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Biomedical subjects

A R Williams

Publications and source records attributed to A R Williams.

At least 37 records · Page 2Linked to original sources
PubMed2000

Intrauterine polyps--a cause of unscheduled bleeding in women using the levonorgestrel intrauterine system: case report.

The levonorgestrel intrauterine releasing system is a contraceptive that has been shown to reduce menstrual blood loss dramatically. Breakthrough bleeding, however, is a relatively common occurrence as with all methods of progestogen-only contraception and this limits its acceptability for women. Amenorrhoea can be achieved in the majority of women within 12 months of insertion. Any new pattern of bleeding after amenorrhoea or a persistence of heavy bleeding may be due to co-existing intrauterine pathology such as endometrial polyps. The use of out-patient techniques such as hysteroscopy and saline infusion sonography are indicated in these instances to exclude other intrauterine pathology.

Adult↗
PubMed2000

A longitudinal study of HPV detection and cervical pathology in HIV infected women.

OBJECTIVE: To monitor the presence and persistence of high risk (HR) human papillomavirus (HPV) in cervical brushings from HIV infected women. METHODS: Prospective observational cohort study of HIV infected women. Women were enrolled from the cohort of 164 HIV infected women who attend the colposcopy clinic at the Edinburgh Regional Infectious Diseases Unit. A single cervical brush scrape was obtained from 39 women and two or more samples from 63 women who attended regularly at approximately 6 monthly intervals. HPV typing was carried out using a commercial hybrid capture assay (HCA). Details of antiretroviral therapy, cytological assessment, and histological evaluation were made available and the interrelation with HR-HPV detection analysed. RESULTS: Abnormal cervical cytology, particularly of low grade, was common in these HIV infected women. HR-HPV types were detected in 25% of the women with normal cytology, while over 80% of those with abnormal cytology of any grade were HR-HPV positive. Persistent HR-HPV, as defined by two or more consecutive HPV positive results, was common and found in 27/63 women from whom multiple samples were obtained. HR-HPV was detected at high levels whether or not patients were receiving antiretroviral therapy. Profound immunosuppression was not necessarily associated with progression of cervical disease and no cases of invasive cervical disease were seen. CONCLUSION: While mild dyskaryosis (low grade squamous intraepithelial lesion (LSIL)) and persistence of HR-HPV are common in HIV infected women in Edinburgh, regular cytological and colposcopic evaluation with appropriate intervention and treatment appears to limit the progression of cervical disease.

Adult↗
PubMed2000

Balinese mothers' developmental timetables for young children.

The study examined Balinese mothers' expectations for children's development and mothers' child-rearing practices, as influenced by selected variables (child's gender and ordinal position, mother's education, and rural or urban residence). Rural (n = 100) and urban (n = 100) mothers responded to structured questionnaires read aloud to them by trained interviewers who recorded responses. All children were between 4 and 6 years. Equal numbers of male and female children were included, and the entire economic and educational ranges of families were represented. MANOVA results showed significant interaction effects of residential location and maternal education on mothers' expectations of children's cognitive, F(2, 170) = 4.31, p = .04, and psychosocial development, F(2, 170) = 4.35, p = .01. Significant interaction effects were found for maternal education, residential location, child's ordinal position, and gender, F(3, 170) = 5.92, p = .001, on maternal child-rearing practices. Two developmental timetables were constructed.

Adult↗
PubMed2000

Head protection in England before the first World War.

Man has sought to protect himself from physical injury resulting either from the vicissitudes of an arbitrary natural environment or from the calculated activity of his fellow creatures since at least the beginning of recorded time. The earliest substantial British evidence of this activity dates from shortly after the Roman invasion of 55 BC. The head has always been seen by both assailant and defender as a region of particular vulnerability, where an incapacitating blow might most effectively be landed. We present an overview of the evolution and development of English military head protection through the ages, with particular reference to the advances made in metallurgical technology at Greenwich through the course of the 16th century. Much of this represents original research by the authors (particularly ARW), published here for the first time. We include the first metallographic data on armor excavated from the Wisby grave-pits (1361), the first scientific analysis of the textile composition of medieval helmet linings from the Wallace Collection, and the first metallurgical study of the Windsor Castle suit, the personal armor of King Henry VIII, perhaps England's most famous monarch. We combine this with our own experimental data, also previously unpublished, relating to the attack energy available from ancient weaponry (whose technology determines the design of defenses, then as now) in an attempt to assess the effectiveness of helmets. Finally, we set this in the context of contemporary medical technology. The latter is found to be woefully inadequate when presented with serious head injuries. Nevertheless, mortality from battlefield injury has been reduced from ancient times to the present day, despite advances in weapons technology.

Craniocerebral Trauma↗
PubMed1999

The substance P antagonist L-760,735 inhibits stress-induced NK(1) receptor internalisation in the basolateral amygdala.

The distribution of NK(1) receptor immunoreactivity in the amygdaloid complex, induction of NK(1) receptor endocytosis in the amygdala following immobilisation stress, and the ability of pretreatment with the substance P antagonist L-760,735 or imipramine to block this response were examined in gerbils, a species with human-like NK(1) receptor pharmacology. Highest levels of immunolabelling were observed in the anterior, amygdalo-hippocampal and medial nuclei. Less dense labelling was observed in the basolateral nucleus, where it was possible to clearly visualise the distal dendrites of NK(1) immunoreactive neurones and quantify the effect of immobilisation stress on NK(1) receptor endocytosis morphology, a marker of local substance P release. Immobilisation for 1 h caused an approximately 60% increase in the number of dendritic processes undergoing NK(1) receptor endocytosis in the basolateral amygdala that was inhibited by acute pretreatment of animals with L-760,735 (3 mg/kg), but not by imipramine (10 mg/kg). These findings are consistent with other evidence that the amygdala represents a possible site of action for the antidepressant and anxiolytic efficacy of substance P antagonists.

Amygdala↗
PubMed1999

Filtroporation: A simple, reliable technique for transfection and macromolecular loading of cells in suspension.

Cultured Chinese hamster ovary (CHO) cells suspended in their growth medium were forced by gas pressure through the uniformly sized micropores of filter membranes. This procedure caused transient damage to the plasma membrane, which increased the permeability of the cells to exogenous molecules. This "filtroporation" was indicated by uptake of fluorescent dextran molecules up to 500,000 MW in cells deemed viable by trypan blue dye exclusion. The macromolecular uptake was increased if the driving pressure was increased at constant micropore size, or if the micropore size was decreased at constant driving pressure. Larger membrane perturbations permitted uptake of a luciferase reporter plasmid, which resulted in transfection of the CHO cells with the surviving cells expressing luciferase activity after 2 days in culture. This simple and general new method of porating cells in suspension may be optimized to incorporate the desired macromolecules while retaining the maximum viability.

Animals↗
PubMed1999

Airway management of a child after tracheal resection.

PURPOSE: To report a strategy for minimizing airway risks and optimizing airway management in the post-reanastomosis phase of the anesthetic management of a patient undergoing tracheal reconstruction. CLINICAL FEATURES: A 14-yr-old boy with squamous cell carcinoma of his trachea underwent a tracheal resection and end-to-end reanastomosis for removal of tumour. This procedure was accomplished through a right thoracotomy. A thoracic epidural had been placed before induction of anesthesia through which 3 mg morphine and 10 ml bupivacaine 0.25% with epinephrine were administered during surgery. After chest wall closure the patient was allowed to recover spontaneous respiration and the trachea was extubated during deep anesthesia to eliminate airway response with coughing which might have stressed the anastomosis. An infusion of bupivacaine 0.0625% and morphine (100 microg x ml(-1)) was maintained until the third postoperative day. The patient had an unremarkable postoperative course and was discharged on the eighth postoperative day. CONCLUSION: In this case thoracic epidural analgesia and tracheal extubation during deep anesthesia was a safe and effective strategy for minimizing airway risks and optimizing airway management in after the reanastomosis phase of tracheal resection.

Adolescent↗
PubMed1999

Fatigue in mothers of infants discharged to the home on apnea monitors.

A comparative study was done to determine differences in caregiver fatigue between two groups of mothers of preterm infants at baseline, in the hospital (Time 1), 1 week postdischarge (Time 2), and 1 month postdischarge (Time 3). Group 1 infants were discharged home on apnea monitors (AM) (n = 28), and Group 2 infants were not on apnea monitors (nonAM)(n = 46). Measured by the Multidimensional Assessment of Fatigue (MAF) scale, mean fatigue scores from Time 1 to Time 3 markedly increased for the monitor group and decreased for the nonmonitor group. The scores were significantly different between the two groups at Times 2 and 3 but not at baseline. Two-way analysis of variance (ANOVA) with repeated measures showed group by time interaction effects on fatigue. Monitoring and alleviation of fatigue in home caregivers of preterm infants on apnea monitors are necessary.

Adolescent↗
PubMed1999

Marked prolongation of the succinylcholine effect two hours after neostigmine reversal of neuromuscular blockade in a patient with chronic renal insufficiency.

Prolonged neuromuscular blockade from succinylcholine after neostigmine administration has been reported in patients with frank renal failure. We present a case of prolonged neuromuscular blockade from succinylcholine administration, given 2 hours after neostigmine reversal of neuromuscular blockade in a patient with chronic renal insufficiency. This case shows that patients with chronic renal insufficiency, like patients with renal failure, are at risk for prolonged succinylcholine blockade if they have recently received anticholinesterase reversal of neuromuscular blockade. Administration of succinylcholine for facilitation of urgent endotracheal intubation may be required soon after reversal of nondepolarizing muscle relaxants, particularly in patients who return to the operating room for emergency care.

Aged↗
PubMed1999

Anesthetic management of a patient with tetra-amelia.

The case presented is that of a parturient with tetra-amelia, the congenital absence or near absence of all limbs. The difficulties encountered with monitoring and venous access due to absence of extremities illustrate the necessity for a detailed management plan with emphasis on early intervention. The reasons for the high incidence of operative delivery are outlined.

Anesthesia, Obstetrical↗
PubMed1999

Mortality one-year postdischarge from a Veterans Affairs geriatric evaluation and management unit: assessing mortality risks.

OBJECTIVE: To assess at Geriatric Evaluation and Management Unit (GEM) admission factors that affect mortality 12-months postdischarge and to develop a preliminary risk scoring protocol to guide targeting of GEM care. SETTING: A 24 bed-GEM at a Veterans Affairs (VA) Medical Center. DESIGN: Relative risks (RR) were assessed using prospective data; a risk protocol from 1988-1989 data was tested on 1990-1991 patients. SUBJECTS: A total of 283 male patients, aged 60 to 102, discharged over 4 years. RESULTS: Age at GEM admission did not correlate with death (r = .14; P = .145), but did correlate with risk scores (r = .33, P < .001). The risk protocol had a sensitivity of .67 and specificity of 1.00. High and low risk patients had mortalities of 51% versus 20%, a Wilcoxon (Gehan) statistic of 15.22, df = 1, and P < .001. Differences in mortality ceased about 100 days postdischarge. Three univariate RR exceeded 1.00 at a 99% Confidence Interval (CI): IADL score (RR: 1.12; CI, 1.03-1.21); nursing acuity score (RR: 1.78; CI: 1.02-3.11); and a primary diagnosis of pneumonia/sepsis (RR: 3.95; CI, 1.60-9.78). Four RRs exceeded 1.00 at a 90% CI: dementia (RR: 1.78; CI, 1.02-3.09); transfer into the GEM from a medical service (RR: 1.47; CI, 1.02-2.12); deconditioning/functional decline (RR: 1.67; CI, 1.12-2.48); and use of a Foley catheter (RR: 2.22; CI, 1.11-4.45). Thirteen other potential risk factors were found in a multivariate analysis. CONCLUSIONS: The point estimates of risk factors may help clinicians target GEM care, but the development of a useable risk protocol requires additional work. Causal models may be needed to assess patient conditions related to successful treatment in GEMs.

Aged↗
PubMed1999

Effect of using templates on the information included in histopathology reports on specimens of uterine cervix taken by loop excision of the transformation zone.

AIM: To determine the change in information relayed from histopathologists to clinicians by using templates for reporting specimens of uterine cervix sampled by loop excision of the transformation zone (LETZ). METHODS: Minimum datasets for the information required from LETZ specimens received from the colposcopy clinic, Royal Infirmary, Edinburgh, were incorporated into templates on the clinical service computer (Pinnacle) of the pathology department, University of Edinburgh. Pathologists completed hard copy versions, which were transcribed into the computer templates for report generation. The effect of the changes on the quality of the pathology reports was studied. The number of cases in which each item in the dataset received comment in template generated reports was compared with that in traditional prose reports compiled before the use of the templates and in prose reports issued after the introduction of the templates. Questionnaire studies were undertaken of clinicians' and pathologists' opinions of the template reports. RESULTS: In the template reports nearly all items received comment in almost 100% of cases. In the prose reports issued both before and after the templates were in use, most items were mentioned in a significantly lower proportion of cases. Clinicians thought the template reports were clearer and the information could be more readily assimilated than from the prose versions. CONCLUSIONS: The use of template reports in these types of specimen allowed more consistent and detailed information transfer. The change appeared to result from the use of the templates rather than from increased awareness of the items to be reported.

Biopsy↗
PubMed1999

Role of inflammatory mediators in human endometrium during progesterone withdrawal and early pregnancy.

The role of progesterone (P4) in the regulation of inflammatory mediators interleukin-8 (IL-8), monocyte chemoattractant protein-1, and cyclooxygenase-2 (COX-2) and in the recruitment of leukocyte subpopulations in the endometrium has been examined, by employing a model of P4 withdrawal and maintenance in vivo. Messenger RNA and protein expression have been investigated in endometrial biopsies: 1) during the midsecretory phase (LH+8 to 10); during the maintained luteal phase (P4 administered vaginally for 4 days from LH+8) and biopsies collected 2) 24 h and 3) 48 h post withdrawal of P4; and 4) during pseudo pregnancy (lifespan of corpus luteum extended by 7 days with CG; (decidua collected from women with 5) an ectopic gestation and 6) from women undergoing first-trimester termination of pregnancy). CD56+ large granular lymphocytes remain the major leukocyte subtype, both 24 and 48 h after P4 withdrawal, and in decidua (CG supported or ectopic). Higher numbers (P < 0.05) of macrophages (CD68+) were present in endometrium 48 h post P4 withdrawal and in pseudo pregnant endometrium, compared with normal decidua. Significantly more macrophages (P < 0.01) were present in decidua from an ectopic pregnancy. A significant elevation of IL-8 (P < 0.01) and COX-2 (P < 0.05) messenger RNA was detected 48 h post P4 withdrawal. Evidence is provided for up-regulation of IL-8 and COX-2 in response to P4 withdrawal.

Chemokine CCL2↗
PubMed1998

Structural optimization affording 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-oxo-1,2,4-triazol-5-yl)methylmorpholine, a potent, orally active, long-acting morpholine acetal human NK-1 receptor antagonist.

Structural modifications requiring novel synthetic chemistry were made to the morpholine acetal human neurokinin-1 (hNK-1) receptor antagonist 4, and this resulted in the discovery of 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-ox o-1 ,2,4-triazol-5-yl)methyl morpholine (17). This modified compound is a potent, long-acting hNK-1 receptor antagonist as evidenced by its ability to displace [125I]Substance P from hNK-1 receptors stably expressed in CHO cells (IC50 = 0.09 +/- 0.06 nM) and by the measurement of the rates of association (k1 = 2.8 +/- 1.1 x 10(8) M-1 min-1) and dissociation (k-1 = 0.0054 +/- 0.003 min-1) of 17 from hNK-1 expressed in Sf9 membranes which yields Kd = 19 +/- 12 pM and a t1/2 for receptor occupancy equal to 154 +/- 75 min. Inflammation in the guinea pig induced by a resiniferatoxin challenge (with NK-1 receptor activation mediating the subsequent increase in vascular permeability) is inhibited in a dose-dependent manner by the oral preadmininstration of 17 (IC50 (1 h) = 0.008 mg/kg; IC90 (24 h) = 1.8 mg/kg), indicating that this compound has good oral bioavailbility and peripheral duration of action. Central hNK-1 receptor stimulation is also inhibited by the systemic preadministration of 17 as shown by its ability to block an NK-1 agonist-induced foot tapping response in gerbils (IC50 (4 h) = 0.04 +/- 0.006 mg/kg; IC50 (24 h) = 0.33 +/- 0.017 mg/kg) and by its antiemetic actions in the ferret against cisplatin challenge. The activity of 17 at extended time points in these preclinical animal models sets it apart from earlier morpholine antagonists (such as 4), and the piperidine antagonists 2 and 3 and could prove to be an advantage in the treatment of chronic disorders related to the actions of Substance P. In part on the basis of these data, 17 has been identified as a potential clinical candidate for the treatment of peripheral pain, migraine, chemotherapy-induced emesis, and various psychiatric disorders.

Acetals↗