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Biomedical subjects

J R Roberts

Publications and source records attributed to J R Roberts.

At least 91 records · Page 5Linked to original sources

Benefit/risk ratio of the antihistamines (H1-receptor antagonists) terfenadine and chlorpheniramine in children.

There are few objective studies of the benefit/risk ratio of H1-receptor antagonists in children. We hypothesized that terfenadine would provide as effective peripheral H1 blockade as chlorpheniramine in young patients, but would cause less central nervous system dysfunction. We tested this hypothesis with epicutaneous histamine tests to monitor peripheral H1 blockade, P300-event-related potentials as a measure of cognitive processing, and a visual analog scale for somnolence, in a double-blind, single-dose, placebo-controlled, three-way crossover study in 15 children with allergic rhinitis (mean age, 8.5 +/- 1.4 years). On 3 different days the children received terfenadine, 60 mg, chlorpheniramine, 4 mg, or placebo; the tests were performed before and 2 to 2 1/2 hours after dosing. Both terfenadine and chlorpheniramine suppressed the histamine-induced wheal and flare compared with baseline and with placebo; terfenadine was significantly more effective (p < 0.05). Terfenadine did not increase the latency of P300-event-related potentials at the parietal (Pz) or frontal (Fz) scalp electrodes compared with baseline, in contrast to chlorpheniramine and placebo, which did increase P300 latency. Terfenadine and placebo did not increase somnolence compared with baseline, but chlorpheniramine did. In children, as previously documented in adults, terfenadine has a more favorable benefit/risk ratio than chlorpheniramine, as shown by production of significantly greater peripheral histamine blockade and significantly less central nervous system dysfunction.

Action Potentials↗

Effect of nephropathogenic infectious bronchitis viruses on renal function in young male broiler chickens.

1. The acute effects of challenge with Australian T-strain infectious bronchitis virus (IBV) on renal function were evaluated, following primary vaccination in 1-d-old male broilers. 2. Challenge with T-strain IBV decreased body weight and induced kidney hypertrophy and kidney asymmetry. 3. Haematocrit was reduced in birds challenged with the Australian T-strain IBV and plasma uric acid was elevated in unvaccinated birds exposed to the IBV challenge. 4. Challenge with T-strain IBV caused significant increases in urinary water losses, accompanied by decreased urine osmolality and increased fractional excretion of sodium, calcium and potassium. 5. Vaccination at 1-d-old with Vic S-strain IBV provided a limited degree of protection against an heterologous challenge with T-strain IBV at 15 d of age.

Analysis of Variance↗

Reappraisal of the "coma cocktail". Dextrose, flumazenil, naloxone, and thiamine.

Flumazenil is an important adjunct to the diagnosis and treatment of benzodiazepine toxicity. It must be used cautiously with attention to a number of clinical caveats. Currently it is advised that flumazenil should not be used routinely in all patients with altered mental status, but when used selectively, it is a very safe and extremely useful antidote.

Animals↗

Tetanus in a parenteral drug abuser: report of a case.

Tetanus is an infection caused by Clostridium tetani. In the United States, tetanus remains a significant problem primarily among nonimmunized or inadequately immunized individuals. This article reports a fatal case of tetanus that occurred in a 45-year-old parenteral drug abuser who presented to Harlem Hospital Center with nuchal rigidity, trismus, dysphagia, and spasms of the pectoralis musculature. Multiple cutaneous ulcerations also were observed. Despite aggressive measures that included: endotracheal intubation, administration of human tetanus, hyperimmune globulin, tetanus toxoid, and intravenous penicillin, the patient rapidly deteriorated and manifestations of heightened sympathetic nervous system activity, seizures, and cardiac arrest ensued. The diagnosis of tetanus must be based upon clinical grounds. Clinicians must remain aware of the possibility of tetanus, especially among drug abusers who also are more likely to be evaluated for complications of human immunodeficiency viral infection, which in some cases may mimic tetanus or make the diagnosis more difficult to establish.

Humans↗

Groin lymphorrhea complicating revascularization involving the femoral vessels.

Seven (4%) of 193 patients developed lymphoceles in 8 (2%) of 316 groin wounds after 211 arterial reconstructive procedures. Included were 91 aortic, 15 extra-anatomic, and 105 infrainguinal revascularizations. Lymphoceles developed in otherwise uncomplicated wounds in 6 (8%) of 73 patients with oblique incisions and bilaterally in 1 (1%) of 120 patients with vertical incisions (p = 0.01). This difference may be related to the surgical technique, with increased lymphatic damage and inadequate wound closure in the oblique approach. No increased incidence of lymphorrhea was noted in those patients undergoing aortic reconstruction regardless of the type of incision used (p = 0.15), or when compared with patients who had undergone extra-anatomic or infrainguinal bypass (p = 0.14). Each lymphocele was persistent, and external fistulas spontaneously occurred in three. Diagnosis was based upon clinical awareness and the appearance of the groin mass. Conservative management was uniformly unsuccessful, and operative ablation of the lymph fistula and lymphocele proved to be definitive therapy.

Adult↗

A clinical trial of escalating doses of flumazenil for reversal of suspected benzodiazepine overdose in the emergency department.

STUDY OBJECTIVE: To determine if flumazenil, when used in doses higher than those currently recommended, could reverse the effects of a benzodiazepine (BDZ) overdose in patients who might not otherwise respond and whether the higher dose was associated with increased adverse effects. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, balanced, with parallel groups. Open-label flumazenil administration was available if a patient failed to respond or became resedated. SETTING: Sixteen emergency departments in the United States. POPULATION: Patients presenting to the ED with clinically significant signs and symptoms of a known or suspected BDZ overdose. INTERVENTIONS: Patients were randomized to receive 10 mL/min of placebo or flumazenil (1 mg/10 mL) each minute for ten minutes. If there was no response, up to 3 mg of open-label flumazenil could be administered. MEASUREMENTS AND MAIN RESULTS: Of 170 patients enrolled, 87 received flumazenil and 83 received placebo. The demographic characteristics of both groups were comparable. Ten minutes after the beginning of study drug infusion, patients were evaluated using the Clinical Global Impression Scale (CGIS), Glasgow Coma Scale (GSC), and Neurobehavioral Assessment Scale (NAS). The mean +/- SD CGIS score at ten minutes for BDZ-positive patients was 1.41 +/- 0.72 for patients who received flumazenil and 3.41 +/- 0.91 for the placebo group (P < .01). There was no difference in the mean CGIS score between the flumazenil (3.25 +/- 1.15) and placebo (3.75 +/- 0.69) groups in BDZ-negative patients. The GCS and NAS were also significantly better in patients who were BDZ-positive and received flumazenil. The mean +/- SD dose of flumazenil administered during the double-blind phase was 71.3 +/- 34.2 mL (7.13 mg) compared with 95.06 +/- 16.03 mL of placebo. Of the 39 patients who had BDZ-positive drug screens and received flumazenil, 29 (74%) responded to 3 mg or less. Six additional patients responded to 4 or 5 mg, and one patient responded to 8 mg. The most common adverse effects in patients who received flumazenil were injection site pain (10.3%), agitation (8%), vomiting (3.4%), dizziness (3.4%), headache (3.4%), tachycardia (3.4%), and crying (3.4%). Three patients developed seizures. Two were associated with significant tricyclic antidepressant overdoses and one with propoxyphene ingestion. Two patients had positive drug screens for BDZ. CONCLUSION: Flumazenil rapidly and effectively reverses the clinical signs and symptoms of a BDZ overdose. Most patients will respond to 3 mg or less, but a small number may require a higher dose for reversal of clinical symptoms. Patients with concomitant tricyclic antidepressant overdose may be at risk for developing seizures.

Adolescent↗

The use of glucagon in a case of calcium channel blocker overdose.

The hypotension and myocardial depression that result from calcium channel blocker ingestion often are refractory to standard therapeutic modalities. Anecdotal reports on the use of glucagon have failed to show significant hemodynamic improvement. We report the first case of calcium channel blocker overdose that responded to glucagon. We conclude that glucagon is safe and effective in the management of hemodynamic instability associated with calcium channel blocker poisonings.

Acute Disease↗

Glucocorticoid receptor function in rat pituitary intermediate lobe is inhibited by an endogenous protein.

Though glucocorticoids inhibit proopiomelanocortin (POMC) gene expression and POMC-derived peptide release from corticotroph cells of the anterior pituitary, the regulation of this gene by glucocorticoids is less clear in the melanotroph cell of the pituitary intermediate lobe. To examine the difference between glucocorticoid sensitivity of the anterior lobe (AL) and intermediate lobe (IL) of the pituitary we have examined glucocorticoid receptor (GR) status of these two tissues and the role glucocorticoids play in regulating IL POMC gene expression. The rate of in vivo GR gene transcription, measured by nuclear run-on assay was consistently higher in the pituitary neurointermediate lobe (NIL) compared with the AL of the same animals. On a concentration basis, cytoplasmic GR mRNA in the NIL was similar to that found in the AL, and GR binding using [3H]dexamethasone (DEX) as ligand demonstrated similar concentrations of specific [3H]DEX binding in acutely isolated AL and NIL tissues. The specific Type II corticosteroid receptor ligand RU28362 displaced [3H]DEX binding to levels equivalent to non-specific binding, thus indicating that DEX was binding only to Type II corticosteroid receptors. To assess the direct action of glucocorticoids on POMC gene expression, NIL cells were cultured for 7 days and then treated with DEX. One hour DEX treatment of NIL primary cultures had no effect on levels of POMC heteronuclear RNA levels; in contrast, DEX induced a rapid and potent inhibition of POMC heteronuclear RNA levels in cells treated with the protein synthesis inhibitor puromycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstanols↗

Prevalence and risk factors for iron deficiency anemia in weanling rhesus macaques.

Standard epidemiologic methods were used to determine the prevalence and risk factors for iron deficiency at weaning in 143 weanling rhesus macaques (Macaca mulatta) raised indoors at the California Primate Research Center, Davis, CA. Maternal, infant, and management factors were investigated. Prevalence of iron deficiency anemia was 19%, as defined by mean corpuscular volume less than or equal to 66 femtoliters. It was found that animals raised entirely or partially in the nursery had less iron deficiency than dam-reared offspring. Results also suggest multiparous dams were more likely to have iron-deficient weanlings than primiparous dams. These results were discussed in relation to human and nonhuman primate pediatric medicine.

Anemia, Hypochromic↗

Functional outcome of below-knee amputation in peripheral vascular insufficiency. A multicenter review.

A retrospective functional outcome study was performed on 299 patients treated with below-knee amputations for peripheral vascular disease during a three-year period in six Veterans Administration special amputee centers. Sixty-one percent of the patients were diabetic, and 25% were previously unilateral amputees. Surgery was performed with a long posterior flap in 92.3%, sagittal flaps in 20%, and guillotine open technique in 5.7%. Wound management was accomplished with rigid plaster dressings in 75.3%, pneumatic compression dressing in 14%, and soft dressings in 10.7%. At follow-up evaluation one to two years later, 36.1% had died. Thirteen percent suffered wound complications, with 6.7% requiring revision to a more proximal amputation level. Eighty-seven percent of community ambulators maintained their ambulatory status. A comparable percentage maintained their ability to walk with a prosthesis.

Amputation, Surgical↗

Renal function and plasma arginine vasotocin during an acute salt load in feral chickens.

Renal clearance experiments were conducted on feral chickens descended from birds collected from a coral island off the coast of Queensland, Australia. Following a control period when 0.13 M NaCl was used as a vehicle for the renal function markers, a salt load was imposed by infusion of 1 M NaCl. The hypertonic NaCl infusion resulted in increases in glomerular filtration rate (GFR), effective renal blood flow (ERBF), and urine flow rate (V), whereas filtration fraction decreased. Haematocrit was reduced and plasma osmoality, sodium, chloride and potassium concentrations increased. Plasma arginine vasotocin (PAVT) levels increased from 31.4 +/- 2.3 pg.ml-1 during the control infusion to 56.0 +/- 1.7 pg.ml-1 following a salt load of 12 mmol NaCl.kg-1. The sensitivity of release of AVT was 0.69 +/- 0.11 pg.ml-1 per mosmol.kg-1. The concentrations of Na and Cl in urine increased, whereas urine osmolality and potassium concentration decreased. The expansion of the extracellular fluid volume induced by the salt loading would tend to suppress the release of AVT, whereas the osmotic stimulus would provide a stimulus for the release of AVT. In this study, GFR, ERBF and ERPF increased at the same time as PAVT increased.

Animals↗

Acetyl-coenzyme A synthesis from methyltetrahydrofolate, CO, and coenzyme A by enzymes purified from Clostridium thermoaceticum: attainment of in vivo rates and identification of rate-limiting steps.

Many anaerobic bacteria fix CO2 via the acetyl-coenzyme A (CoA) (Wood) pathway. Carbon monoxide dehydrogenase (CODH), a corrinoid/iron-sulfur protein (C/Fe-SP), methyltransferase (MeTr), and an electron transfer protein such as ferredoxin II play pivotal roles in the conversion of methyltetrahydrofolate (CH3-H4folate), CO, and CoA to acetyl-CoA. In the study reported here, our goals were (i) to optimize the method for determining the activity of the synthesis of acetyl-CoA, (ii) to evaluate how closely the rate of synthesis of acetyl-CoA by purified enzymes approaches the rate at which whole cells synthesize acetate, and (iii) to determine which steps limit the rate of acetyl-CoA synthesis. In this study, CODH, MeTr, C/Fe-SP, and ferredoxin were purified from Clostridium thermoaceticum to apparent homogeneity. We optimized conditions for studying the synthesis of acetyl-CoA and found that when the reaction is dependent upon MeTr, the rate is 5.3 mumol min-1 mg-1 of MeTr. This rate is approximately 10-fold higher than that reported previously and is as fast as that predicted on the basis of the rate of in vivo acetate synthesis. When the reaction is dependent upon CODH, the rate of acetyl-CoA synthesis is approximately 0.82 mumol min-1 mg-1, approximately 10-fold higher than that observed previously; however, it is still lower than the rate of in vivo acetate synthesis. It appears that at least two steps in the overall synthesis of acetyl-CoA from CH3-H4folate, CO, and CoA can be partially rate limiting. At optimal conditions of low pH (approximately 5.8) and low ionic strength, the rate-limiting step involves methylation of CODH by the methylated C/Fe-SP. At higher pH values and/or higher ionic strength, transfer of the methyl group of CH3-H4folate to the C/Fe-SP becomes rate limiting.

Acetyl Coenzyme A↗

Micropuncture study of avian kidney: effect of prolactin.

Renal function was studied in anesthetized European starlings (Sturnis vulgaris) by micropuncture and clearance techniques. A previous study had shown some changes in the renal function of birds in molt. Endogenous prolactin levels have been shown to be elevated at this time. In the present study, renal function was studied during the infusion of an isotonic sodium chloride solution and then when ovine prolactin was added to the infusion. Ovine prolactin resulted in an elevation of plasma urate concentration but had no significant effects on other plasma parameters or on the concentration of the various ions in tubular fluid samples. Urine flow rate was significantly higher during prolactin infusion, although whole animal glomerular filtration rate, single nephron glomerular filtration rate, and the percentage fluid reabsorption in the proximal tubule (up to the point of micropuncture) were unaltered. The whole animal fractional excretions of sodium and chloride were significantly higher, those of magnesium and potassium were significantly lower, and the fractional excretion of phosphate tended to be lower during prolactin infusion. At the level of the proximal tubules of the reptilian-type nephrons, prolactin infusion caused a slight reduction in the net reabsorption of sodium and chloride. Therefore the main effects of prolactin on renal function are occurring in the distal nephron of the reptilian-type nephrons or in the mammalian-type nephrons. It appears that prolactin may affect renal function in avian species and that these actions may be modulated by a range of factors as has been demonstrated in mammals.

Absorption↗