[The results of treating pulmonary tuberculosis patients with different concomitant diseases by using millimeter-wave resonance therapy]. The authors investigated the clinical and biochemical efficacy of millimeter-wave resonance therapy in patients with destructive pulmonary tuberculosis associated with different concomitant diseases. It was established that inclusion of millimeter-wave resonance therapy in the complex treatment of this patient category favoured the efficacy of tuberculosis treatment. The treatment produced also a favourable effect on concomitant diseases.


[The use of a sodium lactate solution in the combined conservative treatment of patients with kidney stones]. A method is presented of complex medical treatment of patients with nephrolithiasis including intravenous systemic alkalinization of the urine with 1/6 M solution of sodium lactate, litholysis by citrates, use of urostatics and mineral waters of local origin. It is shown that complex medical treatment of nephrolithiasis including systemic alkalinization of the urine with a 1/6 M sodium lactate solution may be considered as a method of choice in obstructing calculi as non-operative treatment.


[The combined action of an ultrahigh-frequency electrical field bitemporally and decimeter waves on the thymus area in the combined therapy of rheumatoid arthritis patients]. The thymus of rheumatoid arthritis (RA) patients was exposed to combined action of bitemporal UHF electric field and decimeter waves to study immunomodulating effect of the combination. Biochemical, immunological and endocrinological findings during the patients follow-up gave evidence for conclusion on activation of the hypothalamic-hypophyseal-thymic axis. A response was achieved in RA seronegative variant with concomitant synovitis. This may be due to genetic factors.


[Immunological disorders in pregnant women with inflammatory kidney diseases and nephropathy]. The humoral and cellular immunity was investigated in 168 pregnant with different diseases of the kidneys. A detailed study of the blood lymphocyte population, immunoglobulins, immune complexes, hemolytic activity revealed changes of immunologic homeostasis which may be used as diagnostic criteria of activity of the pathological process and for treatment tactics.


[The korinfar and actovegin treatment of patients with a chronic ischemic disorder of the cerebral circulation]. A study is presented of 42 patients with different stages of dyscirculatory encephalopathy of atherosclerotic genesis who showed disorders of the cerebral hemodynamics, microcirculation, increase of the aggregational capacity of thrombocytes and activation of lipid peroxidation. The patients were treated with corinfar and actovegin and this resulted in normalization of the microcirculation and rheological properties of the blood. Corinfar also reduced activation of lipid peroxidation processes.


[The clinical picture, diagnosis and treatment of chronic subdural hematomas]. A study is presented of 37 cases of chronic subdural hematomas. Initial manifestations: headache, epileptic seizures, mental disorders. Involvement of the III, V, VII cranial nerves, anisocoria almost in 50% on the contralateral side were noted. CSF xanthochromia is of certain diagnostic significance. Carotid angiography is the most informative method. Osteoplastic trephination with evacuation of the hematoma is the method of choice.


[The antioxidant treatment of patients with acute intestinal infections due to gram-negative microorganisms]. It was established that administration of S. typhimurium lysate causes activation of the processes of free-radical oxidation. Introduction of unithiol in combination with magnesium sulfate returns the intensity of these processes to the initial level. Unithiol and alpha-tocopherol acetate protect the animals form lethal effects of S. sonnei lysate. Use of a combination of pharmacological agents consisting of unithiol, magnesium sulfate and alpha-tocopherol acetate in the treatment of patients with acute intestinal infections due to gram-negative pathogens (shigellae, salmonellae, proteus, klebsiellae, pseudomonas) resulted in decrease of the length of the intoxication and diarrhea syndrome, decrease of the frequency of repeat bacteria elimination and protracted forms of these infections, more rapid normalization of immune system functions.


[The autopsy: its importance for modern clinical medicine]. Autopsies are absolutely necessary for the progress of modern clinical medicine and for solving many problems: diagnostic, control of treatment quality, detection of infectious, hereditary and systemic diseases, establishing causes and mechanisms of sudden death, qualification of unclear diseases and syndromes, classification and nomenclature of nosological entities, detection and study of spontaneous and induced pathomorphosis. The pathologist performing autopsies should except necropsy also make macrochemical examination and send the material for microbiological and biochemical examination. Special attention should be paid to establishing the diagnosis and clinicoanatomical epicrisis. Undoubtful is the role of autopsy in teaching and training, postgraduate education, accumulation of archives and their retrospective analysis, creation of macro- and micromuseums of human diseases. Physician's errors, general requirements and cadaveric tissue observation are also discussed.


[Borderline neuropsychic disorders in persons subjected to ionizing radiation exposure]. Results were compared of a study of mental disorders in 365 participants of liquidation of sequelae of the Chernobyl atomic station disaster subjected to the effect of ionizing radiation showing psychic disorders, in 475 somatic patients and in 42 Afghan soldiers suffering of traumatic cebrebrasthenia. Clinical aspects of manifestation of nervous and mental disorders and their effect on the dynamic structure of mental and somatic premorbid state, presence of somatic diseases, specific psychotrauma situation and organic effects of the ionizing radiation. Stages of development of these disorders were singled out and signs of their endogeneity and progression were established. The possibilities of psycho-social adaptation are discussed.


[The hormonal functions regulating carbohydrate metabolism in participants in the cleanup of the sequelae of the accident at the Chernobyl Atomic Electric Power Station with a neurocirculatory dystonia syndrome]. Radioimmunoassay revealed in participants of Chernobyl disaster sequelae preclinical changes of some hormonal functions: moderate increase of the basal concentration of blood insulin, somatotropin, C-peptide against the background of persistent hypercortisolemia. Increase of the level of "hyperglycemic" hormones (cortisol, somatotropin, C-peptide) is explained by adaptative and compensatory reactions of the body in response to lesioning effects of ionizing radiation and other negative factors of the Chernobyl accident. Relative hyperinsulinemia is, apparently, compensating the total hyperglycemic effect of these hormones leading to stabilization of the blood sugar level.


[The effect of laser irradiation of the blood on the adenosine triphosphatase activity of the erythrocyte membranes and on the cardiac activity indices in patients with ischemic heart disease]. The activity of potassium, sodium, magnesium and Ca-ATP-ase of the erythrocytic membrane, index of erythrocyte deformability, changes of the hemodynamics and some cardiac function during bicycle ergometry [correction of veloergometry] tests before and after a course of laser irradiation of the blood were studied in 36 patients with exertion stenocardia. It was established that laser therapy is accompanied by increase of the activity of ATP-ase, index of erythrocyte deformability and positive changes of the cardial function. The possibility is discussed of improving the cardiac function under the effect of laser irradiation as a result of optimization of the structural-functional organization of the cellular membrane.


[Radionuclide ventriculography as a method for assessing the functional status of the heart ventricles in patients with supraventricular tachycardia]. Left and right ventricular function was evaluated by means of radionuclide ventriculography in 44 patients with paroxysms of supraventricular tachycardia without sings of circulatory insufficiency of coronaro- and noncoronarogenic origin. Depending on the efficacy of antiarrhythmic treatment the patients were subdivided in two groups: patients amenable to treatment and patients with refractory arrhythmia. It was established that radionuclide ventriculography allows to objectively evaluate the functional state of both ventricles and to reveal early signs of deterioration of the hemodynamic productivity of the heart in patients with paroxysms of supraventricular tachycardia. Reduction of the pumping function of the right ventricle in patients with refractory tachycardia along with hyperkinesia of its separate segments, changes of left ventricular rate and an increase of the terminal diastolic and systolic volumes of both ventricles without changes of the stroke volume may be a criterion of refractoriness of arrhythmia in this category of patients.


[The circadian rhythm dynamics of myocardial ischemia in patients with unstable stenocardia during one year of observation]. Dynamics of circadian rhythms of myocardial ischemia in patients with nonstable stenocardia within one year of observation was studied in 50 patients by means of Holter monitoring. By the second admission depending on the clinical course of the disease 4 groups of patients were singled out and their painful and nonpainful heart ischemia was assessed with 6-hour intervals. Comparison of results of painful arrhythmia during the first and repeat admission indicated that the diurnal dynamic and peaks of myocardial ischemia duration coincide as to time and direction. Nonpainful ischemia appears mainly during the night hours.


[Changes in the parameters of the central and regional hemodynamics in patients with unstable stenocardia treated by the methods of quantum hemotherapy]. A study of 116 patients with nonstable stenocardia (age of the patients: 29-68 years). In 54 of them laser irradiation of the blood (LIB) was used, in 62--autorheography revealed a selective character of influence of LIB and ATIB on the hemo-hemotransfusion of irradiated blood (ACIB) and 32 received only drugs. Tetrapolar dynamics: tendency to averaging of the cardiac ejection. In patients with initially low values--an increase and with initially high values--a reduction. Possibly, this reaction has a nonspecific character and reflects the reaction of circulation to stabilization of the patients' condition. The hemodynamic parameters did not deteriorate below critical levels. Hence, these methods may be used in patients with nonstable stenocardia associated with initial disorders of the central and peripheral hemodynamics.


[The significance of the association of erythrocytic antigens in rheumatism]. A study is presented of ABO system, rhesus, MN, P, Lewis factor in 78 patients with rheumatism. Taken separately their information value was low. At the same time in patients with O (I), A (II), B (III) blood groups association of antigens were often met that allows to isolate among healthy persons groups of high risk as related to rheumatism with the purpose of realizing primary prophylaxis.


[The effect of microwave resonance therapy and hypnotherapy on the links in the pathogenesis of peptic ulcer]. Results of a study are reported of a study of the concentration of biologically active substances such as histamine, serotonin, noradrenaline, adrenalin, corticotropin and indices of gastric secretion in ulcer disease patients at the stage of exacerbation receiving microwave resonance therapy and hypnotherapy. The obtained results evidence that hypnotherapy and microwave resonance therapy are pathogenetic methods of treatment of patients with ulcer disease. Combined treatment proved more effective.


[Fibronectin and the phagocytic activity of the neutrophilic granulocytes in patients with different clinical variants of bronchial asthma]. A study of 125 cases of bronchial asthma revealed low contents of fibronectin. The degree of the decrease depended on the severity of the clinical course of the disease and treatment with glucocorticoid hormones. Patients with bronchial asthma showed an essential reduction of the number of neutrophilic granulocytes capable of phagocytosis. In the process of incubation of polynuclears with fibronectin occurs restoration of their phagocytic activity which was less pronounced in patients receiving glucocorticoids.


[The role of pharmacological tests in detecting disorders in the bronchial patency and bronchial reactivity of patients with chronic glomerulonephritis]. Data are reported of a study of the effect of atrovent, salbutamol and acetylcholine on bronchial patency and reactivity of the bronchi in 89 patients with glomerulonephritis (age: 17-49 years) with normal renal function and at the stage of chronic renal failure. The tests proved highly informative. Latent bronchospasm was found in 12.1% of patients with chronic glomerulonephritis. In 76.3% of patients at the stage of chronic renal failure hyperreactivity of the bronchi was found. The revealed changes require early diagnosis and treatment.


[The intestinal mechanisms of the protein metabolic disorder in kidney failure]. Data are reported on intestinal mechanisms of protein metabolism in renal failure in patients and experimental animals. These disorders are characterized by inhibition of the intestinal absorption capacities, disturbances of intestinal mechanisms of the amino acid kinetics and they develop along with a reduction of the total excretory renal function.


[Acute gastrointestinal hemorrhages].

[Acute gastrointestinal hemorrhages]. It was thought formerly that gastrointestinal hemorrhage is an integral part of gastric ulcer. At present this is not a regularity, occurs only in some patients with ulcer disease and in other kinds of pathology (liver cirrhosis, dilated esophageal veins and oth.). Surgical treatment during hemorrhage is connected with risk for the patients. We recommend temporary tamponade of the bleeding blood vessels, improvement of the general condition of the patient and then transferring the patient to a surgical department for determination of further tactics.


[Lipidemia in the nephrotic syndrome and the atherogenicity of the plasma]. The nephrotic syndrome is characterized by proteinuria, hypoalbuminemia and hypercholesterolemia. Hypercholesterolemia is in some cases a risk factor for atherosclerosis in this group of patients. The lipid plasma spectrum was studied in 45 patients with the nephrotic syndrome. Most pronounced changes of the lipid composition of the plasma were revealed in patients with systemic lupus erythematosus and a special form of mesangio-proliferative glomerulonephritis which is characterized by a torpid course and rapid development of chronic renal failure. Plasma atherogenicity was calculated according to the index of plasma atherogenicity. A high atherogenicity index was revealed in patients with an association of the nephrotic syndrome and arterial hypertension. Plasma atherogenicity is determined mainly by the level of high-density-lipoprotein cholesterol.


[The characteristics of lipid peroxidation in patients with an acute disorder of the cerebral circulation]. A study is presented of 89 inpatients with cerebral stroke. Lipid peroxidation was determined during the first days of the diseases (1-7 days). The state of the patients was evaluated by the clinical picture, manifestation of neurological symptoms, biochemical indices of the blood, coagulogram, ECG, REG, state of lipid peroxidation. The obtained data suggest a major role played by lipid peroxidation of the cell membranes, its elevation in of the activity in stroke. The concentration of lipid peroxidation depends on the severity of the condition and, thus, it may be used for evaluation of treatment efficacy and prognosis of the disease.


[The effect of death cup poison on the morphology of human erythrocytes]. Incubation of heparinized blood of donor (37 degrees C) resulted in an insignificant amount of changed erythrocyte, forms mainly at the expense of stomatocytes and echinocytes, reduction of medium diameter and sphericity index. In incubation of blood with Amanita phalloides [correction of Agaricus bulbosus] poison (0.5LD100) changed forms made up 66.2% with prevalence of poikylocytes, schizocytes and hemolyzed forms.


Is asthma an inflammatory disease?

Is asthma an inflammatory disease? In the 1950s, asthma was defined in terms of reversible airflow obstruction; and then during the 1980s, the emphasis on the diagnosis and treatment of asthma centered on airway hyperreactivity. Recent advances in molecular biology and immunopathology have focused diagnosis and treatment of asthma on inflammatory mechanisms. This article briefly reviews some of the inflammatory components of asthma and the rationale for using inhaled (topical) anti-inflammatory agents in treatment. It also calls attention to some potential and actual adverse effects of inhaled corticosteroids. It mentions some agents used as alternate therapy for "steroid resistant" patients. The alteration of airway immunopathology of asthmatics before and after use of inhaled corticosteroids is described. There is evidence that treatment directed solely towards airway inflammation without use of inhaled B-agonist agents does not eliminate airway hyperresponsiveness.


[The setting of hygienic standards for the insecticide sonet in potatoes]. A study of the toxic properties of sonet in chronic experiment on white rats established the threshold and non-acting dose of the insecticide. The accumulation of the insecticide in the potato tubers during the entire vegetation period as well as its effect on the potato quality were investigated. The author recommends 0.05 mg/g of sonet per 1 g of potato as a maximum permissible level.


Nursing in Nazi Germany.

Nursing in Nazi Germany. German nursing did indeed change during the Nazi period. There were external changes, in terms of the improved social status of nursing, the tightening and unification of professional nursing organizations, the laws affecting nursing, and the politicization of the profession. Articles written by nurses at the time and more recent interviews suggest that there were internal changes as well. It appears that at least a portion of German nurses accepted the National Socialism reinterpretation of professional nursing ethics and humanitarian principles in the assumption that through their obedience they were doing good. This historical research points to clear lessons for contemporary nurses. Nurses in Nazi Germany were under the illusion that they were remaining true to their professional ethics, unaffected by the social change around them. This apolitical professional consciousness made it possible for the profession to be subsumed as a part of the larger political system. I believe that we must be clear that nursing never takes place in a value-free, neutral context; it is always a socially significant force. This means that we cannot simply observe what is taking place around us but must take a stand and get involved, helping to shape sociopolitical developments. I also believe that we must deal with the history of our profession, especially its darkest hours, so that we may remain sensitive to any signs of inhumanity. We must call into question traditional principles, such as obedience, and replace them with professional competence, professionalism, and creative self-consciousness. And not least, we have a moral obligation to the millions of victims of National Socialism, even if it only means that, through historical research, we assure that they are not forgotten. By taking responsibility for this part of our history, we can become more sensitive for the future, with eyes and ears open for all social injustices.


[Evaluation of clinical effectiveness and adverse effects of Polnitrin]. In a double-blind, randomized, placebo cross-controlled trial the effectiveness and the adverse effects of two types of buccal tablets containing 5 mg nitroglycerin: Polnitrin produced by Warsaw Pharmaceutical Works POLFA and its analogue of foreign origin, were assessed. The third compared preparation was sublingual nitroglycerin in 0.5 mg tablets. The longest dissolution in the buccal cavity showed Polnitrin (mean 6.6 hours). Polnitrin significantly increased the resting heart rate during 3 hours, and during 6 hours at maximal effort. The foreign analogue decreased significantly the systolic pressure during 3 hours after application. No significant differences were noted in the effects on the basic haemodynamic parameters between the compared buccal tablets. Exercise tolerance and coronary reserve were assessed with repeated exercise tests on moving track (Marquette Case-12). Immediately after being stuck to the gum Polnitrin, its analogue and sublingual nitroglycerin significantly prolonged the marching time: total, till pain, and till ischaemia. After 6 hours the marching time till pain appearance was significantly longer after Polnitrin than after placebo or its analogue. Local adverse effects connected with the presence of the tablet in the oral vestibule may hamper the treatment with Polnitrin in some cases. The most frequent side effect were headaches which are known to occur usually after all nitrates.


[Effect of resuming occupational work after myocardial infarction on recurrence and mortality]. The effect of resuming occupational work on the mortality and the frequency of infarction recurrence was studied in a group of 771 patients with a history of at least one myocardial infarction. The group of 216 patients who resumed occupational work in industry or administration were compared with 280 patients remaining without occupation, and another comparison was done between 170 patients working and living in towns and 131 working on farms. The material was divided also according to prognostic groups: good, moderately good and poor. All patients were aged over 60 years. The follow-up was 2 to 10 years. A beneficial effect was found of continuation of occupational work, with the exception of heavy physical work, after infarction in the first 3 years.


[Structure of psychological needs of patients over 60 years of age, hospitalized for ischemic heart disease complicated by asthenic- depressive syndrome, and in healthy persons]. Using psychotherapy methods such as MMPI-Wiskad, ACL-37 and 16PF the patterns of psychological needs were studied in postproductive-age subjects with ischaemic heart disease complicated or not with asthenia-depression syndrome and in healthy subjects. Statistical analysis showed that in relation to old people with ischaemic heart disease or without it patients with ischaemic heart disease and depression with asthenia showed a higher psychological sensitivity and their needs were concentrated around the need for self-manifestation, aid-seeking and taking care of oneself. In old people a tendency was maintained for persistence of psychological needs in the previously formulated forms.


[Effect of smoking on the indicators of immunity and the acute-phase reaction in persons professionally exposed to solvents]. In 156 men, 46 non-smokers, 47 smokers, 19 non-smokers exposed to organic solvents and 41 smokers exposed also to solvents the levels of immunoglobulins, lysozyme, C3c, C4, alpha 1-acid glycoprotein, coeruloplasmin and haptoglobins were determined in serum, besides that the counts of circulating T, B and non-T non-B lymphocytes were calculated. A synergistic depressing effect of cigarette smoke and organic solvents was found on certain immunity parameters. This depression was manifested also as changes in the concentrations of IgA, IgD, IgG, lysozyme and T-lymphocyte subpopulations.


[Socioeconomic factors and the incidence of premature labor in a polluted environment]. The effects of socioeconomic factors on the incidence of premature births were studied in Chorzów. For a better evaluation of the socioeconomic conditions a scoring system was used based on such parameters as marital status of the mothers, educational level, living conditions, flat equipment, property owned by the family and economic status. The incidence of prematurity was 14.1%. In over 40% of cases premature births were associated with poor conditions of life. Occupational work under stressful conditions significantly increased the rate of prematurity. After a review of similar studies of other authors it is accepted that environmental pollution is an additional risk factor for the fetus.


[Pseudotumor cerebri in children].

[Pseudotumor cerebri in children]. The authors observed 6 cases of brain pseudotumours in children aged from 3 to 15 years. All patients had been referred with the diagnosis of brain tumour, with headaches, eye fundus changes fundus changes. Some children had nystagmus, squint, vomiting and dizziness. One child had pharyngitis, two had sinusitis. Contrast brain examinations gave normal results. Diet with salt and fluid restriction and oedema-reducing drugs (glycerol, mannitol, decadron) were used. In all patients the neurological and ophthalmological signs regressed within 3 to 12 weeks.


[Basic indicators of physical development of schoolchildren living in the area of an industrial plant processing non-ferrous metals]. The purpose of the study was an analysis of the basic indices of somatic development of school children in the Olkusz area with mines of zinc, lead and cadmium, and metallurgic plants processing the ores of these metals. The studied group comprised 747 children aged 5 to 14 years attending randomly selected schools in Olkusz, Bukowna and Bolesław. The height and body mass were measured on medical scales with height scale. The obtained results were compared with those of similar measurements of children in other parts of the country with different degrees of environmental pollution with non-iron metals. In the Olkusz area the height of the children was slightly smaller than in other parts.


[Effectiveness of Cefobid in pediatric practice]. The sensitivity to Cefobid was evaluated in vitro in 37 bacterial strains obtained from 37 patients. Good effectiveness of the drug against the strains was found in 78.3%, moderate in 13.5%, none in 8.2%. The clinical examinations were carried out in 16 children and again a high clinical effectiveness of Cefobid was found, with cure in 14 cases (87.5%). Cefobid was ineffective in 2 children with infection of Tenckhoff catheter, which required finally exchange of the catheter. No side effects of Cefobid were noted. Cefobid is a safe and effective antibiotic which may be given to small children and patients with renal failure. The broad spectrum and the possibility of drug use without dosage modification facilitate the treatment of patients with various grades of renal failure.


[On the treatment of orbital fractures]. The author discusses the management of fractures of the orbit reviewing the present state of the pertinent knowledge. The diagnostic problems and therapeutic possibilities are mentioned.


[Evolution of post-traumatic hematoma of the liver monitored by ultrasonography]. The results of 20 months of follow-up of posttraumatic hepatic haematoma are presented. The haematoma developed as a result of blunt abdominal trauma and was diagnosed intraoperatively. Monitoring was based on ultrasonography. A significant change in the echographic pattern and size of the haematoma indicated its organization. The purpose of the study was calling attention to the ultrasonographic findings in hepatic haematoma in relation to the time after trauma. It is worth stressing that hepatic haematoma healed well although it had not been managed during the operation (even not drained).


[Neurofibromatosis of the head and neck]. The source of development of neurofibromas, their incidence, tendency for recurrences and malignant transformation are reviewed. The main signs of von Recklinghausen disease and the difficulties in its diagnosis are discussed. A case of faciocervical neurofibromatosis with recurrences is presented stressing the importance of adequate therapeutic-prophylactic management is stressed, in view of increased predisposition to recurrences and malignant transformation.


[Current views on the pathogenesis and treatment of pulmonary emphysema and chronic bronchitis]. In recent years a rising interest has developed among the authors studying the problems of pathogenesis and treatment of chronic bronchitis and pulmonary emphysema in the factors responsible for the immune equilibrium of the respiratory system. In particular, the correlation has been stressed between the levels of inflammation mediators and the activity of proteolytic enzymes and their inhibitors in lung tissue. Most studies seem to confirm the validity of the elastase-antielastase concept. Among the environmental factors directly responsible for the development of these diseases tobacco smoke and other irritant fumes (SO2NO2) are mentioned. This concept had been the foundation for trials of therapeutic use of inhibitors of elastolytic enzymes.


Endoscopic management of nonvariceal gastrointestinal bleeding. Endoscopic management of upper gastrointestinal bleeding has been expanded from a purely diagnostic role to a therapeutic role in many patients. In addition to controlling active bleeding, it is an option in a patient who is clinically at a high risk of rebleeding, or in patients who have peptic ulcers with visible vessels or stigmata indicating high risk. Several methods have been studied, and currently the most useful include thermal cautery with the heater probe or bipolar electrocoagulation, and injection using epinephrine and/or sclerosants. Endoscopic hemostasis can effect permanent control of bleeding in many patients, but should be considered complementary to conventional surgical control in other patients, where temporary control to stabilize the patient is a desired end.


Endoscopic intervention for enteral access. Contrary to total parenteral nutrition with its relatively recent introduction into modern clinical medicine, enteral nutrition has a long and colorful history. Prior to development of fiberoptic endoscopy, physicians attempting to feed patients who could not or would not eat were limited to the blind placement of intestinal tubes or radiologically assisted placement of these devices. Previous to these modern attempts, the use of nutrient enemas was attempted for which there was evidence of occasional success. With the introduction of fiberoptic flexible endoscopy, guidance of tubes into the upper intestinal tract under direct vision became feasible. The manner in which tubes were positioned, advanced, or manipulated are myriad and attest to the ingenuity of clinicians. A revolution in endoscopic intervention occurred with the introduction of the percutaneous endoscopic gastrostomy in 1980. This provided secure access to the stomach without a laparotomy. This technique was also modified to allow decompression of the stomach with feeding distally into the small intestine and also direct puncture and placement of tubes into the small intestine. The most recent advance in enteral nutrition is taking place at the present time with the introduction of laparoscopic techniques in the creation of gastrostomies and jejunostomies.


Approaches to the endoscopic treatment of esophageal varices. Endoscopic therapy is commonly employed for both initial and subsequent definitive treatment of variceal bleeding. Sclerotherapy performed with a flexible endoscope is currently the most widespread technique. Available data suggests that such treatment does not improve outcome in the acute treatment of variceal bleeding (first 30 days) but appears superior to conventional medical management in the long term. Sclerotherapy does not appear better or worse than pharmacological therapy or surgical therapy when these treatments are compared in the elective setting. Although effective, endoscopic sclerotherapy is recognized to be associated with many major and minor treatment-related complications and a significant incidence of recurrent hemorrhage. In response to these shortcomings newer forms of endoscopic therapy such as polymer injection and endoscopic ligation have been developed. Polymer injection appears well suited for patients with active bleeding and for those with gastric varices but does not have advantages for chronic treatment aimed at variceal eradication. Endoscopic ligation appears at least as effective as conventional sclerotherapy for control of acute bleeding and prevention of rebleeding and is associated with few treatment induced complications. While endoscopic therapy will likely continue as the most commonly employed treatment for patients with hemorrhage from esophageal varices, newer methods with wider margins of safety and efficacy seem destined to supplement or replace conventional endoscopic sclerotherapy.


Endoscopic management of common bile duct stones. Endoscopic sphincterotomy has become the undisputed method of choice for removing common bile duct calculi following previous cholecystectomy. This approach has also been applied to selected patients with intact gallbladders deemed unfit for surgery. More recently, endoscopic clearance of the bile duct has been used in concert with laparoscopic cholecystectomy to avoid laparotomy. Modalities available for stone therapy via the endoscope include baskets and balloons, mechanical lithotripters, electrohydraulic lithotripsy probes, and laser energy. In difficult cases stents may be placed to provide drainage in lieu of stone extraction.


Endoscopic therapy for biliary obstruction. Endoscopic management of biliary obstruction is feasible in most patients and has emerged as standard treatment. Aside from the removal of bile duct stones, placement of a biliary stent is the most commonly employed modality of management. In experienced hands, this is successful in over 90% of patients. Lower procedure-related complications and the relative non-invasive nature of endoscopic treatment has relegated surgical management to a subsidiary role. Hospitalization time rarely exceeds 1-2 days. In most patients with advanced malignant disease and short life expectancy, stenting affords effective palliation. For the majority of patients endoscopic management is preferable to the percutaneous transhepatic approach due to lower overall mortality and morbidity. Stent occlusion necessitating replacement remains a problem, but improvements in this area can be expected. New plastic stent designs are undergoing investigation. Expandable metallic stents are promising but controlled comparative trials with conventional plastic prostheses are needed. Use of expandable stents should be judicious since these cannot be removed. In the future we can look forward to advances in peroral cholangioscopic technology which may permit targeted treatment of intraductal biliary malignancies.


Therapeutic colonoscopy.

Therapeutic colonoscopy. Therapeutic colonoscopy has replaced or lessened to a significant degree the need or extent of traditional open surgical procedures. The common uses of therapeutic colonoscopy are hemostasis, resection and ablation of benign and malignant disease, decompression and recanalization of obstructed or dilated bowel, as well as foreign body extraction. Bleeding from arteriovenous and other vascular abnormalities can be controlled with 40% to 80% success rates using endoscopically delivered, monopolar, bipolar, or laser coagulation. The palliation of bleeding recurrent or inoperable colorectal cancer is achieved in up to 90% of patients. Virtually all pedunculated adenomas and most sessile adenomas are regularly removed colonoscopically, while large and recurrent villous adenomas in high risk individuals can be successfully managed by endoscopically delivered laser ablation techniques. Emergency colonoscopic reduction of sigmoid volvulus is performed pre-operatively and decompression of the dilated colon of non-obstructive colonic ileus is now regularly achieved. Colonic strictures have been dilated with a variety of techniques ranging from divulsion with through-the-scope balloon dilators to laser recanalization. Pre-operative endoscopic laser relief of tumor obstruction is employed to avoid preliminary or decompressing colostomy. Endoscopic laser debulking and recanalization of recurrent or inoperable cancer has been achieved with up to 80% success and various foreign bodies may be extracted from the colon with a number of endoscopic techniques. The morbidity of therapeutic colonoscopy has ranged from 1% to 2% for polypectomy to 11% for laser palliation of bleeding from advanced cancer, often with obstruction.


Laparoscopic cholecystectomy: the state of the art. A report on 700 consecutive cases. Born in secret in 1987, developed in an atmosphere of skepticism and even hostility throughout 1988, the laparoscopic cholecystectomy triumphed in 1989-90 and caused a veritable revolution in the world of general surgery. The 700 consecutive cases that we report here reflect the spirit of these various periods. From prudently restrictive, our indications widened to include 90% of all patients with gallbladder lithiasis. Sclero-atrophic gallbladders constitute the greatest challenge for endoscopic maneuvers. This group of patients should be treated by the most experienced operators only. The figures for mortality (0.1%) and complications (3%) are very comparable and even better than those for traditional cholecystectomy. The quality of recovery is infinitely better; there is absence of pain, a short period of hospitalization, return to normal physical activity within 10 days, rapid return to work, and total preservation of the abdominal muscles for participation in sports activities. All these advantages are assets of the laparoscopic cholecystectomy which are not available to the 6% of patients for whom an intra-operative conversion to open surgery is necessary. These patients recover within the conditions of a traditional cholecystectomy which are far from being poor. The large multicenter studies, such as those carried out in France and Belgium recently involving 3,708 patients, arrive at identical conclusions. The laparoscopic cholecystectomy is on its way to becoming the gold standard of treatment for gallbladder lithiasis. It is the first successful step towards surgical techniques of the 21st century which will be carried out inside the musculo-cutaneous envelope of the unopened human body.


Laparoscopy in the emergency setting.

Laparoscopy in the emergency setting. Laparoscopy has been available for 90 years and was actively undertaken by the gynecologists. Today the vast majority of gynecological procedures are performed by this route. Despite the efforts of a few enthusiastic surgeons, the general surgical community did not incorporate laparoscopy into their armamentarium until the advent of laparoscopic cholecystectomy. However, this endoscopic technique has much to contribute, especially in the setting of emergency care. It is of value in formulating a treatment algorithm and in avoiding unnecessary laparotomy in both blunt and penetrating trauma. Laparoscopy helps to define the nature of obscure abdominal diagnoses, avoids unnecessary appendectomy, and provides the window of opportunity for surgery in mesenteric ischemia due to either arterial or venous thrombosis or embolus. It is also of value in patients with pain or fever of unknown origin, displaced gastrostomy or dialysis tubes, and in the rare patient with gastrointestinal bleeding where other diagnostic modalities have been unable to yield the diagnosis. In this article the instrumentation and techniques will be outlined and the role of laparoscopy in each of the above situations will be detailed. As with all surgical procedures, it is vital that the surgeon be well-trained and knowledgeable about the correct use of the technique, its possible pitfalls and how to avoid them, as well as knowing the contraindications.


The spectrum of laparoscopic surgery.

The spectrum of laparoscopic surgery. Laparoscopic procedures have begun to replace many conventional operations because of the avoidance of major surgery and the rapid recovery of the patient. The majority of these traditional operations will be performed laparoscopically in the future. For example, patients who suffer from achalasia will be able to undergo laparoscopic cardiomyotomy and patients with non-cardiac chest pain of esophageal origin will be able to undergo thoracoscopic myotomy. Likewise, a viable alternative to long-term medication with H2 blockers or omeprazole will be laparoscopic posterior vagotomy and anterior lesser curve seromyotomy. As methods are developed to deal with the extraction of large specimens, many ablative procedures will be undertaken by the laparoscopic route. Extraction techniques must not compromise the need for histopathological examination of the resected specimen in cancer resections. The ultimate spectrum of laparoscopic surgery will be determined by the progress in remote handling technology, overcoming the manipulative restrictions inherent in the current instrumentation. Research evaluating the efficacy of new methods will be essential.


Endosonography in patient selection for surgical treatment of esophageal carcinoma. A prospective study was carried out to examine the usefulness of endosonography (ES) in the pre-operative staging of patients with carcinoma of the esophagus, and its relevance in predicting resectability and the type of resection. The results of ES were compared with staging by conventional pre-operative methods and with operative staging according to the new American Joint Commission of Cancer staging classification. Of the 89 patients studied, 62 had a resection, 22 a bypass operation, and 5 had no operation. ES examination was unsuccessful in 19 patients because of complete or near complete tumor obliteration of the esophageal lumen and was incomplete in 13 patients because of distal tumor obstruction. These 32 patients accounted for 36% of all ES examinations, 27% of resection group, 55% of bypass group, and 60% of no operation group. The 45 patients who had a satisfactory ES examination and who had underwent a transthoracic resection were analyzed. The sensitivity and specificity of ES in detecting the depth of esophageal involvement were 89% and 96%, respectively, and for lymph node metastasis were 85% and 86%, respectively. However, ES was neither sensitive in detecting extra-esophageal infiltration to mediastinal organs nor was it able to determine the extent of intra-abdominal spread. The accuracy of pre-operative staging was 82% by ES compared with 51% by conventional staging (p < 0.001). ES correctly identified more advanced stage of disease in 14 (31%) patients as compared with conventional staging. On the evaluation of resectability, which was based on conventional investigations without ES, the result was unaffected even if the additional findings of ES were available.(ABSTRACT TRUNCATED AT 250 WORDS)


Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer. In a prospective multicenter study, 186 patients with squamous cell esophageal carcinoma, who after evaluation were considered suitable for surgery, were randomized to 4 treatment groups: Group 1, surgery alone; Group 2, pre-operative chemotherapy (cisplatin and bleomycin) and surgery; Group 3, pre-operative irradiation (35 Gy) and surgery; Group 4, pre-operative chemotherapy, radiotherapy, and surgery. Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy. Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival. Female patients had a significantly better survival than males. The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival, whereas the chemotherapy regime used did not influence survival.


Gastrointestinal motility of patients with Roux-en-Y reconstruction. The electromyographic activity of the gastrointestinal tract was studied in 28 patients undergoing gastric, biliary, and pancreatic operations with reconstruction of the gastrointestinal tract with a Roux-en-Y limb. The Roux-en-Y limb was constructed 1 to 5 years before the study in 8 patients (chronic Roux-en-Y) and at the operation in which the electrodes were implanted in 20 patients (recent Roux-en-Y). All four phases of the migrating motor complex (MMC) were identified in the gastrointestinal tract, including in the Roux-en-Y limb. The duration of the MMC was 82.4 +/- 22.3 min in the patients with chronic Roux-en-Y and 89.0 +/- 25.1 min in the patients with recent Roux-en-Y. Food ingestion converted the MMC to the fed pattern in the entire gastrointestinal tract, including the Roux-en-Y limb in 16 (76.2%) of 21 recordings of the patients with chronic Roux-en-Y and in 27 (84.4%) of 32 recordings of the patients with recent Roux-en-Y. The duration of the fed pattern was 170 +/- 34 min in the patients with chronic Roux-en-Y and 154 +/- 26 min in the patients with recent Roux-en-Y. The findings of this study indicate that the electromyographic activity of the Roux-en-Y limb is normal during both fasting and fed states, even many years after the construction of the Roux-en-Y.


Optimization of isolated hyperthermic limb perfusion. During isolated limb perfusion, we studied the impact of limb temperature on the concentration of cytostatic drugs in the tissue to identify a possible selective absorption of cytostatic agents by the various tissues. Ten consecutive patients with malignant melanoma were randomly divided into two different groups and perfused with 1 mg cisplatin per kg body weight. In one group the cytostatic agents were injected under hyperthermic conditions (39.5 degrees C) and in the other group under normothermic conditions (37 degrees C). The platinum concentration in the melanoma was twice as high in the hyperthermic group as in the group under normothermic conditions. In the tumor-free tissue the platinum concentration decreased with temperature while it remained constant in the musculature. This selective concentration of cisplatin in the tumor under hyperthermic conditions is accompanied by fewer side effects. Follow-up will show whether the oncological results will be improved in the hyperthermic conditions as one might expect.


The effects of positive airway pressure and intra-abdominal pressure in diaphragmatic rupture. Arterial blood gases (80% oxygen), intraperitoneal pressure (IP), stomach position relative to the diaphragm (S/D by fluoroscopy), blood pressure, and cardiac output were monitored in 16 anaesthetized New Hampshire piglets with a 12 cm laceration of the left hemidiaphragm. Group I (8 animals) were spontaneously breathing. Group II (8 animals) had a pneumatic antishock garment (PASG) inflated to an IP of 40 torr for 15 mins followed by positive pressure ventilation (PPV) of 20 cm H2O for 15 min and PPV of 40 cm H2O (PPV-40) for 30 more minutes. All Group I animals survived. Three Group II animals died by 15 min after PASG inflation. Seven Group I animals showed no displacement of the stomach above the diaphragm. Blood pressure, cardiac output, and blood gases remained unchanged in Group I compared to baseline with pO2 varying from 436 +/- 44 torr to 417 +/- 31 torr, pCO2 from 38 +/- 1 torr to 39 +/- 1 torr, and pH 7.4 +/- 0.02. Blood pressure in Group I was 109 +/- 3 torr at baseline to 110 +/- 2 torr at 60 mins, and baseline cardiac output was 3.9 +/- 0.2 L/min and 3.8 +/- 0.2 L/min at 60 min. Group II animals had a baseline arterial pO2 of 423 +/- 15 torr and 100 +/- 15 torr at 15 min after PASG. With PPV-20 arterial pO2 increased to 178 +/- 13 torr and further increased to 230 +/- 9 torr at PPV-40.(ABSTRACT TRUNCATED AT 250 WORDS)


Long-term functional results and quality of life after ileal pouch-anal anastomosis and cholecystectomy. Among 971 patients with chronic ulcerative colitis who underwent ileal-pouch anal anastomosis during an 8-year period from January, 1982 to December 1989, 30 patients were randomly selected from each year (total = 240 patients) for an assessment of their long-term functional results and quality of life as of 1990. Patients undergoing cholecystectomy during each of the same years served as "controls" (20 patients/year, total = 160 patients). All 400 patients completed a written questionnaire that measured bowel habits, overall quality of life, general health, and performance in sports/recreation, travel, sex life, family relationship, occupational work, social activities, and household activities. Ileo-anal patients had more frequent stools (median, 6 stools/day) and more fecal spotting (68% of patients had episodes) than cholecystectomy patients (median, 1 stool/day, 13% had episodes, p < 0.05). In spite of the altered bowel habits, 90% of ileo-anal patients had an excellent overall quality of life, 76% enjoyed good health, and 91% had good performance scores in the areas examined. In fact, quality of life and performance were similar among ileo-anal patients and cholecystectomy patients. Moreover, quality of life and bowel habits remained steady in both groups of patients during the 8-year follow-up. In conclusion, functional results were satisfactory and quality of life was excellent after ileal pouch-anal anastomosis; neither deteriorated as patients aged over an 8-year period after operation.


Routine versus selective intra-operative cholangiography during laparoscopic cholecystectomy. Opinion is divided whether intra-operative cholangiography should be performed routinely or on a selective basis during laparoscopic cholecystectomy. We therefore performed the first prospective randomized trial of static cholangiography in patients who did not have indications for cholangiograms. Laparoscopic cholecystectomy was attempted on 164 consecutive patients, of whom 49 (30%) patients were excluded from the trial due to indications for or against cholangiography. In the remaining 115 (70%) patients, 56 were randomized to the cholangiography group while 59 patients did not receive cholangiograms. Duration of postoperative hospitalization and interval to return to full activity were identical in the two groups. Static cholangiograms added 16 +/- 1 min (mean +/- SEM) to the procedures (p < 0.01). Cholangiography increased the total charges for the operation by almost $700 (p < 0.01). Cholangiograms were performed successfully in 94.6% of the patients and changed the operative management in 4 (7.5%) patients. There was 1 (1.9%) false negative study. Intra-operative cholangiography did not reveal aberrant bile ducts at risk of injury from the operative dissection. There was no mortality or cholangiogram-related morbidity in either group. In follow-up ranging from 2-12 months, there has been no clinical evidence of bile duct injury or retained common bile duct stones. In summary, in patients without indications for cholangiography, the performance of static cholangiograms markedly increased the operative time and cost of laparoscopic cholecystectomy. The operative management of a minority of patients was changed by the information obtained, but laparoscopic cholecystectomy may be performed safely in the absence of cholangiograms with little risk of injury to the major ductal system or retained calculi.


Prostacyclin release from the human saphenous vein in diabetics in lower than in nondiabetics. The balance between prostacyclin and thromboxane has been suggested to be of great importance for the maintenance of patency in veins. In order to investigate prostacyclin and thromboxane release, segments from the human saphenous veins were investigated in 53 patients. Twenty-seven patients (10 males, 17 females) underwent surgery for varicose veins. Twenty-six patients (14 nondiabetics, 12 diabetics) underwent surgery for lower limb ischemia (rest pain or gangrene) with use of the saphenous vein as arterial conduit. Vein segments were gently excised and perfused ex vivo for five 15 minute periods, with a balanced salt solution and determination of the stable degradation products 6-keto-PGF1 alpha and TxB2. Saphenous veins from patients with varicose veins had an initial prostacyclin release of 61 +/- 13 pg/mm2/15 min declining to 4 +/- 1 pg/mm2/15 min after 60 min (p < 0.001) and increasing after addition to arachidonic acid to 37 +/- 7 pg/mm2/15 min (p < 0.001). Segments from nondiabetic patients with lower limb ischemia did not differ from those of varicectomy patients, but diabetic segments had a significantly lower prostacyclin release than both these groups, 34 +/- 11 pg/mm2/15 min, 1 +/- 1 pg/mm2/15 min, and 7 +/- 5 pg/mm2/15 min, respectively (p < 0.05). The addition of arachidonic acid failed to increase the prostacyclin release in diabetics. Three patients from each group were studied regarding thromboxane release and there was almost no detectable thromboxane in any group. These findings suggest that diabetics have a lowered prostacyclin release from the saphenous vein and that the deficiency is at the cyclo-oxygenase level.(ABSTRACT TRUNCATED AT 250 WORDS)


Bleeding varices of the small bowel as a complication of pancreatitis: case report and review of the literature. A case of a 48 year old male with a history of alcohol abuse, chronic relapsing pancreatitis, and massive hemorrhage into the small intestine is reported. The patient had previously undergone a cholecystojejunostomy. Imaging studies demonstrated occlusion of the splenic, superior mesenteric, and distal portal veins with large varices in the jejunum. He recovered following jejunal resection and Roux-en-Y cholecystojejunostomy. The mechanism for formation of varices in the small bowel in this clinical setting is discussed.


Thromboembolic complications in thermally injured patients. The frequency of thromboembolic complications in burn patients has been estimated to range from 0.4% to 7%. The clinical significance of these events is often debated and has prompted some centers to adopt the routine prophylactic use of low dose heparin prophylaxis. A 10 year review of 2,103 burn patients treated at this institution was undertaken. Twenty-five (1.2%) patients, with a mean age of 40.0 years and an average burn size of 49.3% total body surface area (TBSA), were identified as having significant pulmonary thromboembolism (PTE). In only 3 (0.14%) patients was the thromboembolism considered to be a cause of death. Nineteen (0.9%) patients, with an average age of 36.7 years and a mean burn size of 48.3% TBSA, developed clinically evident deep venous thrombosis (DVT); however, in only 1 (0.05%) patient did the disease progress to fatal PTE. A review of the literature reveals a 0.6% to 5% incidence of complications related to low dose heparin therapy which includes bleeding, thrombocytopenia, and arterial thrombosis. We feel that the infrequency of clinically significant PTE and DVT in burn patients and the comparable or greater rate of complications associated with heparin prophylaxis mitigate against the routine use of low dose heparin therapy except in patients at high risk for these events.


Injury to the popliteal vessels: the Lebanese war experience. Our experience with 118 patients who underwent surgery for a total of 178 popliteal vessels injuries is reported. Forty-nine per cent had injury to both artery and vein and 44% had associated bony fractures. Fourteen patients subsequently needed amputation for a rate of 11.9%. There were no deaths. Delay in repair (> 6 hours from injury), associated fractures, and a shocked condition resulted in increased limb loss. Arterial as well as venous repair, external skeletal fixation, and fasciotomy when necessary lead to improved limb salvage.


Acute acalculous cholecystitis complicating trauma: a prospective sonographic study. Acute acalculous cholecystitis (AAC) is a well known complication in severely traumatized patients. Existing data of AAC originate from retrospective analyses and episodic case reports. In a prospective study 45 polytraumatized patients admitted to our intensive care unit from January 1989 to June 1990 were clinically and sonographically screened for this condition at defined time intervals. Trauma scoring was performed according to the injury severity score and polytrauma score. AAC was defined as a combination of hydrops of the gallbladder, an increased wall thickness (> 3.5 mm), and the demonstration of sludge. We were able to document this diagnostic triad in 8 (18%) of 45 patients. As a consequence early elective cholecystectomy was performed in 1 of the 8 patients. The remaining patients were treated conservatively. The incidence of AAC in severely traumatized patients is higher than figures so far published suggest. Ultrasound is a reliable method of early detection and follow-up of this complication.


Role of metabolism and pharmacokinetic studies in the discovery of new drugs--present and future perspectives. 1. The impact which pharmacokinetics and drug metabolism studies have made to drug discovery programmes is reviewed with examples from the anti-infective, cardiovascular, anti-inflammatory and CNS therapeutic areas. 2. Contributions that advances in analytical technology have made to the early application of pharmacokinetics and drug metabolism are discussed. 3. Some future perspectives are given on the advances being made in basic science and technology and how this will provide the basis for further growth in the contribution to the drug discovery process.


Living unrelated donor kidney transplantation between spouses. From November 3, 1975 to November 3, 1990, 874 kidney transplants were performed at out centers. Of these, 675 (77.2%) were from living donors and 199 (22.8%) were from cadaver donors. Five hundred eighty (66.4%) of the living donors were first degree related while 99 (11.3%) were unrelated or second degree related donors, 29 of which were spouses. All donor recipient pairs were ABO-compatible, with the exception of one pair. Donor recipient relations were wife to husband in 25 cases and husband to wife in 4 cases. All were first grafts and started functioning during surgery. In this series, the follow-up for the recipients was 4 to 64 months (mean 33.5 +/- 4.5 months). One-year patient survival and graft survival rates were 92.4% and 81.9%, respectively. Two-year patient survival and graft survival rates were 92.4% and 78.2%, respectively. The single ABO-incompatible case is also doing well, 21 months postoperatively. This study demonstrates that the interspouse kidney transplantation may be used when cadaver organ shortage is a problem. While providing the couple with a better quality of life, interspouse kidney transplantation also enables the couple to share the joy of giving and receiving the "gift of life" from one another.


Drug analysis of biological samples. A survey of validation approaches in chromatography in the UK pharmaceutical industry. 1. The results of a survey on validation of analytical chromatographic methods are reported. The survey was carried out in 1990 within most of the principal British Pharmaceutical Companies. 2. A general method of validation is established from the collated results. 3. A comparison is made with existing reports from international meetings.


Present status of sclerotherapy and surgical treatment for esophageal varices in Japan. Japanese Research Society for Portal Hypertension and Japanese Research Society for Sclerotherapy of Esophageal Varices. A nationwide survey on the treatment for esophageal varices was performed in 1990 jointly by the Japanese Research Society for Portal Hypertension and the Japanese Research Society for Sclerotherapy of Esophageal Varices to clarify the present status and strategy of this treatment in Japan. A total of 12,675 cases, including 4,159 cases of nonshunting procedures and 7,612 cases of sclerotherapy, were collected from 101 institutions. The number of patients had greatly increased in the first half of the 1980s. With regard to the therapeutic strategy, surgical procedures were not recommended in either emergency or prophylactic cases in terms of the timing of the operation, or in Child C cases in terms of the degree of hepatic insufficiency. Endoscopic injection sclerotherapy became the leading method of treatment and in 1988 only 16% of 1,528 cases were treated by surgical procedures. The strategy for the same group of patients differed between medical and surgical institutions. With regard to sclerotherapy, repeated intravariceal injection and combined intra- and paravariceal injection were the two main techniques and 10-year cumulative survival rates were 62.8% in Child A cases, 47.7% in Child B cases, and 13.2% in Child C cases. With regard to surgical procedures, 10-year survival rates were 50.6% in esophageal transection, 42.5% in gastric transection, 53.1% in cardiectomy, and 43.0% in selective shunt procedures. We are quite convinced that this report will prove useful in determining the future strategy for treating esophageal varices.


Application of 19F-n.m.r. spectroscopy to the identification of dog urinary metabolites of imirestat, a spirohydantoin aldose reductase inhibitor. 1. Urine from a dog dosed orally at 20 mg/kg with 14C-imirestat, a spirohydantoin aldose reductase inhibitor, contained 17.7 and 12.5% of the administered radioactivity at 0-48 and 48-72 h respectively. 2. Radio-h.p.l.c. of the 0-48 h urine revealed a complex mixture of metabolites and a small proportion of parent drug (1.6% of dose). Direct 19F-n.m.r. spectroscopy of this urine showed the fluoride ion, numerous metabolites which were predominantly glucuronide conjugates and, as a minor component, the parent drug. 3. After incubation with beta-glucuronidase the 0-48 h urine gave a 19F-n.m.r. spectrum showing fewer signals. This finding is consistent with aromatic ring hydroxylation followed by glucuronidation being the major metabolite pathways. 4. Deconjugated urine was analysed by proton-coupled 19F-n.m.r. and two-dimensional 19F-19F correlated spectroscopy. Results indicate that major components included three monohydroxy metabolites, a diphenol with both phenolic functions in the same ring, and a phenolic metabolite containing only one fluorine atom. 5. Semi-preparative h.p.l.c. of 0-48 h dog urine gave individual glucuronides isolated as mixtures of C-9 epimers. These fractions were hydrolysed and purified a second time by h.p.l.c. to give aglycones which were analysed by multi-nuclear n.m.r. and g.l.c.-mass spectrometry. The 3- and 4-hydroxy derivatives of imirestat were identified, as was the 2-hydroxy product obtained during or following defluorination. The other major aglycone was postulated to be the 3-fluoro-2-hydroxy metabolite. This represents a novel 'NIH-shift' type pathway for the metabolism of fluorobenzenes.


One liver for two: partition of the portal elements. A cadaver liver is divisible into two transplants by section between right and left lobes, or section between left medial segment and left lateral segment medial to the umbilical cleft. To establish the ideal basis of partition of the portal elements, an anatomic study of 33 livers was performed. It is preferable to section the left portal vein, longer and more constant than the right, the right branch of the hepatic artery, larger and more constant than the left, and the left hepatic duct because of the vascularization of the common hepatic duct. To use the length of the left portal vein, it is necessary to section all its branches to segment I and then to resect this segment. After a section between the left medial segment and the left lateral segment medial to the umbilical cleft, the left medial segment always loses its total portal venous vascularization and should be resected. Before a split-liver, cholangiography and arteriography should be performed to detect anatomical variations without performing an extensive dissection which may endanger the vascularity of the bile ducts.


Disposition of the enantiomers of cromakalim in rat and cynomolgus monkey. 1. Disposition of the 3R,4S(+) and 3S,4R(-) enantiomers of the racemic antihypertensive drug cromakalim has been studied in rats and cynomolgus monkeys using the 14C-drug labelled in either the 3R,4S(+) or the 3S,4R(-) enantiomer. 2. After oral administration to rat, blood concentrations of the 3R,4S(+) enantiomer were up to fourfold higher than those of the 3S,4R(-) enantiomer. Metabolism of the former was not as extensive as that of the latter and consequently plasma and urinary radiometabolite patterns were quantitatively different. 3. In contrast to rat, there were much greater differences in the disposition of the two enantiomers following oral administration of cromakalim to the cynomolgus monkey. Plasma concentrations of the 3R,4S(+) enantiomer were approximately 100 x those of the 3S,4R(-) enantiomer and the rate of urinary 14C elimination for the 3R,4S(+) enantiomer was much faster than that for the 3S,4R(-) enantiomer. Plasma and urinary radiometabolite patterns were very different for the two isomers. Metabolic end products of the 3R,4S(+) enantiomer were predominantly phase I metabolites whereas the 3S,4R(-) enantiomer was almost entirely metabolized by glucuronidation. 4. A study of the racemic drug alone would have led to a misunderstanding of the fate of the compound in these species.


Comparative metabolism of flunarizine in rats, dogs and man: an in vitro study with subcellular liver fractions and isolated hepatocytes. 1. The biotransformation of 3H-flunarizine ((E)-1-[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine dihydrochloride, FLUN) was studied in subcellular liver fractions (microsomes and 12,000 g fraction) and in suspensions or primary cell cultures of isolated hepatocytes of rats, dogs and man. The major in vitro metabolites were characterized by h.p.l.c. co-chromatography and/or by mass spectrometric analysis. 2. The kinetics of FLUN metabolism was studied in microsomes of dog and man. The metabolism followed linear Michaelis-Menten kinetics over the concentration range 0.1-20 microM FLUN. 3. A striking sex difference was observed for the in vitro metabolism of FLUN in rat. In male rats, oxidative N-dealkylation at one of the piperazine nitrogens, resulting in bis(4-fluorophenyl) methanol, was a major metabolic pathway, whereas aromatic hydroxylation at the phenyl of the cinnamyl moiety, resulting in hydroxy-FLUN, was a major metabolic pathway in female rats. In incubates with hepatocytes, these two metabolites were converted to the corresponding glucuronides. 4. In human subcellular fractions, aromatic hydroxylation to hydroxy-FLUN was the major metabolic pathway. In primary cell cultures of human hepatocytes, oxidative N-dealkylation at the 1- and 4-piperazine nitrogen and glucuronidation of bis(4-fluorophenyl)methanol were observed. The in vitro metabolism of FLUN in humans, resembled more than in female rats and in dogs than that in male rats. 5. The present in vitro results are compared with data of previous in vivo studies in rats and dogs. The use of subcellular fractions and/or isolated hepatocytes for the study of species differences in the biotransformation of xenobiotics is discussed.


Roux-en-Y hepaticojejunostomy with subcutaneous access and the use of Gianturco stents for the management of biliary tract strictures. The need to control recurrent biliary strictures implies the practice of repeated major surgical procedures. The hepaticojejunostomy with subcutaneous jejunal access (Chen's procedure) allows the permanent option of a non-operative management of recurrent biliary tract anastomosis complications. Through the subcutaneous jejunal access, the application of a Gianturco metallic prosthesis is permitted and the correction of biliary-intestinal anastomosis strictures with non-operative methods is possible. This report is a review of a series of 20 patients treated with the Chen procedure, of whom 3 patients also had implantation of Gianturco stents via hepaticojejunostomy with subcutaneous access.


Metabolism of calcium antagonist Ro 40-5967: a case history of the use of diode-array u.v. spectroscopy and thermospray-mass spectrometry in the elucidation of a complex metabolic pathway. 1. The calcium antagonist, Ro 40-5967, is metabolized to a multitude of products by the rat and drug-related material is excreted predominantly via the bile. 2. Diode-array u.v. spectroscopy, following reverse phase h.p.l.c. separation of the partially purified metabolites, has been used to classify these compounds into six spectral classes which have been correlated with different metabolic reactions. 3. Connection of a mass spectrometer directly to the h.p.l.c. equipment by a thermospray interface, produced useful mass spectra. These, together with the u.v. spectra, enabled the structures of many metabolites to be elucidated. 4. Confirmation of structural assignments was provided by n.m.r. spectra of the major metabolites. 5. Major metabolic pathways included N-demethylation (16% of the biliary metabolites), hydrolysis of the ester side-chain (32%), hydroxylation at 4- (19%) and 5- (29%) positions of the benzimidazole ring, aromatization of the tetrahydronaphthyl system (26%), loss of the benzimidazole (15%) and glucuronidation of hydroxyl groups (81%).


Measurement of oxybutynin and its N-desethyl metabolite in plasma, and its application to pharmacokinetic studies in young, elderly and frail elderly volunteers. 1. A quantitative h.p.l.c. plasma assay for oxybutynin (OB) and its active metabolite, N-desethyl oxybutynin (DEOB) is described. The method is linear with coefficients of variation ranging between 4 and 11.8% for OB and 4.6-9.1% for DEOB over the typical concentration range measured. Minimum detectable levels were 0.5 and 5 ng/ml for OB and DEOB respectively from a 2 ml sample. 2. Pharmacokinetic parameters were obtained after a single oral dose of OB and after administration two or three times daily to frail elderly and elderly volunteer groups respectively. Single dose results were also compared with data from young healthy volunteers. 3. There was a wide range in peak blood levels and high levels of parent drug were matched by high DEOB metabolite levels. Plasma levels on repeated administration were as would be predicted from the single dose kinetics. 4. Area under the plasma time course curve for DEOB metabolite was less than or equal to 5 than that of the parent drug. 5. A trend of increasing peak plasma levels and bioavailability was observed with increasing age and frailty, with the differences more apparent between the active elderly and frail elderly groups than between the active elderly and young volunteers. 6. Results indicate that for frail elderly patients a lower initial starting dose of 2.5 mg OB given two or three times a day may provide adequate therapeutic blood levels of the drug.


Value of early pharmacodynamic and pharmacokinetic investigations with anticancer drugs: data from phase I tolerance studies on a new vinca alkaloid derivative. 1. A novel anticancer vinca alkaloid derivative (I) has been given as an i.v. bolus to cancer patients, using four different dosage regimens with dose levels ranging from 0.04 to 0.84 mg/m2 (equivalent to between 0.12 and 1.35 mg per dose), and the pharmacokinetics determined up to 72 h after dosing. In addition, secondary effects of leukopenia and neutropenia, were related to drug exposure using a sigmoid Emax model. 2. Plasma levels of I declined in a triphasic manner with a terminal half-life of approximately 50 h; most drug elimination (55%) being associated with the terminal phase. 3. Clearance of I was relatively low (245 +/- 160 ml/min) and remained constant with increasing doses. Initial distribution volume was low (approximately 71) but once distribution was complete, it was comparatively high (327 +/- 2121). 4. Both leukopenia and neutropenia were fitted successfully to a sigmoid Emax model showing that these effects were related to the total exposure to the drug. The Hill constant was less than 1, indicating a relatively shallow exposure/response curve and a predictable, graded increase in response with increasing I exposure, rather than a sudden quantal response. 5. Pharmacokinetically, I shows some similarities to other vinca alkaloids in its plasma level decline profile, although there are some notable differences which can be exploited clinically. In addition, the ability to model both leukopenia and neutropenia to the exposure to I, provides a valuable tool in the design of the most appropriate dosage regimen for the drug, as well as for dose adjustment taking into account inter-individual variations.


Statistical aspects of bioequivalence--a review. 1. Over the past 20 years a number of statistical methods have been proposed for use in bioequivalence testing. This review examines these methods and reflects current thinking of regulatory authorities. 2. The standard bioequivalence study is conducted as a controlled, single-dose crossover design in a small number of healthy male adults. Blood and/or urine samples are taken at predetermined times for drug/metabolite assay from which pharmacokinetic parameters are derived and compared statistically. Sample size calculations should be determined by the error variance associated with the primary characteristic to be studied, the significance level, the power of the test and the deviation from the reference product compatible with safety and efficacy. 3. In general, bioequivalence is assessed using three parameters namely, Cmax, tmax and AUC. Urinary excretion data may also be used if the amount excreted unchanged is significant. These parameters are best obtained using a simple model-independent approach. 4. The parameters of Cmax and AUC should be logarithmically transformed prior to analysis. For tmax, parametric statistical procedures are not appropriate. 5. Classical hypothesis testing using the power approach is not applicable to the practical problem under consideration in bioequivalence trials. 6. Classical 90% confidence limits and the 2 one-sided t-test approach are operationally identical and are the methods of choice for assessing bioequivalence (Cmax and AUC). When tmax is an important parameter from the clinical point of view then the use of non-parametric confidence intervals is recommended.


Immunomodulatory action of propolis: IV. Prophylactic activity against gram-negative infections and adjuvant effect of the water-soluble derivative. The efficacy of the water-soluble derivative (WSD) of natural propolis (bee glue) was examined for augmentation of host resistance against experimental infections caused by Gram-negative pathogens (Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Pseudomonas aeruginosa). The substance was found to induce significant non-specific protection, but did not inhibit the in vitro growth of the same strains. Pretreatment with WSD prior to the standard scheme for tumour necrosis factor (TNF) induction (BCG and two weeks later lipopolysaccharide (LPS)) provoked an interval-dependent reduction in the lytic capacity of serum against L 929 target cells. The replacement of the triggering or priming signal with WSD markedly increased TNF production. In vivo administration of WSD led to a rapid and route-dependent change in the alternative complement pathway haemolysis. The alteration in C1q complement component and total protein synthesis, and also in nitroblue tetrazolium reduction, suggests that macrophage activation makes a major contribution to the capacity of WSD to prevent infections.


Nasal antibody response to mumps virus after vaccination and natural infection. Nasopharyngeal secretions and sera were collected during an epidemic of mumps in a semi-closed institution. None of the children who received live attenuated mumps vaccine 5 months previously developed any symptoms of mumps. Neutralizing and IgA antibodies against mumps virus were measured by the peroxidase-antiperoxidase method and the fluorescent antibody to membrane antigen method, respectively. The immune responses in nasopharyngeal secretions and serum were studied in four groups (apparently infected, non-apparently infected, non-infected and vaccinated). We found that IgA, which has neutralizing activity, was produced after vaccination as well as after natural infection. It is suggested that local antibody induced by vaccination may contribute to protection against the mumps virus.


Immunogenicity of a Streptococcus pneumoniae type 4 polysaccharide--protein conjugate vaccine is decreased by admixture of high doses of free saccharide. In this study we report that the priming capacity of a Streptococcus pneumoniae type 4 polysaccharide-protein conjugate to booster immunizations with the native capsular polysaccharide is dose dependent. Furthermore, it is shown by admixture experiments that simultaneous administration of high doses of free saccharide (0.5-25 micrograms) of different chain lengths (varying from M(r) 1.6-120 kDa) decreases the anti-polysaccharide antibody response. Presence of low doses of saccharide (up to 10%), which are usually present in conjugates prepared by the carbodiimide coupling procedure, did not influence the anti-polysaccharide antibody response in adult and neonatal mice.


Safety and immunogenicity in volunteers of a recombinant Plasmodium falciparum circumsporozoite protein malaria vaccine produced in Lepidopteran cells. A recombinant Plasmodium falciparum circumsporozoite (CS) antigen (rPfCSA) was produced in insect cells using a baculovirus expression vector containing the entire CS gene. This near full-length CS antigen was adsorbed onto aluminium phosphate for use as a malaria vaccine. In a study of safety and immunogenicity, 20 volunteers were divided into four groups of five each and inoculated intramuscularly with 10, 100, 500 or 1000 micrograms of vaccine. Primary vaccinations were followed by two booster immunizations at 2 and 6 months. Three volunteers developed prominent local reactions manifested as tenderness, redness and swelling at the injection site following the second or third vaccination. All symptoms resolved spontaneously within 72 h. Postimmunization sera from six of 20 volunteers showed seroconversions as measured by Western blot, using rPfCSA as antigen. However, specific anti-CS protein antibody could not be detected by indirect immunoflourescence against intact sporozoites or by ELISA using rPfCSA or peptide to the repeat region. In addition, 18 of 20 volunteers developed antibody to baculovirus proteins as determined by ELISA and/or Western blot. Antigen-driven replication studies using peripheral blood mononuclear cells from vaccinees failed to detect proliferative responses specific to CS protein. This recombinant CS protein vaccine, as formulated, was minimally immunogenic in humans.


Impaired response to hepatitis B vaccine in HIV infected children. Eighteen human immunodeficiency virus (HIV) vertically infected children (HIV group) and 33 seroreverted children (SR group), who had completed hepatitis B vaccination (Engerix B, 20 micrograms dose) were studied. Four out of 18 (22%) HIV children failed to develop protective antibody levels (anti-HBs titres less than 10 mIU ml-1) compared with 1 out of 33 (3%) SR children (p less than 0.05). Magnitude of response among HIV children was significantly lower than among SR children. In HIV children the probability that anti-HBs titres persist above the protective levels was significantly lower than in the SR group at any time during the 24 month follow-up. These results show that HIV children have a suboptimal response to hepatitis B immunization and the protection is less durable. Further studies are needed to determine the optimal protocol for hepatitis B immunization in HIV children.


Antigenic characterization of the live attenuated Japanese encephalitis vaccine virus SA14-14-2: a comparison with isolates of the virus covering a wide geographic area. In China, a live attenuated Japanese encephalitis (JE) vaccine, based on strain SA14-14-2, has been derived from the wild-type strain SA14 as an alternative to the current inactivated vaccines such as Nakayama-NIH and P-3. SA14-14-2 has been characterized using monoclonal antibodies derived in mice, using HAI and neutralization tests, and compared with other Chinese live vaccine clones and 14 wild-type strains of JE virus. Wild-type strain SA14 was found to be a poor immunogen and antigenically distant from all other viruses examined. The vaccine derivatives SA14-5-3 was more immunogenic than its wild-type parent, while SA14-14-2 (derived from SA14-5-3) was more immunogenic than SA14-5-3 and elicited a cross neutralizing antibody response. Our studies indicated that JE virus strain Nakayama elicited as good a neutralizing antibody response in hyperimmunized mice as the SA14-14-2 vaccine clones grown in either primary hamster kidney (PHK) or primary dog kidney (PDK) cells. A single dose of live SA14-14-2 (PHK) also elicited a good antibody response. Antigenic variation between wild-type and vaccine clones of JE virus were detected but were not considered significant in terms of controlling JE virus infections by vaccination.


Specific and non-specific immunity and protection of macaques against SIV infection. The simian immunodeficiency virus is a retrovirus closely related to the human immunodeficiency viruses; it induces an AIDS-like disease in macaques, and provides therefore an obvious animal model for anti-lentiviral drug and vaccine strategy assessments. In our experiment, we immunized rhesus macaques with a purified and formalin-inactivated whole SIVmac251 antigen preparation. Most of these monkeys were still protected for more than 4 months following a heterologous SIVsm intravenous challenge. Both virus stocks, for vaccine preparation and challenge, were provided by culture supernatants of infected T cells of human origin. Four of the protected macaques were then reimmunized with the same antigen preparation and rechallenged intravenously with a homologous rhesus cell grown SIVmac251. Unexpectedly, all animals developed clinical and biological evidence of infection by day 15 after the second challenge.


Endothelins.

Endothelins. The endothelins (ET) represent a novel family of at least three isopeptides (ET-1, ET-2, ET-3), each consisting of 21 amino acids and two disulfide bridges. ET has originally been isolated from the supernatant of porcine aortic endothelial cells and has been found to be the most potent and long lasting vasoconstrictor agent yet discovered. ET is synthesized as a preprohormone and cleaved by unusual proteolytic processing. The different isoforms of ET seem to differ in their biological activity which may be due to interaction with different ET-receptor subtypes (ETA, ETB, ETC) and their tissue distribution. Besides its vasoactive properties, ET evokes a variety of other effects, such as positive inotropic and chronotropic actions on the heart, the release of other regulatory substances (EDRF, prostanoids, ANP), as well as cellular mitogenesis. Therefore, the endothelins have been implicated in the pathophysiology of a variety of cardiovascular disorders, however their precise role remains to be elucidated. Such research might have potential application on veterinary medicine learning about factors responsible for vascular damage and consecutively being able to treat or prevent various vascular diseases more specifically.


Demonstration of immunoglobulins and complement in canine and feline autoimmune and non-autoimmune skin diseases with the direct immunofluorescence and indirect immunoperoxidase method. Skin sections from 71 dogs and 10 cats with bullous autoimmune skin diseases and various non-autoimmune dermatopathies were studied for the presence of immunoglobulins (canine IgG, IgM, IgA; feline IgG) and complement (canine C3) using the direct immunofluorescence method (DIF) and the indirect immunoperoxidase method (IIP). In cases of autoimmune skin diseases (9 dogs, 3 cats) both methods were of comparable sensitivity for the detection of epidermal deposits. In canine cases with non-autoimmune dermatopathies, epidermal immunoreactivity was found in 16.1% of cases with the DIF method, and in 29.0% of cases with the IIP method. With both methods, epidermal deposits were most frequently seen in skin sections of dogs with bacterial diseases. Furthermore, positive reactions were found in canine cases with hypersensitivity disorders, endocrine dermatosis, dermatomycosis, parasitic disease, cutaneous Leishmaniasis and in cases with non-specific dermatopathies of uncertain aetiology. In the majority of canine cases intercellular deposits of IgG were found. Immunohistological results should always be interpreted in conjunction with clinical and histomorphological findings in order to establish a diagnosis of autoimmune skin disease and to prevent misdiagnoses.


Studies on abnormal moulting in the farm-raised blue fox (Alopex lagopus). In a farm-raised, adult female blue fox (Alopex lagopus) it was observed that apparently the winter coat was shed abnormally. Furthermore, the individual was never recorded as being on heat. Comparative histological and clinical-chemical examinations showed that the winter coat cycle was postponed approximately 6 months, and that the hair growth therefore took place in the spring. At first a kind of biological summer coat was produced, and then a biological mature winter coat. This was compared with and partly documented by changes in plasma estradiol and cortisol profiles. It could be concluded that the hair growth cycle and the plasma estradiol profile showed an abnormal seasonal variation in the abnormal fox. The two variables seemed, however, to be correlated as in a normal animal.


Blood levels of prostaglandin metabolites (PGFM, PGEM) after parturition in cows with and without retained placenta considering spontaneous calving and dystocia. Blood samples were taken from 71 Holstein Friesian cows at 0, 3, 24 and 48 hours after parturition. Peripheral plasma concentrations of prostaglandin F2 alpha and E2 metabolites (PGFM, PGEM) were determined by radioimmunoassay. The cows were divided into 4 groups, according to type of calving (spontaneous, dystocia) and discharge of placenta. Group 1: spontaneous calving, shedding of placenta within 12 hours (SC, NRP, n = 19); group 2: spontaneous calving, retained placenta (SC, RP, n = 7); group 3: Dystocia, shedding of placenta within 12 hours (Dys, NRP, n = 32); group 4: Dystocia, retained placenta (Dys, RP, n = 13). The PGFM concentrations decreased within 3 hours after parturition only in NRP cows (groups 1 and 3, p < 0.05). Three hours after calving the animals of group 3 had considerably higher PGFM levels than those in group 4 (0.46 +/- 0.26 vs 0.26 +/- 0.11 ng/ml). Significant decreases (p < 0.05) in PGEM concentrations occurred in cows that shed the placenta within 24 hours after parturition. Cows that retained the placenta showed a significant slower decrease of the PGEM levels. It is concluded that postpartum prostaglandin levels are influenced by stress during parturition (dystocia, transportation) as well as by retained placenta.


[The effect of the energy intake of cows on the rumen metabolism studied using the excretion of allantoin in milk]. With two groups of dairy cows (A: 12 German Black and White- and 6 German Simmental Cows; B: 16 German Black and White- and 11 German Simmental Cows) allantoin concentrations of blood plasma (A) and milk (A and B) were analysed by HPLC. There exists a close correlation (r = 0.758) between allantoin concentration in blood plasma (370.6 +/- 79.1 mumol/l) and milk (474.1 +/- 78.9 mumol/l). The relation between milk yield and allantoin excretion with milk seems to be non-linear (r = 0.936). On the other hand there is a close correlation between energy intake with feed and allantoin excretion via milk (r = 0.885). In a further experiment the allantoin concentrations in blood plasma of 5 Angler steers were monitored for 24 h every second hour with feeding twice daily. There were remarkable fluctuations in the allantoin concentration from nearly 156 to 129 mumol/l. After that the rumen of the steers was emptied, while plasma concentrations were still monitored the same way as before. Concentrations of allantoin declined for about 55% to 65 mumol/l.


[The use of rapid progesterone tests (Serozyme-Progesterone, Ovucheck) for the diagnosis of pregnancy in Austrian mountain sheep]. To determine the oestrous cycle length of mountain sheep 10 ewes were stimulated with intravaginal sponges (Chronogest) and ten with prostaglandins (Iliren) and a PMSG injection (500 IU), respectively. Independent of the synchronisation mode the Serozyme-progesterone levels indicated a cycle length of 17 days. Progesterone was not detectable by the test system during oestrous, it reached its maximum on the 10th day (mean = 3.9/3.7 ng/ml) and decreased to non-detectable levels again on day 17. For early pregnancy diagnosis the Serozyme-progesterone as well as the Ovucheck gave useful results. On day 17 and 19 after mating the progesterone concentration of pregnant ewes remained on the same level as on day 10, whereas barren ewes had non-detectable progesterone levels on day 17 and 19, using the Serozyme-progesterone and below 1 ng/ml on day 19 using the Ovucheck. The accuracy of the Serozyme-progesterone referring to the declaration "non pregnant" was 100%, that of the Ovucheck 37.5% on day 17 and 100% on day 19. The use of both test systems for determining pregnancy of unknown length was examined by collecting blood-samples three times with a five and a seven day interval. Precise results were obtained only with the Serozyme-progesterone test. At least one of three blood samples of all the barren ewes (n = 8) contained amounts of progesterone beneath the sensitivity of this method. The Ovucheck results could not help at all to distinguish barren or pregnant ewes with unknown mating data.


[The acid-base equilibrium in the blood of calves suckled by their mothers and in milk-fattened calves]. The influence of different housing systems on the acid/base balance in the blood of 39 calves in a suckler cow herd of the breeds Deutsche Schwarzbunte and Deutsche Rotbunte, and 25 veal calves of the breeds Deutsche Schwarzbunte and Holstein-Friesian was examined in a period from the first to the sixth month of life. 1. No differences between the test groups were present in the pH of blood. 2. The body temperature was significant higher in calves of the suckler cow herd. 3. Hemoglobin content of the veal calves was significant higher till the third month of life. With increasing age the relations are changed, and at the end of the experimental period significant higher values were found in calves of the suckler cow herd. 4. Marked differences were also present in the carbon dioxide pressure with significant higher values in veal calves. 5. With regard to the metabolic factors of the blood acid/base balance--buffer base, bicarbonate and base deviation--significant higher values were also seen in veal calves. The results are discussed in connection with problems of intensive fattening of calves in comparison to the conditions of calves in suckler cow herds.


A comparative study of arterial and venous blood acetate concentration in cows fed different diets close to parturition. Blood samples were collected from the coccygeal artery and a jugular vein two weeks before expected calving, one to five days after calving and three weeks after calving of cows which were fed either a high roughage or a low roughage diet from four weeks before to 14 weeks after calving. The mean venous acetate concentration ranged from about half to three-quarters of the arterial concentration. No differences were observed at any time between concentrations of acetate in either the arterial or venous blood of the cows on the different diets.


Hepatic encephalopathy associated with acquired portosystemic shunts in a dog. An 8-month-old dog with a history of gastrointestinal disturbances and neurological signs was presented with hyperammonemia. Necropsy revealed ascites, portosystemic collaterals, and an irregularly surfaced small liver. Histologically, there were diffuse neuronal necrosis and focal spongiform changes in the brain, and marked fibrosis in the liver. Hepatic encephalopathy was diagnosed.


Effect of endothelin 1 on plasma glucose and lipid levels in pygmy goats. The effect of endothelin 1, a recently discovered vasoconstrictor hormone, on levels of plasma glucose and lipids was investigated in pygmy goats. Endothelin 1 was injected intraperitoneally (1.72 micrograms/kg BW) and blood samples were taken by puncturing the jugular vein immediately before and 60, 150 and 240 min post injection. Endothelin 1 in comparison to vehicle significantly increased plasma glucose and FFA levels, whereas plasma triglycerides were significantly reduced. Thus, beside its vasoconstrictive action, endothelin 1 also has metabolic effects. Whether these effects are directly caused by endothelin 1 or whether they are due to a release of a metabolic hormone, e.g. epinephrine, remains to be investigated.


[The effect of a different energy supply on the growth intensity and skeletal development of growing Great Danes. 2. Effect on insulin-like growth factor I and on thyroid hormones]. In an experiment with 13 growing Great Danes (littermates) fed ad libitum (4 dogs) or restrictively (70% of ad libitum energy intake; 9 dogs), concentrations of insulin-like growth factor I (IGF-I), 3,5,3'-triiodothyronine (T3) and thyroxine (T4) were measured in blood samples until the age of 6 months. In the ad libitum fed group, levels of T3 and T4 were partially and of IGF-I were significantly (p < 0.01) elevated as compared with the control dogs. Postprandial changes of IGF-I were absent in growing Great Danes as well as in a reference group of 3 adult beagles. Increased concentrations of IGF-I, T3 and T4 could be causally related to osteochondrosis, which frequently occurs in intensively fed dogs.


Monofrequency oscillation technique in healthy and pneumonic calves younger than 2 months--physiological values and methodological aspects. Using the monofrequency oscillation technique, the oscillatory measured resistance of the respiratory system (Ros) was determined in healthy and pneumonic calves younger than 2 months. Using a face mask, measurements were done in unsedated animals directly in the calfhouse. 106 clinically healthy calves were examined to determine the physiological range of Ros. Calves suffering from pneumonia showed significantly higher values of Ros which were positively correlated with the severity of pneumonic lesions as established by pathological investigations. In healthy calves, the variability of Ros due to biological aspects was found to be much higher than methodologically caused variability. It is concluded that the monofrequency oscillation technique is useful especially in individual investigations, e.g. control of therapy.


Renal lesions in Norwegian slaughter pigs. Macroscopic and light microscopic studies. Six hundred and sixty-eight consecutive carcasses of slaughtered swine were examined for renal lesions at meat inspection. The macroscopic lesions were divided into 7 categories: D1 = depressions of the external surface and partial persistence of fetal lobation; D2 = focal leukolymphocytic nephritis (acute focal tubulo-interstitial nephritis); D3 = cysts; D4 = interstitial fibrosis; D5 = infarct-like lesions; D6 = fatty degeneration, and D7 = hydronephrosis. 396 (59.3%) of the examined carcasses were diagnosed as having one or more of these renal lesions. Two hundred and seventy-two (40.7%) of the carcasses were macroscopically judged as having normal kidneys. A selected material of 250 kidneys representative for each group of lesions based on macroscopic examination and 50 normal kidneys were prepared for histological examination. In the group of kidneys with the macroscopic diagnosis interstitial fibrosis (D4), an accompanying histological finding was proliferative glomerular changes with fatty degeneration of the proximal tubules. Cortical infarct-like lesions (D5) were observed in the absence of thrombo-embolic disease and were considered to have developed in association with local arterial alterations similar to polyarteritis nodosa.


Influence of medicinal herbs on phagocytosis by bovine neutrophils. Twenty-six herbal preparations made from 24 medicinal herbs, categorized as antipyretics in Chinese materia medica, were tested in vitro to determine their effects upon phagocytosis of 32P-labelled Staphylococcus aureus by neutrophils isolated from bovine blood and milk. The percentage of phagocytosis was determined after incubating (1 hour at 37 degrees C) 1.25 x 10(7) neutrophils, 1 x 10(8) 32P-labelled S. aureus and 10% skimmed milk with herbal solutions. Concentrations of herbal preparations tested were 100%, 10% and 1% (v/v). When compared with PBSS (0.01 M phosphate buffered saline solution) controls, most of the herbs at high concentrations inhibited phagocytosis while at lower concentrations phagocytosis was increased. All 26 herbal preparations significantly increased blood neutrophil activity at their proper concentrations. The most active herbs in promoting blood neutrophil phagocytosis were observed for Herba verbenae, Flos chrysanthemi, Flos lonicerae, Radix sophorae flavescentis, Herba houttuyniae, Radix isatidis, Herba patriniae, Berberini sulfatis at the lowest concentration and for Folium hibisci at the high concentration with the increased percentage of more than 40.0% in comparison with PBSS control. Of the 19 herbal preparations tested with milk neutrophils, 18 herbs greatly increased phagocytosis at suitable concentrations. The most active preparations in stimulating milk neutrophil functions included Folium hibisci, Flos chrysanthemi, Radix bupleuri, Radix stellariae, Herba houttuyniae, Herba senecionis scandentis, Caulis lonicerae and Flos lonicerae which increased phagocytosis by over 35.0%.