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Biomedical subjects

R A Hughes

Publications and source records attributed to R A Hughes.

At least 19 recordsLinked to original sources
PubMed1992

Motor nerve biopsy in severe Guillain-Barré syndrome.

We undertook a biopsy of a terminal branch of the musculocutaneous nerve in a man with severe Guillain-Barré syndrome and very small distally evoked action potentials. The biopsy showed pronounced subperineurial edema, macrophage infiltration, and many axons that had been completely demyelinated, some associated with intratubal macrophages. The biopsy unequivocally identified the pathological process as primary demyelination, not axonal degeneration, and was more informative than previous reports of sural nerve biopsies in patients with Guillain-Barré syndrome.

Axons↗
PubMed1992

Lipidic peptides. V: Penicillin and cephalosporin acid conjugates with increased lipophilic character.

Lipophilic, double-ester derivatives of beta-lactam antibiotics with methylene, ethylene, and propylene spacers were prepared by crown-ether-assisted coupling of halogenoalkyl esters of 2-(tert-butoxycarbonylamino)decanoic acid to either penicillin G or cefuroxime. The hydroxyethyl ester of penicillin G and the tert-butoxypropyl ester of cefuroxime were also prepared. The lipophilic, double-ester conjugates, the hydroxyethyl ester of penicillin G, and the tert-butoxypropyl ester of cefuroxime showed weak or no antibiotic activity in vitro, as expected. The lipophilic penicillin G conjugates and the tert-butoxypropyl ester of cefuroxime were active in vivo against a nonpenicillinase-producing strain of Staphylococcus aureus after subcutaneous administration. The penicillin G double ester with propylene spacer and the tert-butoxypropyl ester of cefuroxime were inactive in vitro, a fact indicating that both compounds were hydrolyzed in vivo, as desired. After oral administration, the lipophilic, double-ester conjugate of penicillin G with methylene spacer and the tert-butoxypropyl ester of cefuroxime were active.

Administration, Oral↗
PubMed1992

The effect of aspirin on the risk of stroke in patients with nonrheumatic atrial fibrillation: The BAATAF Study.

Recent randomized trials have consistently demonstrated the marked efficacy of warfarin in reducing the risk of stroke caused by nonrheumatic atrial fibrillation. These trials have provided conflicting evidence on the effect of aspirin. We report the aspirin analysis from the BAATAF study, a trial in which control patients could choose to take aspirin. There we two strokes in 446 person-years with warfarin (annual rate of 0.45%); eight strokes in 206 person-years with aspirin, most at 325 mg per day (annual rate of 3.9%); and five strokes in 271 person-years among patients taking neither aspirin nor warfarin (annual rate of 1.8%). Simultaneously controlling for the other significant determinants of stroke in the BAATAF study (age, mitral annular calcification, and clinical heart disease), the relative rates (95% confidence interval) of stroke were: (1) warfarin/aspirin = 0.135 (0.029 to 0.64); (2) aspirin/(no aspirin and no warfarin) = 1.95 (0.64 to 5.97); and (3) warfarin/(no aspirin and no warfarin) = 0.263 (0.051 to 1.36). Our "treatment received" analysis argues that warfarin is strikingly more effective than aspirin in preventing stroke in nonrheumatic atrial fibrillation.

Aged↗
PubMed1992

T cell responses to myelin proteins in Guillain-Barré syndrome.

We have investigated the hypothesis that the pathogenesis of Guillain-Barré syndrome (GBS) involves an autoimmune T cell response to P0 and P2 proteins of peripheral nerve myelin. The proliferative responses of blood mononuclear cells (MNC) to myelin proteins and synthetic peptides derived from them were determined in patients with GBS and chronic idiopathic demyelinating polyradiculoneuropathy (CIDP), normal controls (NC) and patients with other neuropathies (ONP). Twelve out of 19 GBS patients responded to P0 or P2, 6 to P0 and its peptides only, 3 to P2 and its peptides only, and 3 to both P0 and P2 antigens. Responses to at least one of the antigens were also found in 6/13 of CIDP patients, but in only 4/17 NC and 2/6 ONP. Immune responses in GBS are heterogeneous. The early T cell responses to P0 protein, described here for the first time, may be important in the pathogenesis of some cases.

Adult↗
PubMed1992

Central monoaminergic changes induced by morphine in hypoalgesic and hyperalgesic strains of domestic fowl.

The present research examined morphine dose-response effects on both the formalin test and on CNS monoamine (MA) levels and the metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in hypoalgesic (76) and hyperalgesic (SN) strains of domestic fowl. Morphine produced a significant hypoalgesic response in the 76 strain at 15-45 mg/kg and a significant hyperalgesic response in the SN strain at 5-10 mg/kg. In subsequent experiments, analyses of whole brain (minus tectum), brainstem, and spinal cord MA, DOPAC, and 5-HIAA via high-performance liquid chromatography with electrochemical detection (HPLC-EC) were performed following morphine administration in both the 76 and SN strains. Morphine produced a significant elevation of brain dopamine (DA) and a significant elevation of brain, brainstem, and spinal cord serotonin (5-HT) in both the 76 and SN strains. Morphine elevated brain norepinephrine (NE) in the 76 strain. However, morphine failed to affect brain NE in the SN strain. This distinct morphine effect on brain NE differentiates strain-dependent hypoalgesia and hyperalgesia in domestic fowl.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Time-dependent codeine hypoalgesia and hyperalgesia in domestic fowl.

Recent research demonstrated that codeine produced hypoalgesia and morphine produced hyperalgesia against a noxious thermal stimulus in young domestic fowl. The bidirectional effects of these opiate agonists on nociception are inconsistent with the notion that codeine's algesic effects result through in vivo demethylation of codeine to yield morphine. In Experiment 1, the temporal pattern (15,30,60 and 120 min) of codeine (30 mg/kg) effects on thermal nociception and respiration were examined in 15-day-old cockerels. Codeine produced a time-dependent biphasic response: hypoalgesia at 15 min and hyperalgesia at 60 and 120 min. Respiration was depressed by codeine at all test intervals. To assess for opioid specificity, Experiment 2 examined the action of naloxone (5 mg/kg) on the temporal pattern (15 and 60 min) of codeine effects (30 mg/kg) on thermal nociception and respiration. Bidirectional codeine algesic effects were observed at the 15- and 60-min test intervals. Naloxone increased the codeine jump latency scores at the 15-min interval and decreased codeine jump latency scores at the 60-min interval. These results suggest that codeine engages opposed nonopioid-mediated hypoalgesic and opioid-mediated hyperalgesic nociceptive systems in this animal model. Codeine depressed respiration at both the 15- and 60-min test intervals and this respiratory depression was reversed by naloxone. These findings support the notion that codeine respiratory effects are mediated by opioid system activity.

Animals↗
PubMed1992

Morphine hyperalgesic effects on developmental changes in thermal nociception and respiration in domestic fowl (Gallus gallus).

Domestic fowl tested at 3, 5, and 7 days posthatch jumped from a heated grid more rapidly than animals tested at 14 days posthatch. Morphine (2.5 mg/kg) decreased jump latency in 14-day-old chicks but did not significantly affect jump latency in younger chicks. Respiration was lower in 3-day-old chicks than in the older groups but morphine depressed respiration at each age. In a second experiment morphine significantly decreased jump response latency in 5-day-old chicks when thermal stimulus intensity was lowered and morphine dose increased (5 mg/kg). Posttest respiration rate was depressed by morphine. Morphine hyperalgesia and respiratory depression were reversed by naloxone (5 mg/kg). However, naloxone alone increased jump response latency. Young domestic fowl are more sensitive and/or reactive to a noxious thermal stimulus and are less sensitive to morphine than 14-day-old chicks but morphine hyperalgesia was evident in both 5- and 14-day-old chicks. These hyperalgesic chicks may be tolerant at birth to morphine hypoalgesic effects on nociception.

Aging↗
PubMed1992

The effect of exercise training on salivary immunoglobulin A and cortisol responses to maximal exercise.

The salivary immunoglobulin A (s-IgA) and cortisol responses to maximal exercise were examined in 24 adult males (X +/- SD; 22.1 +/- 3.0 yrs) before and after 10 weeks of run training. The subjects performed an incremental treadmill test to exhaustion and were randomly assigned to one of three groups: control (CON; n = 5), low intensity training (LO; n = 8), or high intensity training (HI; n = 11). Following the ten weeks of training, the subjects performed a second maximal treadmill test. Saliva samples were collected before, as well as immediately and 1 hr following each of the maximal treadmill tests and were analyzed for s-IgA and salivary cortisol. Maximal oxygen consumption (VO2max) increased significantly (p < 0.05) in the LO and HI groups but remained unchanged in the CON group. The s-IgA levels decreased significantly (p < 0.05) immediately post-exercise but returned to pre-exercise levels by one hour recovery. In addition, s-IgA and cortisol levels were not significantly (p > 0.05) correlated at any of the sampling times. These findings indicated that the s-IgA response to maximal exercise was unaffected by moderate (70% of VO2 max) to heavy (86% of VO2max) training (designed to develop cardiorespiratory fitness in healthy non-athletic adults) and independent of salivary cortisol.

Adult↗
PubMed1992

Septic bone, joint and muscle lesions associated with human immunodeficiency virus infection.

Ten episodes of musculoskeletal sepsis have been seen in nine patients with HIV infection. Seven patients had AIDS, circulating CD4-positive lymphocyte counts being less than 0.1 x 10(9)/l in six. Septic arthritis recurred in seven patients, osteomyelitis in three and pyomyositis and bursitis each occurred in one patient. Staphylococcus aureus was isolated from four patients, atypical micro-organisms being found in three. Presentation of musculoskeletal infection in this patient group may be atypical but rapid diagnosis is important as early antimicrobial therapy is often successful.

Adult↗
PubMed1992

Plasma exchange treatment and prognosis of Guillain-Barré syndrome.

A retrospective analysis of case notes was undertaken for 52 patients presenting to Guy's Hospital with Guillain-Barré syndrome between August 1987 and September 1990. Twelve months after onset 61 per cent of patients had recovered completely, 35 per cent were still significantly disabled and two patients (4 per cent) had died. Forty-eight of the patients (92 per cent) were treated with plasma exchange. The frequency of morbidity related to this treatment was low, and plasma exchange was not responsible for either of the deaths. Outcome for all patients treated with plasma exchange between January 1985 and September 1990 was compared with that of 64 patients with Guillain-Barré syndrome seen in 1983 and 1984 who were not treated in this way. Time to walking unaided was significantly better (median 58 days compared with 86 days, p = 0.031), as was the median duration of ventilation (16.5 compared with 36 days, p = 0.004). Factors which had been found to predict an adverse outcome in previous studies (requirement for ventilation, age over 40 years, time to becoming bedbound less than 4 days, and small distally evoked abductor pollicis brevis muscle action potential) were not significantly associated with a poor prognosis in this study. The features associated with persisting disability were time to improvement more than 21 days, preceding diarrhoea and older age.

Bacterial Infections↗
PubMed1992

The effect of exhaustive exercise on salivary immunoglobulin A.

The purpose of this study was to examine salivary immunoglobulin A (s-IgA) responses to exhaustive exercise. Twenty-nine, college age (means +/- SD = 21.45 +/- 3.1 yrs; range 18-29 yrs) moderately active males (running < 10 miles per week) performed an incremental treadmill test to exhaustion. Unstimulated salivary samples, collected before as well as immediately and one hour following the test, were analyzed for s-IgA using an enzyme-linked immunosorbent assay (ELISA). Mean s-IgA levels decreased significantly (24.4%, p < 0.05) immediately following the maximal test, and remained depressed (16.9%) one hour after the test. Of the 29 subjects, five exhibited an increase (range = 1.3 to 53.3%) in s-IgA following the exercise bout. The results of this study suggest that exhaustive exercise may temporarily reduce salivary IgA levels.

Adolescent↗
PubMed1992

A study of neuropathy in HIV infection.

A prospective study of possible aetiological factors for neuropathy associated with HIV infection was performed in 80 patients and 28 homosexual controls. At entry to the study twelve patients (15 per cent) had evidence of a generalized neuropathy not due to any other cause and a further three patients developed symptomatic neuropathy during a mean (SD) follow-up of 20 (7.5) months. All but two of these neuropathies were of the distal symmetrical sensory type. Electrophysiology was consistent with an axonal pathology and nerve biopsy confirmed this as the major pathological change. Warming threshold was the diagnostic test most frequently abnormal, sometimes in the absence of other electrophysiological abnormalities. No association was seen with opportunistic infection (cytomegalovirus, herpes simplex, Pneumocystis pneumonia, toxoplasmosis, Cryptococcus infection or tuberculosis). HIV proviral DNA could not be detected in paraffin sections of peripheral nerve in six patients with neuropathy. The presence of the neuropathy did not show significant correlation with depression of the number of CD4+ T cells in the blood, impaired T cell function tests, or IgG, IgM, or IgA levels. Immune complexes containing C1q, but not those containing IgG, IgM, IgA or C3c, were significantly more common among neuropathic patients (p = 0.01).

AIDS-Related Opportunistic Infections↗