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Biomedical subjects

G V Williams

Publications and source records attributed to G V Williams.

36 records · Page 2Linked to original sources
PubMed1991

Early undifferentiated connective tissue disease. I. Early clinical manifestation in a large cohort of patients with undifferentiated connective tissue diseases compared with cohorts of well established connective tissue disease.

We identified a cohort of 410 patients with connective tissue disorders (CTD) of less than or equal to 1 year duration among the participating clinics of the Cooperative Systematic Studies of the Rheumatic Diseases Program. Fifty-seven had rheumatic arthritis (RA), 57 systemic lupus erythematosus, 37 poly/dermatomyositis, 46 scleroderma, and 213 early undifferentiated CTD, including patients with Raynaud's phenomenon, unexplained polyarthritis or at least 3 CTD manifestations such as rashes, myalgias, etc. Baseline clinical data are now being reported. The followup of these patients may prove to be valuable in understanding these diseases. To our knowledge no similar cohort of patients is available for further investigation.

Adolescent↗
PubMed1990

Concentration-dependent actions of stimulated dopamine release on neuronal activity in rat striatum.

Voltammetric analysis was combined with single unit recording to measure the effects of endogenous dopamine, released by electrical stimulation of the median forebrain bundle, on neuronal activity in the rat striatum in vivo. Fast differential ramp voltammetry, a more sensitive form of fast cyclic voltammetry, was used to measure extracellular dopamine levels during a 50-ms scan epoch every 500 ms. Using the same carbon fibre microelectrode, neuronal activity was recorded in between the electrochemical epochs. A steady-state electrochemical signal equivalent to about 100 nM dopamine was seen in the unstimulated striatum. The responses of 122 striatal units to stimulated dopamine release were recorded in 37 acute experiments. Ninety-one units which displayed a large spike amplitude (greater than or equal to 50 microV) were recorded during stimulated release of dopamine initially to levels of between 100 and 500 nM. The majority (49) showed a profound excitation, 23 showed inhibition, and nine units gave complex responses. Only 10 units were unresponsive. All the responses of these large units outlasted the transient increase in dopamine levels, often for more than 1 min. In contrast, all the 31 units which displayed a small spike amplitude (less than 50 microV) were powerfully activated by dopamine release within this range. Administration of alpha-methyl-para-tyrosine (250 mg/kg i.p.) abolished both dopamine release and the response of the five large units and four small units examined, indicating that the neuronal response was directly attributable to dopamine. Dopamine release was increased by increasing the stimulus duration over the range 0.25-10 s. With increasing levels of dopamine release the excitatory response of large units rose to a maximum and then decreased until it was eventually transformed entirely into an inhibition at dopamine levels above 1 microM. In contrast, the excitatory response of small units always increased in magnitude with increasing dopamine release to levels greater than 1 microM. The large units that showed inhibition at low levels of dopamine were also inhibited at high levels. Tail-pinch stimuli excited 21/23 large units and all seven small units tested, although this stimulus did not evoke a detectable rise in dopamine levels. We suggest that the fundamental action of dopamine in the striatum is excitation, whether involving D1 or D2 receptors. The small units described here could be inhibitory interneurons which convert the excitatory response of large units into inhibition. Dopamine may regulate striatal function by enhancing particular input-output pathways while also activating lateral inhibitory mechanisms serving to "gate-out" alternative outputs.

Animals↗
PubMed1989

Effects of iontophoresis of noradrenaline and stimulation of the periaqueductal gray on single-unit activity in the rat superficial dorsal horn.

Recordings were made with a new form of low-noise carbon fibre microelectrode from 75 units in the superficial laminae of the lumbar dorsal horn of the anaesthetized rat. The response of each unit to adequate stimulation of its peripheral receptive field, to noradrenaline (NA) applied iontophoretically, and to electrical stimulation of the periaqueductal gray (PAG) was investigated. Only units that could be excited by iontophoresis of glutamate (10-100 nA) were analyzed. Recording sites in the spinal cord and stimulation sites in the brainstem were identified histologically at the end of each experiment. Forty-six units with low-threshold receptive fields and small spike amplitudes were found, mainly located in laminae II and III. Both stimulation of the PAG and NA iontophoresis excited the majority (32/46) of these units. The rest were unaffected. Eight high-threshold (HT) units were located in the region of lamina I. Twenty-one wide-dynamic-range (WDR) units were found mainly in deeper laminae. Both WDR and HT units were inhibited by NA and PAG stimulation. This inhibition affected both glutamate-evoked activity and responses to nociceptive stimuli. We suggest that the small LT units are inhibitory interneurones of the substantia gelatinosa (SG), which act on the WDR and HT units to produce nociceptive-specific inhibition. The inhibition can be modality-specific without necessarily being presynaptic because of the laminar arrangement of the dorsal horn. The PAG could thus exert its known antinociceptive effects at least partly via descending noradrenergic axons that excite these SG cells.

Animals↗
PubMed1989

A cytopathological investigation of Autographa californica nuclear polyhedrosis virus p10 gene function using insertion/deletion mutants.

The role of the Autographa californica nuclear polyhedrosis virus p10 gene in viral cytopathology and morphogenesis was examined using classes of p10 deletion mutants with and without lacZ (beta-galactosidase) gene fusion. Mutant-infected cells did not form the fibrillar cytoplasmic and nuclear structures normally observed late in infection with wild-type (wt) virus, and the cells failed to lyse even at 2 weeks post-infection. Based on wt and mutant cytopathology, we suggest lysis may be facilitated by stepwise exhaustion of the host nuclear membrane, and may require a function resident in the carboxy region of p10; this portion of the molecule is also essential for formation of the p10-rich fibrillar bodies. Additional changes in cytopathology were correlated with the level of p10/LacZ fusion protein expression. The insertional mutant designated Ac229, which encodes 51 N-terminal amino acids of p10 fused to LacZ, caused intranuclear accumulation of granular structures at sites corresponding to the fibrillar bodies of wt viral infections. Occlusion body membranes, which associate with the fibrillar bodies in wt infections, were also formed in mutant virus-infected cells. However, membranes did not associate with occlusion bodies in Ac229 infections, and were aberrantly attached to occlusion bodies in cells infected with mutants having simple p10 deletions (represented by Ac231). Loss of the outer membrane increased sensitivity of the occlusion bodies to disruption by physical stress; a partially attached membrane afforded some protection from disruption.

Animals↗
PubMed1983

Delta associated hepatitis in Australia.

Hepatitis B associated delta infection was found in Australian born narcotics users, patients with cirrhosis and hepatoma from Italy and Greece and in south east Asian immigrants. About 9% of patients with chronic hepatitis B were found to have intranuclear delta antigen in liver biopsies with immunofluorescence or anti-delta antibody in serum by radioimmunoassay. Delta may have been imported from southern Europe and Asia and a reservoir of delta infection may exist in narcotics users. Anti-delta was not found in hemophiliacs despite exposure to hepatitis B. Delta occurs in Australia and causes acute and particularly chronic hepatitis in addition to that caused by hepatitis B.

Adult↗
PubMed1982

Retrospective comparison of 'Cheno' and 'Urso' in the medical treatment of gallstones.

In two groups of gallstone patients ideally suited for medical treatment, the effect of six to 18 months' therapy was compared retrospectively in 52 given chenodeoxycholic acid (CDCA) and 46 given ursodeoxycholic acid (UDCA). The minimum dose (mg kg-1 day-1) required to desaturate bile consistently was 10.1 for UDCA and 14.3 for CDCA. In patients completing six months' treatment, 23 of 35 (66%) taking a mean of 7.7 (+/- SEM 0.5) mg UDCA and 34 of 42 (81%) taking 14.7 +/- 0.2 mg CDCA showed partial or complete dissolution of gallstones. The mean dose in the UDCA-treated patients, however, was artefactually lowered by previous dose-response studies: in those who had not taken multiple doses, the mean UDCA intake in the 'responders' at six months was 9.1 +/- 0.3 mg kg-1 day-1. At six months, more UDCA (five of 35 or 14.3%) than CDCA (four of 42 or 9.5%)-treated patients showed complete dissolution of gallstones, but, by one year, the situation was reversed, 20 of 41 (49%) CDCA-treated and eight of 30 (27%) UDCA-treated patients showing complete dissolution of gallstones. Cumulative efficacy at one year had risen to 76% for UDCA and 89% for CDCA. Both treatments reduced the frequency of dyspepsia and biliary colic; 37% of CDCA and 2.6% of UDCA-treated patients showed hypertransaminasaemia; diarrhoea developed in 60% of the CDCA group but in none of the UDCA group.

Chenodeoxycholic Acid↗
PubMed1980

Campylobacter: common cause of enteritis in an infectious diseases hospital.

Eleven patients were referred to the infectious diseases wards of the Prince Henry Hospital, Sydney, between August and December, 1979, with acute infectious diarrhoea acquired within Australia. Nine of the 11 had infection with Campylobacter species as the sole pathogens. In contrast, a variety of pathogens was isolated from the stools of 13 patients referred to the hospital with enteritis acquired during overseas travel, including three Shigella species, but only one Campylobacter species. The patients with campylobacter enteritis suffered fever, abdominal discomfort and diarrhoea, often with some blood. Complications of campylobacter enteritis included colitis, severe abdominal pain, renal failure, severe muscle cramps, headache with meningism, myalgias and arthralgias. Campylobacter enteritis resolved with cessation of solid food intake, together with intravenous or oral fluid therapy. Some patients were treated with erythromycin, with prompt improvement, though a role for antibiotic therapy has not yet been established.

Adolescent↗
PubMed1980

The value of a wide range of tests in the assessment of lung function in carcinoma of the bronchus.

Tests of forced ventilation, lung volume, transfer factor, flow-volume and arterial blood gas measurements were made on 209 patients before thoracotomy for carcinoma of the bronchus. The patients whom the surgeons subsequently considered to be unsuitable for operation had significantly poorer results in tests of forced ventilation than those who were selected for operation. There was little or no significant difference between these groups in respect of the RV, TLC, transfer factor and arterial blood gas measurements. There was no marked difference in the results of any of the measurements between those who developed complications and those who were complication free. It was therefore concluded that clinical assessment together with forced ventilation tests could not be bettered by adding further lung function tests, when these were interpreted as simple 'normal or abnormal'. However, more complex analysis of test findings, such as discriminant analysis, may be of more value.

Aged↗
PubMed1980

Mycobacterium fortuitum: an unsuspected cause of synovitis and osteomyelitis.

Two men with progressive synovitis and osteomyelitis of the wrist were found to have infection with Mycobacterium fortuitum. Immunological defects were demonstrated in both cases in association with renal failure and renal transplantation respectively. Failure of appropriate antibiotic therapy to eradicate infection necessitated amputation in one case. M. fortuitum is frequently sensitive to only amikacin or kanamycin. Treatment with amikacin alone was unsuccessful. This organism is widespread in the environment and may need to be considered in undiagnosed chronic infection in the immunologically suspectible host, as it poses unusual problems in diagnosis and therapy.

Humans↗
PubMed1976

Bird breeder's hypersensitivity pneumonitis: progress studies of lung function after cessation of exposure to the provoking antigen.

Lung function and immunologic studies have been performed in 9 patients with bird breeder's hypersensitivity pneumonitis at the time of diagnosis and at intervals from 8 to 30 months after they ceased exposure to the provoking antigen. All 9 patients had evidence of small airway obstruction at the time of diagnosis. Complete recovery of lung function occurred in 4 patients. The other 5 all had evidence of interstitial damage; 3 of them had progressive increase in the degree of airway obstruction, and one had progressive loss of elastic recoil. The patients were nonsmokers, and these progressive changes could not be explained by occult exposure to antigen because the tests of immunologic sensitivity to relevant avian antigens became negative. Neither the nature or degree of lung function abnormality nor the form of clinical presentation was related to the development of residual damage. The period of exposure to antigen after symptoms developed and the age of the patient appeared to be the most important factors determining recovery of lung function.

Adolescent↗
PubMed1975

Familial hypersensitivity pneumonitis.

Two families are described in which seven members of a total of 19 were found to have hypersensitivity pneumonitis due to exposure to avian antigens. Diagnosis was made on the basis of characteristic roentgenologic changes together with respiratory function and immunologic studies. The latter included screening for precipitins, macrophage migration inhibition (MMI) to specific antigens in avian serum and droppings, quantitation of immunoglobulin and alpha1 antitrypsin (AAT) levels and assessment of the complement system. Specific precipitins to pigeon and/or budgerigar serum were found in the serum of only four of the seven patients. Six of these seven patients, however, had a positive MMI. Thus, the MMI test, at least in this group of patients appeared to be a more sensitive indicator of active disease. The finding of seven members of two families with disease led to a search for predisposing factors, either genetic or environmental. Evidence for a genetic predisposition came from tissue typing studies. In the first family, both paternal haplotypes were associated with disease; the maternal haplotype HLA3,7 was not inherited by any child with disease. In the second family, the disease developed in three of four members with the haplotype HL-A2,W15, who were significantly exposed to avian antigen. In the light of recent studies showing an association between immune response (Ir) genes, histocompatibility antigens and disease susceptibility, these findings were interpreted as possible evidence for a subtle genetically linked immune defect in hypersensitivity pneumonitis. Evidence for an environmental predisposition was less clear cut, but it is interesting that members of both families used a gamma isomer of hexachlorobenzene (Nickoff) to eradicate mite infestations in their birds which might have damaged the bronchial mucosa or acted as an immunologic adjuvant in a person with underlying susceptibility to disease. The presence of subclinical respiratory disease in two family members is reported, and the importance of performing a range of investigations of respiratory function in order to detect disease and monitor its progress is emphasized.

Adolescent↗
PubMedDate not supplied

The adherent gastric antral and duodenal mucus gel layer thins with advancing age in subjects infected with Helicobacter pylori.

BACKGROUND: Peptic ulceration and Helicobacter pylori infection increase with advancing age. In the upper gastro-intestinal tract the first line of mucosal defence is the adherent mucus gel layer. OBJECTIVE: We have examined, using a novel histological fixation technique, the thickness of the adherent mucus gel layer (1) in the gastric antrum and (2) in the duodenum in relation to advancing age and H. pylori status. METHODS: The subjects had macroscopically normal stomach and duodenum at endoscopy. Measurement of the gastric antral mucus thickness was carried out on four antral biopsy specimens from within 2 cm of the pylorus (H. pylori positive n = 25, negative n = 21). The duodenal mucus thickness (D1) was measured from two biopsy specimens (H. pylori positive n = 7, negative n = 13). All specimens were snap frozen and cryostat sections stained using a modified PAS/AB stain. RESULTS: In all sections the mucus layer was continuous. In both duodenum and gastric antrum, the mucus thickness was not significantly different between H. pylori positive and H. pylori negative age-matched samples. In duodenum and gastric antrum from H. pylori negative subjects, there was no correlation between mucus thickness and age. However, in H. pylori positive subjects, there was a significant thinning of the adherent gastric antral mucus gel layer (p = 0.005, r = -0.54) and the duodenal mucus thickness (p<0.001, r = -0.99) with advancing age. CONCLUSION: This study shows a significant thinning of the adherent mucus gel layer in H. pylori positive individuals, as stomach and duodenum age. In those without H. pylori, the mucus gel thickness is preserved in stomach and duodenum.

Aged↗
PubMedDate not supplied

Liquid chromatographic determination of medroxyprogesterone acetate in tablets.

A reverse-phase liquid chromatographic method is described for the assay of medroxyprogesterone acetate in tablets. An octadecylsilane (C18) column with a mobile phase of methanol-0.01M dibasic ammonium phosphate (80 + 20 v/v, pH 7.2 +/- 0.1) and photometric detection at 254 nm separates medroxyprogesterone acetate from excipients. Detector responses were linear to concentrations of medroxyprogesterone acetate over the range 50-150 micrograms/mL (r = 0.999). Mean recovery of medroxyprogesterone acetate added to tablet excipients was 100.8%. Mean assay results were 101.3% (n = 3). The assay results are comparable to those obtained by the compendial liquid chromatographic method.

Chromatography, Liquid↗
PubMedDate not supplied

Gastroenterology in the elderly.

Elderly patients are admitted acutely to most hospital departments. In medical and surgical departments many of them present with gastroenterological symptoms and diseases. In this review, those situations encountered regularly are highlighted and their management is discussed.

Aged↗