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Biomedical subjects

S Gardner

Publications and source records attributed to S Gardner.

At least 37 records · Page 2Linked to original sources
PubMed1998

Iditis: protein structure database.

The validation, enrichment and organization of the data stored in PDB files is essential for those data to be used accurately and efficiently for modelling, experimental design and the determination of molecular interactions. The Iditis protein structure database has been designed to allow the widest possible range of queries to be performed across all available protein structures. The Iditis database is the most comprehensive protein structure resource currently available, and contains over 500 fields of information describing all publicly deposited protein structures. A custom-written database engine and graphical user interface provide a natural and simple environment for the construction of searches for complex sequence- and structure-based motifs. Extensions and specialized interfaces allow the data generated by the database to used in conjunction with a wide range of applications.

Database Management Systems↗
PubMed1998

Early hepatitis C virus-RNA responses predict interferon treatment outcomes in chronic hepatitis C. The Consensus Interferon Study Group.

In previous studies employing interferons (IFNs) in the treatment of chronic hepatitis C, there have been few reliable predictors of sustained responses. We retrospectively evaluated the predictive value of hepatitis C virus (HCV)-RNA measurements in the first few months during consensus interferon (CIFN) treatment using a sensitive reverse-transcriptase polymerase chain reaction assay to determine sustained responses. Data from two large treatment trials, one of IFN-naive patients and one of retreated relapsers and nonresponders, were used, including serum samples at 2-week intervals in the naive study and 8-week intervals in the retreatment study. Patients received initial CIFN (9 microgram) treatment for 6 months and were assessed 6 months after treatment. There were 28 sustained viral responders of 232 CIFN-treated patients. Of the sustained responders, 48% had already cleared HCV RNA from serum (<100 copies/mL) by week 2, 78% by week 4, 81% by week 6, and 96% by week 12. Patients with early HCV-RNA clearance were more likely to have sustained responses than those who responded later. Early clearance of HCV from serum was also associated with greater likelihood of a sustained response to 48 weeks of retreatment with 15 microgram CIFN. Ninety-five percent of the sustained responders were HCV-RNA-negative by week 8 of retreatment. Early assessment of HCV RNA may help in the prediction of sustained responses to IFN and allow the value of continued treatment to be determined early in the course of IFN therapy.

Antiviral Agents↗
PubMed1998

Nursing assessment: impact on type and cost of interventions to prevent pressure ulcers.

OBJECTIVE: To describe pressure ulcer preventive interventions and their cost, and to compare the preventive intervention use and cost with level of risk. DESIGN: Comparative, descriptive design. SETTING AND SUBJECTS: A large midwestern Veteran's Affairs Medical Center with 260 long-term care beds. Thirty-one chair- or bed-bound residents from 1 long-term care unit comprised the study sample. MAIN OUTCOME MEASURES: The outcome variables included demographic information (patient record), Braden Risk Assessment score, institutional risk assessment score (Pressure Ulcer Risk Tool), type and frequency of preventive interventions, and the related costs. METHODS: Subjects were assessed on a weekly basis for type and frequency of preventive intervention and for the development of a pressure ulcer. Each subject was observed until death, discharge, pressure ulcer formation, or the end of the 3-month study period. RESULTS: The 3-month pressure ulcer incidence rate was 13%. All subjects were at risk for pressure ulcer development according to Braden scores; whereas only 74% were assessed at risk with use of the facility's risk assessment tool. Preventive measures included regular repositioning (87%); 67% were placed on mattress support surfaces. There was no relationship between level of risk (facility risk tool score) and type of prevention used. The total cost of pressure ulcer prevention to the nursing unit was $14,926, representing a mean of $497 per subject, and $5.55 per subject per day. CONCLUSION: As compared with previous studies, the higher cost of prevention described in this study may be attributed to inadequate linkage of preventive interventions to risk level.

Aged↗
PubMed1998

Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors.

PURPOSE: To evaluate a strategy that avoids radiotherapy in children less than 6 years of age with newly diagnosed malignant brain tumors, by administering myeloablative consolidation chemotherapy with autologous bone marrow reconstitution (ABMR) after maximal surgical resection and conventional induction chemotherapy. PATIENTS AND METHODS: Between March 1991 and April 1995, 62 children (median age, 30 months) with newly diagnosed malignant brain tumors were enrolled onto this trial. Children received conventional induction chemotherapy with vincristine, cisplatin, cyclophosphamide, and etoposide, repeated every 3 weeks for five cycles. Children without disease progression on induction chemotherapy were offered consolidation with myeloablative chemotherapy that incorporated carboplatin, thiotepa, and etoposide followed by ABMR. Irradiation was used only for residual tumor at consolidation or for progressive/recurrent disease. RESULTS: Induction chemotherapy was well tolerated by most patients; however, progression was noted in 17 children (27%) and four (6%) died of treatment complications. Of 37 children who received consolidation chemotherapy with ABMR, 15 are free of disease progression (median post-ABMR without further treatment, >44 months). The remaining 22 all progressed within 15 months of ABMR; three of 37 (8%) died of treatment-related complications. The 3-year overall survival (OS) and event-free survival (EFS) rates from diagnosis for all children are 40% (95% confidence interval [CI], 28% to 52%) and 25% (95% CI, 13% to 37%), respectively. Radiotherapy was administered to 19 of 62 children: 17 for progressive disease (PD) and two for residual disease at the time of ABMR. CONCLUSION: A significant proportion of children with malignant brain tumors can avoid radiotherapy and prolonged maintenance chemotherapy yet still achieve durable remission with this brief intensive chemotherapy regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Myeloablative chemotherapy with autologous bone marrow rescue in young children with recurrent malignant brain tumors.

PURPOSE: This study evaluates the outcome of myeloablative chemotherapy and autologous bone marrow rescue (ABMR) with or without radiotherapy in children younger than 6 years of age with recurrent malignant brain tumors who had not previously been exposed to conventional fractionated external-beam irradiation. PATIENTS AND METHODS: Patients underwent surgery and/or conventional chemotherapy at the time of recurrence to achieve minimal residual disease (two of these patients also underwent local single-fraction gamma-knife radiosurgery). Myeloablative chemotherapy was then administered with carboplatin, thiotepa, and etoposide (16 patients), thiotepa and etoposide (three patients), or thiotepa, etoposide, and carmustine (BCNU; one patient). Autologous bone marrow was re-infused 72 hours after chemotherapy. Twelve patients received external-beam irradiation after recovery from ABMR. RESULTS: Twenty patients with recurrent brain tumors aged 0.7 to 5.9 years (median, 2.9 years) at ABMR were evaluated. Two patients died of toxicity related to myeloablative therapy. Eight patients died of progressive disease. Ten of 20 (50%) patients (primitive neuroectodermal tumor (PNET)/medulloblastoma, three patients; cerebral PNET, three patients; glioblastoma multiforme, two patients; anaplastic astrocytoma, one patient; pineal PNET, one patient) are alive and disease free at a median of 37.9 months (range, 9.7 to 98.2 months) from ABMR (3-year overall survival [OS] rate of 43% +/- 13% and event-free survival [EFS] rate of 47% +/- 14%]. Seven of these 10 patients also received irradiation post-ABMR. CONCLUSION: Myeloablative chemotherapy with ABMR followed by additional external-beam irradiation appears to be an effective retrieval therapy for some young children with recurrent malignant brain tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Evidence that the age at diagnosis of IDDM is genetically determined.

OBJECTIVE: The aim of this study was to determine the impact of genetic or environmental factors on the age or time of onset of IDDM by studying pairs of twins and siblings concordant for the disease. RESEARCH DESIGN AND METHODS: From 404 twin pairs referred to a diabetic twin study, we selected pairs concordant for IDDM: 1) 116 identical pairs with an index twin diagnosed diabetic under age 60 years and 2) 12 identical and 12 nonidentical matched twin pairs. From 972 families referred to a population-based diabetic family study, we selected sibling pairs with IDDM: 33 pairs with an index case diagnosed diabetic under age 21 years. Twin and sibling pairs were analyzed for intraclass correlations for age and time of diagnosis. RESULTS: Of twins concordant for IDDM, the age at diagnosis correlated 1) in 116 identical pairs (R = 0.94; P < 0.000001) and 2) more closely in 12 identical twins (R = 0.96, P < 0.000001) than 12 nonidentical twins (R = 0.59, P = 0.046). Of 33 sibling pairs with IDDM, the age, but not the time, of diagnosis was correlated (R = 0.53, P = 0.0016). CONCLUSIONS: Correlations within pairs of twins and siblings for age, not time, at diagnosis suggest that much of the variability of the age at diagnosis of IDDM is genetically determined.

Adolescent↗
PubMed1996

Intraocular dexamethasone produces a harmful effect on treatment of experimental Staphylococcus aureus endophthalmitis.

BACKGROUND: We created a standardized model of severe Staphylococcus aureus endophthalmitis in the aphakic rabbit eye to test various treatment strategies involving corticosteroid administration in addition to vitrectomy and antibiotic treatment. MATERIALS AND METHODS: In 71 aphakic New Zealand albino rabbit eyes, experimental endophthalmitis was created by injecting 10(5) colony-forming units of Staphylococcal aureus. The animals were divided into 5 groups. One control group was followed up without treatment, while 4 groups were treated with vitrectomy and intraocular cefazolin injection. Two groups were also treated with intramuscular methylprednisolone, 1 group beginning on the day of surgery and 1 group beginning on the following day. In the final group, dexamethasone, 400 micrograms, was injected into the vitreous cavity at the close of surgery. Culture results were compared on the first 2 days after surgery. Inflammatory scores, including development of total corneal opacity, were assessed over a 21-day follow-up period, and histopathologic grading was carried out at the conclusion of the clinical observations. RESULTS: Simultaneous administration of systemic corticosteroids beginning on the day of vitrectomy decreased inflammatory scores 1 week after institution of therapy but did not affect final scores. Delay of initiation of intramuscular corticosteroid until the first postoperative day negated the positive effects. Administration of intraocular corticosteroids was associated with an increase in inflammatory scores throughout the period of observation, an increase in percentage of eyes that developed opaque corneas, an increase in choroidal inflammation graded moderate or severe, and an increase in retinal necrosis compared with vitrectomy and cefazolin injection alone. CONCLUSIONS: This data suggest caution in the use of intraocular corticosteroids in treatment of severe endophthalmitis.

Animals↗
PubMed1996

Comparative treatment of experimental Staphylococcus aureus endophthalmitis.

PURPOSE: To compare treatment strategies for Staphylococcus aureus endophthalmitis, we created an animal model in an aphakic rabbit eye and tested six different approaches to treatment. METHODS: Rabbit eyes were rendered aphakic, and three weeks postoperatively, S. aureus organisms were injected into the vitreous cavity. One group was maintained as a control. Twenty-four hours after bacterial injection, six different treatment groups were created for comparison. Clinical inflammation scores, culture results 48 hours after treatment, histopathologic gradings, and development of total corneal opacity three weeks after treatment were assessed. RESULTS: Injection of vancomycin hydrochloride into the vitreous cavity was more effective than injection of cefazolin sodium (P = .01) in reducing the percentage of eyes that had positive culture results and also resulted in lower inflammation scores. Vitrectomy plus injection of either antibiotic was more effective than injection of the same antibiotic alone in reducing culture-positive results and reducing clinical inflammation scores. addition of systemic corticosteroids to intravitreal antibiotic injection did not improve any measure of outcome. Vitrectomy and injection of intravitreal vancomycin was the most effective strategy to sterilize the vitreous cavity, resulting in the lowest inflammation scores and the smallest percentage of eyes with opaque corneas. CONCLUSION: In an animal model of S. aureus endophthalmitis, the combination of vitrectomy and injection of intraocular vancomycin was the most effective strategy for rapidly controlling the infective process and improving the outcomes measured three weeks after treatment.

Animals↗
PubMed1996

The effect of prolonged pneumoperitoneum on renal function in an animal model.

BACKGROUND: Prolonged, increased intra-abdominal pressure (IAP) during laparoscopic surgery has been associated with oliguria and anuria. STUDY DESIGN: The objective of this study was to evaluate the effects of various levels of IAP on renal function. Ten groups of three adult female farm pigs were given a general anesthetic, followed by establishment of an IAP of 0, 5, 10, 15, or 20 mm Hg with CO2, 20 mm Hg with argon gas, abdominal wall lift device, renal vein occlusion (RVO), 15 mm Hg with CO2 plus dopamine administration at 2 microgram/kg/minute, or 20 mm Hg retroperitoneal CO2 insufflation. The following studies were recorded: baseline central venous pressure (CVP), pulmonary wedge pressure (PWP), cardiac output (CO), renal vein flow (RVF), renal artery pressure (RAP), selective urine output (UO), urinary osmolarity, and creatinine clearance; the parameters were repeated every 30 minutes for the four hours of the IAP study and two hours after release of the IAP. RESULTS: The results were analyzed within two main IAP groups: less than 15 mm Hg and greater than or equal to 15 mm Hg. There was no clinically significant variation in the CVP, PWP, and RAP. The CO decreased slightly and this was more significant in the greater than or equal to 15 mm Hg group. The RVF and UO decreased concomitantly and significantly in the greater than or equal to 15 mm Hg group. Even after two hours of desufflation, the RVF did not return to baseline, although the UO improved. Creatinine clearance decreased significantly in the greater than or equal to 15 mm Hg group. The RVO group exhibited similar changes in the study parameters as those seen in the greater than or equal to 15 mm Hg group, although the RVF did not improve on release of the renal vein in the RVO group. Changes were the same with an argon or CO2 IAP of 20 mm Hg. The abdominal wall lift device had an associated decrease in RVF at 15 KG force but no alteration in UO. Retroperitoneal insufflation resulted in the same decrease in RVF and UO as seen with the same IAP. Dopamine did not afford a protective effect on UO during an IAP of 15 mm Hg. CONCLUSIONS: The decreased UO during prolonged IAP greater than or equal to 15 mm Hg in the animal model is associated with a corresponding decrease in RVF, but does not appear to be associated with any permanent renal derangement nor any transient histologic changes.

Animals↗
PubMed1995

Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes.

During lymphocyte development, cellular proliferation and positive and negative selection events ensure the production of T and B lymphocytes bearing highly diverse, but self-tolerant, repertoires of antigen receptors. These processes are initiated when engagement of growth-factor receptors, or the T and B lymphocyte antigen receptors, induces tyrosine phosphorylation of specific SH2- and SH3-domain-containing cytoplasmic proteins, including Vav. Here we show that vav-/- embryonic stem cells generate only limited numbers of immature and mature T and B lymphocytes in the RAG-2 blastocyst complementation assay. Furthermore, Vav-deficient T lymphocytes showed severely impaired antigen receptor signalling. Finally, we demonstrate that Vav-dependent signalling pathways regulate maturation, but not CD4/CD8 lineage commitment, during T-cell-receptor-mediated positive selection of immature CD4+ CD8+ precursors into mature CD4+ CD8- or CD4- CD8+ T cells.

Animals↗