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Biomedical subjects

J Keiser

Publications and source records attributed to J Keiser.

35 records · Page 2Linked to original sources

Novel angiotensin receptor subtypes in fowl.

We reported previously that blood vessels of domestic fowl contain angiotensin (ANG) receptors on 1) endothelium, mediating vasorelaxation via endothelium-derived relaxing factor and guanosine 3',5'-cyclic monophosphate; 2) vascular smooth muscles, mediating neither relaxation nor contraction; and 3) presumably adrenergic nerve endings, transmitting vasopressor action via a release of norepinephrine. We aimed in the present study to determine fowl vascular ANG receptor subtypes and relate them to function. [Val5]ANG II (native fowl ANG II) increased mean arterial pressure of anesthetized, ganglion-blocker-treated fowl. The dose-pressor response curve for fowl ANG II was not altered by pretreatment (i.v.) with the ANG receptor subtype 1 (AT1) antagonist Dup-753 (losartan, 10 mg/kg) or the subtype 2 (AT2) antagonist PD-123319 (10 mg/kg). Furthermore, cumulative doses (1-20 mg/kg) of losartan or PD-123319 did not selectively inhibit ANG II-induced pressor responses. In reserpine- and prazosin-treated anesthetized fowl, [Val5]ANG II caused dose-dependent vasodepressor actions inhibited by neither losartan (10 mg/kg) nor PD-123319 (10 mg/kg). Likewise, [Val5]ANG II-induced vasorelaxation of fowl aortic rings in vitro was not inhibitable by PD-123319 or losartan (10(-5) M). Specific binding of 125I-labeled ANG II to the aortic endothelium was markedly displaced by ANG II, but not selectively by PD-123319 or losartan. Specific binding of 125I-ANG II ligand to the membrane fraction of aortic smooth muscles was displaced (50% inhibitory concentration) by [Val5]ANG II (3.3 x 10(-8) M) and slightly by PD-123319 (3.7 x 10(-5) M), but not by losartan or EXP-3174, an active metabolite of losartan.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Effects of renin-angiotensin system in mediating endothelin-induced renal vasoconstriction: therapeutic implications.

PURPOSE: Experiments were designed to determine whether angiotensin converting enzyme inhibition with quinaprilat can prevent endothelin-mediated decreases in renal blood flow and the glomerular filtration rate in the anesthetized dog. METHODS: To mimic the activation of the renal endothelin system that occurs in a number of cardiorenal disease states, endothelin was administered intrarenally in a group of mongrel dogs. Quinaprilat, the major active metabolite of quinapril, was infused in a separate group. One kidney (group 1) or both kidneys (group 2) were exposed in order to measure renal blood flow by an electromagnetic flow probe. Mean arterial blood pressure was measured through a catheter in a femoral vein. Blood samples were taken to determine plasma renin activity. Urine was collected. RESULTS: The infusion of endothelin decreased renal blood flow and the glomerular filtration rate and increased renal vascular resistance. These renal vascular responses were associated with increased plasma renin activity, indicating activation of the renal renin-angiotensin system. Quinaprilat attenuated the renal vascular responses. CONCLUSIONS: These studies provide further evidence of the importance of the renal renin-angiotensin system in mediating the renal vasoconstrictor actions of endothelin and indicate the therapeutic potential for quinapril in opposing the actions of endothelin in states of excessive endothelin activation.

Angiotensin-Converting Enzyme Inhibitors↗

Sequential culturing method improves recovery of Legionella spp. from contaminated environmental samples.

Investigations were undertaken to improve detection and isolation of Legionella spp. from samples containing a large number of non-legionellae isolates. The direct fluorescent antibody staining technique was used in conjunction with a sequential culturing method which was developed to improve the recovery rate of Legionella spp. from such samples. The technique for enrichment and isolation of Legionella spp. from environmental samples includes storage at 4 degrees C and repeated culture on freshly prepared media. Heat and acid treatments were included when deemed appropriate. A DNA probe was used for confirmation of Legionella. Treatment of the water samples, as described, and co-cultivation with amoebae naturally present in the samples are concluded to be responsible for increased success in recovery of Legionella isolates.

Air Conditioning↗

An Analysis of the Predictability of Hypoxemia Following Vertical Banded Gastroplasty.

Postoperative (post-op) hypoxemia is unpredictable, often undetected by physical examination, sometimes fatal. We studied 45 morbidly obese patients with an average age of 37, including 16 smokers, having vertical banded gastroplasty (VBG) for useful preoperative (preop) predictor(s) of post-op hypoxemia during the first five days following VBG. Patient blood gases (arterial blood oxygen, P&infa;O&inf2; in mmHg), pre-op and five post-op days (POD), after 30 min in room air were: pre-op, 85 +/- 9; POD1, 63 +/- 9*; POD2, 61 +/- 9*; POD3, 63 +/- 10*; POD4, 63 +/- 9* POD5, 64 +/- 1 * (* p < 0.05, Student's t-test compared with pre-op). Linear regression showed no practical, predictive value for P.02 for age, Body Mass Index (BMI), pulmonary function tests (PFTs), smokers or preop P&infa;O&inf2;. Post-op atelectasis occurred in 84% of patients, mostly the posterior basilar regions on chest X-ray. No patient developed clinically diagnostic pneumonia. VBG patients experienced profound hypoxemia post-op, the lowest on POD2. There is no reliable method to predict which patient may develop severe hypoxemia. It is, therefore, extremely helpful to uniformly monitor P&infa;O&inf2; post-op in morbidly obese patients.

Journal Article↗

Subclasses of cyclic GMP-specific phosphodiesterase and their role in regulating the effects of atrial natriuretic factor.

Two subclasses of cyclic guanosine monophosphate (GMP)-specific phosphodiesterases were identified in vascular tissue from several beds. The activity of one subclass (phosphodiesterase IB) was stimulated severalfold by calmodulin and selectively inhibited by the phosphodiesterase inhibitor TCV-3B. The activity of the other subclass (phosphodiesterase IC) was not stimulated by calmodulin and was selectively inhibited by the phosphodiesterase inhibitor M&B 22,948. To assess the involvement of both subclasses in regulating cyclic GMP-dependent responses, the ability of TCV-3B and M&B 22,948 to potentiate the in vitro and in vivo responses to the endogenous guanylate cyclase stimulator atrial natriuretic factor (ANF) was evaluated. Both TCV-3B and M&B 22,948 relaxed isolated rabbit aortic and pulmonary artery rings and also potentiated the relaxant effect of ANF. In addition, both inhibitors produced small increases in urine flow and sodium excretion in anesthetized rats and potentiated the diuretic and natriuretic responses to exogenous ANF. M&B 22,948 (30 micrograms/kg/min) produced a threefold increase in the natriuretic response to simultaneously administered ANF, and TCV-3B (10 micrograms/kg/min) produced a twofold increase in the response to ANF. The results of the present experiments suggest that both the calmodulin-sensitive and calmodulin-insensitive subclasses of cyclic GMP-specific phosphodiesterase play a role in regulating the in vitro and in vivo response to ANF.

3',5'-Cyclic-GMP Phosphodiesterases↗

Comparison of in situ hybridization and monoclonal antibodies for early detection of cytomegalovirus in cell culture.

The abilities of each of four diagnostic tests--direct fluorescent monoclonal antibody (direct FA) staining, indirect fluorescent monoclonal antibody (indirect FA) staining, in situ hybridization with biotinylated DNA probes, and in situ hybridization with DNA probes directly linked to enzymatically active horseradish peroxidase-to detect cytomegalovirus soon after culture were compared. Only the indirect FA test and the in situ hybridization method with directly linked HRP-DNA probes provided consistent and reliable cytomegalovirus detection as early as 15 h postinfection.

Antibodies, Monoclonal↗

Increased vasodilator responsiveness to BRL 34915 in spontaneously hypertensive versus normotensive rats: contrast with nifedipine.

The blood pressure-lowering potency and activity of BRL 34915, a new vasodilator and putative stimulator of potassium efflux from vascular smooth muscle, was investigated in conscious spontaneously hypertensive rats (SHR) and normotensive rats (NTR) after intravenous administration and compared with that of the calcium channel blocker, nifedipine. In SHR, BRL 34915 (3-100 micrograms/kg) or nifedipine (10-3000 micrograms/kg) produced similar reductions in mean arterial pressure of 58 +/- 3% and 55 +/- 3%, respectively. BRL 34915 (ED30% = 13.8 micrograms/kg) was 15.3 times more potent than nifedipine (ED30% = 207 micrograms/kg) in SHR. In contrast, only a 1.7-fold difference in potency was observed in NTR between BRL 34915 (ED30% = 123 micrograms/kg) and nifedipine (ED30% = 182 micrograms/kg). The potency ratio (ED30% NTR/ED30% SHR) for BRL 34915 was 8.83 whereas nifedipine had a ratio of 0.88, reflecting the greater responsiveness of the SHR to BRL 34915. Systemic hemodynamics were monitored in anesthetized SHR and NTR to determine the basis for the reductions in blood pressure. BRL 34915 (3-100 micrograms/kg iv) lowered mean arterial pressure in both groups solely by decreasing total peripheral vascular resistance, since no changes in cardiac output were observed. Relaxation responses were also obtained in phenylephrine-contracted isolated aortic strips from both strains of rat to ascertain whether differences in responsiveness existed at this level of the vasculature. No significant difference in the potency of BRL 34915 (3-10 microM) as a vasodilator was found in aortas from SHR or NTR. These results indicate that, unlike nifedipine, BRL 34915 is a more potent vasodepressor agent in SHR than in NTR and suggests that the potassium efflux stimulator may preferentially relax resistance vessels in the hypertensive rat.

Animals↗

Comparative leukocyte esterase-nitrite and BAC-T-SCREEN studies using single and multiple urine volumes.

The Chemstrip LN and BAC-T-SCREEN filtration systems were used to evaluate 980 urine specimens rapidly for the presence of microorganisms. Multiple volumes of individual specimens were also tested using the BAC-T-SCREEN to determine whether this procedure enhanced test performance. Ninety-nine specimens (10%) could not be processed because of interfering substances or clogging of the BAC-T-SCREEN. Analysis of the remaining 881 samples showed these test results for the Chemstrip LN system: sensitivity, 48%; specificity, 93%; positive predictive value (PPU), 88%; and negative predictive value (NPV), 71%. The BAC-T-SCREEN results using multiple urine volumes were (for 1 mL) sensitivity, 88%; specificity, 98%; PPV, 97%; NPV, 92%; for 2 mL, sensitivity, 94%; specificity, 96%; PPV, 94%; NPV, 96%; for 3 mL, sensitivity, 98%; specificity, 95%; PPV, 93%; NPV, 98%. Analyzing multiple urine volumes permitted detection of 92% of urine samples with colony-forming units of 10(4) or less. The BAC-T-SCREEN system proved superior to Chemstrip LN for detecting microorganisms in urine specimens, and analyzing multiple urine volumes enhanced test sensitivity.

Bacteriuria↗

Antimicrobial therapy of Broviac catheter infections in pediatric hematology oncology patients.

Long-term therapy of pediatric oncology patients has been facilitated by permanent indwelling venous catheters. Over a 3-year period, 54 Broviac catheters were placed in 43 oncology patients and two hemophiliacs. There were 20 episodes of sepsis in 14 patients and the most common bacteria were S epidermidis (4), S aureus (4), and K pneumoniae (3). Catheter exit site infections occurred ten times in six patients; S aureus eight of ten. Antibiotic therapy without catheter removal was successful in 18 of 20 children with catheter sepsis and 8 of 10 patients with exit site infections. These data strongly suggest that although catheter-related infections are common, removal of Broviac catheters is not required for successful treatment of the infection.

Anti-Bacterial Agents↗

Colonization of newly arrived house staff by virulent staphylococcal phage types endemic to a hospital environment.

The acquisition of hospital strains of Staphylococcus aureus by new house officers was studied in an 800-bed referral hospital over a 1-year period. S. aureus isolates, including three strains with characteristic phage patterns that had previously been documented to cause disease in patients and colonize hospital personnel, were recovered from the anterior nares of 35 of 54 newly arrived house officers. There was a significant correlation (r = 0.7475; P less than 0.02) between colonization with the dominant hospital strain (S) and exposure to the hospital environment over 12 months. No hospital-wide increase in infections owing to the S strain was seen during this period, which suggests that house staff acquired this strain from reservoirs within the hospital. The finding of colonization with virulent endemic S. aureus strains in house officers working on every ward of the hospital suggests that new strategies for control of S. aureus nosocomial infections must be considered and evaluated.

Bacteriophage Typing↗

Comparison of the Phadebact Gonococcus Test with the rapid fermentation method.

The Phadebact Gonococcus Test (Pharmacia Diagnostics, Piscataway, N.J.), a coagglutination technique, was compared with the rapid fermentation method of Kellogg and Turner (D. S. Kellogg, Jr., and E. M. Turner, Appl. Microbiol. 25: 550--552, 1973). A total of 93 organisms isolated on Martin-Lewis media were determined to be Neisseria gonorrhoeae based on the following criteria: presence of gram-negative diplococci, oxidase positivity, and appropriate reaction in the rapid fermentation method. These 93 isolates were then serologically tested with the Phadebact test. The direct method was attempted on the first 46 N. gonorrhoeae isolates. Difficulty in interpreting results was encountered in 39%. Thereafter, the alternate method of boiling was instituted on an additional 47 N. gonorrhoeae isolates, with 2 isolates producing noninterpretable results. All 93 isolates were frozen for a maximum of 2 months in skim milk at -25 degrees C. These isolates were thawed and retyped with the alternate boiling procedure, with 97% being confirmed as N. gonorrhoeae. In addition, 33 Neisseria meningitidis isolates, 14 Neisseria species, and 7 Moraxella species were tested with similar techniques. No positive reactions were observed. A cost effectiveness study using 5, 10, and 20 microliters of the gonococcal reagent was undertaken to reduce the cost of the test. When 10 and 20 microliters of reagent were used, no difficulty was encountered in interpreting the reaction. The coagglutination technique was difficult to read when 5 microliters of reagent was used.

Agglutination Tests↗

Multiple short-term effects of lead on the renin-angiotensin system.

We previously demonstrated that lead (3 mg/kg iv) sharply raises PRA in dogs. In the present study, the short-term effects of the same dose of lead on renin secretion, hepatic removal of renin, and arterial AII levels were measured in anesthetized dogs. Despite large increases in PRA in all nine lead-treated dogs, renin secretion increased in only three out of nine lead-treated animals (those with the lowest baseline renin secretion). Hepatic extraction of renin was eliminated by lead, and so total hepatic removal of renin became zero by 2 or 3 hr after lead administration. Finally, despite large increases in PRA, AII levels did not rise after lead. The linear relationship of AII to PRA seen in animals not treated with lead was changed, so that after lead, AII levels were disproportionately low for the corresponding level of PRA. It is concluded that lead may increase renin secretion in animals otherwise unstimulated to secrete but that the major mechanism for the short-term rise in PRA after lead is elimination of hepatic removal of renin; further, lead prevents AII from rising proportionately with PRA, presumably by inhibiting angiotensin-converting enzyme.

Angiotensin II↗

Cortical bone density of adult lacto-ovo-vegetarian and omnivorous women.

Lacto-ovo-vegetarian women fifty to eighty-nine years of age lost 18 per cent bone mineral mass while omnivorous women lost 35 per cent. This study established that this difference could not be explained by a greater bone density in the lacto-ovo-vegetarians during the third, fourth, and fifth decades of life. The possibility of higher sulfur content in the meat-containing diet, the effect of excess phosphorus, and the effect of an acid-ash diet are discussed. From the standpoint of a general survey, comsumption of calcium-containing foods was not appreciably different in the two groups. It is, therefore, concluded that lacto-ovo-vegetarian diet may be beneficial in extended protective health care in terms of defense against, or control of, bone mineral loss in the later years of a woman's life.

Adult↗

Selection of materials for ventricular assist pump development and fabrication.

A study was undertaken to select 2 of the most promising bladder materials from a list of 8 carefully chosen polymers. The polymers chosen for testing included a wide spectrum of urethanes, as well as a polyester resin and a millable polyolefin rubber. The following materials were studied: Adiprene LW-500, Avcothane 51, Biomer, Hexsyn, Hytrel 4055, Mobay 240313, Pellethane 2103-80 AE, and Tecoflex HR. The selection process was based on a test matrix which was divided into segmented steps, each a logical sequel from its predecessor, and each of increasing technical complexity. Hydrolytic stability, flexure endurance, fabricability, tissue compatibility, hemocompatibility and chronic tissue compatibility were evaluated, forming the basis for the acceptance/rejection criteria. As a result of this search, 2 biomaterials were identified as most suitable for use in conventionally flocked bladders; Biomer and Tecoflex HR. Both Biomer and Tecoflex HR bladders have demonstrated impressive results in circulatory analog loop endurance tests, with Tecoflex bladders surpassing 50 million flexes to date, and Biomer bladders (the longest running bladders) exceeding 150 million flexes. Tests are continuing.

Alkenes↗

Urbanization and tropical health--then and now.

Since the launch of the Annals of Tropical Medicine and Parasitology 100 years ago, the percentage of the world's population living in urban settings has more than tripled and is now approaching 50%. Urbanization will continue at a high pace, particularly in the less developed regions of Africa and Asia. The profound demographic, ecological and socio-economic transformations that accompany the process of urbanization have important impacts on health and well-being. In industrialized countries, urbanization led to the so-called 'epidemiological transition', from acute infectious and deficiency diseases to chronic non-communicable diseases, many decades ago. In the developing world, surprisingly little research has been carried out on the health-related aspects of urbanization. In a temporal analysis of publications in the Annals of Tropical Medicine and Parasitology, for example, in which the first volume in every decade from 1907 was examined, only 16 (2.6%) of the 604 articles investigated focused on epidemiological and/or public-health issues in urban tropical settings. This review begins with the question 'what is urban?' and then provides a summary of the trends seen in urbanization, and its impacts on human health, over the past century, on both a global and regional scale. For the main tropical diseases, estimates of the at-risk populations and the numbers of cases are updated and then split into urban and non-urban categories. The inhabitants of urban slums are particularly vulnerable to many of these diseases and require special attention if internationally-set targets for development are to be met. Heterogeneity, a major feature of urban settings in the tropics that complicates all efforts at health improvement, is demonstrated in an exploration of a densely populated municipality of a large West African town. Urban planners, public-health experts and other relevant stakeholders clearly need to make much more progress in alleviating poverty and enhancing the health and well-being of urban residents, in an equity-effective and sustainable manner.

Bibliometrics↗