were recognized. Such health promoting and protective effects by low-intensity voluntary exercise and the harmfulness of forced exercise in rats have been reported in researches on cancer, lowering fat and hypertension. Therefore it is important to set up conditions for low-intensity voluntary running. It was also demonstrated by this study that strictly controlled environmental conditions, such as room temperature and humidity, a 12-hr light-dark cycle and prevention of infection and psychological stress to rats, as well as using male rats, which are more inactive, were important factors to establish this model.


[Instantaneous changes in sleep stage due to the sound of a passing truck].

The instantaneous effect of the sound of a passing truck on sleep of five male students, 23 to 25 years of age, was assessed. The peak levels of noise were adjusted to 55, 60, and 65 dB (A) with intervals of 18 and 13 minutes, and a frequency of one per hour. Background noise in the experimental room was Leq 42 dB (A). The sleep stage of each epoch was visually judged based on the criteria of Rechtschaffen & Kales. Data for pre-exposure epochs of sleep stage 2 and rapid eye movement (REM) were collected and 18 epochs, including two under noise exposure, were evaluated. Three sets of polygraphic data were sampled as controls from 10 minutes after 65 dB (A) exposure to the next exposure. Compared with the control, the percentage of stage 2 to shallower stages (stage 1, waking, or movement time (MT)) was significantly increased by exposure to 55, 60, and 65 dB (A). The change lasted for one minute with exposure to 55 dB (A), and 2 to 3 minutes with 60 and 65 dB (A). A decrease in the percentage of stage 2 to deeper stages was observed at 2 to 4 minutes after exposure to 60 and 65 dB (A). The percentage of stage 2 to MT increased at 60 and 65 dB (A). The percentage of stage REM to other stages increased with the exposure to 60 or 65 dB (A) within 4 minutes. The threshold of instantaneous change of stage 2 to shallower stages due to the sound of a passing truck was at the peak level at less than 55 dB (A), and that of stage REM to other stages at 55 to 60 dB (A).


Acute effects of alcohol on cognitive function and central nervous system assessed by auditory event-related potentials.

To clarify which sites of the central nervous system are influenced by acute administration of alcohol at an early stage, auditory event-related potentials (ERP) using a target-selection paradigm were measured in 13 healthy volunteers. In the recorded waveforms of ERPs, the N100, P165, N200 and P300 latencies for the target tone and the N100 and P200 latencies for the non-target tone were determined in each subject before and 1- and 2-hr after ingestion of 200 ml of alcohol (containing 25% ethanol) or of 200 ml of water, for a total of six times on two different days. The P300 latency was significantly prolonged at 1- and 2-hr after alcohol ingestion; and, the N200 latency was significantly prolonged at 2-hr after alcohol ingestion. The 2-hr alteration in the P300 latency after alcohol ingestion was positively correlated with the ethanol dose per body weight. These data suggest that ethanol, in proportion to its dose, affects cognitive function estimated by the P300 latency earlier than other lower central nervous system functions. Evaluating subclinical effects on central nervous function, using the ERPs, of environmental neurotoxins such as organic solvents, researchers should pay particular attention not only to the degree of the drinking habit but also to the interval between the measurement and alcohol intake.


Injury to cultured human vascular endothelial cells by copper (CuSO4).

The effect of copper sulfate (CuSO4) on cultured human vascular endothelial (HVE) cells and cultured human fibroblasts (HAIN-55) was investigated. HVE cells were collected from umbilical veins by enzymatic digestion with collagenase. The viability, subsequent growth and DNA synthesis of both cell types were inhibited concentration-dependently by the addition of copper. The cytotoxic effect of copper on the morphology of these cells was also concentration-dependent. However, the cytotoxic effect of copper on the viability, subsequent growth and DNA synthesis was greater in HVE cells than in HAIN-55 cells. These results suggest that HVE cells are more susceptible to concentration-dependent copper cytotoxicity than HAIN-55 cells are, and that copper could induce vascular endothelial injury, which may be involved in the pathogenesis of cardiovascular disease.


Protective activity of silipide on liver damage in rodents.

The activity of silipide, a silybin-phosphatidylcholine complex (IdB 1016), was tested in different models of liver damage in rodents. After oral administration, silipide exhibited a significant and dose-related protective effect against the hepatotoxicity induced by CCl4, praseodymium, ethanol and galactosamine. The ED50 values for inhibition of the rise in ASAT and ALAT levels caused by CCl4 and praseodymium and for antagonism of the increase in liver triglycerides caused by ethanol ranged from 93 to 156 mg/kg (as silybin). At a dose of 400 mg/kg (as silybin), silipide was also active in protecting against paracetamol-induced hepatotoxicity. Silybin and phosphatidylcholine at doses equivalent to those contained in the active doses of silipide failed to show any significant protective activity in these models. The liver protective effect of silipide is probably related to its antioxidant activities and to a stimulating effect on the hepatic synthesis of RNA and proteins.


Daily variation in the effects of furosemide in rats.

Daily variation in the effects of furosemide, a loop diuretic agent, was examined in Wistar rats maintained under conditions of light from 7 a.m. to 7 p.m. and dark from 7 p.m. to 7 a.m. Furosemide (30 mg/kg) was given orally at 12 p.m., 4 a.m., 8 a.m., 12 a.m., 4 p.m. or 8 p.m. Urine was collected for 8 hr after furosemide administration, and urinary excretions of sodium and furosemide were determined. There were significant daily variations in the urine volume and urinary excretions of sodium and furosemide with a peak at 8 a.m. and a trough at 12 p.m. Significant correlations were observed between the urinary amount of furosemide and its diuretic effects (urine volume and urinary sodium excretion). These results suggest that the diuretic effects of furosemide show daily variations which are, at least in part, caused by the daily variation in the urinary excretion of furosemide.


Effect of DS-4574, a novel peptidoleukotriene antagonist with mast cell stabilizing action, on acute gastric lesions and gastric secretion in rats.

DS-4574 is a peptidoleukotriene antagonist with mast cell stabilizing activity. In the present study, we studied the effects of this compound on gastric secretion and various acute gastric lesions in rats. Intraduodenal administration of DS-4574 at doses of 5 to 10 mg/kg significantly and dose-dependently inhibited gastric acid secretion in pylorus-ligated rats, but a further increase in the dose up to 50 mg/kg did not cause any further inhibition. Shay ulceration in response to pylorus ligation was dose-dependently prevented by DS-4574 (10-25 mg/kg, i.d.). Water-immersion restraint stress- and aspirin-induced gastric ulcers were also significantly prevented in a dose-related manner by oral pretreatment with DS-4574 (10-50 mg/kg). The lower doses of DS-4574 (1-10 mg/kg, p.o.) significantly and dose-dependently protected the gastric mucosa against the necrotizing action of either absolute ethanol or concentrated hydrochloric acid, indicating that this compound possesses a potent gastroprotective activity. These antiulcer and gastric protective effects of DS-4574 were more potent than those of cimetidine used as a reference drug. These findings suggest that DS-4574 is useful for peptic ulcer therapy, as well as for the therapy of various allergic diseases, including asthma.


Regional vascular responses to thromboxane A2 analogue and their blockade with vapiprost, a selective thromboxane receptor blocking drug, in anesthetized dogs.

Regional vascular responses to the thromboxane A2 analogue U46619 and effects of the selective thromboxane receptor blocking drug vapiprost on these responses were examined in anesthetized dogs. Hemodynamic responses to U46619 (0.5 micrograms/kg into the left atrium), norepinephrine (NE, 0.3 microgram/kg, i.v.) and angiotensin II (AII, 30 or 60 ng/kg, i.v.) were periodically tested before and after administration of vapiprost (10, 30 or 100 micrograms/kg, i.v.) or its vehicle. In the absence of vapiprost, U46619 increased total peripheral (TPR), vertebral (VR), coronary (CR) and renal (RR) vascular resistance by 60.1 +/- 4.7%, 33.6 +/- 4.9%, 15.3 +/- 1.3% and 120.8 +/- 17.4%, respectively, indicating that vasoconstrictor responses to U46619 were most prominent in the renal vascular bed as compared to those in the vertebral or coronary vasculatures. Vapiprost as well as the vehicle did not affect the base-line hemodynamics. However, vapiprost apparently inhibited the U46619-induced vasoconstriction in all measured vascular beds in a dose-related manner without attenuating vasoconstrictor responses to NE compared to the inhibitions of VR and CR. These results demonstrate that there was a regional difference both in the vasoconstrictor responses to U46619 and in the blocking effects of vapiprost, and indicate that vapiprost is a potent and selective antagonist for thromboxane receptors in vivo.


Fluorescent probe-labeled lipid microsphere uptake by human endothelial cells: a flow cytometric study.

Lipid microspheres have been used as carriers of drugs such as prostaglandin E1 (lipo-PGE1) and corticosteroid (liposteroid). Lipo-PGE1 is used for the treatment of chronic arterial occlusive diseases because its activity is far greater than that of free PGE1 in vivo. To verify the fact that the drug carriers, lipid microspheres, are preferentially taken up by endothelial cells, we labeled lipid microspheres with a fluorescent probe, DiI (DiI-LM), and observed them in some in vitro models. Stoichiometric fluorescence was obtainable, and the fluorescence was stable between pH 3.3 and pH 8.9. Human umbilical vein endothelial cells and cells of a human endothelial cell line, ECV304, showed increased uptake of DiI-LM, 81% and 61%, respectively. In contrast, uptakes were less than 7% in human skin fibroblasts, 3T3 cells, and human neutrophils. Prominent perinuclear fluorescence was also observed in endothelial cells by fluorescence microscopy. DiI-LM and flow cytometric analysis will be useful for studies to elucidate the precise mechanism of the selective accumulation of lipid microspheres by cells in blood vessel walls.


Involvement of nitric oxide in endothelium-dependent, phasic relaxation caused by histamine in monkey cerebral arteries.

Monkey cerebral artery strips partially contracted with prostaglandin F2 alpha responded to histamine with biphasic patterns of relaxation. The delayed and sustained relaxation was suppressed by cimetidine, whereas the phasic response was abolished by treatment with chlorpheniramine and NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor. The inhibition by L-NA was reversed by L-arginine. D-NA was without effect. Endothelium denudation abolished the phasic relaxation. We hypothesized that endothelium-dependent, phasic relaxations caused by histamine are mediated by NO that is released by H1-receptor stimulation, whereas the sustained relaxation is associated with the activation of H2-receptors in the smooth muscle of monkey cerebral arteries.


Heparin inhibits the progression phase of subcultured endothelial cell proliferation in rat aorta.

The anti-proliferative effects of heparin on subcultured endothelial cells (EC) of rat aorta were investigated to determine whether heparin inhibits the competence phase or the progression phase in the cell cycle using the starting time and the rate of proliferation. Fetal bovine serum (FBS)-stimulated EC proliferation increased to 1.5-times in cell number, but decreased to 0.5-times in 3H-thymidine incorporation, compared with the proliferation of rat primary cultured smooth muscle cells (SMC). The FBS-effects on EC proliferation were attributed to the progression phase rather than the competence phase. Heparin (1, 10 or 100 micrograms/ml) significantly inhibited the proliferation of FBS (5%)-stimulated EC, and the extent of inhibition was the same in both cell number and 3H-thymidine incorporation. In the 3H-thymidine incorporation every 3 hr, heparin reduced the rate of incorporation into G0-arrested EC, but did not affect the starting time of DNA synthesis. When the index of competence phase, starting time, was plotted against that of progression phase, rate of proliferation, the inhibition of heparin was attributed to the progression phase. These results demonstrate that heparin selectively inhibits the progression phase in subcultured EC of rat aorta.


Protective effect of eurystatins A and B, new prolyl endopeptidase inhibitors, on scopolamine-induced amnesia in rats.

Eurystatins A and B, which are produced by Streptomyces eurythermus R353-21, potently inhibited Flavobacterium prolyl endopeptidase (PED) with IC50 values of 0.004 and 0.002 micrograms/ml, respectively, while no inhibition was observed against another 5 proteases, even at 100 micrograms/ml. The protective effect of eurystatins A and B against scopolamine (3 mg/kg, i.p.)-induced amnesia in rats was evaluated by the step-through one-trial passive avoidance method. When administered i.p. 30 min prior to the acquisition trial, both eurystatins A, at 2-8 mg/kg, and B, at 4-8 mg/kg, significantly protected rats from the amnesic effect of scopolamine without behavioral side effects.


Effects of acute administration of nicotine on convulsive movements and blood levels of corticosterone in old rats.

The convulsive movements, blood levels of corticosterone and pharmacokinetics of nicotine after an acute intraperitoneal injection of nicotine (5 mg/kg) were examined in young (6-week-old) and old (2-year-old) rats. In pharmacokinetic study, blood nicotine levels during the elimination phase were significantly higher in old rats than in young rats. However, the duration of convulsions and the elevation of corticosterone levels after the nicotine injection showed significant decreases in old rats compared with those in young rats. These differences of nicotine-induced responses between young and old rats may be involved in the decrease in nicotine sensitivity.


Flow cytometric estimation of the effect of Ginkgo biloba extract on the content of hydrogen peroxide in dissociated mammalian brain neurons.

The effect of Ginkgo biloba extract (GBE) on the content of hydrogen peroxide was estimated in cerebellar neurons dissociated from rats, by means of a flow-cytometer and 2',7'-dichlorofluorescein (DCF) diacetate, a fluorescent dye for intracellular hydrogen peroxide. The GBE started to reduce the DCF fluorescence of the neuron at 0.1 microgram/ml to 0.3 microgram/ml. Further increases in the GBE concentration (up to 3 micrograms/ml) produced a dose-dependent decrease in the DCF fluorescence, suggesting that GBE reduces the content of hydrogen peroxide or suppresses the reactive oxygen species (ROS) formation of cerebellar neurons. The present technique may be useful for preliminary evaluations of agents affecting the ROS formation in mammalian brain neurons.


Calcium channel blocker-like action of 1,9-dideoxyforskolin in vascular smooth muscle.

The inhibitory effect of 1,9-dideoxyforskolin (DFK) on the contraction of rat aorta was compared with that of forskolin. DFK inhibited the contraction induced by high K+ more strongly than that induced by norepinephrine, whereas forskolin more strongly inhibited the norepinephrine-induced contraction. The inhibitory effect of DFK on high K(+)-induced contraction was antagonized by an increase in extracellular Ca2+ concentration. DFK inhibited the increase in cytosolic Ca2+ level and contraction in parallel whereas forskolin inhibited the contraction more strongly than the cytosolic Ca2+ level. These results suggest that DFK, but not forskolin, inhibits vascular smooth muscle contraction by a Ca2+ channel blocker-like action.


Antiproliferative effects of the traditional Chinese medicine shimotsu-to, its component cnidium rhizome and derived compounds on primary cultures of mouse aorta smooth muscle cells.

Antiproliferative effects of the Japanese-Sino medicine Shimotsu-to (a combined prescription of cnidium rhizome, angelica root, peony root and rehmannia root) were investigated in the primary culture of smooth muscle cells (SMC) of mouse aorta. Fetal bovine serum (10%)-induced proliferation of primary cultured SMC was inhibited by Shimotsu-to at 4, 20, 100 or 500 micrograms/ml. The inhibitory effect was selective on SMC and due to cnidium rhizome or angelica root. The IC50 values of senkyunolide H, senkyunolide A, ligustilide and butylidenephthalide derived from cnidium were below 0.1, 1.52, 1.68 and 3.25 micrograms/ml, respectively. These results indicate that the antiproliferative effect of Shimotsu-to may depend on these cnidium-derived phthalides.


KCl-depolarization potentiates the Ca2+ sensitization by endothelin-1 in canine coronary artery.

In Ca(2+)-free solution containing endothelin-1 (ET-1), depolarization by high KCl increased the force of contraction without any changes in intracellular calcium concentration ([Ca2+]i) in canine coronary artery. The [Ca2+]i-force relationships were examined in the absence or presence of ET-1 in 5 or 90 mM KCl. The relation curve in the presence of ET-1 in 90 mM KCl-PSS was shifted to the left and upward compared with that in 5 mM KCl. These results suggest that KCl-depolarization potentiates the Ca2+ sensitization by ET-1.


Pediatric cardiology: auscultation from 280 miles away.

New long-distance audio/video and data communications links among health-care facilities promise to reduce rural patients' travel time and waiting time for subspecialty consultations. To offer a satisfactory alternative to face-to-face examination, the long-distance system must meet the subspecialty's minimum criteria. For pediatric cardiology in particular, the system has to permit satisfactory cardiac auscultation. A preliminary test of remote auscultation that uses an electronic stethoscope involved two pediatric cardiologists, one listening hands-on with an acoustic stethoscope, the other listening independently at long distance with the electronic instrument. Taking the acoustic findings as the reference standard, the electronic stethoscope did not miss the one case of heart disease, correctly recommended echocardiogram follow-up in the two cases requiring it, and agreed on 80% of the murmurs' qualitative specifics. The patients' parents also indicated that the system was highly acceptable. We are following up these results with a full-scale study of the effectiveness and parental acceptance of remote auscultation.


[Increased fibrinogen and factor VII activity levels in patients after myocardial infarction].

Functional and biochemical parameters of the haemostatic system in coronary heart disease (CHD) are still not well defined. Epidemiological studies indicate a positive correlation between fibrinogen (F) level and cardiovascular morbidity and mortality. Two independent ways of factor VII activation in the coagulation cascade suggest a special role of this factor in clot forming (Fig. 1). 22 patients (pts) under 55 yrs with a history of myocardial infarction (MT) and 22 healthy control men were studied for F level and factor VII activity (fVIIa). We found increased F level (M-363.3 mg/dl) and high level of VIIa (M-150.3%) in plasma of pts with a history of MI. Furthermore a strong positive correlation between fVIIa in plasma and F level (r = 0.62), serum cholesterol (chol) (r = 0.35), serum triglycerides (tg) (r = 0.32) (Tab. 2) was bound. Calculations were performed for all subjects: pts and control combined in one group. A possible influence of diet on fVIIa level is discussed. One should consider the usefulness of oral anticoagulants in the prophylaxis of MT.


[Diurnal variability of heart rate during paroxysmal ventricular tachycardia].

The aim of this study was to assess the diurnal variability of heart rate during VT. For the purpose of this investigation VT was considered to be a minimum of 3 consecutive ventricular beats in duration at a rate more than 100 bpm. From the group of 287 patients with VT during 24-hour ECG monitoring, a selection was made of 52 patients in whom episodes of monomorphic VT occurred in the day-time and night-time without any changes of the QRS morphology. Thirty one patients had ischemic heart disease, 10--dilated cardiomyopathy, 2--mitral valve prolapse and 10 patients had no evidence of heart disease. In these patients the rate of VT (HR-V), basic heart rate (HR-S) before VT, and coupling interval (CI) of VT initiating beat were measured during day-time and night-time. The mean VT rate was 170 +/- 34 bpm during day-time and 149 +/- 36 bpm during night-time (p < 0.001). The mean sinus rhythm rate was significantly (p < 0.001) greater during day-time (88 +/- 16 bpm) than at night (78 +/- 19 bpm). There was significant difference in the mean values of the CI between day-time and night-time (504 +/- 122 vs 589 +/- 181 ms). A significant correlation was noted between HR-V and HR-S at night (r = 0.73; p < 0.001) but not during day-time (r = 0.38). Thus, HR-V similarly as HR-S is greater during day-time than during night-time. Diurnal variability of HR-V may be related to changes in autonomic nervous system tone.


[Complications of percutaneous transluminal coronary angioplasty (PTCA)].

Between 1981 and 1990, 714 patients underwent 756 percutaneous transluminal coronary angioplasty (PTCA) procedures. A total of 52 patients (6.9%) had major in-hospital complications: 5 patients (0.66%) died, Q-wave or non Q-wave myocardial infarction were observed in 13 patients (1.66%) during procedure and in 8 (1%) outside the catheterization laboratory, before discharge. Because of periprocedural occlusion 11 patients (1.5%) were managed with bypass surgery, 8 (1%) had a transient occlusion that was reopened with PTCA. 21 patients (2.8%) were not ++re-dilated but managed pharmacologically. Dissection, intracoronary thrombus and previous thrombolytic treatment were often associated with occlusion. The risk of dissection was related to lesion morphology. Long-(more than 1 cm) lesion, eccentric stenosis and tortuosity of the vessel segment undergoing dilatation were risk factors for occlusive dissection. There was a high risk of side branch occlusion if its take-off was narrowed and side branch originated from the target lesion. One of the most important risk predictors is the amount of jeopardized myocardium supplied by the target coronary artery. Acute closure of an artery supplying large amount of myocardium may cause abrupt hemodynamic collapse. Hypotension secondary to the artery occlusion may cause a decrease of the flow in the other coronary arteries, leading to cardiogenic shock. Although it is important to note that patients with unstable angina, intracoronary thrombus, long and complex lesion, severe multivessel disease and compromised left ventricular function are at higher risk of acute complication, PTCA is a relatively safe procedure.(ABSTRACT TRUNCATED AT 250 WORDS)


[Aneurysms in acute myocardial infarction (multicenter studies)].

The authors present outcomes concerning frequency of appearance and clinical course of aneurysms after acute myocardial infarction. The study population consisted of 730 patients (mean age 54 +/- 9 years) with acute myocardial infarction, including 579 men and 151 women. The diagnosis was based on the following criteria: 1) coronary artery disease history, 2) physical examination, 3) ECG, 4) 2-dimensional echocardiography, 5) biochemical data. Post-infarction aneurysm was revealed in 42 patients (5.8%, 33 men and 9 women); antero-lateral aneurysm--in 36 patients (85.7%), and inferior-posterior aneurysm--in 6 patients (14.3%). Ventricular arrhythmias in the first day of infarction had a high frequency in both groups; with aneurysm--92.9%, without aneurysm--82.2%. The frequency of arrhythmia in 21-st day of infarction decreased similarly in both groups with aneurysm--40.5%, without aneurysm--38.9%. There was no statistically significant difference among both groups. There was no correlation between localisation of aneurysms and degree of contractility disturbances of the heart muscle (dyskinesis, akinesis). Heart failure--class III and IVK (Killip-Kimball classification) occurred in 19.0% of patients with aneurysm and in 10.4% of patients without aneurysm. That was no essential correlation between localisation of aneurysms and advancement of the heart failure.


[2 episodes of ventricular fibrillation in a patient with mild paroxysms of Wolff-Parkinson-White syndrome].

In a patient with an overt Wolff-Parkinson-White syndrome and short paroxysms of atrio-ventricular tachycardia, episodes of atrial fibrillation occurred twice at age of 21 and 24. Atrial fibrillation degenerated into ventricular fibrillation. Intravenous injection of verapamil in this patient (with a short refractory period of the accessory pathway) could have facilitated ventricular fibrillation. The patient was resuscitated successfully. Electrophysiologic study revealed double accessory pathways--in the left free wall (effective refractory period in both directions--below 200 ms) and right posterior ++para-septal localization. 20th Nov 1990 A. Biederman M.D. performed surgical dissection of both accessory pathways. In control electrophysiologic studies there was no evidence of abnormal atrio-ventricular conduction. During one year follow up the patient reported no paroxysms of tachycardia.


[Recurrent bacterial endocarditis with involvement of the tricuspid valve after surgical correction of congenital heart defect].

A case of recurrent tricuspid valve endocarditis after surgical closure of ventricular septal defect is presented. Intensive medical treatment lasting nearly ten years completely failed. There were still vegetations attached to the septal leaflet of the tricuspid valve with positive cultures (Ps. aeruginosa). Persistent sepsis without signs of heart failure required surgical intervention. Tricuspid valvuloplasty with excision of infected patch was successfully performed. Six months later the patient remained symptomless.


[A case of direct right pulmonary artery-left atrium fistula].

An unusual case of cyanotic heart disease in a 20-year-old male has been presented. Cyanosis was due to right to left shunt through direct right pulmonary artery--left atrium fistula. After successful operative ligation of the fistula, the patient got rid of cyanosis and is doing well.


[Heart failure in acute myocardial infarction: comparing infusions of nifedipine and nitroglycerin].

The impact of intravenous infusion of nifedipine and nitroglycerin on invasive central hemodynamic parameters and microcirculation was compared in 94 patients with acute myocardial infarction complicated by heart failure. The artery dilating effects of nifedipine were associated with baseline peripheral vascular tone, so the comparison was made separately in the groups with and without vasoconstriction. Nifedipine seems to be beneficial in the management of heart failure due to acute myocardial infarction in patients with systemic vasoconstriction. In patients with severe pulmonary congestion and normal left ventricular afterload, the intravenous vasodilators are preferable.


[Features of the clinical and functional state of myocardial infarction patients with psychogenic silent ischemia].

A total of 111 patients with myocardial infarction were studied in the early, period of the disease. Exercise and information load tests, impedance plethysmography, electrocardiography, and large-framed fluorography were performed. Among the patients with myocardial infarction who responded to information load by exhibiting transient silent ischemia, vasospastic reactions were demonstrated to be diagnosed mainly in those with posterior myocardial infarction. The patients with anterior myocardial infarction responded to psychoemotional stress mainly by showing ischemia formed under the conditions of higher myocardial oxygen uptake due to increased blood minute volume. In most patients, the area of silent psychogenic vasospastic ischemia coincided with that of infarct-related myocardium, whereas ischemic changes were largely located in the anterior left ventricular wall despite the area of myocardial necrosis when psychogenic ischemia developed with increased myocardial oxygen uptake.


[Effectiveness of pre-hospital thrombolytic therapy in acute myocardial infarction].

The efficacy and risk of prehospital thrombolysis for acute myocardial infarction (MI) were evaluated in a randomized trial. Patients received streptokinase, 500,000 U, and heparin, 10,000 U, intravenously within 5-10 minutes before (Group 1, n = 50) or after (Group 2, n = 50) hospital admission. One hundred patients took conventional therapy (Group 3). The mean time interval between the onset of symptoms and thrombolytic therapy was 2.2, 4.5, and 3.8 hours in Groups 1, 2, and 3, respectively (p < 0.001). Severe hemorrhages were absent. The rate of ventricular fibrillation was the same in Groups 1 and 3 prior to hospitalization. Left ventricular contractility was identical in Groups 1 and 2. By the end of the fourth week, Group 1 showed a 14% increase in ejection fraction and a 14.5% decrease in akinetic segment, these parameters substantially unchanged in Group 2. The MI size assessed by ECG and the maximum myoglobin concentrations was significantly less in Group 1 than that in Group 2. The patients from Group 1 had fewer MI complications than those from Groups 2 and 3. Three patients died in Group 1, 6 in Group 2, and 16 in Group 3. (p < 0.05).


[Development of myocardial infarction in aspirin-treated unstable angina pectoris. Repeated studies of platelet aggregation and of the thromboxane-prostacyclin system].

Platelet functional parameters (platelet aggregation, blood circulating reversibly and irreversibly aggregated platelet complexes, thromboxane B2, 6-keto-PGF1 alpha) were examined in unstable angina treated with aspirin in a daily dose of 320 mg in relation to the outcome of the disease: Group 1, stabilization and Group 2, evolving myocardial infarction. Differences were found in the baseline platelet functional parameters between the groups. The findings suggest that platelet functional parameters show a varying response to aspirin depending on the outcome of the disease. Despite the effective inhibition of thromboxane A2 synthesis, aspirin was found to fail to prevent enhanced platelet aggregatory activity in case of myocardial infarction developed during the therapy.


[Clinical and functional characteristics of patients with ischemic heart disease in long-term remission of angina pectoris].

Long-term (5-15-year) prospective surveys of 171 angina patients have yielded clinical, coronarographic, and bicycle ergometric criteria for predicting the favourable course of the disease. A prolonged (at least 3 years) clinical anginal remission was observed in 43 (25.1%) patients. The patients had typical features: a short (less than 6-9 months) history of classical angina, the age at the onset of CHD under 50 years; high performance during bicycle ergometric test, lack of angina after sustained so-called "accomplished" myocardial infarction. The coronarograms of patients with a long-term anginal remission most frequently displayed severe stenosis or occlusion of "unsafe" site of a large coronary artery. The duration of remission was less than 10 years if atherosclerosis also affected the remaining coronary arteries. That of remission was more than 10-15 years, if the remaining coronary arteries proved completely intact.


[Use of loading tests to detect silent myocardial ischemia].

A total of 74 patients with postinfarct cardiosclerosis (PC) and stable angina (SA) were examined by Holter monitoring, bicycle ergometry, echocardiography and 201Tl chloride myocardial scintigraphy and loading tests (transesophageal cardiac pacing and isometric hand exercise test). The detection rate for silent myocardial ischemia (SI) was found to be 57.1% with Holter monitoring, 52.3% by bicycle ergometry, 62.5% with echocardiography, 100% with myocardial scintigraphy with loading test and 88.8% with that without the loading test. The detection rate for PC was 33.9, 32.0, 64.7, 81.8, and 56.7%, respectively. Higher SI detection rates in postinfarct patients were more frequently observed when echocardiography and myocardial scintigraphy in combination with loading tests in patients with PC without angina. The efficiency of SI detection in patients with various coronary heart disease increases when loading tests are employed. The loading tests in echocardiography and myocardial scintigraphy ensure the most complete detection of SI in postinfarct patients without angina.


[Microcirculatory changes in patients with hypertensive disease caused by excessively lowered blood pressure after clofelin administration].

In 20 patients with Stage II hypertensive disease, erythrocyte and platelet aggregation to response to ATP was photooptically studied, skin oxygen tension was polarographically examined, and the diameters of conjunctival vessels were microscopically measured. In the patients, excessive decreases in blood pressure were found to lead to lack of microvascular tone coordination, to increases in platelet and erythrocyte aggregation and to decreases in tissue oxygen supply. It was emphasized that the microcirculation and tissue oxygen supply should be monitored when clofelin dosages are chosen individually in the treatment of hypertensive disease.


[Role of the inositol phosphate cycle in the cardioprotective effect of adaptation to intermittent hypoxia].

The impact of adaptation to intermittent hypoxia of different duration (for 20 and 40 days) on the inositol triphosphate-diacylglycerol (ITP-DAG) regulatory contour in the heart was investigated. For this, isolated heart alpha 1-adrenoreactivity to phenylephrine and phospholipase (PhL-C) activities were studied in cardiac plasma membranes. On day 20 of adaptation, the heart inotropic response to phenylephrine stimulation was somewhat reduced and the activity of Ca(2+)-dependent PhL-C did not differ from that in the controls within the range of Ca2+ physiological concentrations. Forty days after adaptation, both positive inotropic responses of the heart to phenylephrine and activity of Ca(2+)-dependent PhL-C were enhanced, i.e. activation of the ITP-DAG regulatory cascade occurred. Early studies have shown that a phenomenon of adaptive stabilization develops at this stage of adaptation. The phenomenon appears as a significant increase in heart resistance to thermal injury, toxic catecholamine levels, Ca2+ paradox and high Ca2+ concentrations. Thus, the revealed activation of the ITP-DAG regulatory contour was accompanied by the development of a phenomenon of adaptive structure stabilization (PhASS) in the hearts of adapted animals. The findings suggest that the ITP-DAG regulatory cascade plays an important role in the cardioprotective effect of adaptation to intermittent hypobaric hypoxia and in PhASS formation.


[Myocardial perfusion in mitral valve prolapse with arrhythmic syndrome].

Myocardial perfusion was studied in 12 patients with mitral valve prolapse concurrent with cardiac arrhythmias by using two-dimensional 201Tl myocardial scintigraphy at rest and during exercise test. Signs of myocardial ischemia were revealed only in one case. Five patients were found to have steady-state perfusion defects whose extent correlated with the depth of mitral valve prolapse. There was an irregular distribution of myocardial blood flow, which ceased on exercise in 10 out of 12 patients. Patients with ventricular premature contraction displayed a decreased reserve of myocardial blood flow as compared to those with supraventricular premature contraction, presumably by enhancing myocardial perfusion at rest.


[Alterations in the functional activity of platelets in patients with angina pectoris during the cold test].

The functional activity of platelets was examined in patients with coronary heart disease and healthy individuals during cold test (CT). Patients prone to vasospastic responses to CT exhibited platelet activation along with beta-thromboglobulin release and formation of spontaneous platelet aggregates. Comparison of functional changes in platelet functional activity which occurred during cold test and intravenous ergometrine test suggest that the response to CT may be substantially higher if platelet aggregability is concurrently determined. The unidirectional changes in platelet aggregability during cold and ergometrine tests in patients with signs of dynamic coronary occlusion may indicate a relation of platelets with coronary vasoconstriction.


[Carbohydrate composition of native and desialylated low density lipoproteins in the plasma of patients with coronary atherosclerosis].

The monosaccharide content was examined in apoprotein B and lipids of total low density lipoprotein (LDL) preparations isolated from the blood of healthy individuals and patients with coronary atherosclerosis, as well as in desialylated and sialylated LDL obtained by affinity chromatography on Ricinus Communis Agglutinin-agarose. The glycoconjugates of total apoprotein-B of healthy subjects' LDL were found to consist of N-acetylglycosamine, galactose, mannose and sialic acid in a molar ratio of 2:1:2.5:1. The content of protein-bound neutral sugars was the same in healthy subjects and patients, while there was a lower sialic acid amount in the patients. The level of protein-bound sialic acid in patients' desialylated LDL was 2- to 3-fold lower than that in sialylated LDL. In contrast to apoprotein-B glycoconjugated, the lipid-bound carbohydrate chains of total LDL preparations had N-acetylgalactosamine and glucose, but not mannose. In total LDL from patients, the content of all lipid-bound carbohydrates was 1.5- to 4-fold lower than that in LDL from healthy subjects. In healthy subjects and in patients alike, the neutral sugar content of a lipid subfraction of desialylated LDL was lower than in those of sialylated LDL. It is concluded that atherogenic desialylated LDL differ from non-atherogenic sialylated LDL in neutral sugar levels.


[Hepatic function in circulatory insufficiency. Mathematical modeling of 137I-labelled rose bengal transport in the body].

131I-labelled bengali pink was used to perform radiohepatography in patients with circulatory failure. Both amplitude-time parameters of blood clearance curves and hepatograms and the generalized index of parameters of the linear 3-chambered reversible model of this tracer transport in the body indicate that the decrease of hepatic absorptive and excretory function in the presence of 131I-labelled bengali pink occurs in a direct relationship to the degree of circulatory insufficiency and developed in parallel with bilirubin metabolic disturbances. In some patients, hepatic lesion in the presence of Stages IIB-III circulatory insufficiency with signs of hepatocellular failure and cholestasis was accompanied only by moderate hepatic absorptive and excretory dysfunction against 131I-labelled bengali pink and by an increase in blood total bilirubin levels no more than that in Stage IIA circulatory insufficiency.


[Prognosis in the outcome of relaparotomy].

The analysis and processing with the use of a special method of 54 direct observations and 342 case records of the patients with early postoperative intraabdominal complications were carried out. A method for syndrome prediction of the outcomes of relaparotomy has been developed. The syndromes of the most significant predictive value have been revealed: those of intoxication, respiratory and hepatorenal failure, impaired hemodynamics and electrolytic metabolism, hemocoagulation. Use in clinical practice of the method mentioned as well as the methods promoting timely detection of the intraabdominal complications permitted to reduce lethality after relaparotomy from 21.4 to 15.3%.


[The value of biochemical indices of the blood in early diagnosis of gastric cancer].

The results of biochemical blood analysis in 75 patients with I-II stage gastric cancer have been analysed. The control group was comprised of 210 patients with gastritis, callous ulcer and polyps of the stomach. By means of a correlation-regression analysis, the non-linear relations between I-II stage gastric cancer and biochemical indices of the blood were revealed. The highly significant indices for diagnosis of the disease in mass examination of the population have been developed.


[Three methods of placing a single-row layer-by-layer everted intestinal suture].

The three methods for placing a single-row layer-by-layer everted intestinal suture with the suture ligature knots situated in a different manner relative to anastomotic surfaces are presented. Using the methods suggested, 53 patients were operated on, who underwent formation of 87 anastomoses. The results of studies indicate that the use of a single-row layer-by-layer everted suture permits to reduce considerably the incidence of postoperative complications, promotes early restoration of a function of the organ operated on.


[Importance of immunologic protection factors in predicting the development of purulent septic complications after appendectomy].

In 66 patients with acute appendicitis, the immunocompetent system was studied in dynamics, significant decrease in all the parameters considered before and at different time after the operation was revealed. In patients with complicated forms of the disease, disorders in immunity were more pronounced, and didn't disappear by the moment of clinical recovery. Sharp reduction (more than 40-50%) of both humoral and cellular links of immunity by day 1 and 3 after the operation can be used as an early prognostic sigh of the development of a postoperative wound suppuration.


[Specifics of resistance dosing at expiration in spontaneous respiration with positive pressure at the end of expiration in the postoperative period in obese patients].

The indications and regimens of spontaneous respiration with positive pressure at the end of expiration (SR with PPEE) in patients with morbid obesity are not established. The individual selection of resistance at expiration is necessary. In 53 patients, the selected resistance at expiration has proved to be the optimal, contributing to significant improvement of parameters of pulmonary ventilation without deterioration of hemodynamic indices. An inverse dependence of the values of optimal resistance at expiration and excess in ideal body mass was established. By multiplying the values mentioned, the K coefficient is obtained equal to 530.3 + 7.66. In patients over 60, K was 400.3 +/- 11.52. The use of a nomogram (in numerical and graphic versions) to dose resistance at expiration in patients with concomitant morbid obesity contributed to significant improvement of the indices of pulmonary ventilation and gas exchange without disorders in hemodynamics after seances of SR with PPEE.


[Managing the postoperative period after gastric resection in an experimental study].

In 60 mongrel dogs of both sexes, gastric resection was performed under endotracheal narcosis. Depending on peculiarities of conducting the postoperative period, the animals were subdivided into three groups: in group 1 animals, total parenteral nutrition was used, in group 2--total enteral nutrition, in group 3--combined therapy. Combined parenteral (dextrans) and enteral (energetic and plastic substrates) administration of drugs and nutrients is an optimal method of corrigative therapy after resection of the stomach.


[Gastrectomy at the peak of gastric bleeding].

The technique for performance of gastrectomy under conditions of emergency surgery permitting to shorten the duration of intervention and increase its effectiveness is presented. Gastrectomy was performed in 7 patients with gastric cancer complicated by profuse bleeding. All the patients are alive, no anastomotic suture failure occurred.


[Intraabdominal hemorrhage after surgery on the abdominal organs requiring relaparotomy].

The results of 76 relaparotomies performed for intraabdominal postoperative hemorrhage after emergency and elective operation on the abdominal organs are presented. The clinical features, diagnosis of profuse and capillary postoperative hemorrhage, causes and indications for relaparotomy performance are considered. Lethality in intraabdominal postoperative hemorrhage was 18.4%.


[Simultaneous surgeries in the treatment of stomach and duodenal diseases].

The results of diagnosis and treatment of diseases of the stomach and intestine associated with diseases of the abdominal organs: hiatal hernia (97 cases), commissural disease of the peritoneum (31), calculous cholecystitis (28), abdominal wall hernia (22) are presented. In 34 patients, 3 and more diseases were revealed. Simultaneous operations were performed in 181 patients. At the long-term period, a good result was noted in 68.6%, a satisfactory one--in 25.5%, and unsatisfactory result--in 5.9%. The substantiated performance of simultaneous operations in patients of the given category is a perspective trend in surgery, it ensures the high medico-social and cost effectiveness of treatment.


[Early diagnosis and treatment of a pyloroduodenal ulcer complicated by stenosis of gastric outlet].

Treated were 193 patients with pyloroduodenal ulcer complicated by stenosis of gastric outlet. Compensated stenosis was noted in 14 (7.2%) patients, subcompensated--in 147 (76.2%), decompensated--in 30 (15.5%), gastric tetany--in 2 (1.04%). Studied were the immunologic indices, peripheric blood flow by means of a roentgenologic method under conditions of double contrasting and artificial hypotony, gastric and duodenal function, bioelectric activity--by the method of duodenokinesiography. Gastric resection was performed in 87 patients, vagotomy with drainage operation and without it--in 82, gastroenterostomy--in 14, antrum resection with vagotomy--in 12, Roux resection of the stomach--in 2. The postoperative lethality was 1%. Good and excellent results after gastric resection were noted in 82.1%, after vagotomy--in 88.4% of the patients.


[Perforation of a giant duodenal ulcer].

The results of operative treatment of 20 patients with a perforated giant duodenal ulcer have been analysed. The difficulties associated with closure of a perforated hole and duodenal stump management in performance of gastric resection were noted. It was established that closure of a giant perforated duodenal ulcer was a palliative measure, which saved the patients from death but entailed the disease recurrence requiring reoperation.


[Immediate result of surgical treatment of ulcer disease in morbidly obese patients].

From 1975 to 1989, 97 patients with ulcer diseases and concomitant obesity were operated on at the Tashkent branch of the All-Union Scientific Surgical Centre, Academy of Sciences of the USSR. The patients with a gastroduodenal ulcer, II and higher degree of morbid obesity accounted for 2.4% of the total number of patients operated on for ulcer disease. Gastric ulcer was diagnosed in 20 patients, a duodenal one--in 77. All the patients were operated on for disease complications. Of them, 36 underwent Billroth-II gastric resection, the remaining patients--Billroth-I gastric resection and truncal vagotomy with drainage operation. The best immediate result was noted after performance of truncal vagotomy with drainage operation. Use of gastric resection in a given category of patients is accompanied by the development of a large number of local and general complications.


[Indices of acid-base and pepsin-acid coefficients in the gastric contents of patients with duodenal ulcer].

The indices of acid-base and pepsino-acid coefficients (ABC and PAC) in 99 patients with a duodenal ulcer, who previously underwent closure of its perforation and in 22 patients with uncomplicated course of the disease were studied. The control group included 22 healthy subjects. In patients after closure of a perforative duodenal ulcer, the low ABC and PAC indices may be indicative of the absence of stable disease remission and possibility of the development of a repeated complication.


[Surgical treatment of complicated ulcer disease of the stomach and duodenum at the health department of a metallurgical factory].

The case records of 419 patients with complicated gastric and duodenal ulcer disease were analysed. Frequent asymptomatic course of the ulcer disease was noted in workers of the metallurgical and engineering industry. Different modifications of Billroth resection of the 2/3 of the stomach were used in 240 patients, selective proximal vagotomy (SPV) with ulcer excision--in 87, transverse gastric resection with preservation of the pyloric sphincter--in 30, closure of a perforative hole--in 60, closure of a perforative hole with excision of the ulcer margins and bilateral truncal vagotomy--in 2. The most favourable long-term result was noted in patients after SPV with ulcer excision and transverse gastric resection with preservation of the pyloric sphincter.


[Primary diseases of the greater omentum in children].

The results of treatment of 12 children with primary acute diseases of the greater omentum, in whom preoperative diagnosis is difficult, have been analysed. At operation, primary omentitis was revealed in 4 children, in 6--torsion of the omentum, in 2--its idiopathic infarction. Two more children were operated on for lymphangioma of the greater omentum. The result of treatment is positive, and prognosis of the disease is favourable.


[Loop colostomy in patients with cancer of the colon and rectum].

At the clinic of Scientific Research Institute of Proctology, Ministry of Public Health of Armenia, in 97 patients with complicated cancer of the colon and rectum, a two-barrel loop colostomy was created for the recent 10 years. Use of intraperitoneal method contributed to 3-fold decrease in incidence of postoperative purulent complications. Irrigation of a tumour site with antibacterial preparations in perifocal inflammation of colonic cancer together with carrying out the complex antibacterial therapy permits to perform the radical operations.


[The effect of selective proximal vagotomy on mucus production of the stomach in pyloroduodenal ulcer].

Secretion of the main component of gastric juice mucus-fucoglycoproteins (FGP) in uncomplicated and complicated by stenosis of gastric outlet ulcer disease of the stomach and intestine, the effect of selective proximal vagotomy (SPV) and drainage operations on FGP exchange were studied. Dependence of fucose production on severity of the course of ulcer disease has been established. Early after SPV, preservation of FGP concentration in the gastric juice at initial level and significant decrease in their hour production were noted. FGP concentration in patients with its low initial values restored within the first year of follow-up, debit--later on. The data obtained can be used in assessment of the SPV results, and in revealing the patients with high risk for development of ulcer disease recurrence.


[Social costs of visual handicap and blindness. Rehabilitation resources for blind patients].

The number of blind and partially sighted persons in Germany is growing. Increasing social cost and human suffering are related. Measures to counteract this development (e.g. prevention, rehabilitation) are needed. This work gives an overview of the social cost of visual impairment; rehabilitation efforts and needs for eye diseases are considered. Data from several sources have been analysed in regard to social cost of blindness and rehabilitation efforts for eye diseases: e.g. from the Bavarian and Federal statistical agencies (number of blind and partially sighted), form the German veterans administrations (number of early retired) etc. The results relate to the former Federal Republic of Germany before unification; data from the five new states are not yet available. 1. social cost: The funds needed for blindness compensation payments increased steadily; new figures from Bavaria indicate that in Germany a total of 1,000,000 DM is needed. As a trend the yearly rise over the last 10 years was 6% in Bavaria. Indirect social cost ist caused by early retirement of blind or visually handicapped people; yearly 1% (2000 cases) of all early retirement is due to eye diseases. 2. rehabilitation efforts: For the annual incidence of blind and partially sighted--an estimated 17,000 blind and 50,000 partially sighted--only 12,000 rehabilitation measures are provided in Germany. For the age group over 65 years (which makes up to 60% of all visually impaired) only 800 rehabilitation measures are being completed yearly. In the ophthalmology sector the provision of low vision aids to visually handicapped people is incomplete. A maximum of 60% of all practising ophthalmologists in Bavaria provide this service. On the basis of own data (and from the medical service of medical assistance insurances) it is obvious that 20-50% of the prescribed low vision aids do not fit the requirements of the visually handicapped. In general too high a magnification is prescribed. More visual rehabilitation services are needed to cope with the growing demand, especially for low vision aids. A prerequisit for a higher coverage with low vision aids is a better reimbursement of the prescribing ophthalmologist by medical assistance insurances.


[Short-term effect of megadose steroid therapy in optic neuritis].

15 patients with unilateral optic neuritis and 2 patients with bilateral optic neuritis were treated with 1000 mg methylprednisolone i.v. per day for 5 days. In the cases of unilateral optic neuritis, visual acuity was reduced to < or = 0.1, in those with bilateral optic neuritis to < or = 0.6 in the better eye. The treatment was started one to 70 days after the onset of the neuritis. We examined whether vision recovered rapidly during the treatment. As a rapid recovery we defined a fourfold improvement on a logarithmic scale during the 5 days of methylprednisolone medication. Such a rapid recovery was found in 11 of the 15 patients with unilateral and in 1 of the 2 patients with bilateral optic neuritis. A similar recovery was not found before and after the treatment interval. Although we did not have a control group, the correlation in time between the therapy and the rapid recovery suggests that the megadose steroids were effective in our patients. This interpretation is compatible with the results of the randomized controlled multicenter trial of Beck et al. (New Engl. J. Med. 326:81, 1992): However, the beneficial effect was seen up to 6 months only; one year after treatment, visual functions did no longer differ between the megadose and the placebo groups. Low-dose oral steroids did not improve visual function at any time and carried a higher risk for new episodes of neuritis, compared to placebo. Therefore, the "traditional" low-dose steroid therapy for optic neuritis has become obsolete.


[Evaluation of the image quality of bi- and multifocal intraocular lenses with a new optical system].

By means of a new optical device developed by Reiner, an "optical implantation" of 6 different bi- and multifocal intraocular lenses (MIOLs) was performed in 20 young healthy subjects, and results were compared with those of a monofocal reference IOL. The following parameters were investigated: distance and near visual acuity, depth of focus and contrast sensitivity. The median of distance visual acuity was 1.0 in all IOLs with the exception of a 7-zone refractive MIOL (0.75). Near acuity without near addition was 1.0 in all MIOL models; through focus curves of all MIOLs showed an increase in depth of focus with a typical two peak course. Contrast sensitivity at high contrasts was reduced for the 7-zone-model, but contrast sensitivity at low contrasts was significantly reduced for all MIOLs, except the 2- and 3-zone refractive models.


Evolution of metabolic pathways by chance assembly of enzyme proteins generated from sense and antisense strands of pre-existing genes.

In order to get an insight into the evolutionary aspect of metabolic pathways, especially of the ubiquitous glycolytic pathway, we have carried out an extensive search of sense-sense and sense-antisense similarities for enzyme proteins in the glycolytic pathway, the pentose phosphate cycle, alcohol and lactate fermentation pathways and the TCA cycle. This investigation of amino acid sequences reveals a curious pattern of similarity relations; no similarity can be found between the enzyme proteins in a section of the glycolytic pathway where the glyceraldehyde-3-phosphate or even glycerol-3-phosphate is converted into the pyruvate while many examples of sense-sense and sense-antisense similarities are found even between enzyme proteins in distant blocks, e.g. between the proteins in the TCA cycle and those in the pentose phosphate cycle, as well as between the functionally associated proteins in each of these blocks. Complementary to this characteristic pattern of amino acid sequence similarity, the search for similarities of nucleotide sequences also finds that the similarities of glycolytic enzyme genes, some sense-sense and others sense-antisense similarities, are concentrated on the nucleotide sequences of prokaryotic 16S or eukaryotic 18S ribosomal RNA gene with its flanks, although some of the copy sequences are also found in transfer RNA genes as well as in 23S or 26S ribosomal RNA gene. These results strongly suggest that the metabolic pathways have been developed by the chance assembly of enzyme proteins generated from the sense and antisense strands of pre-existing genes, e.g. the fermentation pathways and pentose phosphate cycle by the proteins from the genes of enzymes in the glycolytic pathway and the TCA cycle from all these successively increased genes, ascribing the origin of metabolic enzyme genes to the close relation between the glycolytic enzyme protein genes and the RNA gene cluster.


A model for simulating cognate recognition and response in the immune system.

We have constructed a model of the immune system that focuses on the clonotypic cell types and their interactions with other cells, and with antigens and antibodies. We carry out simulations of the humoral immune system based on a generalized cellular automaton implementation of the model. We propose using computer simulation as a tool for doing experiments in machine, in the computer, as an adjunct to the usual in vivo and in vitro techniques. These experiments would not be intended to replace the usual biological experiments since, in the foreseeable future, a complete enough computer model capable of reliably simulating the whole immune would not be possible. However a model simulating areas of interest could be used for extensively testing ideas to help in the design of the critical biological experiments. Our present model concentrates on the cellular interactions and is quite adept at testing the importance and effects of cellular interactions with other cells, antigens and antibodies. The implementation is quite general and unrestricted allowing most other immune system components to be added with relative ease when desired.


Correlations between the coding and non-coding regions in DNA.

In this paper various aspects of codon usage and k-tuple correlations in the DNA are compared. It is shown that the correlation structures of the coding and the non-coding regions are very similar and that codon usage is reasonably specific for large groups of organisms. These results suggest that the origin of codon usage is related to the origin and structure of the DNA.


Long-range doublet correlations in DNA and the coding regions.

Long-range two-body correlations in a DNA sequence should in theory approach a constant value very rapidly with increasing value of the correlation length. It is shown that for most DNA sequences, the long-range correlations exhibit oscillations superimposed on the constant background. These oscillations persist for very large correlation lengths. The oscillations are shown to be three-point cycles and are related to the coding regions in the DNA. A method for discovering the coding regions in DNA sequences is presented. The limitations of the method are discussed.


Plasmid copy number control: a case study of the quasi-steady-state assumption.

Perelson & Brendel (1989, J. molec. Biol. 208, 245-255) have proposed kinetic models for the control of plasmid copy number, based on experiments by J. Tomizawa and his associates. The quasi-steady-state assumptions (QSSA) made in the analysis of these models are justified in the present paper, thereby providing an example of how QSSA can provide a powerful and reliable tool in the analysis of biological kinetics.


Temporal and spatial scales in epidemiological concepts.

Traditional concepts in epidemiology are reviewed from ecological, cultural, and logical perspectives. In zoological epidemiology (including the study of human and livestock diseases caused by pathogens), temporal and spatial scales are typically not used in definitions, by hypotheses, and theories concerning epidemic and endemic diseases. The same is true for botanical and theoretical epidemiology, although these two subdisciplines use a different definition of an epidemic than does zoological epidemiology. If hypotheses are to be tested and implemented, more precise concepts that include general temporal and spatial scales are needed. Criteria proposed here for identifying temporal and spatial scales are based on the need for consistency of observation and ecological validity. Consistency of observation depends upon the relative life cycles of the hosts and pathogens and upon the environmental effects that lead to stable or unstable population structures. Pathogens are classified as absent, sporadic, or persistent (endemic). Epidemics can occur in the latter two cases but require a separate evaluation. A definition of an epidemic based on temporal and spatial scales and statistics is proposed for use by all subdisciplines. An epidemic occurs when an indicator variable reaches a statistically unusually high value due to transmission of a pathogen in an ecologically proper space-time unit. Threshold theorems in botanical and theoretical epidemiology are also discussed. These proposals do not directly affect modeling, but changes to hypotheses may influence model analyses.


Evaluation of social problem-solving abilities in rural home health visitors and visiting nurses.

A number of studies have shown the value of using home health visitors and visiting nurses in intervention outreach programs designed to provide pre- and postnatal care for low-income women. The purpose of this study was to compare the abilities of a selected sample of professionally trained nurses and nonprofessionally trained home health visitors to suggest and prioritize solutions to a medical dilemma. Data were gathered by the use of a Practical Solutions Test and a Ranking Solutions Procedure. The subjects for the study were 77 females residing in rural counties in West Alabama. The four study groups were comprised of: (a) trained home visitors with 0 to 6 months of experience, (b) trained home visitors with more than 6 months of experience, (c) professionally trained nurses, and, (d) a control group of women with no training or experience. Data were analyzed using one-way analysis of variance (ANOVA). The findings suggest that all of the trained groups were able to generate more solutions to a typical client medical dilemma than could the control group: F(3.76) = 11.79; p = .0001. Faced with the same medical dilemma, the nursing group was more likely to suggest medical options over socioemotional solutions than were the home visitors: chi 2(3.76) = 9.41; p = .02. The nurses also prioritized the solutions differently by ranking them in a different sequence.


Infant gender and sibling dyad influences on maternal separation anxiety.

The purpose of this longitudinal study was to compare maternal separation anxiety by gender of infants and sibling dyad in 40 employed, second-time mothers. Subjects completed two parallel measures of separation anxiety, the Maternal Separation Anxiety. Scale (MSAS) and the Interview-Based Rating Scales (IBRS). The mothers completed the MSAS when the first infant was born and again 2 years later when their second infant was 7 months old (mean age). Following completion of the MSAS (for the second child), the mothers were interviewed and rated on their separation concerns (IBRS) related to both children. No gender differences were noted when t-tests were computed on mothers' MSAS mean scores, but the IBRS revealed that mothers of second-born sons were significantly more anxious about separation (t = 2.01, p < .05) than were mothers of second-born daughters. One-way General Linear Model comparisons of both measures, for the four sibling dyads, revealed significant differences related to the dyad composition. Mothers of girl/girl dyads were significantly more anxious about separation as measured by the MSAS. On the IBRS, mothers of boy/boy dyads were significantly more anxious and mothers of boy/girl dyads were significantly less anxious when compared to mothers of the other dyads.


Preliminary findings: a maximum oral feeding time for premature infants, the relationship to physiological indicators.

Oxygen saturation (SaO2) values, pulse rate and respiratory rate (RR) were monitored using a pulse oximeter during feeding sessions for 21 preterm infants (mean postconceptual age 35.61 weeks) at 3-minute intervals. The purpose of the study was to determine if there is a maximum stressful nippling time span within the context of the prescribed amounts of formula taken and to determine and verify the relationship between: (a) nipple feeding and clinical stress reactions to these variables, (b) the amount of formula taken in the first 3 minutes and (SaO2) values, PR, and RR; and (c) the birthweight of the infant and the length of time from birth to the initial nipple feed. Although the repeated analysis of variance failed to show a significant change (p > .05) from baseline in SaO2, PR, and RR, correlational analysis showed a significant relationship between the amount of formula taken in the first 3 minutes of feeding and the respiratory rate (r = .69, p = .001). Since no significant declines were detected across time in the physiological measures, a maximum stressful nippling time was not established from these data. As expected, a significant relationship between birthweight and the length of time from birth to the initial nipple feed was revealed (p < .05).


Maternal adaptation during pregnancy among adult early, middle, and late childbearers: similarities and differences.

Women 20-24 (n = 10), 25-29 (n = 13), and 30 and over (n = 18) were interviewed and their responses compared on six variables: maternal-fetal relationship, quality of the marital relationship, preparation for motherhood, attitude towards the pregnancy, maternal role conceptualization, and motivation for motherhood. Later childbearing was significantly related to three variables: motivation for motherhood, maternal-fetal relationship, and maternal role conceptualization. Women 25-29 years old were more similar to women 30 years and older than to younger women. The data suggest that young adult women 20-24 years old may experience more difficulty in prenatal adjustment to the maternal role than those 25 and older. Data also suggest the need to reconsider the traditional age-comparative split of the 20s versus the 30s.


Effects of lemakalim and thalium on early afterdepolarization in mouse atrial fibers.

The effects of lemakalim (BRL 38227) and thallium ion (Tl) on action potential (AP) and on early afterdepolarization (EAD) were studied in mouse atrial fibers. Under treatment with lemakalim (25 mcM) or Tl (0.2 mM), the AP was not significantly changed except for the reduction of duration of AP (APD). EAD induced by 3.0 mM K superfusion was abolished by 50 mcM lemakalim and only partially inhibited or was not effected under 25 mcM lemakalim. However, EAD was abolished completely and rapidly by Tl treatment. With addition of K concentration in superfusate to 5.0 mM the EAD could only be partially inhibited. By further increasing the K concentration to 7.0 mM the EAD could be completely abolished. It is suggested that the activator of outward current could inhibit EAD as well as the blockers of inward currents.