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Biomedical subjects

A Falk

Publications and source records attributed to A Falk.

At least 73 records · Page 4Linked to original sources

Potency assay and characterization of lymphocytosis promoting factor in whole cell and acellular pertussis vaccines.

Potency assay in mice to evaluate the immunogenic properties of a number of candidate Lymphocytosis Promoting Factor (LPF) antigen in whole cell and acellular pertussis vaccines is described. Potency was estimated both by the conventional WHO intracerebral challenge test and an LPF-toxin challenge method. The latter method involved intraperitoneal injection of dilutions of test and reference preparations followed by challenging the animals 28 days later by LPF combined with AlPO4 adjuvant and estimating the total white blood cells three days after challenge. The method has been in routine use for the past four years and has given consistent results with reproducible specific activity and ED50 values. LPF antigen prepared by different chemical treatment or by genetic alteration of the molecule showed differences in specific activity, although different batches made by the same procedure appeared to give consistent values. Only two preparations, did not give specific activity close to what was given by LPF in whole cell vaccine by the LPF challenge method. Some preparations did not give any activity. In the intracerebral challenge method, many preparations failed to protect, while some gave a low degree of protection. The content of residual ADP ribosylating activity also varied. These three tests can be used for characterizing the LPF antigen of acellular pertussis vaccines.

Animals↗

Gender differences in TRH-stimulated TSH and prolactin in primary degenerative dementia and elderly controls.

We performed thyrotropin-releasing hormone (TRH) stimulation testing in 18 nondepressed patients with primary degenerative dementia (10 M, 8F; average age +/- SD = 68 +/- 7) and 12 elderly controls (7M, 5F; average age +/- SD = 61 +/- 6). Six patients were retested approximately 2 years later. Initial Mini-Mental State Examination scores for patients ranged from 2 to 28 (average +/- SD = 18 +/- 6) and the scores for the control subjects were all equal to 30. Protirelin (500 micrograms) was injected iv and blood was sampled at 0, 15, 30, 45, 60, and 90 min for thyrotropin-stimulating hormone (TSH) and prolactin (PRL). There were no significant differences between patients and controls in baseline T4, T3 uptake, TSH, or PRL. No significant differences were found between patients and controls for either TRH-stimulated TSH or PRL at all time points. Duration of illness, severity of dementia, and severity of depressive symptoms did not correlate significantly with stimulation test results. There were, however, significantly greater responses in stimulated TSH and PRL for women compared with men in both patients and controls. Upon repeat testing (n = 6), TRH-stimulated TSH and PRL were not significantly different from the initial results.

Aged↗

Liquid/air partition coefficients of four terpenes.

The liquid/air partition coefficients of four common terpenes, alpha-pinene, beta-pinene, 3-carene, and limonene, have been determined in vitro using head space technique. The liquids used were water, human blood, and olive oil. alpha-Pinene, beta-pinene, and 3-carene were practically insoluble in water and limonene was slightly soluble; all were readily dissolved in olive oil. The oil/air partition coefficients ranged from 2900 to 5700 in the order alpha-pinene, beta-pinene, 3-carene, and limonene. The blood/air partition coefficients ranged from 15 to 42 in the same order as for oil/air.

Bicyclic Monoterpenes↗

Cardiopulmonary dysfunction in a feline septic shock model: possible role of leukotrienes.

The aim of the present study was to explore the possible involvement of leukotrienes (LTs) in the development of cardiopulmonary dysfunction in experimental septic shock. Sepsis was induced in anesthetized cats by infusion of liver Escherichia coli bacteria. One series (N = 6) was pretreated with diethylcarbamazine (DEC), a 5-lipooxygenase inhibitor; another series (N = 7) was pretreated with FPL 55712, a LTC4-D4 antagonist; and a third series (N = 8) served as septic controls. After 2 hr of bacteremia, there were no differences in cardiac function in the three series. By subjecting the heart to volume load, two points on a Starling curve were obtained, indicating the limits of the functional cardiac reserve. This loading procedure disclosed a significantly better preserved left ventricular function in the DEC-pretreated group as compared with the other two groups. Pretreatment with DEC and FPL 55712 had no effects on early pulmonary vascular reactions. However, the tracheal pressure response was less pronounced after pretreatment compared with septic controls. Calculated airway resistance was less increased and pulmonary compliance less decreased in the two pretreated groups. Furthermore, arterial hypoxia was prevented by pretreatment. It is concluded that this study suggests that LTs are involved in the development of myocardial insufficiency in experimental bacteremic septic shock. Moreover, the results strongly indicate that LTs may be of importance in compromising pulmonary gas exchange, partly by effects on the smaller airways.

Airway Resistance↗

Cardiopulmonary function as related to thromboxane A2 synthesis in experimental septic shock.

The aim of the present study was to explore the possible involvement of thromboxane A2(TxA2) in the development of cardiopulmonary dysfunction in experimental septic shock. Sepsis was induced in anesthetized cats by intravenous (i.v.) infusion of live Escherichia coli. One series (No. = 12) was pretreated with a specific TxA2 synthetase inhibitor, dazmegrel; another (No. = 8) served as a septic control series. In both series a systemic arterial hypotension developed after 2 hr; no differences in cardiac function were detected. After 2 hr bacteremia cardiac preload was increased by a rapid infusion of dextran. This showed that cardiac function was significantly more preserved in dazmegrel-pretreated cats compared with septic controls. Pretreatment with dazmegrel totally prevented the pulmonary vascular response to bacterial infusion. The pulmonary compliance decreased to 40% in controls but to only 75% in the dazmegrel series, and airway resistance increased to 300% and 140%, respectively. The ventilation-perfusion ratio was less impaired in the pretreated series. Pretreatment with dazmegrel abolished the increase in thromboxane B2 (TxB2), the stable metabolite of TxA2, seen in the untreated series. The rise in 6-keto-prostaglandin F1a (6-keto-PGF1a), the stable metabolite of prostaglandin I2PGI2, was evident in both series. We concluded that TxA2 is important for the impaired cardiac performance in septic shock. Furthermore, TxA2 is involved, but not as the only factor, in the development of pulmonary dysfunction.

Airway Resistance↗

The role of prostanoids in the feline intestinal vascular and central haemodynamic responses to i.v. infusion of live E. coli.

Bacterial infusion in the cat, causing experimental septic shock, induces an early vascular response mainly characterized by pulmonary hypertension and intestinal vasoconstriction. Prostanoids are held to be important mediators of the pulmonary vascular reaction. This study was performed to explore the involvement of prostanoids in the central haemodynamics and the small intestinal vascular reactions in experimental septic shock. Aortic blood pressure was continuously monitored, as were aortic blood flow, the pressure in a. pulmonalis and the small intestinal venous outflow. All cats (n = 24) were given live E. coli (10(10) ml-1) as a continuous intravenous infusion. One series was pretreated with indomethacin, another with UK-38,485, a specific thromboxane A2 synthetase inhibitor, and a third series served as untreated control. The pulmonary hypertensive response was clearly attenuated in the two pretreated series, in fact abolished in the one given UK-38,485. The early intestinal vasoconstriction was eliminated in the two pretreated series. Later during bacteraemia, when untreated and indomethacin-pretreated cats showed intestinal vasoconstriction, UK-38-485-pretreated animals kept intestinal blood flow within the preseptic range. These data suggest that in the cat, thromboxane A2 is the prostanoid mediating the vascular reactions, not only in the lung but also in the small intestine.

Animals↗

Intestinal vascular obstruction in the cat. Right heart function in a shock model.

Cardiovascular function was studied in a model of intestinal vascular obstruction in cats. To measure right ventricular end diastolic pressure and maximal dP/dt, a tip transducer catheter was placed into the right ventricle. The intestinal vascular obstruction resulted in shock with decreases of blood pressure, cardiac output, and external cardiac work. Small intestinal mucosal lesions were found in all shocked cats. At an increased preload to the heart, right ventricular function was depressed in shocked cats. The model corresponds to one used earlier in the rat, where cardioinhibitory activity in venous blood was found in vitro. In this corresponding model of intestinal shock in the cat a depressed function of the right ventricle of the heart was found in vivo.

Animals↗

Peritonitis and septic shock--an evaluation of two experimental models in the rat.

Two different experimental models for inducing septic shock have been characterized. In one, septic shock was induced by intraperitoneal injection of live Escherichia coli bacteria. This resulted in a dose-dependent mortality. Those animals surviving the first 24 h are considered as permanent survivors. In the other models, septic shock and peritonitis was induced by ligation and needle punctures of the cecum. This resulted in a slower development of shock which was almost invariably lethal within 96 h. Arterial blood pressure remained within the normal range in both models for up to 3 h after inducing peritonitis. Then a rapid deterioration was noticed in animals injected with live E. coli. White blood cells and platelets in arterial blood were reduced compared to controls in both groups. This reduction was more pronounced in animals injected with live E. coli. Both models are considered as useful tools in further studies of the pathophysiology of peritonitis and septic shock.

Animals↗

Histamine2-receptor antagonists in gastroduodenal ulcer haemorrhage.

This paper reviews randomised trials in which the effects of histamine2-receptor antagonists have been studied in gastroduodenal ulcer haemorrhage. There is a trend in these studies that histamine2-receptor antagonists may reduce the number of rebleedings, especially in elderly patients with gastric ulcers. A randomised trial comparing cimetidine and ranitidine in high risk patients with massive gastroduodenal haemorrhage is also presented. The total mortality in this study was 12%, 15% for gastric ulcer patients and 11% for duodenal ulcer patients. There was no difference in mortality, amount of blood transfusion required, rebleedings or need for emergency surgery between the two treatment models.

Aged↗

Intestinal hemodynamic effects of dextran-induced hyperviscosity in the cat.

A hyperviscous state with red cell aggregation and increased plasma viscosity was induced in cats by intravenous infusion of high molecular weight dextran. A segment of the small intestine was isolated with intact vascular and nervous supply and placed in a plethysmograph for determination of the intestinal tissue volume and capillary filtration coefficient. The intestinal blood flow was measured by a drop recorder unit. Measurements of intestinal blood flow, flow resistance and capillary filtration coefficient were performed during normotension and regional hypotension before and after infusion of high molecular weight dextran. After infusion of high molecular weight dextran, there was a twofold increase of blood viscosity and a threefold increase of plasma viscosity. Erythrocyte sedimentation rate exceeded 100 mm/h. Intestinal blood flow decreased by 35% during normotension and by 45% during regional hypotension. Intestinal flow resistance increased by 45% during normotension and by 65% during hypotension. The capillary filtration coefficient was not affected by the dextran infusion. It is concluded that the intestinal hemodynamic effects of high molecular weight dextran are mainly dependent of the increased plasma viscosity and that the number of perfused capillaries is not reduced by obstructing red cell aggregates.

Animals↗

Evaluation of percutaneous cholangiography and percutaneous biliary drainage in obstructive jaundice.

104 patients with obstructive jaundice were referred for percutaneous transhepatic cholangiography (PTC) and percutaneous transhepatic biliary drainage (PTBD). The effects of PTBD on postoperative morbidity and mortality were evaluated as well as the occurrence of complications. The results were compared to a group of 33 patients with malignant bile duct obstruction operated without preoperative bile drainage. There was no significant difference in the rate of postoperative complications and mortality between these two groups.

Adult↗

Small intestinal mucosal lesions in feline septic shock: a study on the pathogenesis.

The pathogenesis of small intestinal mucosal damage in septic shock was explored in experiments on 15 cats given live E coli i.v. Villous (absorptive site) blood flow was studied by the carbon monoxide uptake technique using isolated small intestinal segments. In eight of the cats, segments were perfused intraluminally with oxygenated or nitrogenated saline. The main part of the small intestine was unperfused and served as control. Nine cats (60%) developed mucosal damage. They had significantly lower arterial blood pressure at the end of septicemia (56 +/- 6) than cats without mucosal damage (76 +/- 3 mmHg). Total intestinal blood flow was similar before or during septicemia. Villous blood flow before septicemia was 3.7 +/- 0.5 ml/min X 100 g intestine and 5.1 +/- 1.0 (n.s.) in the two groups, respectively, and remained unchanged. Intraluminal perfusion with oxygenated but not with nitrogenated saline prevented the development of mucosal damage. It was concluded that the small intestinal mucosal damage is due to hypoxia in spite of unchanged villous blood supply.

Acid-Base Equilibrium↗

Diagnosis and treatment of superior mesenteric artery syndrome.

Superior mesenteric artery syndrome (SMAS) is a rare clinical condition. Eleven cases of SMAS treated surgically are reported after follow-up periods of 6 months to 6 years. The value of hypotonic duodenography in the diagnosis of the syndrome is emphasized.

Adolescent↗

Ranitidine in the treatment of gastric, prepyloric and duodenal ulcer--a controlled prospective double-blind trial.

Fifty adult outpatients with endoscopically proven gastric, prepyloric or duodenal ulcers were included in a prospective, randomised double-blind trial of ranitidine (40 mg X 3 daily and 80 mg at bedtime) versus placebo. After 4 weeks the ulcers had healed in 21 of 25 patients receiving ranitidine compared with 7 of 23 in patients receiving placebo (p less than 0.001). The ranitidine treated patients had fewer days of pain (p less than 0.001) and lower consumption of antacids (p less than 0.01) than placebo patients. Patients whose ulcers were not healed after 4 weeks went into an open 4 weeks trial with ranitidine. After the second 4 week period there were still 5 unhealed ulcers, all located in the prepyloric region. No serious side effects or haematological or biochemical abnormalities were observed. It is concluded that ranitidine is a very potent and safe ulcer healing substance. Patients with prepyloric ulcers may need a higher dose or a longer period of treatment.

Adult↗

Treatment of acute massive gastroduodenal haemorrhage with cimetidine in elderly patients.

Ninety-two patients over the age of 60 with acute upper GI-haemorrhage were included in a prospective randomized doubleblind three-centre study of the effect of a five day treatment with cimetidine. Twenty patients had to be excluded because of different reasons. The remaining 72 patients bled from either erosive gastritis, gastric ulcer or duodenal ulcer. Thirty-two patients received cimetidine and 39 placebo. There was no difference in the number of transfusions, rebleedings or operative interventions. Mortality was 1/33 (3%) in the cimetidine group compared to 5/39 (13%) in the placebo group (NS). In the gastric ulcer group there was no mortality among 10 cimetidine patients compared to a mortality of 4 of 12 (33%) patients receiving placebo (p less than 0.05). It is concluded with caution that cimetidine might be effective in haemorrhage from gastric ulcer in patients 60 years and older. For convincing conclusions a larger study of patients with bleeding ulcers is desirable.

Acute Disease↗