The association between diabetes medication and weight change in a non-surgical weight management intervention: an intervention cohort study.

AIM: To compare weight change in a lifestyle-based weight management programme between participants taking weight-gaining, weight-neutral/loss and mixed diabetes medications. METHODS: Electronic health records for individuals (≥ 18 years) with Type 2 diabetes who had been referred to a non-surgical weight management programme between February 2008 and May 2014 were studied. Diabetes medications were classified into three categories based on their effect on body weight. In this intervention cohort study, weight change was calculated for participants attending two or more sessions. RESULTS: All 998 individuals who took oral diabetes medications and attended two or more sessions of weight management were included. Some 59.5% of participants were women, and participants had a mean BMI of 41.1 kg/m2 (women) and 40.2 kg/m2 (men). Of the diabetes medication combinations prescribed, 46.0% were weight-neutral/loss, 41.3% mixed and 12.7% weight-gaining. The mean weight change for participants on weight-gaining and weight-neutral/loss diabetes medications respectively was -2.5 kg [95% confidence interval (CI) -3.2 to -1.8) and -3.3 kg (95% CI -3.8 to -2.9) (P = 0.05) for those attending two or more sessions (n = 998). Compared with those prescribed weight-neutral medications, participants prescribed weight-gaining medication lost 0.86 kg less (95% CI 0.02 to 1.7; P = 0.045) in a model adjusted for age, sex, BMI and socio-economic status. CONCLUSIONS: Participants on weight-neutral/loss diabetes medications had a greater absolute weight loss within a weight management intervention compared with those on weight-gaining medications. Diabetes medications should be reviewed ahead of planned weight-loss interventions to help ensure maximal effectiveness of the intervention.

Process evaluation of a cluster-randomised controlled trial of multi-component weight management programme in adults with intellectual disabilities and obesity.

BACKGROUND: Providing effective weight management to adults with intellectual disabilities is necessary to challenge the high rates of obesity. The aim of this process evaluation was to explore the feasibility of conducting a full-scale clinical trial of the TAKE 5 multi-component weight management programme. METHODS: The study was a 12-month pilot cluster-randomised controlled trial. Adults with intellectual disabilities and obesity were randomised to either TAKE 5, which included an energy deficit diet (EDD) or Waist Winners Too, based on health education principles. A mixed-methods process evaluation was conducted focussing on the reach, recruitment, fidelity, implementation, dose (delivered/received) and context. RESULTS: The study successfully recruited adults with intellectual disabilities. Both weight management programmes were delivered with high fidelity and implemented as intended. Only one weight management programme, TAKE 5, demonstrated potential efficacy in reducing body weight and body composition. The effectiveness was largely attributed to the EDD and social support from carers. CONCLUSIONS: The extensive process evaluation illustrated that a full-scale trial of a multi-component programme including an EDD is feasible and an acceptable approach to weight management for adults with intellectual disabilities and obesity.

Presence of obesity is associated with lower mortality in elderly patients with implantable cardioverter defibrillator.

BACKGROUND: Higher body mass index (BMI) is associated with greater prevalence of cardiovascular risk factors, yet an inverse relationship between obesity and survival after cardiovascular events has been described. It is unclear whether a similar relationship exists for patients with implantable cardioverter defibrillators (ICDs) at high risk for mortality. We aimed to assess the impact of BMI on mortality and cardiovascular hospitalization in patients with ICD. METHODS: Patients who underwent ICD implantation in 2010-2011 were divided into normal (<25 kg m-2), overweight (25-29.9 kg m-2) and obese (⩾30 kg m-2) groups based on BMI. Clinical parameters were compared and long-term outcomes were determined using χ2 test, Wilcoxon's rank-sum test, logistic regression models and Kaplan-Meier curves. RESULTS: Of 904 patients (mean age 67±13 years), 26% had normal BMI, 32% were overweight and 42% were obese. No significant baseline differences in ventricular ejection fraction, ICD for primary or secondary prevention, history of heart failure, syncope or cardiac arrest existed. Despite a greater prevalence of diabetes, hypertension and prior myocardial infarction, the obese and overweight groups had lower mortality (10.1% and 7.9%, respectively) than the normal group (22.9%, P<0.001). On multivariate logistic regression, BMI in the obese and overweight range (odds ratio (OR): 0.35; 95% confidence interval (CI): 0.21-0.58 and OR: 0.25; 95% CI: 0.13-0.40, respectively) was protective against mortality, whereas history of diabetes (OR: 2.01; 95% CI: 1.30-3.09), myocardial infarction (OR: 1.76; 95% CI: 1.11-2.80), heart failure (OR: 3.88; 95% CI: 1.56-9.66), stroke (OR: 3.19; 95% CI: 1.63-6.23) and history of cardiac arrest (OR: 2.65; 95% CI: 1.37-5.15) were independent risk factors for higher mortality. CONCLUSIONS: A paradoxical relationship between BMI and mortality risk is present in elderly patients with ICD at high risk of sudden death with a lower mortality in obese or overweight patients than in those with normal BMI.

US Hemophilia Treatment Center population trends 1990-2010: patient diagnoses, demographics, health services utilization.

For several decades, US government agencies have partially supported regional networks of Hemophilia Treatment Centers (HTC). HTC multidisciplinary teams provide comprehensive and coordinated diagnosis, treatment, prevention, education, outreach and surveillance services to improve the health of people with genetic bleeding disorders. However, national data are scarce on HTC-patient population trends and services. The aim of the study was to examine national trends over the past 20 years in patient diagnoses, demographics and health services utilization among the Health Resources and Services Administration (HRSA) and Centers for Disease Control and Prevention (CDC)-supported HTC network. Diagnoses, demographics and health services utilization data from 1990 to 2010 were aggregated from all HTCs using the Hemophilia Data Set (HDS). From 1990 to 2010, the HTC population grew 90% from 17 177 to 32 612. HTC patients with von Willebrand's disease increased by 148%, females by 346%, Hispanic patients by 236% and African Americans by 104%. Four thousand and seventy-five deaths were reported. From 2002 to 2010, annual comprehensive evaluations grew 38%, and persons with severe haemophilia on a home intravenous therapy programme rose 37%. In 2010, 46% of patients were less than 18 years vs. 24% for the general US population. The Hemophilia Data Set documents the growth and diversity of the US Hemophilia Treatment Center Network's patient population and services. Despite disproportionate deaths due to HIV, the HTC patient base grew faster than the general US population. The HDS is a vital national public health registry for this rare-disorder population.

Have early postoperative complications from laparoscopic rectal cancer surgery improved over the past 20 years?

AIM: Laparoscopic rectal cancer surgery has been increasingly used since 1991 following the publication of the first case series. Since then, several studies have confirmed that laparoscopic surgery for rectal cancer is challenging with associated morbidity and mortality. The aim of this study was to determine if the rates of early postoperative complications in laparoscopic rectal cancer surgery have improved over the past 20 years. METHOD: A literature search of the EMBASE and MEDLINE databases between August 1991 and August 2011 was conducted using the keywords laparoscopy, rectal cancer and postoperative complications. Data were analysed using linear regression ANOVA performed in GNUMERICS software. RESULTS: Ninety-seven studies were included for analysis. Over the last 20 years there has been no significant change in the rate of any early postoperative complications (anastomotic leak, conversion, sexual, urinary or faecal dysfunction, wound infection, overall morbidity or mortality). However, in the last 3 years, the rate of positive resection margins has decreased significantly (P = 0.01). CONCLUSION: There was no evidence of a statistically significant change in early postoperative complications until 3 years ago. This may reflect the inherent morbidity associated with rectal surgery regardless of the approach used, the limitations of the current laparoscopic instrumentation or the relatively long learning curve. With increasing experience, a repeat analysis in the near future following the publication of ongoing randomized clinical trials might show improved outcomes.

Opioid and stimulant attributed treatment admissions and fatal overdoses: Using national surveillance data to examine the intersection of race, sex, and polysubstance use, 1992-2020.

BACKGROUND: We use national surveillance data to evaluate race/ethnicity by sex/gender differences and trends in substance use treatment admissions and overdose deaths involving opioid and stimulant use. METHODS: We used data (1992-2019) from the Treatment Episode Dataset-Admissions to identify treatment admissions and the Center for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (1999-2020) to identify overdose deaths. We assessed treatment admissions and related drug overdose deaths per 100,000 adults by sex and race/ethnicity for opioid and stimulant groups: cocaine, opioid, methamphetamines, cocaine and opioid use, cocaine and methamphetamines, and opioid and methamphetamines. RESULTS: We found significant variations in treatment admissions and deaths by race/ethnicity and sex/gender. Cocaine-related treatment admissions and deaths were most prevalent among Non-Hispanic Black individuals over the study years, yet lower rates were evident among individuals from other racial/ethnic groups. Notably, Non-Hispanic Black men experienced larger increases in cocaine-only admissions than men of other racial/ethnic groups between 1992 and 2019. Men had higher opioid and stimulant treatment admissions and overdose deaths than women. We observed skyrocketing methamphetamine deaths among American Indian/Native Alaskan men and women from 1992 to 2019. DISCUSSION: Steep increases in overdose deaths fueled by methamphetamines among Non-Hispanic Native Americans and cocaine among Non-Hispanic Black individuals suggest a need for more effective interventions to curb stimulant use. Variations by race/ethnicity and sex/gender also suggest interventions should be developed through an intersectionality lens.

SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer.

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2-/- mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer.

Restriction to the cell nucleus of virus-induced host RNA's in a rat kidney tumor induced by polyoma virus.

RNA transcripts of repetitive DNA of WF rat kidney, which were derepressed during transformation by polyoma virus, were not transported to the cytoplasm in the tumor cells. Transcripts of repetitive DNA found in the normal cell nucleus were all transported to the cytoplasm in the tumor cells, including those restricted to the nuclei in the normal cells.

Monoclonal antibodies raised against cell membrane components of human bladder tumor tissue recognizing subpopulations in normal urothelium.

Monoclonal antibodies to human bladder carcinoma membrane antigens were produced by fusion of MOPC-21 NS/1 mouse myeloma cells with spleen cells from BALB/c mice immunized against a crude membrane extract from a metastatic bladder carcinoma. Hybrids were screened for antibody production in a solid-phase radioimmunoassay and selected for their reactivity with subpopulations of urothelial cells on normal bladder tissue sections. Three antibody groups were defined: Group I (4-72-2) was urothelium specific and stained the basal and intermediate cells in normal urothelium; group II (3-48-2, 48-1, and 3-50-3) showed reactivity with intermediate and superficial cells; group III (8-30-3, 77-1, 2-94-2, 3-71-1, and 94-3) was restricted to antigens on the luminal membrane of superficial cells. All antibodies recognized antigenic determinants in fixed paraffin-embedded material and within groups showed a range of staining patterns in other tissues. Studies on sections representing different stages of neoplastic progression showed disruption in the antibody-staining pattern in urothelium and, in all cases, a strong distinct staining of invasive tumor areas and metastatic secondary tumors. Biochemical analysis of the antigens defined at least three antigenic systems, two of which consisted of molecules having Mr of 250,000 and 300,000 as judged by Western blot analysis. Antigenic determinants recognized by some antibodies (3-48-2, 48-1, 3-50-3, 8-30-3, 77-1, and 3-71-1) were shown to be carbohydrate by reactivity with glycolipid fraction and suggest that antibodies within groups recognize different epitopes on the same molecule.

The frequency of germ-line mutations in the breast cancer predisposition genes BRCA1 and BRCA2 in familial prostate cancer. The Cancer Research Campaign/British Prostate Group United Kingdom Familial Prostate Cancer Study Collaborators.

Predisposition to prostate cancer has a genetic component, and there are reports of familial clustering of breast and prostate cancer. Two highly penetrant genes that predispose individuals to breast cancer (BRCA1 and BRCA2) are known to confer an increased risk of prostate cancer of about 3-fold and 7-fold, respectively, in breast cancer families. Blood DNA from affected individuals in 38 prostate cancer clusters was analyzed for germ-line mutations in BRCA1 and BRCA2 to assess the contribution of each of these genes to familial prostate cancer. Seventeen DNA samples were each from an affected individual in families with three or more cases of prostate cancer at any age; 20 samples were from one of affected sibling pairs where one was < or = 67 years at diagnosis. No germ-line mutations were found in BRCA1. Two germ-line mutations in BRCA2 were found, and both were seen in individuals whose age at diagnosis was very young (< or = 56 years) and who were members of an affected sibling pair. One is a 4-bp deletion at base 6710 (exon 11) in a man who had prostate cancer at 54 years, and the other is a 2-bp deletion at base 5531 (exon 11) in a man who had prostate cancer at 56 years. In both cases, the wild-type allele was lost in the patient's prostate tumor at the BRCA2 locus. However, intriguingly, in neither case did the affected brother also carry the mutation. Germ-line mutations in BRCA2 may therefore account for about 5% of prostate cancer in familial clusters.

Attrition and weight loss outcomes for patients with complex obesity, anxiety and depression attending a weight management programme with targeted psychological treatment.

The objective of the study is to investigate the effect of baseline anxiety and depression, using different definitions for caseness, on attrition and weight outcomes following a multidisciplinary weight management programme. The study design is a prospective observational study. The Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety and depression with 'caseness' scoring ≥11 and severity ≥14. The participants were all patients who began a weight management programme between 1 October 2008 and 30 September 2009 (n = 1838). The setting was the Glasgow and Clyde Weight Management Service (GCWMS), a specialist multidisciplinary service, which aims to achieve a minimum of ≥5 kg weight loss. The results were as follows: patients with HADS score ≥14 were referred to the integrated psychology service for psychological assessment or intervention. Patients with caseness (HADS ≥11) for anxiety (33%) and depression (27%) were significantly younger, heavier, more socio-economically deprived and a higher proportion was female. There was a significant positive correlation between HADS anxiety and depression scores and increasing body mass index (r(2) = 0.094, P < 0.001 and r(2) = 0.175, P < 0.001, respectively). Attendance and completion was lower throughout follow-up amongst patients with anxiety or depression. More patients with HADS score ≥11 achieved ≥5 kg or ≥5% weight loss and by 12 months those with anxiety had a significantly higher mean weight loss (P = 0.032). Participants who scored for severe anxiety (HADS ≥14) achieved similar weight loss to those without, whilst participants who scored for severe depression achieved significantly greater weight loss than non-cases at 3, 6 and 12 months of follow-up (P < 0.01). Despite a less favourable case-mix of risk-factors for poor weight loss, patients who scored caseness for severe anxiety or depression and were offered additional psychological input achieved similar or better weight loss outcomes.

Relationship between glutathione S-transferase M1, P1 and T1 polymorphisms and early onset prostate cancer.

There is evidence suggesting that polymorphic variations in the glutathione S-transferases (GSTs) are associated with cancer susceptibility. Inter-individual differences in cancer susceptibility may be mediated in part through polymorphic variability in the bioactivation and detoxification of carcinogens. The GSTs have been consistently implicated as cancer susceptibility genes in this context. The GST supergene family includes several loci with well characterized polymorphisms. Approximately 50% of the Caucasian population are homozygous for deletions in GSTM1 and approximately 20% are homozygous for deletions in GSTT1, resulting in conjugation deficiency of mutagenic electrophiles to glutathione. The GSTP1 gene has a polymorphism at codon 105 resulting in an Ile to Val substitution which consequently alters the enzymatic activity of the protein and this has been suggested as a putative high-risk genotype in various cancers. We investigated the relationship between GST polymorphisms and young onset prostate cancer in a case-control study. GSTM1, GSTT1 and GSTP1 genotypes were determined for 275 prostate cancer patients and for 280 geographically matched control subjects. We found no significant difference in the frequency of GSTM1 or GSTT1 null genotypes between cases and controls. GSTP1 genotype was, however, significantly associated with prostate cancer risk: the Ile/Ile homozygotes had the lowest risk and there was a trend in increasing the risk with the number of 105 Val alleles: Ile/Val odds ratio (OR)= 1.30 (95% FCI 0.99-1.69), Val/Val OR = 1.80 (95% FCI 1.11-2.91); Ptrend = 0.026. These results suggest that the GSTP1 polymorphism may be a risk factor for developing young onset prostate cancer. We also found that carrying more than one putative high-risk allele in the carcinogen metabolizing GST family was associated with an elevated risk for early onset prostate cancer (OR 2.48, 95% FCI 1.22-5.04, Ptrend = 0.017).

A comparison of a controlled release (CR/ZOK) formulation of metoprolol, once daily, with conventional metoprolol tablets, twice daily, in mild to moderate hypertension.

In a randomized double-blind multicenter study in 100 hypertensive patients, the effect of once daily (od) dosing with a new controlled release (CR/ZOK) formulation of metoprolol was compared with that of twice daily (bid) dosing with metoprolol conventional tablets. Eligible patients had a resting seated diastolic blood pressure (DBP) greater than or equal to 95 mm Hg and less than 110 mm Hg at the end of a 6-week open placebo run-in. The active treatment phase lasted 8 weeks. The starting dose was 100 mg od in the CR/ZOK group (N = 53) and 50 mg bid in the tablet group (N = 47). The dose was increased to 200 mg od and 100 mg bid, respectively, in nonresponders (DBP greater than 95 mm Hg) at the end of the first 4-week period. Approximately 40% of both groups received concomitant diuretic therapy throughout the study. The SBP, DBP and HR were reduced compared to baseline in both treatment groups after 4 and 8 weeks. After 4 weeks, 85% of the CR/ZOK group and 74% of the tablet group had DBP less than 95 mm Hg. After another 4 weeks, the corresponding figures were 93% and 93%. There was no statistically significant difference between the treatment groups in the decrease in either SBP, DBP or HR, nor was there any difference in the percentage of responders. Both treatments were equally well tolerated. In conclusion, the antihypertensive effect of once daily dosing (100-200 mg) with the new CR/ZOK formulation of metoprolol is as effective as that of twice daily dosing (50-100 mg) with conventional metoprolol tablets.

Failure to void after transurethral resection of the prostate and mode of presentation.

OBJECTIVES: Contemporary audits and reviews of outcome after transurethral resection of the prostate (TURP) make little reference to failure to void following catheter removal after this operation. There have been few reports of the likelihood of a successful trial without a catheter after TURP related to mode of presentation. We report the results of a retrospective review of outcome of TURP related to mode of presentation, age, and prostate histologic findings in a consecutive series of patients in a London Teaching Hospital. METHODS: A consecutive series of 379 patients (381 TURPs) was reviewed to document the incidence of and risk factors for failure to void following initial trial without a catheter after TURP. RESULTS: Twelve percent of men failed to void after TURP on the initial trial without a catheter. In those patients presenting with lower urinary tract symptoms, there were no instances of failure to void. Ten percent of patients with acute retention (painful inability to void, urine volume less than 800 mL), 38% with chronic retention (maintenance of spontaneous voiding, bladder volume greater than 500 mL), and 44% with acute on chronic retention (painful retention, urine volume greater than 800 mL) failed to void after TURP. Only 1% of patients required management by long-term catheterization. Failure to void on catheter removal was not related to age or prostate histologic findings. CONCLUSIONS: Bladder volume at initial presentation in patients with urinary retention provides important information about the likelihood of re-establishing spontaneous voiding catheter removal following TURP. Patients should be warned that there is a significant chance of failure to void after TURP, the exact risk depending on their mode of presentation, but that most will ultimately not require a permanent indwelling catheter.

A dose-response study of the effect of flutamide on benign prostatic hyperplasia: results of a multicenter study.

OBJECTIVES: The objective of this study was to evaluate efficacy, safety, and dose-response profiles of four dosing schemes of flutamide over 24 weeks. METHODS: Patients were randomized to receive one of the following five treatment regimens for a period of 24 weeks: placebo capsule, flutamide capsules 125 mg twice daily, 250 mg once daily, 250 mg twice daily, and 250 mg three times daily. Patients were then evaluated at baseline (0 weeks) and at 4, 6, 12, 18, and 24 weeks after the start of treatment, and 8 weeks after the end of treatment (32 weeks). Evaluation of efficacy was performed by noting changes in urine flow rate, residual urine volume, symptom score, prostate volume, and prostate-specific antigen level. A total of 372 patients were enrolled into the study at 32 centers (14 centers in the United States and 18 international centers). RESULTS: Baseline peak urinary flow rate and percent change from baseline in maximum flow rate showed a dose-related increase at 4 and 6 weeks; this increase was significant in the 250 mg three times daily group. At later time points, no significant differences between the flutamide and placebo groups were observed, largely because of the decreasing number of evaluable patients. At 4 and 6 weeks, 25% of patients in the 250 mg three times daily group had more than 3 cc/s increase in uroflow compared to about 10% of placebo patients (P < 0.05). All flutamide-treated groups had a significant decrease in prostate volume from baseline to the last treatment visit compared to placebo and this reduction was dose related (in comparison to placebo: P < 0.05 for 125 mg twice daily and P < 0.001 for all other treatment arms). Median decrease for the flutamide-treated groups ranged from 6% to 23% at 12 weeks and from 14% to 29% at 24 weeks. All treatment groups showed a subsequent increase in prostate volume after treatment was stopped. Furthermore, there was a significant reduction in residual urine volume at 24 weeks only in the 250 mg three times daily group. It increased following cessation of therapy. Urinary symptoms at 6, 12, 18, and 24 weeks did not show any significant difference between placebo and any flutamide dose group. The most common adverse events were nipple and breast tenderness (42% to 52%), diarrhea (29% to 34%), and gynecomastia (14% to 19%). Each of these adverse events had a significantly higher incidence in all flutamide dose groups compared with placebo, but none appeared to occur in a dose-related fashion. Sixteen percent of patients in the placebo group and 25% to 39% of patients in flutamide groups were discontinued due to diarrhea (12% to 17%) or nipple and breast tenderness (4% to 8%). A total of 1% to 3% of patients in various treatment arms discontinued due to deranged liver enzymes (1% for placebo); and 1% to 4% due to impotence (1% for placebo). CONCLUSIONS: Flutamide reduced the prostate volume in a dose-related fashion and resulted in an increase in peak flow rate at 4 weeks (3% for 250 mg three times daily, P value < 0.05), but the early positive effects did not maintain statistical significance due to an increasing number of dropouts due to adverse events. Effect on postvoid residual volume was observed only at the highest dose and at 24 weeks (median reduction, 23 mL, P < 0.05). Despite volume reduction and early improvement in peak flow rate, there were no significant differences in urinary symptoms among the placebo and flutamide groups. Higher incidences of diarrhea, breast tenderness, and gynecomastia, however, were the main limiting factors in this study and until these problems are overcome, the role of flutamide in the management of benign prostatic hyperplasia remains investigational.

Altered RNA transport without derepression in a rat kidney tumor induced by dimethylnitrosamine.

RNA/DNA hybridization in the presence of competing RNA was used to study transcription and transport of RNA from the nucleus to the cytoplasm in a rat renal tumor induced by a single intraperitoneal injection of dimethylnitrosamine (DMN). Neither repression nor derepression of transcription of repetitive DNA can be detected in this tumor, but transcripts of all active families of such sequences are found in the tumor cytoplasm. This is the pattern of RNA change found in the chemically-induced hepatocellular carcinomas and contrasts with the pattern of virus-induced renal tumors in which both altered transport and derepression of host repetitive sequences have been demonstrated. The alteration of RNA transport is nearly complete in the kidney only two days after the above treatment, but there is no such alteration detectable in the kidney after nine days of feeding a liver carcinogen which is not carcinogenic to kidneys. This data supports the significance and specificity of the loss of ability to restrict certain RNA sequences to the nucleus early during malignant transformation.

Arctic contaminants: sources, occurrence and pathways.

Potentially toxic organic compounds, acids, metals and radionuclides in the northern polar region are a matter of concern as it becomes evident that long-range transport of pollution on hemispheric to global scales is damaging this part of the world. In this review and assessment of sources, occurrence, history and pathways of these substances in the north, the state of knowledge of the transport media--the ocean and atmospheric circulation--is also examined. A five-compartment model of the northern region is developed with the intent of assessing the pathways of northern contaminants. It shows that we know most about pathways of acids, metals and radionuclides and least about those of complex synthetic organic compounds. Of the total annual inputs of anthropogenic acidic sulphur and the metals lead and cadmium to the Arctic via the atmosphere, an estimated 10-14% are deposited. A water mass budget for the surface layer of the Arctic Ocean, the most biologically active part of that sea, is constructed to examine the mass budget for one of the major persistent organochlorine compound groups found in remote regions, hexachlorocyclohexanes (HCH), one isomer of which is lindane. It is concluded that both the atmosphere and the ocean are important transport media. Even for the HCH substances which are relatively easily measured and simple in composition compared to other synthetic organics, we know little about the occurrence and environmental physical/chemical characteristics that determine pathways into the food chain. More environmental measurements, chemical characterization studies and environmental chemical transport modelling are needed, as is better knowledge of the circulation of the Arctic Ocean and the marine food web.

Laparoscopically assisted vaginal hysterectomy. The initial Nashville, Tennessee, experience.

It is now possible to begin a difficult hysterectomy via laparoscopy with or without adnexal removal and then complete the operation vaginally. We report our successful experience with laparoscopically assisted vaginal hysterectomy in 62 of 68 patients. Techniques used for hemostatic separation of the uterus and adnexal pedicles included an automatic laparoscopic stapling device (49 cases), bipolar coagulation with sharp transection (11) and combined techniques (2). Minor complications occurred in four patients. Six patients had their operations converted from laparoscopy to laparotomy because of significant adhesions (three), large fibroids (two) and poor access due to obesity (one). The use of a stapling device required less anesthesia time (1 hour, 57 minutes, vs. 3 hours, 43 minutes), a smaller blood loss (145 vs. 247 mL) and shorter hospital stays (2.53 vs. 2.75 days) than did laparoscopic bipolar coagulation. However, the average hospital costs were greater for disposable automatic stapling devices and trocars when compared to bipolar coagulation techniques ($9,310 vs. $6,227). Postoperative patient satisfaction with the operation was high (98%), with a high rate of symptom resolution (95%). Laparoscopically assisted vaginal hysterectomy is a safe, effective operation in selected cases and may soon become a common alternative to abdominal hysterectomy in certain cases.

Should all patients with ureteric colic be admitted?

A two-part study was undertaken to determine if all patients with uncomplicated ureteric colic require admission. The analgesic requirements and outcome in 31 patients admitted with ureteric colic were assessed; 20/31 (64%) required no further analgesia after admission and 8/31 (26%) required only oral/rectal analgesia. In the second part of the study a protocol was introduced allowing patients with no complicating factors to be discharged directly from the A&E department. Of 58 patients seen in the A&E department, 29 were discharged for outpatient follow-up. Of these patients, 19 required no additional acute hospital treatment, five returned for further parenteral analgesia but outside the time they would have stayed in hospital under our previous protocol (ie beyond 48 h) and three returned within 48 h of their first attendance with pain which had not responded to oral analgesics. No patient discharged from A&E subsequently required intervention for obstruction or infection. We conclude that it is not necessary to admit patients with uncomplicated ureteric colic if the initial colic has been relieved and there is adequate social support.