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Biomedical subjects

A R Williams

Publications and source records attributed to A R Williams.

At least 73 records · Page 4Linked to original sources

A randomized, double-blind placebo controlled cross-over study to investigate the effects of RW94 on the absorption of dietary fat in healthy volunteers.

RW94 is a permitted additive in the food industry, which precipitates fatty acids in vitro. In vivo, this could result in reduced fatty acid absorption by the body, and may, therefore, influence the amount of fat excreted in the faeces. An investigation into the effects of RW94 on bodily fat absorption and excretion was undertaken. The safety, tolerability and efficacy of the product was compared with placebo in a group of 12 healthy volunteers, randomly assigned to receive either RW94 or placebo for a period of four days when dietary fat intake was controlled. After a 10-day washout period, the randomly assigned groups were crossed over to receive placebo and RW94, respectively, for a second 4-day period, when fat intake was similarly controlled. Five grams of RW94 administered orally 30 min after each meal resulted in a statistically significant increase in the amount of excreted faecal lipids compared with placebo (p < 0.05). Following high fat intake, total blood cholesterol was predictably raised in both placebo and RW94 groups, but was less markedly raised with RW94 than placebo. All subjects lost body weight during the study, but the loss while consuming RW94 was significantly greater (p < 0.05) than while consuming placebo. All subjects found the treatments acceptable, though an increased incidence of flatulence, rumbling stomach and abdominal discomfort was noted with RW94 compared with placebo. RW94 was comparable with placebo in respect of safety.

Adult↗

Low-dose droperidol reduces postoperative vomiting in paediatric day surgery.

In a prospective, randomized, blind study, we assessed the effectiveness of droperidol 20 micrograms kg-1 i.v., given at induction of anaesthesia, in preventing postoperative vomiting in paediatric day-case patients. We studied 270 children, aged 1-15 yr, undergoing body surface surgery. There was a significant reduction in the incidence of vomiting in the recovery room (1.4% vs 9.2%, P < 0.005) and in the day ward (9.4% vs 18.3%, P < 0.05) in patients receiving droperidol. There was no significant difference on the journey home (9.5% vs 17.83%, ns) or at home (16.7% vs 10.3%, ns). There was also a reduction in the severity of vomiting in the droperidol group. There were no adverse side effects.

Adolescent↗

Female adnexal tumour of probable Wolffian origin: a clinicopathological and immunohistochemical study of three cases.

The clinical and pathological features of three adnexal tumours of probable Wolffian origin are reported. One case was an incidental finding in a patient who died from ovarian carcinoma; in the other two cases the patients presented with lower abdominal pain. The three tumours were well-circumscribed, solid masses arising in the leaves of the broad ligament and histological examination showed bland epithelial cells forming tubular, solid and microcystic patterns. The immunohistochemical profile of the tumours was similar to that of Wolffian duct remnants. They co-expressed cytokeratin and vimentin and lacked epithelial membrane antigen (EMA) reactivity, in contrast to tumours of Müllerian origin which usually express EMA. The differential diagnosis of female adnexal tumours is discussed.

Adenoma↗

Antinociceptive activity of the tachykinin NK1 receptor antagonist, CP-99,994, in conscious gerbils.

1. The ability of CP-99,994, and its less active enantiomer, CP-100,263, to inhibit spontaneous behaviours and hyperalgesia induced by central infusion of the NK1 receptor agonist, GR73632 or intraplantar injection of formalin was investigated in rats and gerbils. 2. GR73632 (3 pmol, i.c.v.)-induced foot tapping in gerbils was dose-dependently inhibited by CP-99,994 (0.1-1 mg kg-1, s.c.), but not by CP-100,263 (10 mg kg-1, s.c.) using pretreatment times up to 60 min. The centrally active dose-range for CP-99,994 was increased to 1-10 mg kg-1 s.c. with a higher challenge dose of GR73632 (30 pmol, i.c.v.). 3. In gerbils, intrathecal (i.t.) injection of GR73632 (30 pmol) elicited behaviours (licking, foot tapping or flinching and face washing) which closely resembled, but which was less specifically localized than, behaviours seen in animals injected with formalin (0.1-5%) into one hindpaw. 4. In rats, CP-100,263, but not CP-99,994 (up to 30 mg kg-1), inhibited the early phase response to intraplantar injection of 5% formalin (ID50 = 13.9 mg kg-1). The late phase was inhibited by both compounds (ID50 values 36.3 and 20.9 mg kg-1, respectively). In gerbils, there was marginal evidence for enantioselective inhibition of the early phase induced by formalin (2%). The ID50 values were 6.2 mg kg-1 for CP-99,994 and 13.4 mg kg-1 for CP-100,263. 5. Intrathecal injection of GR73632 (30 pmol) caused thermal hyperalgesia in igerbils which was inhibited enantioselectively by s.c. administration of CP-99,994 (ID50= 2.46 mg kg-1), but not by CP-100,263 (30 mg kg-1).6. In gerbils, intraplantar injection of formalin (0.1%) caused thermal hyperalgesia which was inhibited by CP-99,994 (ID50= 1.1 mg kg-1, s.c.). There was a nonsignificant trend for an anti-algesic effect of CP-100,236 (estimated ID50 = 8.2 mg kg-1, s.c.).7 These findings support the proposal that NK1 receptor antagonists may be useful in the clinical management of pain and reinforce the need to dissociate specific and nonspecific antinociceptive effects of available compounds.

Animals↗

Use of hand-held Doppler to identify 'difficult' forearm veins for cannulation.

Intravenous cannulation is a necessary procedure in many hospital patients. Some patients are regarded as having 'impossible' veins that are invisible and impalpable despite venous tourniquet. We investigated the use of a hand-held Doppler to identify veins suitable for percutaneous cannulation in such patients. A total of 24 arms in 12 patient volunteers with invisible and impalpable forearm veins was studied by squeezing the ipsilateral hand and using a hand-held 8 MHz Doppler probe on the forearm. Each venous signal was noted and the loudest chosen. Classification as 'good' or 'poor' was made on signal strength. The best signal was then mapped and the direction was indicated by a line on the skin. Each forearm was examined using a colour-flow Duplex. All veins were noted and diameters measured with and without tourniquet. These results were compared with the best veins found by hand-held Doppler. In all, 23 (96%) arms had the largest vein correctly identified by the hand-held Doppler. All 19 (100%) described as 'good' on signal had a diameter of 2.0-4.2 mm (mean 3.2 mm). All 4 (100%) described as 'poor' on Doppler signal had diameters of 1.4-1.7 mm (mean 1.6 mm). Hand-held Doppler, used as described, can accurately identify forearm veins larger than 2.0 mm in diameter in patients with invisible and impalpable veins with venous tourinquet. These veins should be amenable to percutaneous cannulation.

Catheterization, Peripheral↗

Coaching persons with lung cancer to report sensory pain. Literature review and pilot study findings.

Because clinicians often do not recognize that patients have pain and patients do not spontaneously communicate their pain, clinicians may fail to prescribe or administer adequate pain medications. One method of improving clinicians' assessments of pain is to coach patients to communicate their pain in ways that clinicians recognize. The aims of our pilot study were to (a) examine the feasibility of implementing a randomized clinical trial of a COACHING protocol in 18 outpatients with lung cancer pain and (b) estimate the effects of COACHING on nurses' knowledge of patients' pain location, intensity, quality, and pattern. The expectation was that COACHING would show a trend toward reducing the discrepancy between patients self-report of sensory pain and sensory pain data known to nurse clinicians. Patients were randomly assigned to be COACHED or NOT-COACHED (usual care) and pretest-posttest measures with the McGill Pain Questionnaire (MPQ) and Visual Analogue Scale (VAS) were taken from nurses and patients. Patients- and nurse-completed MPQs and VASs were compared for agreement. Improvement in percent agreement occurred consistently more often (pretest to posttest) between patient self-report of sensory pain and nurses' pain assessments in the COACHED group than in the NOT-COACHED group. Pilot study findings demonstrated feasibility of implementing the COACHING protocol and suggest that COACHING may be effective in reducing discrepancies between patients' self-reports and nurses' assessments of sensory pain. Design modifications are recommended for implementation of future studies.

Communication↗

Differential inhibition of foot tapping and chromodacryorrhoea in gerbils by CNS penetrant and non-penetrant tachykinin NK1 receptor antagonists.

The inhibition of GR73632-induced foot tapping in gerbils by central nervous system (CNS) penetrant of tachykinin NK1 receptor antagonists was investigated. Intracerebroventricular infusion of the highly selective tachykinin NK1 receptor agonist GR73632 (3 pmol) induced a vigorous repetitive hind foot tapping response which was inhibited by CP-99,994 (ID50 = 0.06 mg/kg i.v.) but not by its less active enantiomer, CP100,263 (10 mg/kg i.v.). Similarly, the poorly CNS penetrant quaternised compound, L-743,310, failed to inhibit foot tapping at doses up to 3 mg/kg i.v. In contrast, all three compounds inhibited chromodacryorrhoea induced by systemic administration of GR73632 (0.5 nmol i.v.) (ID50 = 0.06, 2.95 and 0.004 mg/kg i.v., respectively). These findings confirm that foot tapping and chromodacryorrhoea in gerbils provide simple assays for the central and peripheral activation of tachykinin NK1 receptors.

Analysis of Variance↗

p53 mutations in cervical carcinogenesis--low frequency and lack of correlation with human papillomavirus status.

p53 gene aberrations are common in human malignancies, and recent studies suggest that in cervical carcinoma p53 function is inactivated either by complex formation with human papillomavirus (HPV) E6 product or by gene mutation. Using polymerase chain reaction (PCR) followed by denaturing gradient gel electrophoresis (DGGE), we examined the mutational status of the four 'hotspot' regions of the p53 gene in 47 primary cervical carcinomas. HPV status was determined, also by PCR. In 20 of these cases, we examined for loss of heterozygosity (LOH) on chromosome 17p13. In the 47 carcinomas, and in a further 68 biopsy specimens from normal, premalignant and malignant cervix, we investigated aberrant immunocytochemical expression of p53. Immunocytochemically, abnormal p53 expression was detected in 13 of 115 cases (8/57 carcinomas). Somatic mutation in p53 was detected in 1 of 47 cervical carcinomas; 36 were positive for HPV 16, 18 or 33. A low level of allele loss (3 out of 20 cases) was detected on chromosome 17p, occurring in both HPV-positive and HPV-negative cases, and in cases with and without p53 mutations. We conclude that somatic mutation in the hotspot regions of the p53 gene occurs infrequently in cervical carcinomas; that immunocytochemically detectable levels of p53 are also infrequent; and that there is no consistent correlation between p53 mutational status, LOH on chromosome 17p or HPV status in these cancers.

Adenocarcinoma↗

The postmortem incidence of senile ecchymoses.

Although senile ecchymoses are a well-recognized phenomenon on hospital wards, in patients who die in other settings they may be wrongly interpreted as bruising caused by physical assault. Therefore, we studied a total of 410 elderly (> 50 years of age) patients by a prospective examination of autopsy reports to elucidate their nature, including their general frequency, their anatomical distribution, and their physical appearance. We found a clear association with increasing age and a common distribution on the arms, rather than the neck or legs. One unique finding is that ecchymoses are related to place of residence, in that less mobile elderly persons are more likely to develop this condition, possibly as a result of lifting.

Aged↗

Immunohistochemical characterization of endometrial lymphoid cell populations in women infected with human immunodeficiency virus.

OBJECTIVE: To determine whether lymphocytic infiltration of the endometrium accompanies human immunodeficiency virus (HIV) infection. METHODS: Endometrial samples from 12 HIV-infected women and from rigorously matched controls were examined. The following markers were used: common leukocyte antigen (CD45), T lymphocytes (CD3), monocytes-macrophages (CD68), and CD4 and CD8 lymphocytes. Cell counts were performed without knowledge of HIV status. Factors considered in relation to these markers were menstrual symptoms, pelvic pain, peripheral blood CD4+ count, and time since seroconversion. RESULTS: Histology showed conventional features of chronic endometritis in only one case. In the remainder, the endometrium of HIV-infected women, compared with controls, showed an increase in CD45 cells (P < .02) and an increase in CD3 staining cells (P < .05). This appeared to be restricted to those with menstrual symptoms, and this group also had lower peripheral blood CD4 counts. There was no difference in cells of the monocyte-macrophage series (CD68). In contrast to control samples, CD4 lymphocytes were infrequent or absent in the endometrium of HIV-infected women, regardless of peripheral blood CD4 count or presence of menstrual symptoms; however, this was not universal, as one sample showed an area of dense CD4 cell infiltration. The ratio of CD4 to CD8 was reduced in HIV-seropositive samples compared with controls (P < .02). CONCLUSION: We hypothesize that chronic endometritis of a nonclassical form may be common in advancing HIV disease, possibly directed against HIV-infected cells or self-determined antigens. This could be associated with morbidity and may represent a reservoir of infection. Endometrial depletion of CD4 cells is a common, but not universal, feature and may be independent of immune compromise.

Adult↗

The incidence and severity of postoperative nausea and vomiting in patients exposed to positive intra-operative suggestions.

In a double-blind study, the effects of positive intra-operative suggestions on the incidence and severity of postoperative nausea and vomiting were studied in 60 patients randomly selected to undergo routine major gynaecological surgery. Patients who received positive suggestions suffered significantly less nausea and vomiting in the 24 h after surgery.

Anesthesia, General↗

Breast carcinoma metastatic to uterine leiomyoma.

A case report of a woman with a history of breast carcinoma who presented with metastatic infiltration of uterine leiomyoma is described. The previously published literature on the subject is reviewed.

Breast Neoplasms↗

Hyaline globules in ovarian tumours.

Hyaline eosinophilic globules have so far been described in a restricted variety of tumour types. We have noted their presence in a variety of gynaecological malignancies, in particular mixed Müllerian tumours and other epithelial ovarian tumours. We therefore studied their incidence and distribution in a series of malignant, borderline and benign epithelial ovarian tumours, and endometrial and endocervical adenocarcinomas. Hyaline eosinophilic globules were found in all 30 mixed Müllerian tumours from various sites in the female genital tract, 22 of 30 clear cell carcinomas, seven of 30 serous, two of 30 mucinous, and one of 30 endometrioid carcinomas examined, and were also seen in metastases from these tumours. They were present in only two of 25 borderline serous, one of 25 borderline mucinous tumours, and in four of 50 benign serous and one of 50 benign mucinous tumours. The globules were not found in any of 25 Brenner tumours examined, nor in 30 endometrial or 30 endocervical adenocarcinomas. The globules were periodic acid-Schiff positive after diastase, stained positively with PTAH, and were immunoreactive for alpha-1-antitrypsin. This study therefore demonstrates that eosinophilic globules are not specific for any particular tumour. However, their frequency in malignant mixed Müllerian tumours suggests that this diagnosis should be carefully excluded whenever these globules are present in epithelial tumours of the female genital tract.

Adenocarcinoma↗

Antinociceptive activity of NK1 receptor antagonists: non-specific effects of racemic RP67580.

1. Release of substance P in the dorsal horn is considered a primary event in the perception of pain. The profile of racemic RP67580, a non-peptide antagonist at the NK1 (substance P) receptor, was examined in a range of antinociception tests on rodents. 2. At doses up to 30 mg kg-1, s.c. racemic RP67580 exhibited antinociceptive activity in writhing and formalin paw tests in mice and gerbils. Acetic acid induced writhing and the licking response to formalin were reduced to 40-50% of the level observed in vehicle-treated animals (P < 0.05). However, this agent was not active in mouse tail flick, rat paw pressure or rat and guinea-pig formalin paw tests. 3. Like racemic RP67580, the calcium channel blockers nifedipine (30 mg kg-1, i.p.) and verapamil (10 or 20 mg kg-1, s.c.) inhibited the response to formalin by approximately 60% in gerbils (P < 0.05 compared with vehicle-treated animals). 4. Evidence for calcium channel antagonist activity of RP67580 was obtained in vitro. Racemic RP67580 inhibited calcium entry into depolarized strips of guinea-pig ileum longitudinal muscle myenteric plexus (apparent KB = 587 +/- 115 nM), inhibited [3H]-diltiazem binding to rabbit skeletal membranes (IC50 = 298 nM) and depressed high threshold calcium currents in neurones cultured from rat cortex (10% inhibition at 10 microM). 5. These findings indicate that the acute antinociceptive effects of RP67580 may not be attributable to a specific interaction with NK1 receptors and may be mediated via calcium channel blockade.

Analgesics↗

Diffuse leiomyomatosis of the uterus with local pelvic spread.

The clinical and pathological findings of a case of diffuse leiomyomatosis of the uterus are described. The unique feature of this case is the extension of the disease process to the pelvic mesocolon. The diagnostic difficulties encountered in the histological assessment of smooth muscle tumors of the uterus are discussed.

Adult↗