On the legacy of normalization

In 1998 Howard Parker, Judith Aldridge & Fiona Measham published Illegal Leisure, a ground‐breaking study of profound changes in British youth cultures in the 1990s, and the place of drugs and drug use in these upheavals. This work introduced the ‘normalization thesis’ to the social sciences, offering a novel vocabulary for re‐imagining the normative character of young people's attitudes towards and experiences of illicit drug use. Arriving at the dawn of the new century, the book offered a thoroughgoing re‐thinking of the character of youth cultures at a time of great social, cultural, economic and technological disruption. In so doing, the book deftly anticipated many of the most interesting currents of critical drug studies that followed.     

The effect of placental removal method on the incidence of postcesarean infections

OBJECTIVE: Our purpose was to determine whether the incidence of postoperative endometritis and wound infection is associated with the method of placental removal at the time of cesarean section.STUDY DESIGN: Parturients undergoing cesarean delivery were prospectively randomized to have the placenta removed manually or spontaneously. Patients were excluded from participation if they had received intrapartum prophylactic antibiotics or had been determined to have chorioamnionitis. After delivery of the infant women in the manual group had the placenta extracted by the primary surgeon, whereas women in the spontaneous group had the placenta delivered by gentle traction on the umbilical cord. All study subjects received perioperative prophylactic antibiotics. The primary outcome variable was a postcesarean infection, defined as postcesarean endometritis or wound cellulitis requiring drainage and antibiotic therapy.RESULTS: A total of 333 women were enrolled in the investigation, with 165 assigned to the manual removal group and 168 allocated to have spontaneous removal. There were no statistically significant differences in mean gestational age, frequency or duration of ruptured membranes, frequency or duration of labor, or mean number of vaginal examinations between the two study groups. Postoperative infections occurred in 25 of 168 (15%) women in the spontaneous delivery group compared with 44 of 165 (27%) women in which the placenta was manually extracted (relative risk 0.6, 95% confidence interval 0.4 to 0.9, p = 0.01). Subset analysis of patients delivered with ruptured membranes similarly demonstrated a statistically significant reduction in the incidence of postoperative infections with spontaneous placental removal compared with manual extraction (20% vs. 38%, relative risk 0.5, 95% confidence interval 0.3 to 0.9, p = 0.02). There was a similar trend toward a reduction in postdelivery infections associated with spontaneous placental removal in women with intact membranes; however, this difference did not attain statistical significance.CONCLUSIONS: Spontaneous delivery of the placenta after cesarean delivery is associated with a decrease in the incidence of postcesarean infections. (Am J Obstet Gynecol 1997;176:1250-4.)     

Genetic analysis of the interleukin‐1 receptor antagonist and its homologue IL‐1L1 in alopecia areata: strong severity association and possible gene interaction‡

Alopecia areata is an inflammatory hair loss disease with a major genetic component. The presence of focal inflammatory lesions with perifollicular T‐cell infiltrates reflects the importance of local cytokine production in the pathogenesis. In addition to its fundamental pro‐inflammatory role, the interleukin‐1 (IL‐1) system has major effects on hair growth regulation in vitro, with the inhibitory actions of IL‐1α and IL‐1β being opposed by the receptor antagonist IL‐1ra. The novel interleukin‐1 like molecule 1 (IL‐1L1) which has greatest gene sequence homology with IL1RN, the gene encoding IL‐1ra, is another potential IL‐1 antagonist. In view of previous studies suggesting a significant role for IL1RN polymorphisms in the pathogenesis of autoimmune/inflammatory disease, we have analysed polymorphisms of IL‐1ra (IL1RN+2018) and its homologue IL‐1L1 (IL1L1+4734) in a case–control association study on 165 patients and a large number of matched controls. Homozygosity for the rare allele of IL1RN (IL1RN*2) was significantly associated with alopecia areata [odds ratio (OR) = 1.89, 95% CI (1.09, 3.28); P = 0.02], confirming our previous findings of significant association with the IL1RN variable number tandem repeat (VNTR). The results also revealed a novel association involving a polymorphism of the interleukin‐1 receptor antagonist homologue IL1L1 at position + 4734, IL1RN+2018, and alopecia areata. The effect of a genotype combining three copies of the rare alleles at the IL1RN and IL1L1 loci conferred a more than additive increase in the risk of disease compared to IL1RN+2018 or IL1L1+4734 alone [OR 3.37 (1.60, 7.06); P = 0.002], suggesting possible synergy between the IL1RN and IL1L1 genes. This effect was stronger in patients with severe disease (alopecia totalis/universalis) [OR 4.62 (1.87, 11.40), P = 0.0022], and in those with early age at onset (< 20 years) [OR = 6.38 (2.64, 15.42), P = 0.0002]. Our results suggest that these polymorphisms within IL1RN and IL1L1 themselves or a gene in linkage disequilibrium with IL1RN and IL1L1 predispose to the more severe forms of alopecia areata.     

The value of a domiciliary nurse as part of a hospital diabetes service — Report on a 12 month study

SINCE 1976 the standard inpatient and outpatient service for diabetic patients at the Mater Hospital has been supplemented by a day centre facility incorporating education and management. We feel that the service could be improved further by the availability of a specialist nurse who would visit patients at their homes. A pilot study was carried out over a twelve month period and this paper details the benefits of such a service.     

Benzazepinone calcium channel blockers. 2. Structure-activity and drug metabolism studies leading to potent antihypertensive agents. Comparison with benzothiazepinones.

As part of a program to discover potent antihypertensive analogues of diltiazem (3a), we prepared 1-benzazepin-2-ones (4). Benzazepinones competitively displace radiolabeled diltiazem, and show the same absolute stereochemical preferences at the calcium channel receptor protein. Derivatives of 4 containing a trifluoromethyl substituent in the fused aromatic ring show potent and long-acting antihypertensive activity. Studies of the metabolism of 4 lead to the metabolically stable antihypertensive calcium channel blockers 5a and 5c. Benzazepinone 5a is a longer acting and more potent antihypertensive agent than the second generation diltiazem analogue TA-3090 (3e).     

Myoblast transfer in duchenne muscular dystrophy

One biceps muscle of 8 patients with Duchenne muscular dystrophy was injected at 55 sites with a total of 55 million viable, purified, and contamination-free normal myoblasts (myoblast transfer). The other biceps of each patient was injected with a placebo to serve as a control. The procedure was blinded to the patients, parents, and investigators. Myoblasts derived from a biopsy specimen of the fathers were cultured and purified under strict conditions and carefully screened for microbial contamination. All patients received cyclophosphamide for immunosuppression for 6 or 12 months. No serious complications were observed after myoblast transfer, indicating that the procedure is safe. The overall therapeutic efficiency of myoblast transfer was poor as judged by the results in maximal voluntary force generation, dystrophin content of the muscle, magnetic resonance imaging of the muscle, and the lack of donor-derived DNA and dystrophin messenger RNA in the injected muscle. An improved efficiency of the take of myoblasts might be achieved by using younger cells and injecting the myoblasts with a myonecrotic agent (to increase the prevalence of regeneration) and a basal laminal fenestrating agent.