Histological changes over time around the site of sustained release naltrexone-poly(DL-lactide) implants in humans.

In order to assess the histological tissue changes over time around the site of implant, tissue biopsies were taken at 1 to 38 months post-implant from 54 (34 male) consenting human subjects who had received the Australian subcutaneous naltrexone-poly(DL-lactide) implant for heroin dependence. The implant consists of multiple tablets containing compressed naltrexone-poly[trans-3,6-dimethyl-1,4-dioxane-2,5-dione] (DL-lactide) loaded microspheres. Assessment of tissue samples by pathologists showed an early phase (up to 12 months post-implant) of inflammation, foreign body reaction, and fibrosis. This subsided gradually over the next 12 months until tissue returned to normal by 25+ months. Sufficient evidence was not available to conclude that the poly(DL-lactide) implant matrix was totally biodegradable within the study period. While implant material was not identified in most of the latter biopsies, its presence was noted in one biopsy at 26 months post-implant. Nevertheless the study results did demonstrate the implant's biocompatibility by the lack of inflammation, foreign body reaction, and fibrosis detected by 25+ months. It seems highly probable that surgical technique rather than the implant itself was associated with the additional finding of fat necrosis. Moderate fat necrosis was observed as a common feature of biopsies carried out during the first 6 months following implant. It subsided to mild levels over the next 18 months, and was notably absent by 25+ months. The results of the study indicated that the Australian naltrexone-poly(DL-lactide) implant is well tolerated and may have a role for use in the management of medical conditions such as heroin dependence.     

Late spontaneous recovery of chronic thrombocytopenia.

Five cases are reported of spontaneous remission of chronic childhood thrombocytopenia four or more years after diagnosis. Other than typical features of chronic idiopathic thrombocytopenic purpura there were no obvious markers predictive of late remission, although a slow progressive recovery was common to four of the patients. In light of this experience splenectomy is not recommended in clinically mild thrombocytopenia.     

Trimethoprim resistant dihydrofolate reductases in normal faecal flora isolated in India.

A high incidence of resistance to trimethoprim has been shown in the normal faecal flora in a population in south India. The dihydrofolate reductase (dhfr) genes mediating transferable resistance to trimethoprim have been identified. Unusually, in this study, the dhfrV was shown to be the predominant resistance gene (dhfrV 50% of transconjugants, dhfrIa 30%), the dhfrIb was also detected being distinguished from the dhfrV by an oligo-probe. However, when non-transferable resistance was considered, the dhfrIa was the most prevalent of the dhfrs identified. All those plasmids harbouring the dhfrIa were shown to possess Tn7. All the plasmids that probed positive for the dhfrV and the dhfrIb were shown to be associated with the integrase of the Tn21-like transposons, but 8 of the dhfrV genes were not associated with the Tn21 resolvase. The dhfrIV was shown to be present in all seven plasmids that produced low level trimethoprim-resistance. The dhfrV, first characterized in Sri Lanka, would seem to have a local distribution in this region of Asia but is distinguishable from the dhfrIb only by the use of an oligo-probe.     

Evidence for a Type 1 diabetes‐specific mechanism for the insulin gene‐associated IDDM2 locus rather than a general influence on autoimmunity

Aims The Type 1 diabetes susceptibility locus, IDDM2, has been mapped to a variable number of tandem repeats (VNTR) region 5′ upstream of the insulin (INS) and insulin‐like growth factor (IGF2) genes on chromosome 11p15. The function of the VNTR is uncertain; however, it may influence the thymic expression of the insulin gene and affect the development of immune self‐tolerance. The aim of this study was to investigate whether the INS VNTR region is a Type 1 diabetes‐specific locus or acting as a general autoimmunity gene. Methods We genotyped the INS‐IGF2 VNTR [using the surrogate INS?23 HphI single nucleotide polymorphism (SNP)] in 823 Graves’ disease (GD)/multiple sclerosis (MS) families, 1433 GD/MS patients and 837 healthy control subjects. Results We found no evidence of excess transmission of the allele associated with Type 1 diabetes to individuals affected by GD or MS within the families. Analysis of the case–control dataset showed no genotypic or allelic difference between the two populations. Conclusions These data suggest that the INS‐IGF2 VNTR is acting as a Type 1 diabetes‐specific susceptibility gene rather than as an influence on general autoimmunity.     

Clustering of autoimmune disease in parents of siblings from the Type 1 diabetes Warren repository.

AIMS: Autoimmune disorders co-exist in the same individuals and in families, implying a shared aetiology. The aim of this study was to compare the prevalence of the common autoimmune diseases in the parents of siblings from the Type 1 diabetes Warren repository with the general population. METHODS: Between 1989 and 1996, 505 British families with at least two siblings affected by Type 1 diabetes were recruited. Clinical information was collected regarding the presence of autoimmune disease in the parents and the prevalence of disease in the parents was compared with that expected in the general population. RESULTS: The prevalence of autoimmune disease in the parents was significantly higher in the repository compared with that expected in the general population [P-value = 1.98 x 10(-5) (female), P-value = 1.1 x 10(-8) (male)]. Type 1 diabetes was recorded in 63/1010 (6.2%) parents with a marked paternal preponderance (9.5 vs. 3%P = 0.002). Other autoimmune diseases affected 27% of parents with diabetes and 13.2% of parents without diabetes (P < 0.01). CONCLUSION: These data confirm the importance of family history as a significant risk factor for the development of Type 1 diabetes and support the hypothesis that the common autoimmune diseases share at least some aetiological mechanisms.     

Sudden postoperative death caused by unheralded Mallory Weiss tears.

Mallory Weiss tears are a common cause of upper gastrointestinal bleeding, typically reported as following repeated vomiting after an alcoholic binge. This association may have been overemphasised, and these lesions could be caused by a wide range of spontaneous and iatrogenic events. A case of sudden postoperative death caused by massive haematemesis, unheralded by any evidence of vomiting or retching, as a result of Mallory Weiss tears is reported.     

Effects of sleep disruption on cognitive performance and mood in medical house officers.

Twelve medical house officers were tested on a battery of memory, concentration, and work related tasks after three conditions: a night spent off duty; a night spent on call; and a night spent admitting emergency cases. Short term recall, but not digit span, concentration, or work related abilities, was impaired after a night of emergency admissions. A night spent on call had no effect on cognitive performance. Self reported mood scores showed that house officers were more deactivated (indicating a lack of vigour and drive) after nights of emergency admissions but not after nights on call. Significant between subject differences were found for five of the eight cognitive tests. Though loss of sleep and long hours of work have an effect on memory and mood, the individual differences among doctors are the main source of the variance in performance of tasks.     

High dose melphalan and total body irradiation with autologous marrow rescue in childhood acute lymphoblastic leukaemia after relapse

High dose melphalan (HDM 110-140 mg/m2) and total body irradiation (TBI, 10.5 Gy, single fraction) followed by infusion of autologous bone marrow (ABMT) was evaluated for toxicity and efficacy in 24 children with acute lymphoblastic leukaemia (ALL) in second (CR2) or third remission (CR3). Marrow was purged with Campath 1 in six children (four were children in CR3). All children had engraftment with a median of 30 days (range 18-70 days) to neutrophil count greater than 0.5 x 10(9)/l. Four children (16%) died from toxicity 1-4 months after autograft, two from pneumonitis, one from an intracerebral haemorrhage and one from sepsis. Apart from fever and mucositis the procedure was well tolerated. Nine of 17 children treated in CR2 remain in complete remission 6-72 months after ABMT (median 25 months). Seven of these have a follow-up of greater than 12 months. Three of the seven children treated in CR3 are alive 17, 22 and 29 months post ABMT. Seven children relapsed within 10 months (median 4 months) of the autograft. Only one relapse has occurred beyond 10 months. HDM and TBI followed by ABMT is a relatively well tolerated regimen and may contribute to survival in children with relapsed ALL.     

Test-retest reliability of the pain drawing instrument

Test-retest reliability of a pain drawing instrument was investigated. Pain drawings of chronic pain patients (n = 51) were scored for percentage of total body surface in pain and location of pain. A test-retest reliability coefficient of r = 0.85 was calculated for a time interval that averaged 71 days. In addition, a percentage of agreement based on distribution of pain over time was calculated at 88.2%. The effect on reliability of age, gender and time-interval differences was investigated. The utility of the pain drawing instrument as a measure of extent of pain and location of pain over time is discussed.     

Role of topical lignocaine during carotid endarterectomy.

Forty carotid endarterectomies were undertaken in 34 patients. Operations were prospectively randomized to periarterial application of either 1 per cent lignocaine (n = 19) or normal saline (n = 21), and detailed measurements taken of intraoperative pulse rate and blood pressure. Patients receiving lignocaine demonstrated a lower pulse rate, and lower systolic and mean blood pressures than those receiving placebo, with significance in relation to clamp application and shunt removal (P < 0.05). It was particularly noticeable that patients receiving lignocaine demonstrated less intraoperative variation in pulse rate and blood pressure. Topical lignocaine stabilizes pulse rate and blood pressure during carotid endarterectomy.