Deaths of heroin users in a general practice population

Recent evidence suggests that heroin users in the UK are 16 times more likely to die than otherwise expected, although causes of death are varied. The present investigation examines deaths of heroin users at a large Scottish general practice over a four-year period prior to 1 July 1985. A mortality rate of 9.72 per 1000 heroin-user patients per year was observed, roughly half that previously reported, although this difference did not prove to be statistically significant. A higher proportion of the observed deaths were attributed to heroin, and fewer to the misuse of other drugs, and it is speculated that this may reflect the practice's policy of not prescribing opiates to heroin users. Factors associated with heroin-user deaths are examined and areas identified where general practitioners may help to avert some of these deaths.     

Utility of immunostaining for S-100 protein subunits in gonadal sex cord-stromal tumors, with emphasis on the large-cell calcifying Sertoli cell tumor of the testis

This study concerns the immunohistochemical localization of S-100 alpha, S-100 beta, and whole brain S-100 (wbS-100) in testicular large-cell calcifying Sertoli cell tumor (LCCSCT). We examined 8 LCCSCTs (7 benign and 1 malignant), 6 Sertoli cell tumors not otherwise specified (SCTs-NOS), 6 Leydig cell tumors (LCTs), 5 ovarian Sertoli-Leydig cell tumors (SLCTs), and 7 gonadoblastomas (GBLs). The 8 LCCSCTs showed immunoreactivity for S-100 alpha, S-100 beta, and wbS-100. Five of the 6 LCTs and the Leydig cell components in the ovarian SLCTs stained positively for S-100 alpha and wbS-100 but were negative for S-100 beta. SCTs-NOS and the Sertoli cell components in the SLCTs occasionally showed focal and weak/moderate positivity for S-100 alpha, S-100 beta, and wbS-100. Sex cord cells of the GBLs were positive for S-100 beta and wbS-100 and negative for S-100 alpha. Germ cell elements of the GBLs were negative for S-100 alpha, S-100 beta, and wbS-100. In nonneoplastic testicular parenchyma adjacent to the above-mentioned tumors, there was S-100 alpha reactivity in Leydig cells, rete testis, and a few Sertoli cells. S-100 beta reactivity was seen in a few Sertoli cells, Schwann cells, and some endothelial cells. WbS-100 reactivity was present in Leydig cells, a few Sertoli cells, rete testis, Schwann cells, and some endothelial cells. The results indicate that S-100 alpha and S-100 beta can potentially be used as immunohistochemical markers for LCCSCT, especially when differentiating it from LCT, which may mimic LCCSCT on routine histopathology. Although the biological significance of both S-100 subunits expression in LCCSCT remains unknown, these notable calcium-binding proteins may be associated with the characteristic calcification in LCCSCT through regulation of calcium levels in the tumor cells.     

Diagnosis of Ewing's sarcoma and related tumours by detection of chromosome 22q12 translocations using fluorescence in situ hybridization on tumour touch imprints

It is increasingly recognized that the identification of t(11;22)(q24;q12) is a useful aid in the accurate diagnosis of Ewing's sarcoma and related tumours. However, cytogenetic studies have a low success rate and adequate tumour is not always available. This study describes the use of fluorescence in situ hybridization (FISH) to detect translocations at 22q12, the site of the EWS gene involved in t(11;22)(q24;q12), on tumour touch imprints made from true cut core-needle biopsy and frozen tumour. Of the seven tumours analysed, five diagnosed as Ewing's sarcoma or primitive neuroectodermal tumour demonstrated chromosome translocation at 22q12. This is a rapid and reliable method to detect a diagnostically relevant chromosome translocation using minimal amounts of fresh or frozen tumour.     

Analysis of DNA ligase IV mutations found in LIG4 syndrome patients: the impact of two linked polymorphisms

LIG4 syndrome patients have hypomorphic mutations in DNA ligase IV. Although four of the five identified patients display immunodeficiency and developmental delay, one patient was developmentally normal. The developmentally normal patient had the same homozygous mutation (R278H) in DNA ligase IV as one of the more severely affected patients, who additionally had two linked polymorphisms. Here, we examine the impact of the mutations and polymorphisms identified in the LIG4 syndrome patients. Examination of recombinant mutant proteins shows that the severity of the clinical features correlates with the level of residual ligase activity. The polymorphisms decrease the activity of DNA ligase IV by approximately 2-fold. When combined with the otherwise mild R278H mutation, the activity is reduced to a level similar to other LIG4 patients who display immunodeficiency and developmental delay. This demonstrates how coupling of a mutation and polymorphism can have a marked impact on protein function and provides an example where a polymorphism may have influenced clinical outcome. Analysis of additional mutational changes in LIG4 syndrome (R580X, R814X and G469E) have led to the identification of a nuclear localization signal in DNA ligase IV and sites impacting upon DNA ligase IV adenylation.     

Ventilatory and upper-airway resistance responses to upper-airway cooling and CO2 in anaesthetised rats

The effects of upper airway (UA) cool air and CO₂ on breathing and on laryngeal and supraglottic resistances were studied in anaesthetised rats breathing spontaneously through a tracheostomy. Warm, humidified air containing 0, 5 and 9–10% CO₂ and cool, room-humidity air were delivered at constant flow to either the isolated larynx to exit through a pharyngotomy or to the supraglottic UA to exit through the mouth and/or nose (nose open or sealed). Spontaneous tracheal airflow and UA airflows, temperatures and pressures were recorded. CO₂ had no effect on breathing but caused a slight increase in laryngeal resistance which was abolished by cutting the superior laryngeal nerves (SLN). Cool air caused a decrease in respiratory frequency and/or peak inspiratory flow when applied to the isolated larynx or to the supraglottic airway with the nose closed. These effects were abolished by SLN section. With the nose open, the ventilatory inhibition was not abolished by SLN section. Cool air also caused substantial decreases in laryngeal and supraglottic resistances which were attenuated by SLN section and which persisted following recurrent laryngeal nerve section. In conclusion, whilst UA cooling inhibits breathing and decreases UA resistances, UA CO₂ has minimal effects.     

Fitting Health Care to People: Understanding and Adapting to the Epidemiology and Health Literacy of People Affected by Viral Hepatitis from Culturally and Linguistically Diverse Migrant Backgrounds

Journal of Immigrant and Minority Health - This study explored the epidemiology and health literacy of people affected by viral hepatitis (VH) from migrant culturally and linguistically diverse...     

Capsular Management in Direct Anterior Total Hip Arthroplasty: A Randomized,Single-Blind,Controlled Trial

BackgroundThe direct anterior approach (DAA) is a popular approach to total hip arthroplasty (THA). Unlike the posterior approach, the importance of anterior capsular management is unknown. This randomized controlled trial compares capsular repair versus capsulectomy.MethodsThis single-surgeon, single-blinded, parallel-group randomized controlled trial occurred between 2013 and 2016. Patients undergoing unilateral, primary THA for osteoarthritis consented to undergo blinded, simple randomization to anterior capsulotomy with repair or anterior capsulectomy. Primary outcome measures included hip range of motion, hip flexion strength, and pain with seated hip flexion. Secondary outcome measures included surgical time, estimated blood loss, postoperative complications, and hip disability and osteoarthritis outcome score. Data were prospectively collected intraoperatively, six weeks, six months, an average of over 5 years postoperatively.ResultsNinety-eight patients were ultimately enrolled in the trial; 50 received capsulectomy and 48 received capsulotomy. No significant differences were seen in preoperative demographics or in primary or secondary outcomes during this study. No difference was seen in pain at final follow-up at average > 5 years postoperatively.ConclusionThis study demonstrates that capsular management in DAA THA does not affect postoperative pain or range of motion. The anterior capsule’s role in prosthetic stability after DAA THA remains uncertain, but it does not currently appear that repair provides benefit and may lead to increased surgical time and blood loss. As such, capsular management in DAA THA is at surgeon discretion.     

Anxiolytic-like effects of yohimbine in the murine plus-maze: strain independence and evidence against α2-adrenoceptor mediation

The influence of ₂-adrenoceptor antagonists in animal models of anxiety is quite inconsistent, with results spanning the full range of effect from anxiogenesis to anxiolysis. In the present study, an ethological technique was used to examine the effects of yohimbine (0.5–4.0 mg/kg) on plus-maze behaviour in DBA/2 mice. Results indicated significantanxiolytic-like effects on standard spatiotemporal measures at 2.0–4.0 mg/kg, and on risk assessment measures across the entire dose range. Full-scale follow-up studies with T1 and BALB/c strains confirmed that this action of yohimbine in the murine plus-maze is not peculiar to DBA/2 mice. The more selective ₂-adrenoceptor antagonist, idazoxan (0.63–5.0 mg/kg), exerted much weaker behavioural effects in the maze while the ₂-adrenoceptor agonist, clonidine (0.01–0.1 mg/kg), produced a profile consistent with non-specific behavioural disruption. Data are discussed in relation to the possible involvement of 5-HT_1A receptor mechanisms in the observed anxiolytic-like effects of yohimbine in the murine plus-maze.     

Pharyngo-esophagoplasty by right coloplasty for the treatment of post-caustic pharyngo-laryngeal-esophageal burns: a report of 13 cases

We report a new technique of pharyngoesophagoplasty by right coloplasty, indicated in postcaustic severe pharyngeal stenosis, analyzing the anatomical and functional results in terms of respiratory tract and phonation as well as digestive tract outcome. We compared our results with those obtained with other procedures. Between March 1995 and September 1998, pharyngoesophagoplasty by right coloplasty was performed in 13 patients. All had severe hypopharyngeal stricture with total obliteration of the two piriform sinuses and the upper esophageal sphincter. Nine patients underwent emergency esophagectomy or esogastrectomy by stripping and four had a cicatricial esophagus. Eight patients underwent tracheotomy before the pharyngoplasty due to burns of the laryngeal margin or airway infections. There was no perioperative mortality. The retrospective analysis in February 1998 with a follow-up of 22 months disclosed two deaths, one from septic shock following pneumnia and one suicide. For the 11 other patients, respiratory function had been restored successfully as the tracheostomy tube had been removed. Eight of the patients were on regular oral diet and the jejunostomy tube had been removed. Three had mild dysphagia and the oral diet was supplemented by jejunostomy tube feedings. These results were most successful compared with those obtained with 29 other patients. Pharyngo-esophagoplasty by right colonic transposition appears to be the method of choice for the reconstruction of post-caustic pharyngeal and esophageal stenosis.