The UK Diabetes Research Network--an opportunity and a challenge.

The Department of Health has funded a national diabetes network to support clinical research. The network will facilitate recruitment into clinical trials and has been widely welcomed by clinicians. However, if the network is to reach its full potential, all those involved will need to advocate a change in attitude towards clinical trials and research, encouraging participation and contribution of data. Clinicians need to be willing to take a proactive view about research studies, and to encourage patients to adopt a positive and altruistic attitude towards trial participation. The future of trials and other important clinical research in the UK may depend on it.     

Human papillomavirus--a study of male sexual partners

Male sexual partners of a cohort of women with genital-tract abnormalities which were associated with human papillomavirus infection were examined for evidence of infection with human papillomavirus. Of the 214 male partners who were examined, 93.5% had visible genital lesions. Of the 196 lesions that were biopsied, 72.5% showed histological evidence of infection with human papillomavirus, and only 20.4% of subjects with histological evidence of human papillomavirus were aware of a lesion. An unexpectedly high proportion (6.1%) of lesions on which a biopsy was performed, particularly those with flat, red, indurated morphology, also showed histological evidence of penile intraepithelial neoplasia. This was not significantly more common among the partners of the women with cervical intraepithelial neoplasia than it was among the partners of the women with other evidence of genital human papillomavirus infection. Penile intraepithelial neoplasia was significantly (P less than 0.001) more common among subjects with no history of non-genital warts. We conclude that the male partners of women with human papillomavirus-associated lesions are very likely to be infected with human papillomavirus, and thus may act as a significant reservoir for the reinfection of their female partners. As the awareness of human papillomavirus-associated lesions was low among the male partners, colposcopic examination and treatment of their male partners, and/or barrier contraception, may be a necessary part of the management of women who are undergoing treatment for human papillomavirus-associated genital disease.     

Retinopathy of prematurity in infants less than 29 weeks' gestation at birth

From January 1986 to December 1991 we examined the eyes of 206 infants born at Westmead Hospital, Neonatal Intensive Care Unit who were less than 29 weeks' gestation at birth to determine the incidence of retinopathy of prematurity. Eighty-five infants (41.3%) had no retinopathy of prematurity (ROP) in either eye, 82 infants had stages 1 or 2 ROP (39.8%), 29 had stage 3 ROP (14.1%) and 11 had stage 4 ROP (5.3%). Of these, cryotherapy was performed in 18; six now have bilateral retinal detachment and are blind The more severe stages of ROP were significantly associated with an increase in the number of days of oxygen supplementation, an increase in the number of days of mechanical ventilation and the presence of patent ductus arteriosus. Infants receiving steroids for mechanical ventilator dependence had a significantly greater chance of requiring cryotherapy (11 or 22 receiving steroids versus seven of 43 without steroids; P < 0.01).     

Characterization of purinoceptors mediating depolarization of rat isolated vagus nerve.

1. As part of a broader study to characterize neuronal purinoceptors, the effects of adenosine 5'-triphosphate (ATP) and a range of ATP analogues were investigated on the extracellularly recorded membrane potential of the rat isolated vagus nerve, using a 'grease-gap' technique. 2. ATP evoked depolarization of the rat vagus nerve. The concentration-effect curve to ATP was not monophasic: at the lower concentrations (1 x 10(-5)-1 x 10(-3) M) the curve was shallow (< 50% of the near maximal response to 5-hydroxytryptamine (5-HT)) whilst at higher concentrations the relationship between concentration and amplitude of depolarization was steeper (> 135% of the response to 5-HT at the highest concentration tested, 1 x 10(-2) M). On washout of the high drug concentrations large after-hyperpolarizations were often observed. 3. alpha,beta-methylene ATP (1 x 10(-6)-3 x 10(-4) M), beta,gamma-methylene ATP (1 x 10(-6)-1 x 10(-3) M), and 5'-adenylylimidodiphosphate (beta,gamma-imido ATP; 1 x 10(-6)-1 x 10(-3) M) were all more potent than ATP and produced large depolarizations of the rat vagus nerve at the highest concentrations tested (> 150% of the response to 5-HT). The overall rank order of potency was alpha,beta-methylene ATP > beta,gamma-methylene ATP = beta,gamma-imido ATP > ATP. 4. In contrast, 2-methylthio ATP (1 x 10(-6)-1 x 10(-3) M) produced relatively small depolarizations (< 100% of the response to 5-HT). As was the case with low concentrations of ATP, the concentration-effect curve to 2-methylthio ATP was very shallow.(ABSTRACT TRUNCATED AT 250 WORDS)     

P2X receptors: targets for novel analgesics?

The ability of adenosine 5'-triphosphate (ATP) to evoke acute pain has been known for many years, but its role in nociceptive signaling is only now becoming clear. ATP acts via P2X and P2Y receptors, and of particular importance here is the P2X(3) receptor. It is expressed selectively at high levels in nociceptive sensory neurons, where it forms functional receptors on its own and in combination with the P2X(2) receptor. Recent reports using gene knockout methods; antisense oligonucleotide and small, interfering RNA technologies; and a novel, selective P2X(3) antagonist, A-317491, show that P2X(3) receptors are involved in chronic inflammatory and neuropathic pain. The mRNA for other P2X subunits is also found in sensory neurons, and there is evidence for functional P2X(1/5) or P2X(2/6) heteromers in some of these. These data support the possibility that P2X receptors, particularly the P2X(3) subtype, could be targeted in the search for new, effective analgesics.     

Endoscopic and endoscope-assisted resections of inverted sinonasal papillomas.

OBJECTIVE: To evaluate the success of endoscopic and endoscope-assisted resection of inverted sinonasal papillomas and to assess the indications for adjunctive external procedures. STUDY DESIGN: Retrospective chart review. RESULTS: Fifty patients were treated surgically during the 10-year study period and had greater than 1 year of follow-up care. These patients had a recurrence rate of 14% (7/50) with a mean follow-up of 31.1 months. Of these 7 patients with recurrences, 3 were treated primarily at this institution, and 4 had been treated prior to referral. Recurrence was 11% (3/27) for primary resections and 17% (4/23) for secondary resections. Average time to recurrence was 11.7 months. Of the patients, 38% (19/50) had adjunctive external procedures either during the initial resection or for the management of recurrent disease. CONCLUSIONS: Endoscopic and endoscope-assisted resections of inverted papilloma are effective techniques for managing inverted papilloma. The intraoperative findings, most importantly the site(s) of tumor attachment, dictate whether an endoscopic procedure is sufficient to complete resect the inverted papilloma or whether an adjunctive external procedure is required. Appropriate patient selection and an aggressive surgical approach are necessary for the management of these neoplasms.     

Evaluating the responsiveness of the endometriosis health profile questionnaire: The EHP-30

OBJECTIVES: To evaluate the sensitivity to change of the Endometriosis Health Profile-30 (EHP-30) questionnaire. SETTING: The Women's Center, John Radcliffe Hospital, Oxford. DESIGN: Postal survey to 66 women undergoing conservative surgery for the treatment of endometriosis-associated pain. The EHP-30 and the Short Form-36 (SF-36) were administered 2 weeks before the operation, and 4 months post-operatively. At T2 a transition question was included to evaluate changes in patients health status. To evaluate responsiveness effect sizes, standardised response means, the index of responsiveness and the minimally and clinically important differences were calculated. RESULTS: Forty (66.6%) patients returned the questionnaires at time 1 and 2. Overall less responsive effect size scores were found for the SF-36 (0.1-0.5) compared to the EHP-30 (-0.1-1.1) for all patients who had undergone treatment. Minimally important differences and the index of responsiveness were overall higher for the EHP-30 (0.4-2.0) compared to the SF-36 (0.1-1.0). Change scores for four of the five scales were significantly correlated with women's responses to the transition question. CONCLUSIONS: Results suggest that the EHP-30 is sensitive to change. Its application in clinical trials should prove beneficial in assessing the impact of medical and surgical interventions upon quality of life for women with endometriosis.     

National patterns of aspirin use and Reye syndrome reporting, United States, 1980 to 1985

The number of cases of Reye syndrome reported annually to the Centers for Disease Control declined markedly between 1980 and 1985. In this article, we present pharmaceutical marketing research data that suggest sharp decreases in the use and purchase of children's aspirin between 1980 and 1985. These trends appear to correspond to the decrease in reporting of Reye syndrome cases. Additionally, analysis of physician mentions of aspiring and acetaminophen for treating flu and chickenpox showed statistically significant trends toward decreasing recommendations for the use of aspirin and significant trends toward increasing recommendations for use of acetaminophen. Trends in wholesale purchases of aspirin and acetaminophen by drug stores from 1979 through 1985 demonstrated a significant decline for the 81-mg children's aspirin tablet and an increase in purchases of children's acetaminophen products. Many factors may influence physician and parents' choice of analgesic/antipyretic medication, including information about Reye syndrome. Data suggest that a continuing decline in the use of aspirin for children may be accompanied by a continuing decline in the reported number of Reye syndrome cases.