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Biomedical subjects

J H Kalbfleisch

Publications and source records attributed to J H Kalbfleisch.

At least 55 records · Page 3Linked to original sources

Hyperthermic liver perfusion and release of lysosomal enzymes.

Perfused rat liver was used to study the relationship between the hepatotoxic effects of hyperthermia and the effects of heat on lysosomes. Livers from fed rats were perfused for 180 min at 37-43 degrees C. Release of lysosomal enzymes into the perfusate during perfusion and lysosomal fragility at the end of perfusion were determined. Lysosomes were then incubated in vitro at 37-45 degrees C with xanthine and xanthine oxidase to generate superoxide in order to study lipid peroxidation as a potential causative factor in heat-induced lysosomal lability. Perfusate lysosomal enzymes p-nitrophenyl phosphatase and beta-glucuronidase increased significantly (P less than 0.05) at 42 and 43 degrees C over enzyme levels at 37 degrees C. Significant differences were not observed until after 120 min. Lysosomal fragility was found to be significantly increased (P less than 0.05) after perfusion at 42 and 43 degrees C when measuring p-nitrophenyl phosphatase, but not when measuring beta-glucuronidase activity. Xanthine oxidase acting on xanthine caused labilization of the lysosomes at all temperatures studied when compared to a control at each temperature. There was a temperature effect with an increase in release of p-nitrophenyl phosphatase and beta-glucuronidase from control lysosomes which became significant (P less than 0.05) at 43 degrees C on comparison to 37 degrees C. There were no significant increases in lysosomal lability with temperature in the presence of xanthine and xanthine oxidase. Lastly, salicylic acid peroxidation was used as a measure of superoxide formation from the action of xanthine oxidase with increasing temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Nitrophenylphosphatase↗

Myocardial ischemia during cardiovascular surgery as detected by an ST segment trend monitoring system.

The incidence of intraoperative myocardial ischemia was determined in 312 patients undergoing cardiovascular surgery using ECG recordings obtained from a prototype system that trends ST segment changes. Prior to cardiopulmonary bypass, ischemic ECG changes were observed in 11.9% of patients, the incidence being lower during coronary artery bypass grafting (CABG) procedures (8.1%) than in patients undergoing repeated CABG (23.5%), valve replacement (25.9%), or concomitant valve replacement and CABG (35.3%). The occurrence of intraoperative myocardial ischemia was statistically greater in patients with a history of hypertension, two or more previous myocardial infarctions, or kidney disease. The incidence of ischemia was also significantly greater in patients with left ventricular end-diastolic pressures of 15 mm Hg or higher at cardiac catheterization. The incidence during induction was significantly reduced by the addition of hypnotics to narcotics, and, during maintenance, by the addition of an inhalational agent. The majority of ischemic events were temporally related to some hemodynamic disturbance, and many coincided with surgical manipulation. The incidence of intraoperative myocardial ischemia was substantially less than that reported in comparable studies. Since the incidence decreased significantly following clinical acceptance of the prototype system, the authors conclude that such capability increases sensitivity to small ST segment changes. This heightened awareness and prompt remedial action reduced the incidence of ischemia during CABG to 6% during the final 2 years of the study.

Aged↗

Evidence for abnormal cholinergic neuromuscular transmission in diabetic rat small intestine.

Proximal and distal rat small intestine from control, diabetic, and insulin-treated diabetic rats was cut into strips measuring 6.0 X 10.0 mm. Strips cut along the oral-caudal axis were called longitudinal strips, while those cut 90 degrees to that axis were called circular strips. The strips were stretched to their optimum lengths and subjected to electrical field stimulation (0.1-1.0-ms pulse duration, 30-270 mA, 1-26 Hz) in the presence of Krebs' solution and Krebs' solution plus 10(-6) M atropine. Field stimulation produced atropine-sensitive and atropine-resistant contractions in all strips. Significant differences among the three groups were found in the amplitudes of atropine-sensitive contractions in strips from distal longitudinal muscle. Controls showed the highest amplitude contractions and diabetics the lowest, whereas the insulin-treated diabetics showed contractions intermediate in amplitude. No significant differences were noted among the atropine-resistant contractions. Field stimulation delivered at pulse durations of 5.0 and 50.0 ms in the presence of neural blockade with tetrodotoxin (5 X 10(-6) M) produced similar contraction amplitudes among the three groups. These results suggest that streptozotocin-induced diabetes mellitus is associated with defective cholinergic neuromuscular transmission in the myenteric plexus of the distal small intestine. Insulin therapy seems to improve the abnormality.

Animals↗

Alterations in biochemical functions during hyperthermic isolation-perfusion of the human liver.

Hyperthermia (42-42.5 degrees) was applied to the liver of eight patients with cancer in the liver by a technique of isolation-perfusion. Hepatic functional integrity was assessed during perfusion through measurement of multiple perfusate constituents. Data from seven perfusions were available for analysis. During perfusion there was an increase in perfusate lactate, pyruvate, glucose, urea, potassium, alkaline phosphatase, SGOT, and LDH. All increases in these constituents were significant (P less than 0.05) except for potassium. Lactate accumulated throughout the perfusion from an initial level of 3.8 +/- 1.0 mM to 7.6 +/- 3.5 mM at 4 hr. Pyruvate increased over the first 3 hr of perfusion from 0.14 +/- 0.06 mM to 0.80 +/- 0.37 mM before declining to 0.54 +/- 0.24 mM at 4 hr. The L/P (lactate/pyruvate) ratio decreased during perfusion to less than 10 in the first 2 hr, but rose to within normal limits by the end of perfusion. The decreases in L/P ratios were significant (P less than 0.05). Initially there was a rapid rise in perfusate glucose concentrations from 4.5 +/- 0.8 mM to 20.7 +/- 5.4 mM at 2 hr with nonsignificant changes thereafter. Urea levels increased from 0.64 +/- 0.22 mM to 1.92 +/- 0.76 mM. Perfusate potassium increased from the initial level of 7.0 +/- 1.0 mM during perfusion to 8.3 +/- 1.7 mM at 2 hr before declining. SGOT, LDH, and alkaline phosphatase increased during perfusion from 21 +/- 15, 142 +/- 48, and 16 +/- 6 to 176 +/- 22, 472 +/- 53 and 52 +/- 42, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

alpha-Tocopherol supplements and high-density-lipoprotein-cholesterol levels.

1. In a randomized, double-blind 6-month study, alpha-tocopherol (728 mg) or placebo were administered daily to seventy-eight volunteers (forty-nine men, twenty-nine women) to investigate the possible enhancing effect of vitamin E on plasma high-density-lipoprotein-cholesterol (HDL-C) levels. In addition, the available reported values from short-term (4-6 weeks) studies, as well as the 4-week results from the present study, were combined and analysed for factors which may modify the effect of alpha-tocopherol on HDL-C. 2. No consistent effect of alpha-tocopherol on plasma HDL-C levels was observed either in the combined 4-week values or in the 6-month study. Further analysis of the combined short-term values and 6-month values indicated that, in subjects with low initial HDL-C levels, treatment with alpha-tocopherol or placebo did not produce significantly different HDL-C changes.

Administration, Oral↗

Relationships between alternative complement pathway activation, C-reactive protein, and pneumococcal infection.

In the absence of specific antibody, opsonization of Streptococcus pneumoniae may be mediated by the alternative complement pathway (AP) or by C-reactive protein (CRP) via C1 binding. To determine the role of these mechanisms in pneumococcal (PNC) disease, we studied 19 patients with differing severities of PNC infection. C4 and CRP levels and zymosan-induced consumption of 50% hemolytic complement (CH50) were measured in specimens obtained acutely and then weekly. In patients with complicated illness, the modified mean CH50 in acute sera was 178 +/- 57 U/ml, significantly lower than the mean CH50 of 331 +/- 80 U/ml in patients with uncomplicated illness (P less than 0.05). The values of the two groups on a given day approximated each other on days 7, 14, and 23. Consumption of complement by zymosan was also lower in acute sera of patients with complicated illness, with a mean value of 19 +/- 18 U/ml compared with 58 +/- 30 U/ml in those with uncomplicated illness (P less than 0.05). This difference was also seen on day 7 (P less than 0.05). Disease involving lower-numbered PNC serotypes (less than 10) correlated with reduced availability of AP factors in acute sera, independent of illness severity. Mean CRP levels were inversely related to zymosan-induced complement activation in patients with complicated illness. These data suggest that in vivo depletion of AP factors is significantly greater in patients with complicated illness and is associated with high CRP levels. CRP may enhance AP activation via C3 convertase generation and function with it as a preantibody host defense mechanism.

Adult↗

Effect of head-out water immersion on response to exercise training.

During spaceflight and head-out water immersion (WI) there is a cephalad shift in blood volume. We have recently shown that left ventricular end-diastolic dimension is significantly greater during moderate cycling exercise with WI compared with on land. The purpose of this study was to determine whether the cephalad shift in blood volume and accompanying increase in cardiac preload with WI alters the normal cardiovascular adaptations to aerobic exercise training. Nine middle-aged healthy men trained on cycle ergometers in water, nine trained on land, and four served as controls for 12 wk. Following training, both training groups showed similar increase (P less than 0.05) in stroke volume and similar decreases in heart rate (P less than 0.01) and blood pressure (P less than 0.05) at a given submaximal exercise O2 consumption (VO2). Maximal VO2 increased (P less than 0.01) similarly for both training groups. The control group did not demonstrate any significant changes in submaximal or maximal exercise responses. We conclude that the cephalad shift in blood volume with WI does not alter the normal cardiovascular adaptation to aerobic exercise training.

Adult↗

Erythrocyte aldehyde dehydrogenase: assay of a potential biochemical marker of alcohol abuse.

Erythrocyte aldehyde dehydrogenase (ALDH; EC 1.2.1.3) may be a new biochemical indicator of alcohol abuse. An improved assay for it is described and characterized. We found that expression of erythrocyte ALDH activity in terms of hemoglobin was valid, and preferable to expression in terms of erythrocyte volume. A normal reference interval was determined from results for 375 healthy subjects (236 men, 139 women). We compared these data with results for 109 men admitted to our alcohol detoxification program. The mean erythrocyte ALDH of the alcohol abusers was 30% lower than our mean value for men (p less than 0.001). Values did not change between the time the patient presented for admission and greater than 48 h later (when blood-ethanol concentration was zero). Other variables that affect erythrocyte ALDH activities--changes in pH, temperature, other assay conditions, and drug treatments such as disulfiram and nitrate anti-anginals--are discussed.

Alcoholism↗

Nitrogen metabolism and lipid peroxidation during hyperthermic perfusion of human livers with cancer.

Isolation-perfusion was used as a means of heating human livers with cancer. Perfusion was at 42-42.5 degrees C for 4 h. Perfusate constituents were analyzed in an attempt to identify factors contributing to the hepatotoxic effects of hyperthermia. During perfusion the perfusate constituents analyzed were: urea; total amino acids; uric acid; malonaldehyde; and lysosomal enzymes. Hepatic ammonia for urea synthesis is derived from degradation of amino acids, amines, and nucleic acids. An increase in proteolysis was reflected in the increase in urea from 0.6 +/- 0.2 mM to 1.9 +/- 8 mM and total amino acids from 1.0 +/- 0.6 mM to 4.4 +/- 1.7 mM during the 4 h of perfusion at 42-42.5 degrees C. An increase in purine catabolism occurred as evidenced by an increase in perfusate uric acid from 1.7 +/- 1.0 mg/100 ml to 6.1 +/- 2.7 mg/100 ml. Free oxygen radicals, which can lead to lipid peroxidation, are generated by the action of xanthine oxidase on xanthine. Lipid peroxidation occurring during perfusion was assessed by an increase in malonaldehyde from 2.3 +/- 1.3 microM to 10.4 +/- 10.0 microM. An increase in acid phosphatase in the perfusate from 38 +/- 15 units/liter to 78 +/- 45 units/liter occurred, suggesting labilization of lysosomes, perhaps through lipid peroxidation. Proteolysis and lipid peroxidation are suggested to be two interrelated factors contributing to heat toxicity in the perfused human liver with cancer.

Amino Acids↗

Concomitant therapy with labetalol and hydrochlorothiazide in moderate to moderately severe essential hypertension.

Labetalol is a competitive, nonselective antagonist of both beta 1 and beta 2 adrenoceptors. It has been suggested that labetalol reduces blood pressure (BP) predominantly by decreasing peripheral vascular resistance while maintaining cardiac output. We conducted a double-blind, randomized study to assess the antihypertensive effect of labetalol in patients with a standing diastolic blood pressure (SDBP) between 105 and 119 mm Hg. The study consisted of three separate phases in succession. Phase I was a single-blind, placebo washout phase, two to four weeks in length. Those patients with a SDBP greater than or equal to 105 mm Hg at the end of phase I entered phase II, in which they were administered labetalol in a forced titration of 100 mg bid to 400 mg bid. Those with a SDBP less than or equal to 90 mm Hg on the 400 mg bid regimen for two weeks were maintained on labetalol alone (N = 8). Those patients whose BP was not controlled (SDBP greater than or equal to 99 mm Hg, N = 15) were randomized in a double-blind fashion to receive either hydrochlorothiazide (HCTZ) or placebo in addition to labetalol for the next five weeks. Eight of the 15 patients received HCTZ and seven received placebo. The BPs at baseline and at the end of phase II were similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

The safety of static-dynamic effort soon after myocardial infarction.

Many activities of daily living require static-dynamic effort. To evaluate the safety of such effort 3 weeks after myocardial infarction, 27 male patients underwent a weight-carrying test requiring 5 minutes of treadmill ambulation with graded weight loads of 10 to 30 pounds. The hemodynamic responses with weight carrying were compared to that of a predischarge graded dynamic exercise test. The peak heart rate was significantly lower (p less than 0.01) with weight carrying, the peak systolic blood pressure did not differ, and the diastolic pressure was significantly higher (P less than 0.01). ST segment depression and angina pectoris occurred less frequently with weight carrying. The type and frequency of ventricular arrhythmias were similar between the two tests. We conclude that many men are capable of performing static-dynamic activity equivalent to carrying up to 30 pounds by 3 weeks after myocardial infarction.

Adult↗

Diagnostic precision of echocardiography in mitral valve prolapse.

In order to determine the precision with which currently used echocardiographic criteria can be applied for the diagnosis of mitral valve prolapse, three independent observers (A, B, and C) blindly analyzed the separate M-mode and two-dimensional echocardiograms of 50 patients, 27 of whom had previously been identified clinically as having echocardiographic evidence of prolapse. Observer A's intraobserver repeatability for M-mode echocardiography was 92%, Observer B's was 84%, and Observer C's was 90%. For two-dimensional echocardiography, Observer A's intraobserver repeatability was 98%, Observer B's was 80%, and Observer C's was 82%. We believe that the variability in intraobserver repeatability is related to the frequency with which individual observers diagnosed prolapse. The interobserver repeatability for M-mode echocardiography for Observer A versus B was 64%, for Observer A versus C it was 80%, and for Observer B versus C it was 66%. The interobserver repeatability for two-dimensional echocardiography for Observer A versus B was 54%, for Observer A versus C it was 70%, and for Observer B versus C it was 52%. There was no significant difference between the inter- and intraobserver variability of M-mode versus two-dimensional echocardiography. Review of cases in which readings were discrepant revealed that these cases usually had relatively mild changes. Clinicians should be aware of the inherent variability of echocardiographic interpretation when they make a diagnosis of mitral valve prolapse.

Echocardiography↗

In vivo pretreatment with human chorionic gonadotropin fails to reverse the dysfunction of isolated Leydig cells from chronically uremic rats.

In order to further investigate the previously reported hypogonadal state of chronically uremic rats, we examined the effects of in vivo pretreatment with human chorionic gonadotropin (hCG) on in vivo and in vitro Leydig cell function, comparing paired intact rats with rats made chronically uremic by 5/6 nephrectomy. The in vitro testosterone (T) secretory responses to varying concentrations of hCG or dibutyryl cAMP and the number of gonadotropin receptors were determined following hemicastration. The rats were then treated with hCG for 3 days and the remaining testes were removed and studied as before. Compared with intact rats, the uremic rats had higher serum concentrations of urea nitrogen (P less than 0.001); serum T concentrations were lower in uremic rats before (P less than 0.001), but not after (P greater than 0.6) treatment. Treatment produced increases in serum T only in uremic rats (P less than 0.001). Serum LH was lower in uremic rats before treatment (P less than 0.001) and was reduced (P less than 0.001) to similar levels (P greater than 0.8) in both groups after treatment. Baseline in vitro T secretion was lower (P less than 0.001) from Leydig cells of uremic than intact rats both before and after treatment. Analysis of variance of dose-response curves showed pre- and post-treatment T secretory responses to hCG or dibutyryl cAMP in vitro to be less from Leydig cells of uremic rats (P less than 0.01). Before treatment, Leydig cell gonadotropin receptor number was lower in uremic than intact rats (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of seasonal temperature change on blood pressure in a treated hypertensive population.

To determine the effect of seasonal temperature variation on blood pressure and weight, we conducted a chart review of 39 male patients observed at the Milwaukee VA Medical Center Hypertension Clinic for a 6-year period between 1976 and 1983. Information on blood pressure and body weight was extracted from the charts for the four seasons of spring, summer, fall, and winter. No significant differences were noted in the blood pressure or body weight of our patients during the four seasons using a paired t-test.

Adult↗

Prazosin versus propranolol plus prazosin: a comparison in diuretic-treated hypertensive patients.

The antihypertensive efficacy of prazosin was compared with that of a combination of prazosin and propranolol in 14 patients with essential hypertension. All patients had sitting diastolic blood pressures greater than or equal to 95 mm Hg despite daily therapy with 50 mg of hydrochlorothiazide and 240 mg of propranolol. After a 4-week monitoring period, patients were divided randomly into 2 groups in whom either (1) propranolol was reduced to 120 mg/day (to avoid potential hypotension) and prazosin was added, starting with an initial dose of 1 mg twice daily, or (2) propranolol was tapered and discontinued as prazosin was added. The average doses of prazosin were 7.4 and 7.6 mg/day, respectively. After 12 weeks of therapy, blood pressure was reduced in both groups, and there was no significant difference in the reduction of blood pressure or dose of prazosin in the 2 groups. Mean heart rate increased significantly in both groups (p less than 0.01), but more so in the group of patients who discontinued propranolol therapy. Thus, when a combination of 50 mg/day of hydrochlorothiazide and 240 mg/day of propranolol is insufficient to control hypertension, the addition of prazosin is shown to decrease blood pressure whether or not propranolol is continued.

Aged↗

Allergic bronchopulmonary aspergillosis in cystic fibrosis.

One hundred patients with CF were screened for ABPA. Forty-eight male patients and 52 female patients with age range of 2 to 34 yr (mean 14.2) were studied. Patients were evaluated for skin reactivity and serum precipitating antibodies to Af, predominant sputum organisms, total blood eosinophil levels, total serum IgE, and Af-specific IgE and IgG, as well as abnormalities of pulmonary function and chest x-ray films. Careful evaluation of all patients with CF demonstrated that 10% had features indicative of ABPA, which is another potentially destructive pulmonary disorder. Thus careful evaluation of patients with CF, especially those with asthma, may be rewarding in uncovering a disorder that may slow progression of CF when it is appropriately treated.

Adolescent↗