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Biomedical subjects

J S Brown

Publications and source records attributed to J S Brown.

At least 19 recordsLinked to original sources

Factors that influence the outcome of salvage in free tissue transfer.

INTRODUCTION: The success of salvage techniques for free tissue transfer is well documented. The aim of this study was to identify factors that influenced the results of salvage operations in a group of patients who required early exploration. METHODS: From a database survey of 408 patients who had a total of 427 free tissue transfer reconstructions, 65 (16%) returned to the operating theatre within 7 days. A retrospective analysis of their progress was made from the case records. RESULTS: The flap chart was found to be highly accurate for the 65 patients who had returned to the operating theatre, reporting two false positives and one false negative. Forty patients had compromised flaps and 25 had haematomas that required evacuation. The commonest problem with flaps was venous congestion (33/40, 83%), and 29 flaps were successfully salvaged (73%). Most successful salvage attempts were made within 24 hours of the end of the initial operation. The salvage rate was higher for the radial fasciocutaneous flaps (25/30, 83%), than for composite flaps (2/7, 29%). A total of 24/427 flaps failed (6%). CONCLUSIONS: We now recommend hourly observations of the flap for 24 hours followed by 4-hourly monitoring for 48 hours. Improved monitoring techniques for composite grafts may result in more being salvaged and a better overall survival.

Anastomosis, Surgical↗

Cervical lymph node metastasis in oral cancer: the importance of even microscopic extracapsular spread.

The prognostic significance of extracapsular spread of cervical metastases in oral cancer is still controversial. To investigate the importance of extent of extracapsular spread; the relationship between extracapsular spread and both traditional measures of metastatic disease and clinical/histological features of the primary tumour, and to determine their relative prognostic significance. The survival of 173 patients undergoing radical surgery and simultaneous neck dissection for oral/oropharyngeal squamous cell carcinoma with histologically confirmed nodal metastasis and followed for 2.2-12.3 years is reported and related to pathological features. The most predictive clinical/histopathological features were determined by Cox regression modelling. The 3-year survival probability was similar for patients with macroscopic and only microscopic extracapsular spread (33 and 36%, respectively, compared with 72% for patients with intranodal metastasis). The Cox model showed the most predictive factor was extracapsular spread followed by status of resection margins. Extracapsular spread should be incorporated into pathological staging systems. Even microscopic extracapsular spread is of critical importance and must be sought especially in small-volume metastatic disease.

Adult↗

The prognostic implications of the surgical margin in oral squamous cell carcinoma.

The prime objective of tumour ablation in oral squamous cell carcinoma (OSCC) is the removal, with a 'margin' of normal tissue, of the whole tumour. Definition of what constitutes margin involvement varies. This study aims to examine the factors associated with close and involved surgical margins in the management of OSCC. A cohort of 200 consecutive patients with previously untreated OSCC provided the material for the study. Various clinical, operative and pathological parameters were related to the status of the surgical margin, as well as time to recurrence, and survival. Cox regression analysis of the survival was also undertaken. Of the 200 patients 107 (53.5%) had clear margins, 84 (42%) close and 9 (4.5%) involved. Poor correlation was found between the status of the surgical margin and clinical factors, but in contrast high correlation between histological indicators of aggressive disease and close or involved surgical margins. These results imply that close surgical margins in OSCC could be regarded as an indictor of aggressive disease.

Aged↗

Does weight loss improve incontinence in moderately obese women?

The aim of this study was to evaluate the effect of weight reduction on urinary incontinence in moderately obese women. This prospective cohort study enrolled moderately obese women experiencing four or more incontinence episodes per week. BMI and a 7-day urinary diary were collected at baseline and on the completion of weight reduction. The study included 10 women with a mean (+/-SD) baseline BMI of 38.3 (+/-10.1) kg/m2 and 13 (+/-10) incontinent episodes per week. Participants had a mean BMI reduction of 5.3 (+/-6.2) kg/ m2 (P < 0.03). Among women achieving a weight loss of > or = 5%, 6/6 had > or = 50% reduction in incontinence frequency compared to 1 in 4 women with < 5% weight loss (P < 0.03). Incontinence episodes decreased to 8 (+/-10) per week following weight reduction (P < 0.07). The study demonstrated an association between weight reduction and improved urinary incontinence. Weight reduction should be considered for moderately obese women as part of non-surgical therapy for incontinence.

Adult↗

Factors that influence the method of mandibular resection in the management of oral squamous cell carcinoma.

The method of conservative (rim) resection of the mandible is now well established and provides good control of disease in the primary site. There are few audits of this technique in terms of margins of resection for both rim and segmental resection of the mandible. Consecutive previously untreated patients managed with resection of the mandible as part of their treatment for oral and oropharyngeal squamous cell carcinoma were recruited for the study. The presence and extent of tumour invasion of the mandible was recorded and a retrospective analysis made to establish the incidence of unnecessary segmental resections. The invasion rate was 33% (8/35) for rims and 83% (54/65) in segmental resections of the mandible, which compares favourably with previous studies and indicates a reasonable accuracy of resection. In between 6 and 11 of the 62 cases (10-17%) a rim resection could have achieved a satisfactory resection margin and retained a functioning lower border of the mandible. The accuracy of resection in terms of margins was greater for mandibular resections (94% clear margins) than soft tissues (62% clear margins). The number of compromised margins was significantly greater in the invaded rim resection group (P=0.018). This study indicates that a more conservative mandibular resection was possible in a few cases. This is unlikely to have an adverse effect on the close or involved margin rate, which depends mainly on the accuracy of the soft tissue resection. Angling the horizontal rim resection to take into account tumour entry at the point of contact will help to ensure a clear bone margin if a conservative approach to mandibular resection is an option.

Adult↗

Clinical function after primary surgery for oral and oropharyngeal cancer: an 11-item examination.

The aim of this study was to record clinical function using an 11-item clinical examination and identify the main postoperative functional deficits. Of 132 consecutive patients undergoing surgery for previously untreated disease between January 1995 and June 1997, 130 were recruited in the study. An 11-domain clinical examination was made on the day before operation, and at 6 and 12 months afterwards. This examination assessed lip competence, tongue movement, oral mucosa, dental state, mouth opening, speech, drooling, diet, appearance, oral sensation and shoulder movement. Preoperatively there were deficits in natural dentition, consistency of diet and tongue protrusion. Postoperatively functional scores fell particularly for tongue movements, mouth opening, mucosa, dentition, speech, diet, appearance, lip sensation and tongue sensation. At 1 year, dental status, sensation and oral mucosa were particularly defective. Patients with large tumours, free tissue transfer, or adjuvant radiotherapy had the worst levels of function.A simple clinical examination provides a rapid assessment of function that can be used in conjunction with validated questionnaires to provide a more comprehensive evaluation of outcome.

Activities of Daily Living↗

Health-related quality of life and clinical function after primary surgery for oral cancer.

Clinical function and health-related quality of life (HRQoL) are both important outcome parameters following surgery for oral and oropharyngeal cancer. The aim of this project was to explore the relationship between an 11-point clinical examination and HRQoL. Of 132 consecutive patients undergoing surgery for previously untreated disease between January 1995 and June 1997, 130 were recruited into the study. The University of Washington Quality of Life Questionnaire (UW-QoL) was completed by each patient on the day before operation and 6 and 12 months later. On each occasion the first author made an 11-point clinical examination. The main predictors of cumulative UW-QoL scores were tumour size, clinical functional score and type of operation. The trend was for a fall from preoperative levels at 6 months and then for a slight improvement at 1 year. The differential in respect of baseline function was present at all three time points in each patient group. This suggests that functional deficits at presentation persist following treatment.

Activities of Daily Living↗

Vascularized iliac crest with internal oblique muscle for immediate reconstruction after maxillectomy.

The vascularized iliac crest graft with internal oblique muscle as a method of reconstruction after maxillectomy has been used routinely at the Regional Maxillofacial Unit in Liverpool since 1993. Twenty-four consecutive operations have now been done and this paper reports an audit of our experience. An analysis of case-notes was made retrospectively after checking theatre diaries and records. A detailed inspection of the case-notes was undertaken to ascertain the presenting diagnosis, the complications and the outcome in terms of recurrence and disease survival. The type of defect was recorded, as was whether it had been possible to rehabilitate the patient both dentally and facially. At the time of this study 9 patients (38%) had died of their disease leaving 15 surviving. In 13 cases full dental and facial rehabilitation had been achieved or patients were waiting for an implant-retained prosthesis. Donor site problems important enough to be recorded in the notes were minimal, one case of abdominal wall weakness was noted, which required no intervention. The vascularized iliac crest graft with internal oblique muscle offers a complete solution for reconstruction after maxillectomy, providing there has been no sacrifice of the overlying facial skin and oral sphincter. There is sufficient height and depth of bone to maintain a facial profile and the muscle epithelializes to provide an ideal oral and nasal lining. This flap provides a base to enable full dental and facial prosthetic rehabilitation with either implant-retained or conventional prostheses.

Abdominal Muscles↗

Dependence of thermal mismatch broadening on column diameter in high-speed liquid chromatography at elevated temperatures.

In this paper, we compare a narrow-bore column (2.1-mm i.d.) to a conventional-bore column (4.6 mm i.d.) at elevated temperatures under conditions where thermal mismatch broadening is serious and show that narrow-bore columns offer significant advantages in terms of efficiency and peak shape at higher linear velocities. We conclude that the so-called thermal mismatch broadening effect is largely due to a radial retention factor gradient and not a radial viscosity gradient. The lower volumetric flow rates inherent with the use of narrower columns lead to lower linear velocity in the heater tubing and longer eluent residence times in the heater. Thus, with the same heater tubing at the same column linear velocity, narrow-bore columns give better thermal equilibration between the eluent and the column compared to wider bore columns. This means that high-temperature, ultrafast liquid chromatography no longer requires excessively long preheater tubing to thermally equilibrate the eluent to the column temperature. Consequently, the use of narrow-bore columns at high-temperature improves analysis speed and efficiency over wider bore columns. We also discuss the advantages of using liquid heat-transfer media as compared to air as the heat-transfer media. We show that an air bath ought not be used to heat the mobile phase because at high temperature (>80 degrees C) and high column linear velocity (> 1.5 cm/s) the length of tubing needed to heat the mobile phase to column temperature is prohibitively long. Using accurate, empirical heat-transfer correlations, we estimated the length of tubing needed to heat the eluent as a function of the column linear velocity for both air and liquid heat-transfer media.

Chromatography, Liquid↗

Resolving the origin of the petrogenic hydrocarbon background in Prince William Sound, Alaska.

The dominant sources of the petrogenic hydrocarbon background in benthic sediments of Prince William Sound, AK (PWS), site of the 1989 Exxon-Valdez oil spill, are eroding Tertiary shales and residues of natural oil seepage. Mass balance considerations and statistical analyses of hydrocarbon fingerprints independently indicate that coal contributes generally less than 1% of the polycyclic aromatic hydrocarbons (PAH) and chemical biomarkers in this background. This is environmentally significant because of presumed differences in the bioavailability of PAH in coal, seep oil residues, and shales. Coal particles are present in PWS sediments, but their PAH and chemical biomarker contributions are overwhelmed by those of seep oil residues and organic particles from shales of low-to-high thermally maturity. In the late Tertiary or early Quaternary, the currently exposed and eroding shale formations were heated into the oil-generation window and, consequently, are now relatively rich in extractable PAH and chemical biomarkers. The exposed and eroding coals in the area, in contrast, experienced long hot burial and are now thermally overmature with respect to oil generation. The concentrations of thermally sensitive PAH and biomarker compounds in PWS sediments are not consistent with a mature coal origin but are consistent with the low-to-high maturity shales and seep oils in the area.

Alaska↗

Concentrations of methyl- tert-butyl ether (MTBE) in inputs and receiving waters of Southern California.

The occurrence and concentration of the fuel additive methyl-tert-butyl ether (MTBE) were measured in dry weather runoff, municipal wastewater and industrial effluents, and coastal receiving waters in southern California. Combined, refineries and sewage treatment plants release approximately 214 kg day(-1) of MTBE into the marine environment, with Santa Monica Bay receiving most (98%) of this discharge. Dry weather urban runoff was analysed for samples collected from 25 streams and rivers, and accounted for less than 0.5% of the mass of MTBE discharged to coastal waters. Receiving water samples were collected from 23 stations in Santa Monica Bay, Los Angeles Harbour and Mission Bay or San Diego Bay. MTBE was detected at low concentrations near effluent discharges, however there was no evidence of baywide MTBE contamination related to these outfalls. Marinas and areas used intensively for recreational boating had the highest average MTBE concentration (8.8 microg l(-1)). Surface water contamination was most widespread in San Diego Bay and Mission Bay, areas with no refinery or sewage treatment plant inputs.

California↗

Postmenopausal hormones and incontinence: the Heart and Estrogen/Progestin Replacement Study.

OBJECTIVE: To determine whether postmenopausal hormone therapy improves the severity of urinary incontinence. METHODS: We included measures of incontinence and voiding frequency in the Heart and Estrogen/Progestin Replacement Study, a randomized, blinded trial of the effect of hormone therapy among 2763 postmenopausal women younger than 80 years with coronary disease and intact uteri. This report includes 1525 participants who reported at least one episode of incontinence per week at baseline. Participants were randomly assigned to 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate in one tablet daily (n = 768) or placebo (n = 757) and were followed for a mean of 4.1 years. Severity of incontinence was classified as improved (decrease of at least two episodes per week), unchanged (change of at most one episode per week), or worsened (increase of at least two episodes per week). RESULTS: Incontinence improved in 26% of the women assigned to placebo compared with 21% assigned to hormones, while 27% of the placebo group worsened compared with 39% of the hormone group (P =.001). This difference was evident by 4 months of treatment and was observed for both urge and stress incontinence. The number of incontinent episodes per week increased an average of 0.7 in the hormone group and decreased by 0.1 in the placebo group (P <.001). CONCLUSION: Daily oral estrogen plus progestin therapy was associated with worsening urinary incontinence in older postmenopausal women with weekly incontinence. We do not recommend this therapy for the treatment of incontinence.

Drug Combinations↗

Annual direct cost of urinary incontinence.

OBJECTIVE: To estimate the annual direct cost of urinary incontinence in 1995 US dollars. METHODS: Epidemiologically based models using diagnostic and treatment algorithms from published clinical practice guidelines and current disease prevalence data were used to estimate direct costs of urinary incontinence. Prevalence and event probability estimates were obtained from literature sources, national data sets, small surveys, and expert opinion. Average national Medicare reimbursement was used to estimate costs, which were determined separately by gender, age group, and type of incontinence. Sensitivity analyses were performed on all variables. RESULTS: The annual direct cost of urinary incontinence in the United States (in 1995 dollars) was estimated as $16.3 billion, including $12.4 billion (76%) for women and $3.8 billion (24%) for men. Costs for community-dwelling women ($8.6 billion, 69% of costs for women) were greater than for institutionalized women ($3.8 billion, 31%). Costs for women over 65 years of age were more than twice the costs for those under 65 years ($7.6 and $3.6 billion, respectively). The largest cost category was routine care (70% of costs for women), followed by nursing home admissions (14%), treatment (9%), complications (6%), and diagnosis and evaluations (1%). Costs were most sensitive to changes in incontinence prevalence, routine care costs, and institutionalization rates and costs. CONCLUSION: Urinary incontinence is a very costly condition, with annual expenditures similar to other chronic diseases in women.

Adolescent↗

Cost of pelvic organ prolapse surgery in the United States.

OBJECTIVE: To estimate the annual direct cost to society of pelvic organ prolapse operations in the United States. METHODS: We multiplied the number of pelvic organ prolapse operations identified in the 1997 National Hospital Discharge Survey by national average Medicare reimbursement for physician services and hospitalizations. Although this reimbursement does not estimate the actual cost, it is a proxy for cost, which estimates what society pays for the procedures. RESULTS: In 1997, direct costs of pelvic organ prolapse surgery were 1012 million dollars (95% confidence interval [CI] 775 dollars, 1251 million), including 494 dollars million (49%) for vaginal hysterectomy, 279 million dollars (28%) for cystocele and rectocele repair, and 135 million dollars (13%) for abdominal hysterectomy. Physician services accounted for 29% (298 million dollars) of total costs, and hospitalization accounted for 71% (714 million dollars). Twenty-one percent of pelvic organ prolapse operations included urinary incontinence procedures (218 million dollars). If all operations were reimbursed by non-Medicare sources, the annual estimated cost would increase by 52% to 1543 million dollars. CONCLUSION: The annual direct costs of operations for pelvic organ prolapse are substantial.

Direct Service Costs↗

Urinary tract infections in postmenopausal women: effect of hormone therapy and risk factors.

OBJECTIVE: To assess the effects of hormone therapy on urinary tract infection frequency and to examine potential risk factors. METHODS: We used data from the Heart and Estrogen/Progestin Replacement Study, a randomized, blinded trial of the effects of hormone therapy on coronary heart disease events among 2763 postmenopausal women aged 44-79 with established coronary heart disease. Participants were randomly assigned to 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate or placebo and followed for a mean of 4.1 years. History of physician-diagnosed urinary tract infections and risk factors were assessed by self-report at baseline and each annual visit. RESULTS: Urinary tract infection frequency was higher in the group randomized to hormone treatment, although the difference was not statistically significant (odds ratio [OR] 1.16, 95% confidence interval [CI] 0.99, 1.37). Statistically significant risk factors for urinary tract infections in multivariable analysis included: women with diabetes on treatment (insulin OR 1.81, 95% CI 1.40, 2.34), oral medications OR 1.44, 95% CI 1.09, 1.90), poor health (OR 1.34, 95% CI 1.14, 1.57), childbirth (OR 1.38, 95% CI 1.00, 1.90), vaginal itching (OR 1.63, 95% CI 1.07, 2.50), vaginal dryness (OR 1.30, 95% CI 1.04, 1.67), and urge incontinence (OR 1.51, 95% CI 1.30, 1.75). Urinary tract infections in the previous year were strongly associated with a single urinary tract infection (OR 7.00, 95% CI 5.91, 8.29) as well as multiple urinary tract infections (OR 18.51, 95% CI 14.27, 24.02). CONCLUSIONS: Oral hormone therapy did not reduce frequency of urinary tract infections. Potentially modifiable risk factors in postmenopausal women are different from those in younger women, and include diabetes, vaginal symptoms, and urge incontinence.

Adult↗

A novel mechanism to explain protein abnormalities in schizophrenia based on the flavivirus resistance gene.

The geographical distribution of schizophrenia was previously shown to correlate with the global distribution of tick-borne flaviviruses. The correlation suggests a natural resistance gene to flaviviruses could be involved in schizophrenia. The flavivirus resistance gene, Flv, a gene found in wild mice and certain in-bred strains, confers resistance to flaviviruses through the interaction of cellular proteins with the flaviviral 3' untranslated regions (UTRs). Although the sequence and product of Flv are unknown, translation elongation factor alpha-1 (EF-1) is a protein known to interact with the 3' UTR flavivirus RNA, forming some complexes with long half-lives that inhibit RNA growth. A study was performed to assess the homology between flaviviral UTRs, subunits of EF-1, and selected proteins reported as abnormal in schizophrenia. The UTRs of four flaviviruses with wide geographical and phylogenic distribution were manually translated. Using the National Biomedical Research Foundation protein databank, the amino acid sequences were correlated with the amino acid sequences of selected proteins. The amino acid sequences of the EF-1 subunits were then correlated with the same proteins. Similar amino acid correlations between the proteins, EF-1 subunits and viral UTRs suggest that translational pathophysiology resulting from the product of Flv can be postulated as the cause of protein abnormalities observed in schizophrenia.

3' Untranslated Regions↗

A Streptococcus pneumoniae pathogenicity island encoding an ABC transporter involved in iron uptake and virulence.

Restricted iron availability is a major obstacle to growth and survival of pathogenic bacteria during infection. In contrast to Gram-negative pathogens, little is known about how Gram-positive pathogens obtain this essential metal. We have identified two Streptococcus pneumoniae genetic loci, pit1 and pit2, encoding homologues of ABC iron transporters that are required for iron uptake by this organism. S. pneumoniae strains containing disrupted copies of either pit1 or pit2 had decreased sensitivity to the iron-dependent antibiotic streptonigrin, and a strain containing disrupted copies of both pit1 and pit2 was unable to use haemoglobin as an iron source and had a reduced rate of iron uptake. The pit2- strain was moderately and the pit1-/pit2- strain strongly attenuated in virulence in mouse models of pulmonary and systemic infection, showing that the pit loci play a critical role during in vivo growth of S. pneumoniae. The pit2 locus is contained within a 27 kb region of chromosomal DNA that has several features of Gram-negative bacterial pathogenicity islands. This probable pathogenicity island (PPI-1) is the first to be described for S. pneumoniae, and its acquisition is likely to have played a significant role in the evolution of this important human pathogen.

ATP-Binding Cassette Transporters↗

Evidence for imaging the mandible in the management of oral squamous cell carcinoma: a review.

The accuracy of clinical examination, peroperative periosteal stripping and imaging techniques in predicting tumour invasion of the mandible in oral cancer so far reported have been compared according to their specificity and sensitivity. Clinical examination alone was not shown to be accurate, but periosteal stripping at the time of resection was extremely accurate although so far only one study has investigated it. No single imaging technique will accurately predict the invasion of tumour into the mandible, but a combination of an orthopantomogram and bone scintigraphy is recommended in early invasion. Magnetic resonance imaging is more sensitive than computed tomography and therefore may be more useful if mandibular invasion requires consideration. The decision to resect the mandible as part of the management of oral cancer should be taken on the evidence of clinical examination, periosteal stripping and at least two imaging techniques that complement each other in terms of specificity and sensitivity.

Adipose Tissue↗