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Biomedical subjects

J Allen

Publications and source records attributed to J Allen.

At least 325 records · Page 18Linked to original sources

Long-term studies of pancreas allotransplantation in experimental diabetes mellitus.

Pancreaticoduodenal (PD) allografts (Brown Norway-alloxan-diabetic rats, n = 190) were treated with cyclosporin A (Cy-A) 10 mg/kg/daily and compared with nondiabetics with Cy-A treatment (n = 55), diabetics (n = 50), and diabetics with Cy-A treatment (n = 45). Body weight, blood sugar, blood insulin, blood urea nitrogen (BUN), and creatinine were monitored periodically; there were marked elevations of BUN and creatinine levels, indicating probably nephrotoxicity of Cy-A at this dosage. Some islet cell atrophy in the PD allografts was noted at the conclusion of the study. With respect to the immunosuppressive effect of Cy-A in alloxan diabetic rats, Brown Norway PD transplants into Lewis rats were successful and free of rejection for as long as 15 months post-transplantation. The body weight of these PD transplanted rats, however, never approached values representative of the nondiabetic rats. In our experience, the PD allograft model is acceptable in the clinical situation, particularly in children if the microsurgical technique is mastered and if the Cy-A regimen is used in combination with other immunosuppressant(s).

Animals↗

Behavioral vs beta-blocker therapy in patients with primary hypertension: effects on blood pressure, left ventricular function and mass, and the pressor surge of social stress anger.

We compared the relative effects of relaxation therapy, conventional hygienic techniques, and a beta-receptor blocker, atenolol, on control of arterial pressure, left ventricular mass, and diastolic function in patients with mild primary hypertension. Furthermore, we related these effects to baseline neural tone and its changes and assessed the efficacy of relaxation or the pressor surge of "social stress" anger. In group I left ventricular mass index was related to both systolic and diastolic blood pressure (r = 0.46; p less than 0.05). Plasma norepinephrine was related to age (r = 0.33; p less than 0.01). Slope was inversely related to both plasma norepinephrine (r = -0.29; p less than 0.05) and age (r = -0.31; p less than 0.05). Relaxation therapy reduced both supine systolic and diastolic blood pressures, 4.5% and 7.6%, respectively, but did not affect plasma norepinephrine. Hygienic informational therapy reduced plasma norepinephrine by 18%, (p less than 0.05) and did not change blood pressure. Blood pressure responders to nondrug therapy (i.e., diastolic blood pressure reduction of 7% or more) had a 7% reduction of left ventricular mass index (p less than 0.02). On the other hand, atenolol reduced systolic and diastolic blood pressure by 10% and 15%, respectively, (p less than 0.01) and improved left ventricular function by 17% (p less than 0.05) without a significant change in left ventricular mass index. Finally, relaxation therapy but not hygienic therapy reduced systolic blood pressures 4% and 6%, respectively (p less than 0.01), both before and during social stress anger.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of some neurotransmitters and prostanoids on isolated human intracervical arteries.

Human cervical tissue specimens were excised after hysterectomy at various phases of the menstrual cycle (n = 12), and small intracervical arteries were dissected free by microtechnique. Ring preparations of the vessels were prepared and mounted in organ baths, and isometric circular tension was recorded. Norepinephrine, 3 X 10(-8) to 10(-5) mol/L, produced concentration-dependent contractions, whereas 3 X 10(-7) to 10(-6) mol/L prostaglandin F2 alpha inconsistently produced weak contractions and slightly increased tension induced by 10(-5) mol/L norepinephrine. Prostaglandin I2, 10(-9) to 10(-6) mol/L, prostaglandin E2, 3 X 10(-9) to 10(-6) mol/L, vasoactive intestinal polypeptide, 10(-9) to 10(-7) mol/L, and substance P, 10(-12) to 10(-9) mol/L, induced relaxation of vessels precontracted by 10(-5) mol/L norepinephrine. It is suggested that several mechanisms for the local release of vasoactive compounds may influence cervical blood flow. Thus, sympathetic control of cervical blood flow may be modulated by peptide neurotransmitters such as vasoactive intestinal polypeptide and substance P and by local synthesis of prostaglandins E2 and I2.

Arteries↗

Studies in human lactation: milk volumes in lactating women during the onset of lactation and full lactation.

After validation of test-weighing procedures milk volumes produced by 13 multiparous Caucasian women were followed longitudinally through the first year of lactation. All practiced exclusive breast-feeding for at least 5 mo. Milk transfer to the infant was low on days 1 and 2 and increased rapidly to 498 +/- 129 g/d (means +/- SD) on day 5 and then more slowly to 753 +/- 89 g/d during months 3-5. There was a characteristic milk volume for each mother-infant pair that was significantly related neither to milk yield on days 4-6 nor to birth weight. It was, however, strongly related to infant weight at 1 mo, suggesting that infant and/or maternal factors coming into play during the first month of life are strong determinants of subsequent milk transfer to the infant.

Adult↗

Clinical features of acetaminophen toxicity.

Thirteen patients met our criteria for severe acetaminophen hepatotoxicity over a 5-year study period. Six patients had therapeutic misadventures (not attempting suicide), and seven were attempting suicide. Five of six patients in the therapeutic misadventure group were chronic alcoholics, and three were taking other drugs reported to cause hepatic microsomal enzyme induction. In the suicide group, two of seven patients were alcoholics, and one patient was taking another inducing drug. All six patients in the therapeutic misadventure group had nausea, vomiting, or starvation, whereas two of seven patients in the suicide group had similar characteristics. Starvation could deplete the protective factor glutathione, thus augmenting hepatotoxicity. In the therapeutic misadventure group, four of six patients developed acute tubular necrosis, as compared to two of seven in the suicide group. One patient died in each group. Clinicians should be aware of these features as part of the spectrum of acetaminophen toxicity.

Acetaminophen↗

A new test for screening color vision: concurrent validity and utility.

Recognizing the need for an effective test for screening color vision in young children, we have developed a new pseudoisochromatic (PIC) plate test which is useful for a wide variety of observers at different ages. The test consists of four plates and responses can be used to categorize color vision as normal or as either red-green or blue-yellow defective. Results of this validation study with adults, both color normal and red-green defective, show a high degree of correlation between the new test and the Nagel anomaloscope: there were no false positives and only a few false negatives, which occurred with mild deuteranomalous observers. The validity of the test compares favorably to the Ishihara, F-2, and the AO-HRR screening plates. Results with toddlers (3 to 6 years) indicate that the task demands of the test are well suited for testing young children. The percentage of color defectives identified in the toddler sample using the new test is closer to the adult prevalence than results obtained with the F-2 and AO-HRR screening plates, which gave dramatically higher failure rates. The new test is culture-free and can be administered rapidly to both verbal and nonverbal observers using pointing or preferential looking.

Adult↗

Effects of human calcitonin gene-related peptide and substance P on human intracervical arteries.

The contractile effects of substance P and human calcitonin gene-related peptide (human CGRP) on isolated human intracervical arteries were studied. Human cervical tissue specimens were excised after hysterectomy at various phases of the menstrual cycle (n = 14) and small intracervical arteries were dissected free by microtechnique. Ring preparations of the vessels were prepared and mounted in organ baths, and isometric circular tension was recorded. Neither compound affected resting tension. Both peptides showed potent relaxing effects on vessels precontracted by noradrenaline 10(-5) M. Substance P exhibited the higher potency, while human CGRP showed the higher efficacy. The relaxing effects of the two compounds were unaffected by pretreatment with indomethacin 10(-6) M, propranolol 10(-6) M and atropine 10(-6) M. The results support a role for the two peptides in the regulation of cervical blood flow.

Arteries↗

Labetalol blunts morning pressor surge in systolic hypertension.

Twenty-four-hour ambulatory blood pressure, including the acceleration phase, and left ventricular mass were evaluated in 16 patients with isolated systolic hypertension (standing blood pressure greater than or equal to 160 mm Hg systolic and less than or equal to 95 mm Hg diastolic). After a 4-week, single-blind, placebo period, each patient underwent 24-hour ambulatory blood pressure monitoring and echocardiography. Labetalol therapy was then initiated at 100 mg twice a day in a single-blind manner and increased weekly by 100 mg twice a day until blood pressure control was obtained or a maximum dosage of 400 mg twice a day was reached. Blood pressure control was achieved at a mean daily dose of 363 +/- 46 mg of labetalol. Measurements were repeated at the end of an 8-week maintenance phase. Labetalol therapy significantly reduced the mean 24-hour systolic ambulatory blood pressure from 154 +/- 8 (mean +/- SEM) mm Hg at baseline to 142 +/- 6 mm Hg (p greater than 0.01) and controlled the early morning surge in systolic ambulatory blood pressure. Minor reductions in diastolic blood pressure and heart rate were statistically but not clinically significant. Left ventricular mass was not changed. Labetalol monotherapy provides effective 24-hour control of systolic blood pressure, including the acceleration phase, in patients with isolated systolic hypertension.

Blood Pressure↗

Effects of VIP and PHM in human intracervical arteries.

The relaxing effects of vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) on human intracervical arteries were studied. Cervical tissue specimens were excised after hysterectomy at various phases of the menstrual cycle (n = 12) and small intracervical arteries were dissected free by microtechnique. Ring preparations of the vessels were prepared and mounted in organ baths, and isometric circular tension was recorded. None of the compounds showed any effects in unstimulated cervical arterial preparations. In vessels precontracted by noradrenalin 10(-5) M, VIP 10(-8) - 10(-6) M and PHM 10(-8) - 10(-6) M induced similar, concentration-dependent relaxation with a maximum effect of 73.2 +/- 12.7% relaxation for VIP 10(-6) M and 79.6 +/- 11.8% for PHM 10(-6) M, as compared to 10.7 +/- 3.1% decrease in tension for control preparations treated with solvent (mean +/- SE, n = 6). Simultaneous addition of VIP 5 x 10(-7) M and PHM 5 x 10(-7) M produced additive effects. Pretreatment with indometacin 10(-6) M, atropine 10(-6) M or propranolol 10(-6) M did not significantly influence these responses. Both peptides might be involved in regulation of blood flow in the human cervix.

Cervix Uteri↗

Primary hypertension: left ventricular mass and function, sympathetic nervous system activity, and therapy.

Left ventricular (LV) mass is a predictor of morbidity in patients with hypertension. To elucidate the mechanisms of left ventricular hypertrophy (LVH) in primary hypertension, we examined the relationships of LV mass, arterial blood pressure, and plasma norepinephrine--as a marker of sympathetic nervous system tone--in three populations of patients with mild or moderate hypertension. We found linking of neural tone with (a) arterial blood pressure in mild and moderate hypertension, (b) LV mass in moderate hypertension, and (c) diastolic function in mild hypertension, suggesting that neural tone is a factor in both the pathogenesis and the sequelae of hypertension. Additionally, elevated norepinephrine level may reflect subtle loss of diastolic function before hypertrophy is manifest. Both nondrug and drug therapy may regress LV mass after blood pressure reduction with disparate effects on neural tone.

Adult↗

Efficacy of a new calcium antagonist PN 200-110 (isradipine) in angina pectoris.

Angina pectoris is one of the major syndromes against which to test the therapeutic effectiveness of any new calcium antagonist. An interim analysis of the efficacy and safety of a new dihydropyridine calcium antagonist (PN 200-110 [isradipine]) in patients with confirmed coronary artery disease is reported. The study was carried out in 3 centers; 50 patients of an anticipated 96 have completed the double-blind comparative phases in 3 separate studies. Preliminary results from the placebo-controlled study indicate that PN 200-110 was significantly more effective than placebo in reducing the anginal attack rate and glyceryl trinitrate consumption in the 15 patients so far enrolled. Dose-response comparisons against nifedipine in 21 patients and against isosorbide dinitrate in 14 patients demonstrate that PN 200-110 has a similar antianginal efficacy profile to both drugs. No significant change in any of the monitored safety factors was noted in any of the patients taking PN 200-110. The side-effects profile compared favorably with that of nifedipine. These interim results suggest that PN 200-110 will prove to be an effective and safe drug for the treatment of angina pectoris.

Angina Pectoris↗

Controlled trial of respiratory health worker visiting patients with chronic respiratory disability.

Seventy five patients with chronic respiratory disability were randomised to a group visited by a respiratory health worker (42) or control group (33). The first group was visited monthly by a respiratory nurse, who gave education and support. The effect of the intervention was assessed in terms of quality of life (by questionnaires), the number and duration of admissions to hospital, and the number of deaths. The questionnaires on quality of life showed no changes in either group during the study, but nearly all of the group visited by a respiratory health worker said that they valued the visits and wished them to continue. Their knowledge about their condition also improved compared with that of the controls. The duration of stay in hospital for respiratory reasons in the group visited by a respiratory health worker was longer than that of control patients. This was explained by their being scored as more ill than the controls on admission. Fewer patients died in the group visited by a respiratory health worker than in the control group (p = 0.11). The patients in the group visited by respiratory health workers may have survived longer because they sought help rather than dying at home. If confirmed this could have implications for the cost of their care.

Aged↗

DMSO potentiates aminonucleoside of puromycin nephrosis in rats.

Dimethyl sulphoxide (DMSO), 3 g/kg body weight, administered daily by the intraperitoneal route, potentiated the proteinuria and formation of tubular casts in aminonucleoside of puromycin (PA) induced nephrosis in Sprague-Dawley rats. The effect was evident at 4 as well as 8-9 days following PA administration. In the absence of PA, DMSO did not induce proteinuria or cast formation. The mechanism by which DMSO enhanced proteinuria and cast formation is not known.

Animals↗

Guide for the Salmonella typhimurium/mammalian microsome tests for bacterial mutagenicity.

Since its development by Dr. Bruce Ames and his coworkers, the Salmonella typhimurium/mammalian microsome mutagenicity assay has been used widely throughout the world. Many authors have suggested various modifications and made recommendations in regards to this assay. Although the recommendations of a panel of experts was published in 1979 by de Serres and Shelby, a committee of members of the Environmental Mutagen Society (EMS) initiated this effort in response to the encouragement by the American Society of Testing and Materials (Committee E47.09.01) and because of new developments within the field of microbial mutagenesis testing. Its purpose is to provide a guide for people who perform or evaluate microbial mutagenesis tests, but it is not intended for these recommendations to replace or diminish the usefulness of presently available protocols and procedures.

Animals↗

Molecular structure of mammalian neuropeptide Y: analysis by molecular cloning and computer-aided comparison with crystal structure of avian homologue.

Identification and characterization of the cDNA encoding rat neuropeptide Y revealed the nucleotide sequence coding for a 98-amino acid precursor. The deduced amino acid sequence for rat neuropeptide Y is identical to the human peptide and is highly homologous to avian pancreatic polypeptide. The tertiary structure of avian pancreatic polypeptide has been previously derived from crystallographic data by Blundell and coworkers. The homology between neuropeptide Y and avian pancreatic polypeptide preserves all of the residues essential for the maintenance of the tertiary structure. Thus, it has been possible to compute a three-dimensional model of the mammalian neuropeptide, neuropeptide Y, based on the known structure of the avian homologue. This model suggest that neuropeptide preserves a compact tertiary structure characterized by extensive hydrophobic interactions between an N-terminal polyproline-II-like helix and a C-terminal alpha-helix. The model has been used to identify amino acids residing in key positions within this structure and, thereby, to direct future analysis of neuropeptide Y structure-function relationships.

Amino Acid Sequence↗

Effects of thiopentone or chlormethiazole on human placental stem villous arteries.

Small placental stem villous arteries were micro dissected from specimens obtained at normal term vaginal delivery (n = 25). Ring preparations of the vessels were mounted in organ baths and isometric tension was measured. Prostaglandin F2 alpha (PGF2 alpha) 10(-7)-10(-4) mol litre-1 produced concentration-dependent contractile responses that were inhibited by thiopentone 10(-4)-10(-3) mol litre-1 and by chlormethiazole 3 x 10(-4)-3 x 10(-3) mol litre-1. Thiopentone 10(-4)-10(-3) mol litre-1 and chlormethiazole 3 x 10(-4)-3 x 10(-3) mol litre-1 decreased the tension in vessels previously treated with PGF2 alpha 10(-5) mol litre-1. Chlormethiazole 3 x 10(-3) mol litre-1 inhibited, and thiopentone 10(-4)-10(-3) mol litre-1 abolished contractile responses to 5-hydroxytryptamine. Contractions induced by angiotensin II were inhibited by thiopentone 10(-3) mol litre-1 and chlormethiazole 3 x 10(-3) mol litre-1. The concentrations of the two drugs needed to affect contractile activation of isolated human stem villous arteries exceeded the free plasma concentrations reached during anaesthesia induced by the agents during Caesarean section, and the present results do not suggest any major effects of thiopentone or chlormethiazole on fetal placental vascular resistance during the clinical use of these drugs.

Angiotensin II↗