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Biomedical subjects

S S Gill

Publications and source records attributed to S S Gill.

At least 19 recordsLinked to original sources

Effects of antihypertensive drug treatments on fracture outcomes: a meta-analysis of observational studies.

OBJECTIVE: To quantitatively pool findings from observational studies on the risk of fracture outcomes associated with exposure to five antihypertensive drug classes: angiotensin-converting enzyme (ACE) inhibitors, diuretics (in particular thiazide diuretics), beta-blockers, calcium-channel blockers and alpha-blockers. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Publications listed in the MEDLINE, EMBASE and LILACS databases, the ISI proceedings, and bibliographies of retrieved articles. Sources were searched from the earliest possible dates through December 2005. REVIEW METHODS: We included case-control and cohort studies presenting relative risks and confidence intervals (CIs) for the association between exposure to antihypertensive agents and fracture outcomes. Data were extracted onto a standardized computer worksheet. Study quality was assessed using a 10-point questionnaire specific to case-control or cohort study design. RESULTS: Fifty-four studies were identified. Pooled estimates were computed using the software HEpiMA. The pooled relative risk (RR) of any fracture with use of thiazide diuretics was 0.86 (95% CI 0.81-0.92) and 1.14 (95% CI 0.84-1.54) with use of nonthiazide diuretics. There was a statistically significant reduction of any fracture with use of beta-blockers, (RR 0.86, 95% CI 0.70-0.98). The one study with ACE inhibitor data showed protection (RR 0.81, 95% CI 0.73-0.89). No significant associations were found between fractures and exposure to alpha-blockers or calcium-channel blockers. CONCLUSIONS: Thiazide diuretics and beta-blockers appear to lower the risk of fractures in older adults. However, these agents cannot be recommended as preventive therapies for fractures until data from randomized controlled trials have established their efficacy. Patients who use these inexpensive drugs as treatments for hypertension may also benefit from a reduction in fracture risk.

Adrenergic alpha-Antagonists↗

Oligomerization triggers binding of a Bacillus thuringiensis Cry1Ab pore-forming toxin to aminopeptidase N receptor leading to insertion into membrane microdomains.

Bacillus thuringiensis Cry1A toxins, in contrast to other pore-forming toxins, bind two putative receptor molecules, aminopeptidase N (APN) and cadherin-like proteins. Here we show that Cry1Ab toxin binding to these two receptors depends on the toxins' oligomeric structure. Toxin monomeric structure binds to Bt-R1, a cadherin-like protein, that induces proteolytic processing and oligomerization of the toxin (Gomez, I., Sanchez, J., Miranda, R., Bravo A., Soberon, M., FEBS Lett. (2002) 513, 242-246), while the oligomeric structure binds APN, which drives the toxin into the detergent-resistant membrane (DRM) microdomains causing pore formation. Cleavage of APN by phospholipase C prevented the location of Cry1Ab oligomer and Bt-R1 in the DRM microdomains and also attenuates toxin insertion into membranes despite the presence of Bt-R1. Immunoprecipitation experiments demonstrated that initial Cry1Ab toxin binding to Bt-R1 is followed by binding to APN. Also, immunoprecipitation of Cry1Ab toxin-binding proteins using pure oligomeric or monomeric structures showed that APN was more efficiently detected in samples immunoprecipitated with the oligomeric structure, while Bt-R1 was preferentially detected in samples immunoprecipitated with the monomeric Cry1Ab. These data agrees with the 200-fold higher apparent affinity of the oligomer than that of the monomer to an APN enriched protein extract. Our data suggest that the two receptors interact sequentially with different structural species of the toxin leading to its efficient membrane insertion.

Animals↗

Expression of an Aedes aegypti cation-chloride cotransporter and its Drosophila homologues.

Insects maintain haemolymph homeostasis under different environmental conditions by modulating the concentrations of Na+, K+ and Cl- ions. One group of proteins involved in ion transport across cell membranes consists of cation-chloride cotransporters that form a family of structurally similar proteins. Although much is known about these proteins in mammalian systems, our understanding of them in insects is lacking. The recent sequencing of two insect genomes, Drosophila and Anopheles, enabled us to identify globally members of the family of cation chloride cotransporters in these insects. Using RT-PCR we monitored the transcription of members of this family in development and in several tissues. Our analyses showed that transcription of these genes differ considerably from the ubiquitously and highly expressed CG5594 gene to the almost silent gene CG31547. Comparison of Drosophila CG12773 and its Aedes homologue AaeCG12773 showed that they have similar transcript expression profiles. Immunohistochemical analysis of AaeCG1277 gene expression revealed that it is highly expressed in the gut of larvae and female adults but not in Malpighian tubules. A more detailed analysis showed that this protein is localized predominantly in the basolateral membrane of these tissues. This expression pattern confirmed the results of RT-PCR analysis. We also created a mutant for one of the genes, CG10413, in Drosophila using P-element excision. Analysis of this mutant showed this protein does not appear to be essential for development.

Aedes↗

MRI directed bilateral stimulation of the subthalamic nucleus in patients with Parkinson's disease.

OBJECTIVE: Bilateral chronic high frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has emerged as an appropriate therapy for patients with advanced Parkinson's disease refractory to medical therapy. Advances in neuroimaging and neurophysiology have led to the development of varied targeting methods for the delivery of this treatment. Intraoperative neurophysiological and clinical monitoring is regarded by many to be mandatory for accurate STN localisation. We have examined efficacy of bilateral STN stimulation using a predominantly magnetic resonance imaging (MRI)-directed technique. METHODS: DBS leads were stereotactically implanted into the STN using an MRI directed method, with intraoperative macrostimulation used purely for adjustment. The effects of DBS were evaluated in 16 patients followed up to 12 months, and compared with baseline assessments. Assessments were performed in both off and on medication states, and were based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests. Functional status outcomes were examined using the PDQ-39 quality of life questionnaire. A battery of psychometric tests was used to assess cognition. RESULTS: After 12 months, stimulation in the off medication state resulted in significant improvements in Activities of Daily Living and Motor scores (UPDRS parts II and III) by 62% and 61% respectively. Timed motor tests were significantly improved in the off medication state. Motor scores (UPDRS part III) were significantly improved by 40% in the on medication state. Dyskinesias and off duration were significantly reduced and the mean dose of L-dopa equivalents was reduced by half. Psychometric test scores were mostly unchanged or improved. Adverse events were few. CONCLUSIONS: An MRI directed targeting method for implantation of DBS leads into the STN can be used safely and effectively, and results are comparable with studies using intraoperative microelectrode neurophysiological targeting. In addition, our method was associated with an efficient use of operating time, and without the necessary costs of microelectrode recording.

Aged↗

Chronic subdural haematoma and the enigmatic eosinophil.

The membranes from 50 cases of chronic subdural haematomas were examined histologically and correlated with the duration of the lesion. Cases were divided into three groups based on duration from time of trauma and/or onset of clinical symptoms to date of surgery - Group I: 1 to 30 days, Group II: 31 to 90 days and Group III: >90 days. Infiltration with eosinophils was observed in the vascularised and hyalinised granulation tissue of the subdural membrane in 30 of the 50 cases (60%). There was a trend to correlation both of the frequency and the extent of eosinophilic infiltration with duration of haematoma. Thus, eosinophils were encountered in about half the cases with duration up to 3 months which increased to 80% in cases with duration more than 3 months. The extent of eosinophilic infiltration (mild, moderate or severe) also appeared to correlate with duration of haematoma in that mild infiltration was more common in Group I cases while moderate to severe infiltration were more frequently observed in Group II and III cases. No correlation was observed of the eosinophilic infiltrate with age and sex of the patients or with presence of other cellular inflammatory components of the membrane. Interestingly, a finding hitherto unreported in English literature was the demonstration of mast cells in 7 of 16 membranes (44%) which had been stained using toluidine blue. It is possible that the eosinophils appear at this unusual site due to chemotactic stimulus abetted by these mast cells as well as lymphocytes and haemosiderin pigment. The eosinophils may have an important role in the repair and healing process of these membranes.

Adolescent↗

Laminal fenestration for the treatment of lumbar nerve root foraminal stenosis.

A new technique is reported for the treatment of isolated lumbar nerve root foraminal stenosis. Nerve root decompression is performed via a 5-mm drill hole in the lamina immediately below the superior facet. This technique preserves spinal stability even if done at multiple levels. It also provides early mobility of the patient and subsequently shortens the hospital stay. The technical details are described.

Humans↗

The influence of preoperative nutritional status in wound healing after replacement arthroplasty.

Patient nutritional status was evaluated preoperatively using the serological parameters serum albumin, serum transferrin, and total lymphocyte count in 40 patients who underwent replacement arthroplasty (33 hips and 7 knees). Using the standard criteria, the overall incidence of malnutrition was 40% (16 cases). Ten percent (4 patients) had a negative value in the Rainey McDonald nutritional index. On follow-up, no patient had delayed wound healing or wound infection. Attention to surgeon-dependent factors can offset the high risk of delayed wound healing imposed by patient-dependent factors.

Adult↗

Posterior-only unit rod instrumentation and fusion for neuromuscular scoliosis.

STUDY DESIGN: A retrospective study to determine the efficacy of posterior-only unit rod instrumentation and fusion in a skeletally immature neuromuscular scoliosis population. OBJECTIVE: To determine whether the posterior-only approach to this population adequately addresses the concerns of correction of scoliosis and pelvic obliquity, maintenance of that correction over time, and the incidence of crankshaft phenomenon. SUMMARY OF BACKGROUND DATA: Controversy exists regarding the need for anterior release to improve curve flexibility and the need to obtain an anterior arthrodesis in those skeletally immature patients at risk for crankshafting with continued anterior growth. METHODS: From 1992 through 1997, 28 consecutive skeletally immature patients with neuromuscular scoliosis underwent posterior-only unit rod instrumentation and fusion for the treatment of progressive, symptomatic spinal deformities. Preoperative, immediate postoperative, and final follow-up radiographs were analyzed with respect to scoliosis and pelvic obliquity correction, maintenance of that correction over time, and the development of the crankshaft phenomenon as evidenced by loss of correction and/or increased rib-vertebral angle difference. The average age of the patients was 12.8 years and the average follow-up was 58 months with a minimum of 2 years. RESULTS: Twenty-six patients were available for final follow-up. The initial Cobb angle correction averaged 66%, with 75% of the pelvic obliquity corrected. These corrections were maintained over time. Before surgery 27 of 28 patients were Risser 0, 1, or 2. The triradiate cartilage was open in nine patients, and five patients were < or =10 years of age. At the final follow-up 22 of the 26 patients were Risser 5 and 4 were Risser 4. There was one patient with increased rib-vertebral angle difference over the length of follow-up, with no loss of frontal or sagittal plane alignment. CONCLUSIONS: These results indicate that even in the very young neuromuscular patient, acceptable amounts of curve correction can be achieved and maintained with posterior-only unit rod instrumentation and fusion. The biomechanical stiffness of this construct seemed to be able to prevent the crankshaft phenomenon in the majority of those patients at risk.

Adult↗

Mapping the epitope in cadherin-like receptors involved in Bacillus thuringiensis Cry1A toxin interaction using phage display.

In susceptible lepidopteran insects, aminopeptidase N and cadherin-like proteins are the putative receptors for Bacillus thuringiensis (Bt) toxins. Using phage display, we identified a key epitope that is involved in toxin-receptor interaction. Three different scFv molecules that bind Cry1Ab toxin were obtained, and these scFv proteins have different amino acid sequences in the complementary determinant region 3 (CDR3). Binding analysis of these scFv molecules to different members of the Cry1A toxin family and to Escherichia coli clones expressing different Cry1A toxin domains showed that the three selected scFv molecules recognized only domain II. Heterologous binding competition of Cry1Ab toxin to midgut membrane vesicles from susceptible Manduca sexta larvae using the selected scFv molecules showed that scFv73 competed with Cry1Ab binding to the receptor. The calculated binding affinities (K(d)) of scFv73 to Cry1Aa, Cry1Ab, and Cry1Ac toxins are in the range of 20-51 nm. Sequence analysis showed this scFv73 molecule has a CDR3 significantly homologous to a region present in the cadherin-like protein from M. sexta (Bt-R(1)), Bombyx mori (Bt-R(175)), and Lymantria dispar. We demonstrated that peptides of 8 amino acids corresponding to the CDR3 from scFv73 or to the corresponding regions of Bt-R(1) or Bt-R(175) are also able to compete with the binding of Cry1Ab and Cry1Aa toxins to the Bt-R(1) or Bt-R(175) receptors. Finally, we showed that synthetic peptides homologous to Bt-R(1) and scFv73 CDR3 and the scFv73 antibody decreased the in vivo toxicity of Cry1Ab to M. sexta larvae. These results show that we have identified the amino acid region of Bt-R(1) and Bt-R(175) involved in Cry1A toxin interaction.

Amino Acid Sequence↗

Drosophila RNase H1 is essential for development but not for proliferation.

Ribonucleases H (RNases H) recognize and specifically degrade RNA that is bound to complementary DNA and are thought to be involved in DNA replication and transcriptional regulation. Though it was previously shown that bacterial RNases H participate in DNA synthesis, none of the known mutations in RNase H genes in either prokaryotes or lower eukaryotes is lethal. Here, we report the characterization of the first loss-of-function mutation in an RNase H1 gene in a metazoan organism, Drosophila melanogaster. Genetic studies of this mutant showed that this gene is essential for metamorphosis in Drosophila. However, disruption of the RNase H1 gene does not affect proliferation, but probably alters the regulation of gene expression. The lethal phenotype of this mutant also demonstrates that RNase H1 activity in Drosophila cannot be provided by other cellular RNase H activities. Analysis of the developmental and spatial expression profiles of a reporter gene placed under the control of the RNase H1 promoter revealed increased expression in several larval tissues. In salivary glands this increase was shown to be inducible by treatment with ecdysone.

Animals↗

Comparative strength of three methods of fixation of transverse acetabular fractures.

With the advent of percutaneously placed lag screws for fixation of acetabular fractures, this study evaluated the strength of lag screw fixation compared with traditional fixation techniques of transverse acetabular fractures. Ten formalin-treated human, cadaveric pelvic specimens with bilateral, transtectal transverse acetabular fractures were used for this study. The right acetabular fractures were fixed with a five-hole plate and four screws with the central hole spanning the posterior fracture site. The left acetabular fractures were fixed with two lag screws, one each in the anterior and posterior columns, or with a screw and wire construct stabilizing both columns. The specimens were loaded to implant failure. Stiffness, yield strength, maximum load at failure, and site of failure was recorded. The plate and screw construct showed significantly greater yield and maximum strength when compared with the two lag screws. The stiffness of the lag screw method was 39% higher than that of the plating method, but this result was not statistically significant. In addition, the plate and screw method provided significantly greater maximum strength than the screw and wire technique. The quadrilateral plate seemed to be the weakest area of fixation because 83% of the implant failures occurred in this region. In patients in whom the risks of formal open reduction and internal fixation of acetabular fractures outweigh the possible benefits, such as in patients with burns or degloved skin, the advent of computer-assisted and fluoroscopically guided percutaneous surgical techniques have been instrumental. This study showed there is greater strength of fixation with a plate and screw construct, possibly secondary to supplementary fixation distal to the quadrilateral plate. However, lag screw fixation provided relatively greater stiffness, which may account for its clinical success. Percutaneous lag screw fixation of appropriate transverse acetabular fractures is a viable option.

Acetabulum↗

Small intestinal neoplasms.

Small intestinal neoplasms are uncommonly encountered in clinical practice. They may occur sporadically, in association with genetic diseases (e.g., familial adenomatous polyposis coli or Peutz-Jeghers syndrome), or in association with chronic intestinal inflammatory disorders (e.g., Crohn's disease or celiac sprue). Benign small intestinal tumors (e.g., leiomyoma, lipoma, hamartoma, or desmoid tumor) usually are asymptomatic but may present with intussusception. Primary malignancies of the small intestine-including adenocarcinoma, leiomyosarcoma, carcinoid, and lymphoma-may present with intestinal obstruction, jaundice, bleeding, or pain. Extraintestinal neoplasms may involve the intestine via contiguous spread or peritoneal metastasis. Hematogenous metastases to the intestine from an extraintestinal primary are unusual and are most typical of melanoma. Because the small intestine is relatively inaccessible to routine endoscopy, diagnosis of small intestinal neoplasms is often delayed for months after onset of symptoms. When the diagnosis is suspected, enteroclysis is the most useful imaging study. Small bowel endoscopy (enteroscopy) is increasingly widely available and may permit earlier, nonoperative diagnosis.

Biopsy, Needle↗

Improving prescribing in the elderly: a study in the long term care setting.

OBJECTIVES: To determine the prevalence and predictors of potentially inappropriate prescribing of medications in the long term care setting, and to determine the effectiveness of follow-up pharmacist letters to the prescribing physicians in improving prescribing. PATIENTS AND METHODS: The Improving Prescribing in the Elderly Tool was applied to the charts of all long term care patients aged 65 years and over at Parkwood Hospital, a rehabilitation hospital/long term care facility in London, Ontario. All potentially inappropriate prescriptions were verified by a consensus panel consisting of a family physician, a geriatric medicine specialist and a geriatric pharmacist. Follow-up letters to the prescribing physicians were developed that briefly described the concerns with the potentially inappropriate prescriptions and suggested safer alternatives. These letters were sent to the prescribing physicians, accompanied by a brief survey. Patient charts in which a potentially inappropriate prescription had been noted were reviewed for prescription changes two months after the prescribing physicians had received the follow-up letters. RESULTS: A total of 69 potentially inappropriate prescriptions were found in 65 of 355 long term care patients (18.3%). The most common types of potentially inappropriate prescriptions were anticholinergic drugs to manage antipsychotic side effects (17 cases), tricyclic antidepressants with active metabolites (16 cases), and long-acting benzodiazepines (14 cases). The total number of prescription medications (P<0.001), a history of mental illness (P=0.002) and a high minimum data set (MDS) score for depression (P=0.002) were all highly associated with potentially inappropriate prescribing. Variables that were not correlated with increased rates of potentially inappropriate prescribing included age, sex, code status, a diagnosis of dementia (as documented explicitly in the chart), high MDS scores for delirium or cognitive impairment, the date of the prescribing physician's graduation and the total Charlson comorbidity index score. Potentially inappropriate prescriptions were significantly less common in patients seen by a geriatric medicine specialist (P<0.001). In response to the follow-up letter suggesting safer alternatives, 37.9% of potentially inappropriate prescriptions were changed by the prescribing physician. Ninety-two per cent of responding physicians rated the follow-up letter as a "somewhat" or "very" helpful method for improving prescribing in elderly patients. CONCLUSIONS: Potentially inappropriate prescribing in the long term care setting is common and can be improved by the provision of a follow-up letter suggesting safer alternatives.

Aged↗

Fractures in transfusion dependent beta thalassemia--an Indian study.

AIM OF STUDY: To analyse the incidence of fractures in beta thalassemia patients and to identify causative factors. METHODS: We examined all cases of transfusion dependent beta thalassemia (TDBT) seen at our institute over a two-year period. The transfusion records, incidence of fractures, cause of fracture and Hb levels were recorded. Radiographs of the involved parts were taken in cases with fractures only. RESULTS AND CONCLUSIONS: Amongst 105 cases of TDBT assessed, 14 sustained a total of 28 fractures. Seven patients sustained more than one fracture. Two thirds of these fractures were caused by trivial trauma. All fractures, except one, were of the closed type. Radiologically, fractures frequently showed minimal or no displacement. All fractures were successfully treated by closed modalities of treatment. Majority of the fractures healed within normal union time for a given bone. Permanent deformities and gross limb length discrepancies were uncommon. On reviewing the literature, we noted that the incidence of fractures in our series and in the latest reports was lesser than previously reported. We postulate that this is a result of better and earlier control of hemoglobin status by improved transfusion techniques, and earlier recognition of the disease. Difficulties arise due to inadequate blood transfusion facilities in developing countries.

Blood Transfusion↗

A novel type of RNase III family proteins in eukaryotes.

The RNase III family of double-stranded RNA-specific endonucleases is characterized by the presence of a highly conserved 9 amino acid stretch in their catalytic center known as the RNase III signature motif. We isolated the drosha gene, a new member of this family in Drosophila melanogaster. Characterization of this gene revealed the presence of two RNase III signature motifs in its sequence that may indicate that it is capable of forming an active catalytic center as a monomer. The drosha protein also contains an 825 amino acid N-terminus with an unknown function. A search for the known homologues of the drosha protein revealed that it has a similarity to two adjacent annotated genes identified during C. elegans genome sequencing. Analysis of the genomic region of these genes by the Fgenesh program and sequencing of the EST cDNA clone derived from it revealed that this region encodes only one gene. This newly identified gene in nematode genome shares a high similarity to Drosophila drosha throughout its entire protein sequence. A potential drosha homologue is also found among the deposited human cDNA sequences. A comparison of these drosha proteins to other members of the RNase III family indicates that they form a new group of proteins within this family.

Amino Acid Sequence↗

Tuberculous anal sepsis: report of clinical features in 20 cases.

INTRODUCTION: Tuberculosis is a neglected cause of anal sepsis, often is not recognized, and therefore is not treated properly. METHOD: All patients were reviewed who had tuberculous anal sepsis diagnosed by histology reports of fistulectomy specimens or abscess scrapings from January 1990 to April 1999. RESULTS: Twenty patients (median age, 53 years; 18 males) with anal tuberculous sepsis were identified. They presented with abscesses (n = 2), abscesses and fistulas (n = 6), or fistulas (n = 12). All patients had a long history of anal complaints (3 months to 20 years), for which 15 patients were operated on previously. Nearly all fistulas (17/18) were complex, and secondary tracks or additional complicating features were common, even at first presentation. Eight patients had active concurrent pulmonary tuberculosis, and six showed evidence of previous pulmonary tuberculosis. Six patients had no signs of concurrent or previous tuberculosis elsewhere. Recurrence was observed only in cases where tuberculosis was initially not recognized, and antitubercular treatment therefore was not started. CONCLUSION: Contrary to views held previously, anal tubercular sepsis seems to have characteristic clinical features. It should be considered in cases of known pulmonary or extrapulmonary tuberculosis or if anal sepsis is persistent, recurrent, or complex in nature.

Adult↗

Cognitive functioning after subthalamic nucleotomy for refractory Parkinson's disease.

OBJECTIVE: To evaluate whether subthalamic nucleotomy produces adverse cognitive effects in patients with Parkinson's disease. METHOD: Twelve patients with Parkinson's disease underwent stereotactic surgery to the subthalamic nucleus. Presurgical and postsurgical neuropsychological assessment of attention, memory, executive function, language, and verbal intellect were undertaken with a battery of tests designed to minimise potential contamination of cognitive effects by motor symptoms. RESULTS: There was no statistically significant difference in the cognitive tests results after operation for the group as a whole. Reliable change indexes were generated for the cognitive tests. Reliable change postoperatively was found on specific tests of verbal memory, attention, and planning. Left sided operations were associated with greater incidence of deterioration postsurgery. CONCLUSIONS: Preliminary data on the first reported cognitive changes after subthalamic nucleotomy suggested few adverse cognitive effects of the surgery although discrete neuropsychological changes were seen in some patients. These effects were consistent with current theories on the cognitive functions of the basal ganglia.

Adult↗

Temporal and spatial expression of the cell-cycle regulator cul-1 in Drosophila and its stimulation by radiation-induced apoptosis.

Cul-1 protein is part of the ubiquitin ligase complex that is conserved from yeast to humans. This complex specifically marks cell-cycle regulators for their subsequent destruction. Two null mutations of the cul-1 gene are known, in budding yeast and in nematodes. Although in both these organisms the cul-1 gene executes essentially the same function, the manifestation of its lack-of-function mutations differs considerably. In yeast the mutation causes arrest at the G(1)/S-phase transition, whereas in nematodes excessive cell divisions occur because mutant cells are unable to exit the mitotic cycle. We isolated cul-1 orthologues from two model organisms, Drosophila melanogaster and mouse. We show that the Drosophila full-length cul-1 gene restores the yeast mutant's inability to pass through the G(1)/S-phase transition. We also characterize expression of this gene at the transcript and protein levels during Drosophila development and show that cul-1 gene is maternally supplied as a protein, but not as an RNA transcript. Zygotic transcription of the gene, however, resumes at early stages of embryogenesis. We also found an increase in cul-1 transcription in cultured cells treated with a lethal dose of gamma-irradiation.

Amino Acid Sequence↗