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Biomedical subjects

S Gill

Publications and source records attributed to S Gill.

At least 19 recordsLinked to original sources
PubMed2006

Role of VraSR in antibiotic resistance and antibiotic-induced stress response in Staphylococcus aureus.

Exposure of Staphylococcus aureus to cell wall inhibitors induces massive overexpression of a number of genes, provided that the VraSR two-component sensory regulatory system is intact. Inactivation of vraS blocks this transcriptional response and also causes a drastic reduction in the levels of resistance to beta-lactam antibiotics and vancomycin. We used an experimental system in which the essential cell wall synthesis gene of S. aureus, pbpB, was put under the control of an isopropyl-beta-d-thiogalactopyranoside-inducible promoter in order to induce reversible perturbations in cell wall synthesis without the use of any cell wall-active inhibitor. Changes in the level of transcription of pbpB were rapidly followed by parallel changes in the vraSR signal, and the abundance of the pbpB transcript was precisely mirrored by the abundance of the transcripts of vraSR and some additional genes that belong to the VraSR regulon. Beta-lactam resistance in S. aureus appears to involve a complex stress response in which VraSR performs the critical role of a sentinel system capable of sensing the perturbation of cell wall synthesis and allowing mobilization of genes that are essential for the generation of a highly resistant phenotype. One of the sites in cell wall synthesis "sensed" by the VraSR system appears to be a step catalyzed by PBP 2.

Anti-Bacterial Agents↗
PubMed2006

Chlamydia trachomatis in cervical and vaginal swabs and urine specimens from women undergoing termination of pregnancy.

The study was devised to assess the prevalence of Chlamydia trachomatis in endocervical and vaginal swabs and first pass urine specimens from women presenting for termination of pregnancy (TOP) and to evaluate the performance of the tests used, namely the ligase chain reaction (LCR) and the direct fluorescence antibody (DFA) test. Eight hundred and sixty three (91%) of 948 women invited to participate agreed to do so; a complete set of results for all test-site combinations was achieved for 793 (92%). The overall prevalence of C. trachomatis was 8.54% (95% confidence interval [CI]: 7.6-10.5%) with a significant negative association with age. The sensitivity (95% CI) of the LCR test for cervical, vaginal and urine specimens was 97% (93-99%); 94% (88-99%) and 83% (75-92%), respectively. The sensitivity (95% CI) of the DFA test for cervical, vaginal and urine specimens was 93% (87-99%); 92% (86-99%) and 78% (68-88%), respectively. Concordance between the LCR and DFA test results was very high for specimens from the same site. The results indicate that nucleic acid amplification tests are appropriate for screening women seeking TOP and, indeed, other women in early pregnancy. The sensitivity of the LCR test for urine specimens was less, but the high levels of concordance observed between the LCR and DFA test results for urine specimens indicates that this was due to a lower organism load rather than inhibition of the LCR.

Abortion, Induced↗
PubMed2005

PS-341 and gemcitabine in patients with metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Group (NCCTG) randomized phase II study.

BACKGROUND: PS-341 is a proteasome inhibitor with preclinical activity in pancreatic cancer tumor models and synergistic activity with gemcitabine. This randomized phase II study determined the tumor response rate (RR) for PS-341 alone and the 6-month survival and RR for the combination of gemcitabine and PS-341 in patients with metastatic pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients were randomized to receive 3-week cycles of either arm A: PS-341 1.5 mg/m(2) i.v. bolus (over 3--5 s) on days 1, 4, 8 and 11 or arm B: PS-341 1.0 mg/m(2) (same as arm A otherwise) plus gemcitabine 1,000 mg/m(2) i.v. on days 1 and 8. Patients progressing on arm A were allowed to receive arm B treatment. RESULTS: Arm A: 42 evaluable patients were enrolled with a confirmed RR of 0% (95% CI 0% to 8%), median survival of 2.5 months (95% CI 2.0-3.3), and median time to progression (TTP) of 1.2 months (95% CI 1.1--1.3). Twelve of 43 evaluable patients (28%) experienced at least one grade 4+ AE. Arm B: 39 evaluable patients yielded a 6-month survival rate of 41% (16/39, 95% CI 29.8% to 67.0%), median survival of 4.8 months (95% CI 2.4--7.4), median TTP of 2.4 months (95% CI 1.5--3.1), and confirmed RR of 10% (4 partial responses/0 complete responses, 95% CI 3% to 24%). Eleven of 43 evaluable patients (26%) experienced at least one grade 4+ AE. One patient had grade 5 hypotension. CONCLUSION: The use of PS-341 alone or in combination with gemcitabine did not result in an overall survival and RR better than that expected for gemcitabine alone. Based on the lack of efficacy and the toxicity seen in our trial, there does not appear to be a role for PS-341 in pancreatic adenocarcinoma with either of the schedules used in this trial.

Adenocarcinoma↗
PubMed2005

A probabilistic screening model for evaluating pyrethroid surface water monitoring data.

Synthetic pyrethroids have been detected in recent California surface water monitoring. Filtration is avoided during sample workup because pyrethroids are extremely hydrophobic, tending to sorb to most surfaces. The resultant analytical pyrethroid concentrations reflect both dissolved pyrethroid and pyrethroid associated with suspended sediment in the water column. Such "whole-water" analytical data are not directly comparable to aquatic acute toxicity effect concentrations measured in laboratory sediment-free water. Consequently, any potential aquatic toxicity risk is indeterminate. In this study a simple probabilistic model was developed to allow a screening-level assessment of pyrethroid whole-water monitoring data. The results suggest that water column toxicity of pyrethroids is possible in California's agriculturally-dominated tributaries, and indicate that additional monitoring to better characterize pyrethroid water-column concentrations are warranted. Model refinement will depend on future work that more firmly establishes the relationship between pyrethroid partitioning and bioavailability, and that addresses the potential influence of dissolved organic carbon on pyrethroid sorption and bioavailability.

Adsorption↗
PubMed2003

Review article: colorectal cancer chemotherapy.

Colorectal cancer is a leading cause of cancer death world-wide. There have been important advances in the chemotherapeutic management of colorectal cancer as a result of a deliberate collaborative process of well-designed clinical trials. From the earlier standard of 5-fluorouracil-based therapy alone, the recent availability of newer agents, including capecitabine, irinotecan and oxaliplatin, has significantly expanded the options available for the management of patients with advanced colorectal cancer, with consequent improvements in survival. For patients with resected, high-risk, localized disease, adjuvant systemic chemotherapy improves survival. The identification of new chemotherapy regimens, the use of predictive testing and the integration of novel targeted therapies with cytotoxic chemotherapies are areas of active clinical investigation. A review of the chemotherapeutic management of colorectal cancer is presented.

Antineoplastic Agents↗
PubMed2003

A pilot randomized trial in primary care to investigate and improve knowledge, awareness and self-management among South Asians with diabetes in Manchester.

AIMS: To investigate whether a secondary-primary care partnership education package could improve understanding of diabetes care among South Asians. METHODS: In a pilot randomized controlled trial, in the setting of eight general practices randomized to intervention or control, patients were invited to four or more rotating visits per year by one of a diabetes specialist nurse, dietician or chiropodist working with general practice staff. Participants were from lists of South Asian patients with known Type 2 diabetes in each (general) practice. RESULTS: Patients and practice scores at baseline and 1-year follow-up, from an interview using a questionnaire on knowledge, awareness and self-management of diabetes. Responses were developed into educational packages used during intervention. Of the 411 patients listed at baseline only 211 were traced for interview (refusal only 4%). Mean age was 55.4 years, age of diabetes onset 47.1 years. Fourteen percent were employed and 35% were able to communicate in English fluently. Only 118 could be traced and interviewed at 1 year, although there was no significant difference in demography between those who completed the study and those who did not. Despite a mean of four visits/patient, intervention had no impact on scores for diabetes knowledge, or awareness [score change 0.14, 95% confidence interval (CI) -0.20, 0.49] or self-management (-0.05, 95% CI -0.48, 0.39) between baseline and 1 year. CONCLUSIONS: This form of secondary/primary care support did not transfer information effectively, and we suspect similar problems would arise in other similar communities. Different methods of clinician/patient information exchange need to be developed for diabetes in this South Asian group.

Adult↗
PubMed2003

Clinical experience with porous tantalum cervical interbody implants in a prospective randomized controlled trial.

A prospective randomized study was undertaken to evaluate the radiological appearance and clinical effectiveness of two porous tantalum (Hedrocel) implants in achieving a stable cervical interbody fusion. A prerandomization protocol was used to allocate patients to the three arms of the study: a ring implant containing autologous cancellous bone graft, a solid block implant or autologous tricortical iliac crest bone graft. Patients were followed for 2 years with plain radiological studies, SF-36, and Neck Disability Index questionnaires and neurological assessment. Early in the study the postoperative radiographs of four patients receiving Hedrocel implants showed inferior end-plate lucency raising concerns about delayed or non-fusion. Recruitment to the study was halted by the investigators to allow longer-term follow-up of the implanted patients when only 24 patients had been recruited to the study. Although fusion was subsequently noted in all patients at 12 months there was no further enrolment to the study. At 2 years the radiological and clinical outcomes of the three groups appeared comparable, but the study numbers were too small for any statistical analysis. This study highlights the difficulties that can arise when clinical caution takes precedence over objective measures of clinical progress during a study. In the absence of an independent safety monitoring committee, the investigators were under an ethical obligation to suspend recruitment to this study, until it was clear that the radiological features were not associated with poor clinical outcomes. The use of safety monitoring committees and the clarification of stopping criteria in relation to outcome measures should be considered in open randomized trials of spinal surgical techniques and implants.

Adult↗
PubMed2003

Herbal creams used for atopic eczema in Birmingham, UK illegally contain potent corticosteroids.

AIMS: To determine whether "herbal creams" reported as being effective for the treatment of childhood atopic eczema contained corticosteroids. METHODS: Patients attending the paediatric dermatology clinic at Birmingham Children's Hospital, April 2001 to March 2002, and who reported using "herbal creams" with good effect for atopic eczema were asked to submit the cream for analysis. Hydrocortisone, clobetasone butyrate, betamethasone valerate, and clobetasol propionate were analysed by HPLC. RESULTS: Twenty four creams from 19 patients, median (interquartile range) age 3.82 (0.69-7.98) years were analysed. All five creams labelled Wau Wa and the two labelled Muijiza cream contained clobetasol propionate. Thirteen of 17 unnamed creams contained corticosteroids: clobetasol proprionate (n = 4), clobetasol proprionate + hydrocortisone (n = 1), betamethasone valerate (n = 2), clobetasone butyrate (n = 3), and hydrocortisone (n = 2); there was an unidentified peak in one. Further analysis suggested Wau Wa cream contained approximately 20% proprietary Dermovate Cream in a paraffin base. No parents were aware that the creams contained steroid. CONCLUSIONS: The majority of herbal creams analysed illegally contained potent or very potent topical steroids. There is an urgent need for tighter regulation of herbal creams and for increased public education about the potential dangers of alternative therapies.

Adrenal Cortex Hormones↗
PubMed2003

Descriptive epidemiology of adult critical care transfers from the emergency department.

AIMS: To describe the nature, frequency, and characteristics of adult critical care transfers originating from the emergency department (ED). METHODS: A one year prospective regional descriptive study using multiple data sources of all critically ill adults transferred from an ED or a minor injuries unit (MIU) within the former Yorkshire Regional Health Authority Area or into a regional critical care facility if originating from an ED or MIU elsewhere. RESULTS: 29 EDs transferred 349 adults into the regional critical care facilities. The median number of transfers per department within the region was 18 (range 1 to 42). Seventeen were transferred from outside the region. A total of 263 (75%) patients were transferred for specialist care and 76 (22%) for non-clinical reasons. Altogether 294 (84%) were admitted to intensive care or a high dependency unit at the receiving hospital. The in-hospital documented mortality rate was 26%. A total of 170 patients (49%) had traumatic pathology of which 101 were principally transferred for management of a head injury. Median time in the ED was 3 hours 5 minutes (range 11 minutes to 17 hours 47 minutes). In 146 (42%) patients the decision to transfer was primarily made by the emergency medicine clinician. A total of 251 (72%) patients were intubated. The documented critical incident rate was 15%. CONCLUSION: Trauma is the most common reason for transfer of the critically ill adult from the ED. A significant number of patients are transferred, however, with medical and surgical conditions and for non-clinical reasons. There continues to be problems with the quality of care that these patients receive. Emergency medicine clinicians must be actively involved in the development of regional critical care systems as a significant proportion of all critically ill adults transferred originate from the ED.

Adult↗
PubMed2003

Male breast cancer.

OBJECTIVE: To review cases of male breast cancer. SETTINGS: Histopathology Section, Department of Pathology, The Aga Khan University, Karachi. METHOD: Fifty one cases of male breast cancer specimens, received during a period of 10 years, routinely processed and stained with Haematoxylin and Eosin were analyzed. Special stains and Immunohistochemistry were used in difficult cases. RESULTS: Male breast cancer affected individuals in the sixth and seventh decades of life with a mean age of 56.2 years. Infiltrating ductal carcinoma (IDC) was the predominant type. Skin involvement was seen in 27.45% of the cases. Breast lump was the most common presenting symptom followed by skin ulceration. At the time of presentation 43.13% patients had a tumour size of more than 3 cm. CONCLUSION: Male breast cancer is a rare disease. Most of our findings correspond to the published local and international data.

Aged↗
PubMed2001

Neuroendocrine aspects of aging in women.

In women, the loss of ovarian function at menopause is associated with marked changes in hypothalamic and pituitary function. In addition, the steady decline in serum levels of LH, FSH, and FAS with age following menopause provides clear evidence for age-related neuroendocrine changes independent of the changes occurring owing to loss of ovarian feedback on the hypothalamic and pituitary components of the reproductive axis. An increase in the overall amount of GnRH secreted occurs despite a 30% decrease in GnRH pulse frequency with aging. This observation implies that the amount of GnRH secreted with each secretory bolus is greater in older postmenopausal women when compared with younger postmenopausal women. Thus, there may be a prominent pituitary component to the age-related decline in gonadotropin secretion. Recent studies indicate that the response to estrogen negative feedback at the hypothalamic level is preserved with aging, whereas the response to estrogen positive feedback may decrease with reproductive aging; however, the response to estrogen positive feedback in women has not been investigated with respect to aging, per se. It will be important to determine whether these age-related changes in hypothalamic-pituitary function contribute to reproductive senescence in normal women, as has been suggested for similar changes in animal models.

Aging↗
PubMed2001

Hyperkinetic movement disorder in an 11-year-old child treated with bilateral pallidal stimulators.

Pallidal stimulation is widely used in the treatment of movement disorder in adults but is less well reported in the treatment of dystonia in children. Despite inconsistent results in the past, its use in dystonia in Parkinson's disease is again attracting interest with promising results. Bilateral as well as unilateral pallidotomies have been performed and are felt to be required in some cases of dystonia. Use of depth electrodes to provide long-term electrical stimulation to pallidum and other basal ganglia structures has recently become more widespread. This technique is felt to have a lower morbidity, especially in bilateral procedures. Here we present the case of an 11-year-old boy with severe hyperkinetic movement disorder who showed sustained improvement after bilateral pallidal stimulation implantation.

Cerebral Palsy↗
PubMed2001

Obstacles to residents' conducting research and predictors of publication.

Internal medicine residents at one school identified barriers to and predictors of publishing their research. Insufficient time was the key obstacle to completing research. Residents with previous research experience, senior residents, and men were more likely to publish.

Attitude of Health Personnel↗