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Biomedical subjects

A Patel

Publications and source records attributed to A Patel.

At least 451 records · Page 25Linked to original sources

The effect of theophylline and enprofylline on the late cutaneous response to antigen and compound 48/80.

Theophylline and enprofylline have been demonstrated to reduce mast cell-mediator release, inhibit polymorphonuclear leukocyte activation, and have been reported to reduce the late bronchial response to antigen. The effects of theophylline and enprofylline on the late cutaneous response (LCR) to compound 48/80 and antigen were studied in 29 patients enrolled in a placebo-controlled, double-blind study of the effect of the xanthines in mild asthma. Skin testing to a common environment allergen and compound 48/80 was performed during a baseline period and in the second phase of the study after stable drug levels were achieved, at least 6 weeks later. During baseline, the mean immediate wheal diameter (IWD) with antigen was 15.7 mm +/- 0.5, resulting in 27/29 LCRs with a mean wheal diameter of 37.1 mm +/- 5.2. The mean IWD with compound 48/80 was 16.1 mm +/- 0.7, resulting in 26/29 LCRs with a mean wheal diameter of 19.6 mm +/- 2.8. Repeat skin testing during treatment revealed no statistically significant changes in the LCR elicited by antigen or 48/80 in any of the treatment groups. There was little correlation between the size of the immediate wheal produced by antigen or 48/80 and the resulting size of the late response (r = 0.174 to 0.519). However, for the same IWD, the resulting late response was smaller with 48/80 than with antigen (p = 0.003). We conclude that (1) theophylline and enprofylline have no effect on the LCR to 48/80 and antigen and (2) for equivalent immediate wheal sizes, the resulting late response is smaller with 48/80 than with antigen.

Adult↗

Urinary enzyme output during detoxification of chronic alcoholic patients.

The urinary excretion of N-acetylglucosaminidase, gamma-glutamyl transferase and lactate dehydrogenase was elevated by two to three fold in chronic alcoholic patients when compared to normal controls. After 4 weeks of alcohol abstention, the urinary excretion of these enzymes returned to control values. Increased urinary enzyme excretion was not related to malnutrition or pathological glomerular filtration and is due most probably to a direct effect of alcohol on the renal proximal tubule.

Acetylglucosaminidase↗

Hypoxic pulmonary vasoconstrictor response with asymmetric oleic acid injury in the dog.

The hypoxic pulmonary vasoconstrictive (HPV) response is characterized by two components: intrapulmonary blood flow redistribution and pulmonary artery pressure (PAP) augmentation. Whether both remain intact after oleic acid lung injury has not been assessed. In an asymmetric model of right lung oleic acid edema, we examined the relative magnitude of each component on the HPV response to right lung inspired hypoxia. Before oleic acid administration, right lung hypoxia decreased perfusion to the right lung from 1.41 +/- 0.12 to 1.16 +/- 0.15 L/min (p = .07), while PAP increased from 15.8 +/- 0.8 to 18.1 +/- 0.6 mm Hg (p less than .05). Regional hypoxia caused right lung pulmonary vascular resistance (PVR) to increase from 480 +/- 45 to 797 +/- 114 dyne.sec/cm5 (p less than .01). After right lung injury with oleic acid, regional hypoxia decreased perfusion to the right lung from 0.91 +/- 0.11 to 0.71 +/- 0.10 L/min (p less than .05), while PAP increased from 18.8 +/- 0.8 to 21.5 +/- 1.0 mm Hg (p less than .05). With hypoxia, right lung PVR increased from 1232 +/- 260 to 1933 +/- 336 dyne.sec/cm5 (p less than .01). We conclude that the pulmonary vasoconstrictive response to inspired hypoxia persists after oleic acid lung injury, causing significant increases in PVR. Consequently, both the blood flow redistribution and the PAP augmentation components of the HPV response to inspired hypoxia remain unchanged.

Animals↗

Most women with acne have polycystic ovaries.

Out of 98 female referrals with acne vulgaris it was possible to define ovarian morphology by high resolution ultrasound imaging of the pelvis in 82 (84%). Sixty-eight (83%) were shown to have polycystic ovaries, compared with 19% in a control group without acne. The presence of polycystic ovaries in the acne patients did not correlate with acne severity, infertility, menstrual disturbance, hirsutes, or biochemical endocrinological abnormalities.

Acne Vulgaris↗

Involvement of substance P in noncholinergic excitation of rabbit colonic muscle.

Neurokinins have been implicated as noncholinergic excitatory neurotransmitters in the mammalian gastrointestinal tract. To characterize the myogenic and neurogenic response of colonic muscle to neurokinins we studied the mechanical response of muscle strips from proximal and distal colon and the release of [3H]acetylcholine in response to substance P (SP), neurokinin A (NKA) and neurokinin B (NKB). All neurokinins caused a dose-dependent inotropic response. SP was 80 times more potent in distal compared with proximal longitudinal muscle. The rank order of potencies in proximal longitudinal muscle was NKA greater than SP = NKB and in distal muscle NKA = SP = NKB. Desensitization to SP or pretreatment with a SP antagonist inhibited the mechanical response to SP and the atropine-resistant inotropic off response to electrical stimulation. Only longitudinal muscle from distal colon had an atropine- and hexamethonium-sensitive inotropic component to SP. In contrast, all three peptides were equipotent in releasing [3H]acetylcholine from longitudinal muscle strips preincubated with [3H]choline. These results suggest the following: 1) SP is a potent agonist of rabbit colon with a proximal distal gradient in biological potency; 2) the myogenic response of the distal colon appears to be mediated through a NK-1 receptor; and 3) SP is a major mediator of the noncholinergic component of the off response in distal longitudinal muscle.

Acetylcholine↗

Downregulation and desensitization of A1-adenosine receptors in embryonic chicken heart.

Downregulation of cardiac A1-adenosine receptors and desensitization of the negative inotropic response to adenosine were examined 44 h after pretreatment of 15-day-old chick embryos with phenylisopropyladenosine (R-PIA) or vehicle. The number of A1-adenosine receptors, assessed by 125I-aminobenzyladenosine (125I-ABA) binding to crude cardiac membranes, was decreased by 63% (P less than 0.001) after pretreatment of embryos with 1 mumol of R-PIA, from 16.7 +/- 2.4 to 6.2 +/- 1.4 (SD) fmol/mg protein (n = 6). The KD of 125I-ABA binding to the remaining receptors did not differ significantly from control (0.71 +/- 0.45 vs. 0.79 +/- 0.57 nM). A maximally effective concentration of R-PIA (10(-5) M) decreased the developed tension of electrically paced right ventricular (RV) muscle strips from control embryos by 76 +/- 6% (mean +/- SD, n = 7) from its forskolin-stimulated plateau level, whereas the developed tension of strips from R-PIA-pretreated embryos was decreased significantly less, by 38 +/- 4% (P less than 0.001). The potency of R-PIA and the efficacy and potency of carbachol to decrease contractile tension were not changed. The data suggest that chronic exposure of the heart to R-PIA can produce downregulation of A1-adenosine receptors and homologous desensitization of the negative inotropic response to adenosine.

Adenosine↗

Novel inhibitors of enkephalin-degrading enzymes. II: N5'-substituted-4-thioxohydantoic acids as aminopeptidase inhibitors.

Some 2-substituted-(2'-aminophenyl)-4-thioxohydantoic acids (o-amino PTC-amino acids) have antinociceptive activity when administered (icv) alone (IC50 = 0.04-0.87 microM/animal) and show a striking prolongation of the antinociceptive action of (D-Ala-2 D-Leu5)-enkephalin (DADL) in combination. The effects are thought to be mediated via opioid receptors since they are naloxone-reversible. Although inhibitors of the enkephalin degrading puromycin-insensitive, bestatin-sensitive aminopeptidase (possibly aminopeptidase M) their action is weak (IC50 = 32 microM leucine, 536 microM, glycine) and they might be considered to have a direct antinociceptive effect on opioid receptors. The titled compounds constitute novel 'lead' compounds for the development of potent aminopeptidase M inhibitors.

Aminopeptidases↗

Dilated cardiomyopathy associated with chylous ascites.

Chylous ascites is a well-documented sequelae of traumatic rupture of the thoracic duct and mechanical obstruction of the lymphatic system due to neoplastic, inflammatory, or congenital anomalies. Less commonly, chylous ascites results from altered hemodynamics and lymphatic flow, as seen in cirrhosis and constrictive pericarditis. Rarely, severe right-sided heart failure from a variety of causes has also resulted in chylous ascites or a protein-losing enteropathy. We report a case of chylous ascites due to dilated cardiomyopathy with autopsy findings. The pathophysiology of chylous ascites formation in right heart failure will be discussed, with a review of the literature.

Aged↗

Long-term correction of genetic defect of liver function in rat by transplantation of liver cells after ultraviolet irradiation.

Allograft rejection limits the survival and function of transplanted hepatocytes obtained from allogeneic donors. Presentation of donor antigens by antigen-presenting cells that express class II major histocompatibility antigens (MHC) carried in the graft has been implicated in allograft rejection. Ultraviolet-B (u.v.-B, 280 to 320 nm) irradiation and short-term culture have been shown to modify the function of antigen-presenting cells. In this study, we used u.v.-B irradiation (600 J/m2) of donor hepatocytes isolated from normal inbred Wistar RHA rats, followed by 16 to 20 hours of culture prior to transplantation into histoincompatible genetically analbuminemic rats (Nagase analbuminemic rats, NAR) by intraportal infusion of 10(7) viable hepatocytes. Isolated Wistar RHA hepatocytes without u.v.-B irradiation and/or culture, or NAR rat hepatocytes, were used as control. Survival and function of the transplanted hepatocytes were monitored by serial immunoassay of serum albumin in the recipients. Serum albumin concentration did not increase after transplantation of NAR rat hepatocytes. In NAR rats that received Wistar RHA hepatocytes, serum albumin levels increased from pre-transplantation levels of 0.025 to 0.05 mg/ml to 8 to 10 mg/ml. When freshly isolated liver cells were transplanted with or without u.v.-B-irradiation, but without culturing, serum albumin levels reached a maximum in two weeks and then progressively declined to pretransplantation levels. When the cells were not irradiated but cultured for 16 to 20 hours, elevated serum albumin levels persisted for six weeks, and then progressively declined to baseline concentrations. In contrast, when the isolated normal liver cells were u.v.-B-irradiated and cultured for 16 to 20 hours before transplantation, serum albumin levels persisted at 8 to 10 mg/ml throughout the duration of this study (32 weeks). Immunocytochemistry using anti-rat serum albumin (rabbit) immunoglobulin of liver tissue from NAR rats without transplantation or after transplantation with NAR liver cells showed immunostaining in less than one in 1000 cells. Four to 16 weeks after transplantation of u.v.-B-irradiated and cultured normal allogeneic hepatocytes, one to two per 100 hepatocytes stained positive for albumin. The results indicate that u.v.-B-irradiation followed by short-term culture of allogeneic rat hepatocytes prior to transplantation results in prolonged and perhaps permanent allograft acceptance by NAR rats.

Animals↗

Ophthalmology consultations at a large teaching hospital.

We reviewed 100 consecutive ophthalmology consultations performed on inpatients at a large teaching hospital to help identify areas that may require greater emphasis in the medical school and housestaff curriculum. Nonophthalmologists rarely record visual acuities or perform dilated fundus examinations. If visual acuity determination were more consistently made a part of routine physical examinations, it is possible that more pathology would be detected and non-productive consultations could be minimized. We plan to emphasize these observations in our school's curriculum more than in the past.

Adolescent↗

Role of metronidazole in improving response and specific drug sensitivity in advanced pulmonary tuberculosis.

One hundred and thirty-seven patients of advanced pulmonary tuberculosis were randomly allocated to receive metronidazole 400mg tid (76) or placebo (61) for 2 months in a single blind study. All received streptomycin 0.75 g,INH 30 mg and rifampicin 450 mg daily as standard antitubercle treatment. There were no significant pretreatment differences, among both groups. Compared to placebo group there was superior clinical improvement in metronidazole treated group at 4 and 8 weeks (81% vs 53%-P less than 0.05; 87% vs 72%-P less than 0.05 respectively), greater sputum reduction at 4 weeks (49% vs 9%-P less than 0.001) greater radiologic improvement at 4 weeks (60% vs 43%-P less than 0.01) and a better antituberculous drug sensitivity. Metronidazole seems to have beneficial adjuvant role in the drug treatment of tuberculosis. This may improve response in advanced cases.

Adolescent↗

A capacitance pressure sensor using a phase-locked loop.

We are using a Hercules (model #F4-4R, 100 psi) pressure sensor to measure the pressure between the foot and shoe. An interface circuit converts the capacitance change into voltage. Over the pressure range from 0 to 1300 kPa, the capacitance changes from 275 to 580 pF. A 555 timer circuit converts the capacitance into a frequency range from 30 to 63 kHz. A phase-locked loop (PLL) converts this frequency to voltage from 0 to 5 V, which is then filtered using a first-order, low-pass filter, having a corner frequency of 20 Hz to reduce the ripple to 10 mV. The sensor's hysteresis is about 8 percent at 40 degrees Celsius (C) and 12 percent at 20 degrees C. The sensor has a maximal nonlinearity of 8 percent and a worst-case nonrepeatibility of 7 percent. Its temperature coefficient is -0.147 percent per degree C. Its spatial sensitivity decreases nonlinearly from 1 to 0.17 from the center towards the periphery. The sensitivity of the system is 2.77 mV/kPa and the temperature drift is +0.53 percent per degree C. We monitor the pressure at 7 locations under each foot (the rear and the front heel, great toe, and 4 of the 5 metatarsal heads). A portable data-acquisition system permits continuous monitoring for 7 minutes. Test results for pressure distribution for normal walk and run are presented. Results are useful when studying normal and abnormal gait, and for possibly providing feedback (sensory substitution) to diabetic patients with insensate feet in order to help them dynamically adjust pressure distribution under their feet.

Biomechanical Phenomena↗

The detection of at-risk drinking in a teaching hospital.

We studied a sample of 302 inpatients from all medical and surgical wards of Westmead Hospital. Twenty-six per cent of patients (47% of men and 4% of women) were identified as past or current "at-risk" drinkers. Current drinkers preponderantly were male and were more likely to be admitted to hospital with trauma. Apart from trauma, alcohol-related disease was not diagnosed commonly, and most drinkers were admitted to hospital with diagnoses that were not related clearly to alcohol abuse. Hospital medical staff members appeared reluctant to address alcohol abuse; a low rate of alcohol problems was identified, and alcohol-related diseases appeared to be underdiagnosed.

Alcohol Drinking↗

[Prevention of deep venous thrombosis in arthroplastic surgery of the hip by the combination of heparinotherapy and the antithrombosis stocking].

Two hundred and eighty-six patients were divided into two groups according to the presence or absence of major risk factors. The so-called "at risk" patients were treated with continuous post-operative heparin therapy combined or not with anti-thrombosis stockings. The patients regarded as not at risk were divided into 3 subgroups allocated at random to different treatments based on subcutaneous heparin in effective or sub-anticoagulant doses with and without stocking. All patients underwent phlebography before and 7 days after the operation. The incidence of post-operative thrombosis was significantly lower in the 137 patients treated with heparin and stocking (10.22 per cent) than in the 131 patients treated with heparin alone (19.85 per cent).

Aged↗

Purification of 125I-labeled succinyl cyclic nucleotide tyrosine methyl esters by high-performance liquid chromatography.

Carrier free 125I-labeled succinyl cyclic adenosine monophosphate (ScAMP) and succinyl cyclic guanosine monophosphate (ScGMP) tyrosine methyl esters (TME) were purified by reversed phase high-performance liquid chromatography (HPLC) or descending paper chromatography. Using an isocratic buffer for HPLC, mono-ScAMP-125I-TME and mono-ScGMP-125I-TME were eluted from a C18 column at 8.9 and 6.9 min, respectively. Both of the mono-iodinated radioligands were completely separated from their noniodinated precursors and other iodinated products. The radioligands purified by HPLC or paper chromatography were used for the radioimmunoassay (RIA) of cAMP and cGMP. Cyclic AMP or cGMP inhibited binding of the HPLC purified radioligands at three- to fivefold lower concentrations than the paper chromatography purified radioligands. The sensitivity of the RIA decreased with time if paper chromatography purified radioligands were used, but remained stable for 4 months if the HPLC purified compounds were used, even with storage at 4 degrees C. We attribute these results to better purification of radioligands by the HPLC than by the paper chromatography. Using optimal conditions the HPLC method takes only 10 min and results in a high yield (greater than 95%) of added 125I into the monoiodinated products.

Chromatography, High Pressure Liquid↗

Difference in metabolic profile of potassium canrenoate and spironolactone in the rat: mutagenic metabolites unique to potassium canrenoate.

The metabolic fates of potassium canrenoate (PC) and spironolactone (SP) were compared for the rat in vivo and in vitro. Approximately 18% of an in vivo dose of SP was metabolized to canrenone (CAN) and related compounds in the rat. In vitro, 20-30% of SP was dethioacetylated to CAN and its metabolites by rat liver 9000 g supernatant (S9). Thus, the major route of SP metabolism is via pathways that retain the sulfur moiety in the molecule. PC was metabolized by rat hepatic S9 to 6 alpha, 7 alpha- and 6 beta, 7 beta-epoxy-CAN. The beta-epoxide was further metabolized to its 3 alpha- and 3 beta-hydroxy derivatives as well as its glutathione (GSH) conjugate. Both 3 alpha- and 3 beta-hydroxy-6 beta, 7 beta-epoxy-CAN were shown to be direct acting mutagens in the mouse lymphoma assay, whereas 6 alpha, 7 alpha- and 6 beta, 7 beta-epoxy-CAN were not. These mutagenic metabolites, their precursor epoxides and their GSH conjugates were not formed from SP under identical conditions. The above findings appear to be due to inhibition of metabolism of CAN formed from SP by SP and/or its S-containing metabolites, since the in vitro metabolism of PC by rat hepatic microsomes was appreciably reduced in the presence of SP. The hypothesized mechanism(s) for this inhibition is that SP and its S-containing metabolites specifically inhibit an isozyme of hepatic cytochrome P-450 or SP is a preferred substrate over PC/CAN for the metabolizing enzymes. Absence of the CAN epoxide pathway in the metabolism of SP provides a possible explanation for the observed differences in the toxicological profiles of the two compounds.

Animals↗

Imipenem cross-reactivity with penicillin in humans.

We examined the potential for IgE-mediated cross-reactivity between the carbepenems, a new class of beta-lactam antibiotics, represented by imipenem, and penicillins. In vivo skin testing with the relevant imipenem and penicillin determinants was undertaken. Having determined the concentrations of imipenem materials that did not induce false positive skin tests in nonpenicillin-allergic control subjects, we tested 40 subjects with a history of penicillin-allergic reactions. Twenty of these subjects were found to be nonallergic to penicillin on skin testing, and none of these subjects reacted to the imipendem determinants. In contrast, half the 20 subjects who were positive to one or more penicillin determinants also reacted to imipenem reagents. There was a good correlation between the penicillin and imipenem reagents to which the patients reacted. Imipenem should only be administered to penicillin-allergic subjects with similar precautions of penicillin administration to such patients.

Cross Reactions↗