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Biomedical subjects

J H Kalbfleisch

Publications and source records attributed to J H Kalbfleisch.

At least 19 recordsLinked to original sources

Comparison of the pathogenicity of three species of coagulase-negative Staphylococcus in a mouse model with and without a foreign body.

Staphylococcus schleiferi, Staphylococcus lugdunensis, and Staphylococcus epidermidis produce a high incidence of abscesses in a mouse model with an implanted foreign body. We investigated the significance of the foreign body in this process. Fourteen strains of S. schleiferi, S. epidermidis, and S. lugdunensis were tested in our model. A preadhered foreign body was implanted into one mouse group, followed by injection of a test strain. Another group received injection without implant. Abscesses were assessed at 7 days; foreign bodies and infected tissues were cultured. The percent of samples that developed abscesses or were culture positive was compared for each strain. Nearly all mice infected with S. schleiferi developed abscesses and were culture positive. The foreign body made no difference in abscess formation for three of four S. schleiferi but increased the incidence of both organism recovery and abscess for three of five S. epidermidis. The foreign body enhanced abscess formation for four of five S. lugdunensis, with all five strains yielding significantly more culture recovery. Although the pathogenicity of nine strains was increased by the foreign body, five strains yielded high abscess and culture recovery rates that were not enhanced by its presence.

Abscess

Lipid peroxidation caused by hyperthermic perfusion of rat liver.

The data presented support the premise that hyperthermia-induced hepatocellular injury is the end result of lipid peroxidation. Evidence for lipid peroxidation is the formation of diene conjugates and the decrease in microsomal P450 and glucose-6-phosphatase activity during hyperthermic liver perfusion.

Animals

Randomized comparative study of cefixime versus cephalexin in acute bacterial exacerbations of chronic bronchitis.

Patients with purulent exacerbation of chronic bronchitis were randomized to receive either a single 400-mg daily dose of cefixime or 250 mg of cephalexin, orally, four times a day. Patients were males with a mean age of 63 years. Of the 86 patients, 71 (82%) had bronchitis caused by a single organism (29 by Haemophilus influenzae, 27 by Branhamella catarrhalis, 9 by gram-negative enteric organisms, 6 by Streptococcus pneumoniae), while more than one pathogen was implicated in 15 patients (18%). A total of 70.8% of the cefixime group and 50% of the cephalexin group were clinically cured (chi 2 = 3.89, P less than 0.05); however, when the categories of cured and improved were combined, no significant difference was noted between treatment groups (chi 2 = 3.39, P = 0.06). Analysis of side effects included all 130 evaluable and nonevaluable patients: diarrhea was noted in six patients in the cefixime group and none of the patients in the cephalexin group (P = 0.013 by the Fisher exact test). The diarrhea was mild and self-limited in all cases. B. catarrhalis has emerged as a major cause of exacerbation of bronchitis in our experience; there is an increased need to emphasize the examination of sputum samples by Gram staining if cost-effective antibiotic choices are to be made; any empirically chosen antibiotic should have activity against beta-lactamase-producing strains of B. catarrhalis as well as S. pneumoniae and H. influenzae.

Acute Disease

Pathogenicity of Staphylococcus lugdunensis, Staphylococcus schleiferi, and three other coagulase-negative staphylococci in a mouse model and possible virulence factors.

Staphylococcus lugdunesis and Staphylococcus schleiferi, two newly described species, have been isolated from numerous types of human infections. We compared the pathogenicity of 30 strains of S. lugdunensis, S. schleiferi, Staphylococcus epidermidis, Staphylococcus warneri, and Staphylococcus hominis, using a mouse model in which a foreign body preadhered with the test strain was implanted subcutaneously, followed by injection of the test strain. All five species of staphylococci produced abscesses. Staphylococcus epidermidis, S. schleiferi, and S. lugdunensis yielded species means of 76-91% abscess formation; 80-100% of the infected foreign bodies and tissues were culture positive. These three species were more virulent than S. warneri or S. hominis, which produced abscesses in 54 and 65% of mice, respectively; only 10-48% of the infected samples were culture positive. Transmission electron microscopy of pure cultures of selected strains showed that all species possessed glycocalyx. All species produced a variety of possible virulence factors, such as alpha and delta hemolysins, as well as the aggressins lipase and esterase. The production of exoenzymes did not always correlate with virulence as demonstrated by abscess formation in mice.

Abscess

Structural and functional characteristics of muscle from diabetic rodent small intestine.

After 30 days of streptozotocin-induced diabetes, the small intestine from untreated diabetic, insulin-treated diabetic, and nondiabetic rodents was excised in toto and measured. Despite a net loss in body weight, the diabetic animals showed a near twofold increase in small intestinal weight. This was characterized by a 148% increase in mucosal mass as well as a 39% increase in intestinal smooth muscle mass (P less than 0.05, respectively). The diabetic intestine was significantly longer and had a greater diameter and surface area. Diabetes significantly increased mucosal mass per unit surface area but produced an insignificant decrease in smooth muscle mass per unit surface area. Insulin treatment of the diabetic animals prevented the increase in total mucosal mass and mucosal mass per unit surface area. Insulin treatment also prevented the increase in smooth muscle mass, but reduced smooth muscle mass per unit surface area to a level significantly less than that found in nondiabetic intestine. In vitro dose-response studies of circular and longitudinal small intestinal muscle from the diabetic animals showed normal tension development and sensitivity to both bethanechol chloride and physostigmine. These observations show that the diabetic state produces alterations in not only mucosal but also smooth muscle mass in the small intestine. However, despite these morphological changes, diabetic intestinal smooth muscle retains its sensitivity to cholinergic stimulation and its capacity for tension generation.

Animals

Effect of increased central blood volume with water immersion on plasma catecholamines during exercise.

To examine the influence of an increase in central blood volume with head-out water immersion (WI) on the sympathoadrenal response to graded dynamic exercise, nine healthy men underwent upright leg cycle exercise on land and with WI. Plasma norepinephrine and epinephrine concentrations were used as indexes of overall sympathoadrenal activity. Oxygen consumption (VO2), heart rate, systolic blood pressure, and plasma concentrations of norepinephrine, epinephrine, and lactate were determined at work loads corresponding to approximately 40, 60, 80, and 100% peak VO2. Peak VO2 did not differ on land and with WI. Plasma norepinephrine concentration was reduced (P less than 0.05) at 80 and 100% peak VO2 with WI and on land, respectively. Plasma epinephrine and lactate concentrations were similar on land and with WI at the three submaximal work stages, but both were reduced (P less than 0.05) at peak exertion with WI. Heart rate was lower (P less than 0.05) at the three highest work intensities with WI. These results suggest that the central shift in blood volume with WI reduces the sympathoadrenal response to high-intensity dynamic exercise.

Adrenal Glands

Effects of hyperthermia on xanthine oxidase activity and glutathione levels in the perfused rat liver.

The hepatotoxic effects of hyperthermic liver perfusion were investigated in male Fischer 344 rat livers. Perfusions were carried out at 37, 41, 42, 42.5, and 43 degrees C for 2 hr. During the 2 hr, the perfusate was analyzed for activity of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), N-acetyl-beta-glucosaminidase (NAG), and glutathione (GSH), oxidized glutathione (GSSG), allantoin, and potassium. After perfusion, each liver was homogenized and analyzed for total xanthine oxidase (XO) activity, percentage type-D and type-O XO, and total GSH content. Perfusate AST, LDH, NAG, and potassium levels were increased significantly with time and were significantly different in all hyperthermic perfusions from the 37 degrees C perfusion values by the end of the perfusion. Perfusate GSH + GSSG levels were increased significantly in all hyperthermic perfusions after 60 min. Liver GSH levels were significantly lowered following perfusion at hyperthermic temperatures. There was a temperature-dependent increase in the percentage of XO in the type-O form following perfusion at hyperthermic temperatures, which was strongly and positively correlated with the loss of hepatic GSH. These data support the hypothesis that hyperthermic toxicity to the liver is the result of oxidative stress brought about by conversion of XO to the type-O form.

Acetylglucosamine

Hyperthermic liver toxicity: a role for oxidative stress.

Rat livers were perfused at 37 degrees C, 41 degrees C, 42 degrees C, 42.5 degrees C, and 43 degrees C for 2 hr. Among perfusate constituents analyzed were urea, total amino acids, N-acetyl-beta-glucosaminidase (NAG), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malonaldehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), allantoin, potassium, phosphate, and glucose. After perfusion, livers were homogenized and analyzed for xanthine oxidase (XO) activity, GSH content, and lysosomal lability. Perfusate AST, LDH, NAG, potassium, glucose, and phosphate increased significantly with time, and there were significant differences in the final values between 37 degrees C and 42 degrees C, 42.5 degrees C and 43 degrees C (P less than .05). GSH levels increased significantly at all temperatures after 90 and 120 min, whereas GSSG levels differed significantly at 60, 90, and 120 min for 37 degrees C vs. 42 degrees C, 42.5 degrees C, and 43 degrees C (P less than .05). Mean MDA levels at 37 degrees C differed from those at 41 degrees C and 43 degrees C (P less than .05) at each temperature. Allantoin levels increased significantly with time of perfusion; mean levels at 37 degrees C were significantly different from mean levels at each temperature at 60, 90, and 120 min. GSH liver tissue levels decreased with perfusion at hyperthermic temperatures; mean values at 41 degrees C, 42 degrees C, and 42.5 degrees C, and 43 degrees C differed from 37 degrees C mean values (P less than .01). Type O XO increased after 120 min perfusion from 6.4% +/- 2.0% at 37 degrees C to 55% +/- 30%, 43% +/- 27%, and 63% +/- 29% at 42 degrees C, 42.5 degrees C, and 43 degrees C, respectively. Lysosomal lability increased after perfusion at 42.5 degrees C. There was a significant increase in nonsedimentable NAG activity at 42.5 degrees C (P less than .05). These data support the premise that hyperthermic toxicity to the liver may be a consequence of oxidative stress brought about by enhanced adenosine triphosphate (ATP) consumption and conversion of XO to type O. Such conversion results in superoxide formation and subsequent depletion of cellular GSH, labilization of the lysosomes, and plasma membrane damage.

Allantoin

Evidence for muscarinic inhibitory neurotransmission in rodent small intestine.

The influence of cholinergic and noncholinergic inhibitory nerves was examined in circular and longitudinal muscle from the duodenum. Rodent proximal small intestine was cut into strips measuring 6.0 x 10.0 mm. Strips cut along the oral-caudal axis were called longitudinal strips, whereas those cut 90 degrees to that axis were called circular strips. The strips were stretched to their optimal lengths and subjected to electrical field stimulation in the presence of various concentrations of atropine, pirenzepine or McN-A-343-11. All three drugs inhibited field-stimulated contraction responses and produced or augmented relaxation responses in both muscle layers. All relaxation responses were abolished by tetrodotoxin, indicating they were due to excitation of inhibitory nerves. For each response examined atropine was significantly more potent than pirenzepine (relative potency ratio, 13.36-95.74). The inhibitory effect of McN-A-343-11 on longitudinal muscle was antagonized by both atropine and pirenzepine, indicating the recruitment of cholinergic inhibitory nerves. Neither atropine nor pirenzepine had any effects on inhibitory responses produced by McN-A-343-11 in circular muscle, indicating the recruitment of noncholinergic inhibitory nerves. McN-A-343-11 also increased spontaneous contraction amplitudes in both muscle layers by a direct (tetrodotoxin-resistant) effect on smooth muscle. This effect was also antagonized by atropine and pirenzepine. Thus, both cholinergic and noncholinergic nerves participate in inhibitory neuromuscular transmission in the small intestine. Circular muscle is dominated by a noncholinergic inhibitory innervation. Longitudinal muscle appears to be controlled by both cholinergic and noncholinergic inhibitory nerves.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy

Comparison of ST segment depression in upright treadmill and supine bicycle exercise testing.

Significant differences in the hemodynamic response to upright and supine exercise have been reported in patients with coronary artery disease. The purpose of the present study was to compare the degree of myocardial ischemia as assessed by ST segment depression during upright treadmill and supine bicycle exercise in 98 patients with coronary artery disease and in 34 patients with normal coronary arteries. The amount of ST segment depression at maximal exercise in patients with coronary artery disease was 0.90 +/- 0.80 mm for treadmill and 1.34 +/- 1.09 mm for supine bicycle (p less than 0.001). The amount of ST segment depression during treadmill and supine bicycle exercise tests was also compared at highest similar heart rates (0.68 +/- 0.77 versus 1.17 +/- 1.01, p less than 0.001), at highest similar rate-pressure products (0.71 +/- 0.77 versus 1.08 +/- 1.04, p less than 0.001), at highest similar metabolic equivalents of oxygen consumption (MET) levels (0.69 +/- 0.75 versus 1.20 +/- 1.05 mm, p less than 0.001) and at the onset of angina (0.84 +/- 0.73 versus 1.18 +/- 0.88 mm, p less than 0.001). The rate-pressure product achieved at maximal exercise was similar in both tests (18.74 +/- 5.80 x 10(3) versus 18.81 +/- 5.17 x 10(3), p = NS). The occurrence of angina during treadmill and supine bicycle exercise tests was similar (47 of 98 versus 48 of 98, respectively, p = NS). For the detection of coronary artery disease, the sensitivity was 50.0% for treadmill and 63.3% for supine bicycle (p less than 0.05) and the specificity was 73.5 versus 70.6%, respectively (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Volatile anesthetics attenuate sympathomimetic actions on the guinea pig SA node.

The authors examined and compared the direct effects of three volatile anesthetic agents and three sympathomimetic agonists on transmembrane action potential (AP) characteristics and automaticity of sinoatrial (SA) nodal pacemaker cells. SA nodal tissue was isolated from guinea pig hearts and suffused in vitro with oxygenated Krebs-Ringer solution. Electrophysiologic variables measured were: amplitude of the AP, slopes of phase 4 and of phase 0 of the AP, AP duration, and spontaneous sinus rate. The authors found that 1 and 2 MAC equivalents of each anesthetic, 0.8 and 1.6 vol % halothane, 1.4 and 2.8 vol % isoflurane, and 1.7 and 3.4 vol % enflurane similarly depressed the slopes of phase 4 and 0 of the AP, prolonged AP duration, and slowed the sinus rate at 1 and 2 MAC equivalents. Isoproterenol, 0.25 microM, and epinephrine, 50 microM, maximally enhanced the slopes of phase 4 and 0 of the AP, shortened AP duration, and increased the sinus rate, but phenylephrine, 50 microM, only moderately increased the slope of phase 4 and the sinus rate. Each of the three anesthetics caused baseline depressions of phase 4 and phase 0 slopes and of automaticity of SA nodal cells; the fall in sinus rate was counteracted, but was not reversed maximally by increasing the concentrations of isoproterenol, epinephrine, or phenylephrine. Regression analyses of linearly transformed data showed that each of the anesthetics similarly depressed basal sinus rate, so that changes in rate produced with isoproterenol and epinephrine were not different from those observed with beta agonists in the absence of anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials

Distribution of excitatory junction potential amplitude in cat cerebral arteries: examination of its quantal nature and modulation by opiates.

We used scorpion venom to release small amounts of an excitatory neurotransmitter from adventitial nerves in cat left anterior descending cerebral artery. We used glass microelectrodes to measure and record postsynaptic electrical events of minimal amplitude. These events were similar to postsynaptic spontaneous and electrically evoked excitatory junction potentials (ejp's) seen in skeletal muscle. We performed a frequency analysis of the ejp amplitudes to determine if they fit a unimodal or multimodal distribution. We also investigated the effects of phentolamine, norepinephrine, hydromorphone, and morphine on ejp amplitude and frequency in the artery. Statistical analysis of the ejp frequency and amplitude revealed a multipeaked distribution with decreasing peaks. These results were similar to the distribution reported for acetylcholine release in skeletal muscle. The ejps were inhibited by phentolamine, which suggested that these events were adrenergically mediated. Norepinephrine and the opiates, hydromorphone and morphine, reduced the frequency and amplitude of the ejp's. The vessels also constricted to increasing doses of norepinephrine both under control conditions and in the presence of opiate. These results suggest that norepinephrine blocks the ejp's by a feedback mechanism at the presynaptic membrane and that endorphins and/or enkephalins, also acting at this presynaptic site, may modulate neurotransmission in the cerebral circulation.

Animals

Circulating IgG antibodies against fungal and actinomycete antigens in the sera of farmer's lung patients from different countries.

Sixty-nine farmer's lung patients and 28 normal controls from four countries (Finland, Switzerland, Canada and the United States) were investigated for antibody levels against 13 antigens commonly used for the screening panel for hypersensitivity pneumonitis. Of these antigens, eight were from the Medical College of Wisconsin (United States) and five were from the University of Kuopio (Finland). IgG antibodies against these antigens were studied in 97 sera using a sensitive biotin-avidin-linked enzyme immunoassay. The results indicate that the mean antibody titer against Micropolyspora faeni was highest in the United States (U.S.) followed by Finland. Both Finnish and U.S. antigens reacted almost identically against various groups of patients, although the degree of reactivity varied considerably. Higher antibody levels against Thermoactinomyces vulgaris were detected in Finnish patients than patients from other countries while patients from all four countries showed elevated levels of antibodies against T. candidus. This study demonstrates that antigens from identical species, irrespective of geographic origin, reacted similarly. However, variability between antigens of the same species was still considerably significant. Since the microbiological flora of moldy hay varies widely in different regions, the microbial species associated with the disease at a given geographical area has to be determined before selecting antigens for serological studies. The antigens currently used in various laboratories are crude preparations and need to be purified and standardized for dependable results. Until such antigens are available, all antigenic preparations used in the immunological evaluation of patients should be immunochemically characterized for their reproducibility and reliability although the ultimate goal should be to obtain standardized pure antigens for dependable immunodiagnosis of farmer's lung.

Antibodies, Bacterial

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