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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 397 records · Page 22Linked to original sources
PubMed1997

First-trimester growth restriction and fetal aneuploidy: the effect of type of aneuploidy and gestational age.

OBJECTIVE: Our purpose was to determine the effect of type of aneuploidy and gestational age on first-trimester fetal growth. STUDY DESIGN: Crown-rump length measurement was obtained in pregnancies undergoing chorionic villus sampling in three large prenatal diagnosis centers. One hundred forty-four aneuploid fetuses, from 9 to 13 weeks' gestation, were compared with 440 matched control fetuses for evidence of crown-rump length shortening. Shortening was defined by the observed/expected crown-rump length. Expected values of crown-rump length based on last menstrual period were obtained from regression equations generated from a separate normal group. Threshold values for aneuploidy screening were determined on the basis of receiver-operator characteristic curves. RESULTS: There was significant crown-rump length shortening in trisomy 18 compared with normal fetuses, with observed/expected values < or = 0.80 (odds ratio 13.78, 95% confidence interval 5.64 to 33.88, p < 0.000001); for trisomy 13 the observed/expected crown-rump length was < or = 0.90 (odds ratio 3.64, 95% confidence interval 1.08 to 12.96, p < 0.03). There was no significant shortening of crown-rump length in Down syndrome, with observed/expected values < or = 0.92 (odds ratio 0.86, 95% confidence interval 0.50 to 1.47, p = 0.6). With shortened crown-rump length (observed/expected value < 0.86) the risk of any aneuploidy is increased (odds ratio 2.52, 95% confidence interval 1.6 to 3.96, p < 0.0001). When the first-trimester crown-rump length was shortened by > or = 14 mm, the aneuploidy risk was high (odds ratio 9.04, 95% confidence interval 3.26 to 28.67, p < 0.00001). CONCLUSION: In the first trimester fetuses with trisomy 18 and 13 appear to be growth restricted, in contrast to fetuses with trisomy 21. In at-risk pregnancies crown-length that is shorter than expected significantly increase the odds that aneuploidy is present.

Aneuploidy↗
PubMed1997

The use of perfluorocarbon-associated gas exchange to improve ventilation and decrease mortality after inhalation injury in a neonatal swine model.

Patients with tracheobronchial disease frequently require mechanical ventilation during therapy and experience iatrogenic complications such as barotrauma and volutrauma. The purpose of this study was to determine whether perfluorocarbon-associated gas exchange (PAGE) results in lower ventilatory pressures and more efficient ventilation than that provided by conventional ventilation after tracheobronchial mucosal injury caused by smoke inhalation in neonatal piglets. Ten piglets were used for this prospective, randomized study. After administration of a severe smoke inhalation injury, the piglets were randomly assigned to either the perfluorocarbon or control groups. Group 1 served as the control population and received standard (time-cycled, volume-limited) mechanical ventilation. Ventilator settings were adjusted to maintain physiological pH and PO2 at the lowest tidal volume, rate, and end-expiratory pressure possible throughout the study period. Group 2 was administered intratracheal perfluorocarbon as well as identical mechanical ventilation to attain the same physiological pH and PO2. Oxygenation index, peak and mean airway pressures, and arterial blood gas levels were measured throughout the study period and subjected to statistical analysis. Histological comparison of airway and parenchymal tissues confirmed identical patterns of smoke injury in both groups. Carbon monoxide levels were the same in both groups. There was significant barotrauma and volutrauma in the control group, but none in the PAGE group. All controls died from 13 to 17 hours after injury; one PAGE pig died at 23 hours with all others surviving past 24 hours (P = .0021). Peak, plateau, and mean airway pressures were all significantly higher (P < .05) past 12 hours after injury and continued to increase until death in the controls. Arterial blood gases showed significantly (P < .05) decreased pH, PO2, and elevated PcO2 levels in the control group past 12 hours after injury. The oxygenation index was significantly elevated (P < .05) in the control group past 12 hours after injury. PAGE shows potential for improving ventilation and survival immediately after severe smoke inhalation injury and may have clinical applications in other nonhomogeneous lung injuries.

Animals↗
PubMed1997

Phase I/II trial of low dose cyclosporin A with EP for advanced non-small cell lung cancer.

We and others have shown that cyclosporin A (CsA) reverses resistance to etoposide (E) and cis-platinum (P) in vitro and in vivo. To assess the clinical relevance of combined therapy, we studied CsA with EP in patients with advanced non-small cell lung cancer in a phase I/II clinical trial in a University setting. Patients were treated between July 1989 and June 1994 and included 10 females and 34 males with a median age of 61 years and a mean Karnofsky performance status of 80. CsA was given at escalating doses of 1-6 mg/kg per day on days 1-4 of each 21 day cycle with cis-platinum 25 mg/m2 per day and etoposide 100 mg/m2 per days on days 1-3. Response was assessed after each 2 cycles by measuring index lesions. A total of 44 patients received 133 cycles, 22.7% of patients had a partial response and 36.4% had stable disease with 8% 2-year survival. Patients receiving 1-2 mg/kg CsA had a PR rate of 37.5 and 50% SD compared to 19.4 and 33.3% for doses of 3 mg/kg or more. Although no conclusions should be drawn from this small study, the Kaplan-Meier survival curves were statistically significant different for these two groups by the log-rank test (P = 0.047). The 2-year survival of the former group was 25% compared to 4% for the latter. In light of the potential importance of immunomodulation in cancer control, it seems prudent to balance the effects of CsA on P-glycoprotein and other drug resistance pumps against its dose-dependent immunosuppressive activity. Further studies are needed to validate the activity of low dose CsA in combination with standard chemotherapy for lung cancer.

Adult↗
PubMed1997

Cell-cycle arrest versus cell death in cancer therapy.

In response to anticancer therapeutics, human colon cancer cells growing in vitro either enter into a stable arrest or die, depending on the integrity of their cell-cycle checkpoints. To test whether altered checkpoints can modulate sensitivity to treatment in vivo, xenografts were established from isogenic lines differing only in their p21 checkpoint status. Although all tumors with intact checkpoint function underwent regrowth after treatment with gamma-radiation, a significant fraction of checkpoint-deficient tumors were completely cured. This difference in sensitivity was not detected by the clonogenic survival assay, because both arrest and death preclude outgrowth of colonies. These results demonstrate that checkpoint status affects sensitivity to anticancer treatments in vivo, and these findings have important implications for identifying and testing new therapeutic compounds.

Animals↗
PubMed1997

The use of 'dementia care mapping' as a method of evaluating care received by patients with dementia--an initiative to improve quality of life.

'Dementia care mapping' (DCM) is a method of assessing care standards as received by dementia victims. Through the application of this tool, short-comings in care practice can be highlighted in the hope of achieving improvements. The method was employed by the Elderly Mentally III (EMI) unit of a National Health Service trust in South Wales. Baseline evaluations were undertaken on each of the EMI wards containing dementia patients, and reports delivered to the appropriate members of staff. Mean care scores for the unit as a whole were found to lie in the "good' category, as defined by the method. Staff training in the underlying principles of DCM will be followed by re-evaluations of care standards to evaluate the outcome of the attempts made to engender improvements.

Aged↗
PubMed1997

A marker of terminal stalk cell terminal differentiation in Dictyostelium.

We describe the isolation of staB, a Dictyostelium gene that is selectively expressed in stalk cells. If an aggregate enters culmination immediately staB is expressed in the bottom half of the stalk and in the basal disc but if a migratory slug is formed it is also expressed in the top of the stalk and in a disc of cells that surmounts the spore head. The latter two populations of cells derive from the rear part of the prestalk region, the pstO cells, which would therefore seem to change their transcriptional competency during slug migration. The staB promoter contains a distal region that is required for expression within both the stalk and the basal disc and a proximal region that is required only for expression within the basal disc. This uncoupling of transcriptional specificities suggests that the signalling mechanisms that direct terminal differentiation in these two tissues differ in some way.

Amino Acid Sequence↗
PubMed1997

Benign adrenal cyst presenting in a pregnant patient.

Cystic lesions of the adrenal gland are uncommon, most often diagnosed incidentally during diagnostic imaging or autopsy. An adrenal cyst presenting as a pelvic mass in pregnancy offers the clinician a diagnostic and therapeutic dilemma. A 28-year-old black female presented for routine obstetric care at 26 weeks' gestation and was found on examination to have a 40-cm pelvic-abdominal mass. Ultrasound confirmation revealed the mass to be cystic and arising from the right pelvis. Laboratory tests including hematocrit, white blood cell count, electrolytes, rapid plasma reagin (RPR), and CA-125 were within normal limits. The patient underwent exploratory laparotomy and a 40 x 20 cm right adrenal cyst was identified and resected. Postoperatively, the patient developed preterm labor and delivered a 955-g infant; the infant was discharged home 3 months later with bronchopulmonary dysplasia and delayed developmental milestones. The woman was discharged home without complication on postoperative Day 8. Accurate preoperative determination of the origin of a pelvic mass occurring in pregnancy is helpful in timing therapeutic intervention. Use of ultrasound and magnetic resonance imaging (MRI) modalities can provide detailed anatomical information without risk to mother or fetus. Conservative management of adrenal cyst in pregnancy may lower the morbidity and mortality of the mother and fetus.

Adrenal Gland Diseases↗
PubMed1997

Coordinating rural divisions: the workforce window.

Divisions of General Practice have been established to alleviate the professional isolation which general practitioners face by being excluded from involvement in other parts of the health care system. Divisions facilitate the development of local communication networks and cooperative activities which improve the integration of general practice with other elements of the health system. Coordination of communication is one of the strengths of divisions at the local level and Rural Divisions Co-ordinating Units at the State level. This strength is being effectively utilised to target general practice workface issues. Given the significant proportion of general practitioners in the medical workforce, particularly in rural and remote areas, this has implications for broader medical workforce issues. Australia faces a maldistribution in its general practitioner workforce, with an excess supply in urban areas and a significant shortfall in rural and remote areas. Since 1995-96, the General Practice Rural Incentives Program, which targets the recruitment and retention of rural doctors, has devolved funding to the Rural Divisions Co-ordination Units to coordinate the statewide provision of practical assistance to rural general practitioners, through their divisions, in relation to continuing medical education and the provision of locums. There is potential to build on the success of these initiatives and also to work with urban divisions through the state-based organisational structures which are currently being developed.

Australia↗
PubMed1997

A role for thyroid hormones in the regulation of diet-induced thermogenesis in birds.

The possible involvement of thyroid hormones in avian diet-induced thermogenesis (DIT) was investigated in two lines of cockerels divergently selected for high (R-) or low (R+) food efficiency. For a given body weight, R+ cockerels exhibited a higher food intake than R- cockerels (+49 to +76%) and increased DIT (+25%). Plasma thyroxine (T4) level did not differ between lines whatever the feeding status of the birds. Plasma 3,5,3'-triiodothyronine (T3) level was lower in fasted R+ than in fasted R- cockerels while the opposite was observed after a meal. Iopanic acid injections reduced both plasma T3 concentrations and heat production to the same levels in both lines. Hepatic 5'-deiodinase activity measured with an exogenous sulfhydryl group (dithiothreitol) did not differ between lines, but when the sulfhydryl group was omitted, the activity was higher in R+ than in R- birds (90 v. 42 pmol T3/min per liver). T3-binding capacity of isolated hepatic nuclei was higher (+76%) in R+ than in R- birds. Long-term or acute pair-feeding of R+ cockerels to the level of R- controls did not alter these results. The present results suggest that T3, mainly originating from peripheral conversion of T4 to T3, is involved in DIT in the R+ line. Availability of endogenous sulfhydryl groups appears to play an important part in the modulation of hepatic deiodinase activity. The higher concentration of nuclear T3 receptors may further increase the effects of the hormone, suggesting a major role of thyroid hormones associated with catecholamines in the stimulation of avian DIT. The underlying thermogenic mechanisms remain to be elucidated.

Animals↗
PubMed1997

The isoflavones equol and genistein do not induce xenobiotic-metabolizing enzymes in mouse and in human cells.

1. In view of the anticarcinogenic effects of the isoflavonoid genistein and the known ability of various flavonoids to induce carcinogen-metabolizing enzymes, the ability of the isoflavonoids genistein and equol to induce these enzymes was studied in mouse. 2. In comparison with induction by the positive control beta-naphthoflavone (40 mg/kg i.p. 4 days) neither genistein or equol (0.4-40 mg/kg i.p. 4 days) gave a significant induction of ethoxyresorufin O-deethylase, p-nitrophenol oxidase or immunoreactive CYP1A2 or CYP2E1. There was also no induction of erythromycin-N-demethylase or elevation of immunoreactive CYP3A1. 3. In contrast with the induction by beta-naphthoflavone of glutathione S-transferase protein and activity towards 1-chloro-2,4-dinitrobenzene, neither isoflavone exhibited such induction. 4. Response elements for human CYP1A1, glutathione S-transferase lambda a and the xenobiotic response element (XRE) in HepG2 cells were activated by beta-naphthoflavone but not by genistein or equol. 5. The isoflavones have been found not to induce a range of enzymes involved in carcinogen metabolism. The lack of enzyme induction differs from the characteristics of many other flavonoids. The results do not support the monofunctional induction of GST as a basis of anticarcinogenicity.

Animals↗
PubMed1997

Effect of clonidine on gastric emptying of liquids.

We have investigated the effects of clonidine on gastric emptying of liquids in 30 patients. In a double-blind, randomized design, clonidine 150 micrograms, morphine 10 mg or saline in 1 ml was given i.m. One hour later, the patient drank a paracetamol solution (1.5 g in 50 ml water). Venous blood samples were obtained every 15 min for 90 min thereafter. Plasma paracetamol concentrations were measured using high-pressure liquid chromatography and the area under the concentration-time curve was calculated. The degree of sedation and complications were recorded. The area under the curve for 0-60 min was significantly smaller in the morphine group than in the saline group (P = 0.002; 95% confidence interval (CI) for difference -1237 to -502 micrograms min ml-1), whereas it was greater in the clonidine group compared with the saline group, although this was not significant (95% CI for difference -423 to 1264 micrograms min ml-1). Arterial pressure was significantly lower in the clonidine group compared with the saline group. Both clonidine and morphine appeared to cause mild sedation. We conclude that clonidine 150 micrograms i.m. does not delay gastric emptying of liquids in a similar manner to morphine.

Acetaminophen↗
PubMed1997

'Ending up a GP': a qualitative study of junior doctors' perceptions of general practice as a career.

OBJECTIVE: This study aimed to investigate junior doctors' perception of general practice as a career. METHOD: In-depth interviews with a purposive sample of 54 junior doctors were carried out. RESULTS: Three main criteria were identified: clinical content of practice, lifestyle, and organizational context of practice. Clinical content was most highly valued, but was recognized to conflict with lifestyle. Compared with hospital medicine, general practice was associated with inferior clinical content but superior lifestyle. Views on organizational context were more equivocal. Choice of general practice as a career was often based on negative judgements. CONCLUSIONS: Junior doctors' perceptions of general practice are expressions of a hospital-centric culture. Criteria for career choice are diffuse and complex. There was no evidence that the 1990 GP Contract deterred recruitment. The compromise between intrinsic satisfaction and lifestyle may be significant for GP morale.

Adult↗
PubMed1997

Global health promotion models: enlightenment or entrapment?

This paper suggests that there is a tendency for health promotion to be located within models that consider health to be a product of a range of forces, with practice itself assumed to comprise a similarly wide range of activities. This paper develops a critique of this tendency that is essentially accommodating, all embracing and 'neutral'. It is argued that this leads to the masking of tensions between the conflicting values contained within the different elements of the models. We suggest that for health promoters, this is neither conceptually appropriate nor practically sensible. These notions are developed in five main stages. We start by defining some of the key concepts in the piece, e.g. the nature of a 'model' and examples of 'global' models. We then examine some of the general reasons why global models are favoured, with respect to the emergence of the UK's strategy for health, The Health of the Nation. The third stage of the discussion identifies and considers, within the British context, professional and governmental factors perceived to have driven this choice. The fourth aspect of the paper will introduce a critique of the use of global modelling. The paper concludes by critically questioning this evolving relationship, and suggests that it will be essentially conservative and unproductive. We end by reviewing the implications for practice and suggesting a useful way forward.

Health Policy↗