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Biomedical subjects

R Burke

Publications and source records attributed to R Burke.

At least 19 recordsLinked to original sources

Predicting human thermal comfort in a transient nonuniform thermal environment.

The National Renewable Energy Laboratory has developed a suite of thermal comfort tools to assist in the development of smaller and more efficient climate control systems in automobiles. These tools, which include a 126-segment sweating manikin, a finite element physiological model of the human body, and a psychological model based on human testing, are designed to predict human thermal comfort in transient, nonuniform thermal environments, such as automobiles. The manikin measures the heat loss from the human body in the vehicle environment and sends the heat flux from each segment to the physiological model. The physiological model predicts the body's response to the environment, determines 126-segment skin temperatures, sweat rate, and breathing rate, and transmits the data to the manikin. The psychological model uses temperature data from the physiological model to predict the local and global thermal comfort as a function of local skin and core temperatures and their rates of change. Results of initial integration testing show the thermal response of a manikin segment to transient environmental conditions.

Air Conditioning↗

Glycemia and the quality of well-being in patients with diabetes.

OBJECTIVES: To investigate the cross-sectional relationships among self-reported frequencies of symptomatic hyperglycemia and hypoglycemia, HbA1c, and symptoms in the Quality of Well-Being Self-Administered (QWB-SA), and to examine the associations among these measures of glycemia and health-utility scores. METHODS: The study group included 1522 patients with diabetes who attended University of Michigan Health System clinics. Published studies were reviewed to identify symptoms in the QWB-SA that might be associated with measures of glycemia. Linear-regression analyses were performed to evaluate the strength of the associations among the frequency of self-reported measures of glycemia, QWB-SA symptoms, and QWB-SA-derived health-utility scores. RESULTS: Frequency of hyperglycemic symptoms was associated with 3% of the variance in the QWB-SA-derived health-utility score in type-1 diabetes and with 5% of the variance in type-2 diabetes. Frequency of hypoglycemic symptoms was not associated with the QWB-SA-derived health-utility score in type-1 diabetes but was associated with 1% of the variance in type-2 diabetes. HbAlc levels were not significantly associated with QWB-SA-derived health-utility scores. After controlling for age, gender, and complications, frequency of hyperglycemic symptoms was significantly associated with QWB-SA-derived health-utility scores in type-1 and type-2 diabetes. CONCLUSIONS: Reported frequency of hyperglycemic symptoms is associated with symptoms included in the QWB-SA and with QWB-SA-derived health-utility scores. The QWB-SA may be an appropriate measure to assess the health burden of hyperglycemia.

Adolescent↗

Laparoscopic versus open appendectomy: what is the real difference? Results of a prospective randomized double-blinded trial.

BACKGROUND: The comparison of laparoscopic to open appendectomy has been reviewed in many retrospective and prospective studies. Some report shorter hospital stays, less postoperative pain, and earlier return to work while others fail to demonstrate such differences. We performed a prospective, randomized double-blinded trial to evaluate this ongoing debate. METHODS: Fifty-two consecutive men presenting with signs and symptoms suggestive of acute appendicitis were randomized to undergo either laparoscopic appendectomy or open appendectomy. Length of operative times, hospital stay, lost work days, visual analog pain scores, and operative costs were compared. RESULTS: Length of stay averaged 21.5 h for the laparoscopic group and was not statistically different when compared to the open group. Perceived postoperative pain on postoperative days 1 and 7 were not statistically different between the two groups. Mean time to return to work was 11 days, and there was no statistical difference between groups. Operative costs were >600 dollars greater for the laparoscopic approach. CONCLUSIONS: In this prospective randomized double-blinded trial, laparoscopic appendectomy appears to confer no significant advantage over open appendectomy for postoperative pain or lost work days. It does carry an increase in operating room costs and, contrary to other reports, hospital stay is not shortened. Further studies are needed to determine if specific populations, such as the obese or women, may benefit from a minimally invasive approach to appendicitis.

Absenteeism↗

The physical functioning inventory: a procedure for assessing physical function in adults.

The Physical Functioning Inventory, an instrument designed to assess changes in how and how often activities are performed in persons reporting difficulty with a task as well as in those who do not, is described. The measure is designed for adults. Interrater and test-retest reliability were assessed with active participants in the Baltimore Longitudinal Study of Aging (BLSA). Percentage agreement ranged from 63% to 100%. The instrument was also given to 392 inactive BLSA participants as part of a follow-up telephone interview. Fifty-eight percent of the respondents reported no difficulty in performing a task, yet reported a change in how often they performed that task. The results indicate that the instrument is reliable and effective in detecting early stages of disability in activities of daily living, instrumental activities of daily living, and mobility. The instrument is somewhat less reliable for moderate and strenuous physical activities.

Activities of Daily Living↗

Specificity of preformed alloantibodies causing B cell positive flow crossmatch in renal transplantation.

The specificity of alloantibodies (alloAb) and their clinical significance in association with T-/B+ flow cytometry crossmatch (FCXM) in kidney transplantation are not clearly defined. This study was undertaken to examine the HLA specificity and clinical relevance of Ab causing B+ FCXM in pre-transplant (final XM) recipients' serum samples. Final FCXM serum samples were analyzed from 457 renal transplant patients followed for 10 months post-transplantation. Two hundred and sixty patients had T-/B+ final FCXM. The control group included 197 recipients with T-/B- FCXM at time of transplantation. Class I/class II PRA and specificity of anti-HLA class I and class II Ab in final FCXM serum samples were analyzed by FlowPRA Class I Screening Test and FlowPRA Class II Screening Test. We found no correlation between graft outcome and pre-transplant T-/B- and T-/B+ FCXM status. Additionally, we observed no clinical relevance of B+ FCXM in retransplant patients. However, MCS > or =200 in B+ FCXM retransplant recipients was associated with anti-class II Ab to previous mismatches in regrafted patients (n = 46). This finding was confirmed by specificity analysis of anti-DR/DQ Ab in patients with high ( > or =15%) class II PRA. In 63% (12 of 19) of retransplants having T-/B+ FCXM, we defined the specificity of alloAb to first graft mismatched class II antigens. In contrast, anti-class II Ab was detected in only 5.7% (2 of 35) of single-graft recipients with different PRA values. Significantly greater MCS (240 +/- 61 vs. 163 +/- 48; p = 0.022) was observed in retransplant patients having short ( < or =5 m) previous graft survival time (PGST) than in those with long PGST ( > or =5 m). Only 2% of retransplant recipients with B + FCXM had non-HLA Ab. In contrast, the overwhelming majority of primary recipients had no detectable alloAbs. No significant difference in class I PRA was found between B- and B+ FCXM recipients. However, class II PRA was significantly higher in patients having B + FCXM (p = 0.028). Collectively, these data show that MCS intensity is not always a reliable criterion for anti-HLA Ab detection because of the presence of non-HLA Ab. These results can be explained by low titers of anti-class II Ab, at which concentration these Ab cannot produce a deleterious effect. FlowPRA and Flow screen beads appeared to be reliable and sensitive methods for detection and specificity analysis of anti-class II alloAb.

Antibody Specificity↗

Vaccination of seropositive subjects with CHIRON CMV gB subunit vaccine combined with MF59 adjuvant for production of CMV immune globulin.

The safety and immunogenicity of four different regimens of CHIRON cytomegalovirus (CMV) gB subunit vaccine combined with MF59 adjuvant and administered to seropositive plasma donors were evaluated to ascertain whether vaccination of seropositive subjects would significantly increase antibody titer to gB glycoprotein. This was done to select the best vaccination regimen for generating high-titered plasma for manufacture of CMV immune globulin. No serious adverse events were attributed to this vaccine, and the vaccine was well tolerated. Only the first dose of vaccine in each regimen stimulated a four-fold or greater antibody response to gB glycoprotein and each regimen induced similar antibody titers. However, initial vaccination followed by a 1 week rest from plasmapheresis and two booster vaccinations at 8 and 24 weeks, each followed with another 1 week rest from plasmapheresis, maintained the highest geometric mean gB ELISA titer of the four regimens over the 34-week post-vaccination period. CMVIG manufactured from a pool of high titered plasma units from two of four subject groups had gB ELISA and neutralizing antibody titers nine and six times higher, respectively, compared to Cytogam, indicating that vaccination of seropositive subjects with CHIRON gB vaccine combined with MF59 adjuvant prior to harvesting plasma can enhance functional antibody in a CMVIG product.

Adjuvants, Immunologic↗

Experts recommend minimum nurse staffing standards for nursing facilities in the United States.

The experts concluded that current data show that the average nurse staffing levels (for RNs, LVN/LPNs, and NAs) in nursing homes are too low in some facilities to provide high quality of care. Caregiving, the central feature of a nursing home, needs to be improved to ensure high quality of care to residents. Because detailed time studies have not been conducted on the amount of time that is required to provide high quality of care to residents, expert opinion is currently the best approach to addressing the problem of inadequate staffing. Increases in the education level and training of nursing staff are also strongly recommended as a step to improving quality of care and reducing turnover rates in nursing homes. These recommendations are designed for consideration by Congress, HCFA regulators, policymakers, nursing home administrators, and nurses. Ideally, Congress would pass legislation establishing these recommendations as minimum standards for all nursing homes or direct HCFA to establish detailed minimum nurse staffing standards to ensure that staffing levels take into account the number and the case-mix of the residents. Alternatively, HCFA could introduce minimum staffing standards through the regulatory process. In 1999 there were a number of efforts at the state level to increase minimum staffing levels. Mohler (1999) surveyed selected states and found that 21 states had either proposed new legislation or were considering proposals for new legislation or new regulations. In California, for example, in 1999 the state budget approved $31 million in new state funds (to be matched with $31 million in federal Medicaid dollars) to increase nursing home staffing minimum requirements from 2.8 to 3.2 hr per resident day and to increase wage rates. Overall, nursing facilities need to be held accountable by HCFA for providing adequate levels and types of staffing to meet the needs of their residents, especially because government is paying for 61% of the expenditures. Adopting these minimum standards will have an important impact on improving the quality of the nation's nursing home care. Additional research is needed to determine appropriate levels and types of staff to provide high quality of care to residents. These studies could test the proposed staffing standards against existing staffing levels to examine the impacts on quality. As new data become available on staffing levels, revisions of staffing standards should be made if necessary to ensure that high standards are maintained.

Aged↗

Lack of effect of TP53 status on fluorodeoxyuridine-mediated radiosensitization.

Substantial evidence suggests that TP53 (also known as p53) status can influence the response of cells to chemotherapy and radiation. We wished to determine if TP53 function affected the response of cells to fluoropyrimidines and radiation, a combination used for tens of thousands of patients each year. To assess the role of TP53 in fluoropyrimidine-mediated radiosensitization, we carried out experiments using RKO parental cells (wild-type TP53) and RKO cells overexpressing mutant TP53 (which blocks TP53 function) or expressing E6 (which degrades TP53). We found that TP53 function had no effect on the ability of fluorodeoxyuridine to increase radiation sensitivity. These findings are consistent with the hypothesis that the late G(1)-phase checkpoint, which is mediated by TP53, is not crucial to radiosensitization. Rather, the ability of cells to progress in to S phase in the presence of the drug, which is independent of TP53, is more closely associated with increased radiation sensitivity.

Antimetabolites, Antineoplastic↗

Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified hedgehog from signaling cells.

Members of the Hedgehog (Hh) family of secreted signaling proteins function as potent short-range organizers in animal development. Their range of action is limited by a C-terminal cholesterol tether and the upregulation of Patched (Ptc) receptor levels. Here we identify a novel segment-polarity gene in Drosophila, dispatched (disp), and demonstrate that its product is required in sending cells for normal Hh function. In the absence of Disp, cholesterol-modified but not cholesterol-free Hh is retained in these cells, indicating that Disp functions to release cholesterol-anchored Hh. Despite their opposite roles, Disp and Ptc share structural homology in the form of a sterol-sensing domain, suggesting that release and sequestration of cholesterol-modified Hh may be based on related molecular pathways.

Amino Acid Sequence↗

double-time is identical to discs overgrown, which is required for cell survival, proliferation and growth arrest in Drosophila imaginal discs.

We have isolated the discs overgrown gene of Drosophila and shown that it encodes a homolog of the Casein kinase I(delta)/(epsilon) subfamily and is identical to the double-time gene. However, in contrast to the weak double-time alleles, which appear to affect only the circadian rhythm, discs overgrown alleles, including bona fide null alleles, show strong effects on cell survival and growth control in imaginal discs. Analysis of their phenotypes and molecular lesions suggests that the Discs overgrown protein is a crucial component in the mechanism that links cell survival during proliferation to growth arrest in imaginal discs. This work provides the first analysis in a multicellular organism of Casein kinase I(delta)/(epsilon) functions necessary for survival. Since the amino acid sequences and three-dimensional structures of Casein kinase I(delta)/(epsilon) enzymes are highly conserved, the results suggest that these proteins may also function in controlling cell growth and survival in other organisms.

Amino Acid Sequence↗

Isolation and identification of canine matrix metalloproteinase-2 (MMP-2).

A canine gelatinase, with an apparent molecular mass of 62 kDa in non-reducing zymography, is produced by fibroblasts, chondrocytes and a myelomonocytic cell line. The enzyme has similar characteristics to human matrix metalloproteinase (MMP) 2 and cross-reacts in Western blotting analysis with a sheep polyclonal antiserum raised against human MMP-2. The 62 kDa canine protein was purified from cell culture media, and the N-terminal amino acid sequence determined following blotting on to a polyvinylidene difluoride (PVDF) membrane. The sequence was 87% identical to that published for human MMP-2. We therefore consider this enzyme to be canine MMP-2.

Amino Acid Sequence↗

Pulmonary high-resolution computed tomography versus gallium scintigraphy: diagnostic utility in the diagnosis of patients with AIDS who have chest symptoms and normal or equivocal chest radiographs.

Fifty-six consecutive symptomatic patients with AIDS referred for gallium scintigraphy were prospectively studied with chest high-resolution computed tomography (HRCT). Results of gallium and HRCT were correlated with findings of bronchoscopy or clinical follow-up for 1 month from time of discharge. Twenty-two patients were eventually diagnosed with at least one of the following: Pneumocystis carinii, cytomegalovirus, Mycobacterium avium complex, bacteria, Kaposi's sarcoma, or lymphocytic interstitial pneumonitis. HRCT was more sensitive (82%) and more specific (91%) than gallium (59% and 75%, respectively). HRCT yielded higher positive predictive values (86%) and negative predictive values (88%) than did gallium (62% and 73%, respectively). HRCT was more helpful in guiding the method of biopsy and directing the brochoscopist to the diseased lung segment that would maximize diagnostic yield.

AIDS-Related Opportunistic Infections↗

Hedgehog signaling in Drosophila eye and limb development - conserved machinery, divergent roles?

The secreted signaling molecule Hedgehog plays a key role in patterning Drosophila eyes and limbs. Recently, the transmembrane proteins Patched and Smoothened and the Gli protein Cubitus interruptus have been identified as essential components in Hedgehog signal transduction. Progress has also been made in understanding the function of Decapentaplegic (Dpp) in mediating the Hedgehog signal. Although playing only a minor role in the eye, Dpp governs, at long range, the expression of essential genes such as optomotor blind and spalt in the wing.

Animals↗

Radiologic placement of subcutaneous infusion chest ports for long-term central venous access.

OBJECTIVE: The technical success and complications associated with radiologic placement of subcutaneous implantable chest ports for long-term central venous access were evaluated. MATERIALS AND METHODS: Between May 1, 1996, and December 31, 1996, 80 chest ports were placed in 80 consecutive patients using the right internal jugular vein as the preferred access route. All procedures occurred in interventional radiology suites with patients receiving conscious sedation. Both sonography and fluoroscopy were used for venipuncture and to guide port insertion. Follow-up was obtained by the clinical service and by performing chart reviews electronically. RESULTS: Technical success was 100%, and follow-up was obtained in all patients. One procedural complication occurred that was unrelated to actual catheter placement. Mean catheter use was 155 days (total, 12,168 days; range, 18-303 days). Confirmed catheter-related infection rate was 3%, or 0.016 per 100 access days; symptomatic catheter-related central venous thrombosis rate was 1%, or 0.008 per 100 access days; and 5% of catheters were removed prematurely. No instances of hematoma formation, catheter tip migration or malposition, symptomatic air embolism, spontaneous catheter fracture, or pneumothorax were found. CONCLUSION: With the benefit of both sonographic and fluoroscopic guidance, subcutaneous implantable chest ports can be inserted by radiologists with equal or lower complication rates than those reported in surgical series. Image-guided insertion of chest ports should replace rather than supplement unguided placement.

Catheterization, Central Venous↗

Wallstent deployment to salvage dialysis graft thrombolysis complicated by venous rupture: early and intermediate results.

OBJECTIVE: The feasibility of deploying Wallstents to treat venous rupture occurring during dialysis graft thrombolysis was determined. SUBJECTS AND METHODS: Between June 24, 1994, and February 19, 1997, 23 patients with venous rupture attributed to balloon angioplasty during dialysis graft thrombolysis were treated by Wallstent deployment across the area of rupture. Twenty-one ruptures occurred in peripheral veins and two occurred in central veins. Follow-up was provided by the clinical service at our institution and by electronic review of patients' charts. RESULTS: Stent placement allowed completion of graft thrombolysis in all 23 patients. Complications were limited to four moderate-sized hematomas of the arm, and a single pseudoaneurysm developed 6 months after stent placement in one 27-year-old patient. The primary patency rate of stents was 52% at 60 days, 26% at 180 days, and 11% at 360 days. The secondary patency rate was 74% at 60 days, 65% at 180 days, and 56% at 360 days. CONCLUSION: Treatment of venous ruptures using Wallstents is a safe alternative to intentional graft thrombosis. The patency rates of these devices are similar to those of venous stents placed for other indications.

Aged↗

Hedgehog-dependent patterning in the Drosophila eye can occur in the absence of Dpp signaling.

The progression of retinal morphogenesis in the Drosophila eye is controlled to a large extent by Hedgehog (Hh), a signaling protein emanating from differentiating photoreceptor cells. Adjacent, more anterior cells in the morphogenetic furrow respond to Hh by expressing decapentaplegic (dpp), suggesting that the relationship between Hh and Dpp might be similar to that in the limb imaginal discs where Dpp mediates the organizing activity of Hh. In this study we show that this is not the case. Analysis of somatic clones of cells lacking the Dpp receptors Punt or Tkv reveals that Dpp plays only a minor role in furrow progression and no critical role in subsequent ommatidial development. In contrast, Hh-independent dpp expression around the posterior and lateral margins of the first and second instar eye discs is important for the growth of the eye disc and for initiation of the morphogenetic furrow at these margins.

Animals↗