Pharmacotherapy and airway remodelling in asthma?

Over the last few decades attention has largely focused on airway inflammation in asthma, but more recently it has been appreciated that there are important structural airway changes which have been grouped together under the term "airway remodelling". It is only now that questions have been asked about the impact of treatment on these structural changes. This review examines the nature of these structural airway changes, the mechanisms of their generation, their potential consequences, and what is known about the ability of anti-asthma treatments to modulate these changes.     

Pain management for multiple sclerosis patients

Up to 75% of patients with MS experience pain, yet this symptom is often overlooked and literature on the subject is limited. In this study, pain caused MS patients most concern, second only to reduced mobility. Thorough assessment and management can help patients to cope. Collaboration between a pain clinic and an MS clinic also helps.     

Correlates of prone infant sleeping position by period of birth

Intervention to avoid the prone sleeping position during infancy has occurred in various countries after evidence that it increases the risk of sudden infant death syndrome (SIDS). This study examined cohort data to determine if correlates of the prone position differed by period of birth, before intervention (1 May 1988 to 30 April 1991) compared with after intervention (1 May 1991 to 30 April 1992). The usual prone sleeping position was more closely associated with the following factors after intervention: teenage motherhood, low maternal education, paternal unemployment, unmarried motherhood, non-specialist antenatal care, not reading books to prepare for a baby, poor smoking hygiene, and bottle feeding. For example, the association of usual prone position with being unmarried shown by the odds ratio (95% confidence interval) was 0.54 (0.47 to 0.63) in the period before intervention and 1.92 (1.18 to 3.15) in the period after intervention. The alteration in correlates of the prone position reported here provide an example to support the theoretical concept that well known 'modifiable' risk factors for disease tend to be associated with each other in both populations and individuals. This phenomenon was not evident in the population before intervention, that is, before the prone sleeping position became a well known SIDS risk factor.     

Body changes in adolescent patients with growth hormone receptor deficiency receiving recombinant human insulin-like growth factor I and luteinizing hormone-releasing hormone analogue: preliminary results

Auxological and body composition changes were studied in three adolescent patients (2 female, 1 male) with growth hormone receptor deficiency (GHRD) given insulin-like growth factor I (IGF-I), 120 μg/kg s.c. twice daily, plus a monthly intramuscular injection of 7.5 mg of a luteinizing hormone-releasing hormone (LHRH) analogue. Preliminary results from the first 12 months of the study show that height velocity was increased compared with the pretreatment values. This increase was probably due to the IGF-I therapy, as the LHRH analogue would have suppressed gonadotrophins and gonadal steroid production. There was a reduction in percentage body fat, and increases in lean mass and the leamfat ratio, whole body mineral content and body calcium content, even when expressed per kg body weight. There was also a trend towards increased bone mineral density of the whole skeleton, lumbar spine and femoral structures, as well as a maturation of facial features. These preliminary results indicate that concomitant therapy with IGF-I and an LHRH analogue is safe and efficacious in inducing growth without advancing bone age in patients with GHRD.     

Distribution of glutathione S-transferase isoenzymes in primary epithelial tumors of the ovary

Abstract. Rahilly M, Al Nafussi A, Harrison DJ. Distribution of glutathione S-transferase isoenzymes in primary epithelial tumors of the ovary. Int J Gynecol Cancer 1991; 1 : 268–274.
The glutathione S-transferases play a central role in the detoxification of electrophilic xenobiotics, including cytotoxic drugs and carcinogens, by conjugation with reduced glutathione. There are four major classes of human GST: pi, alpha, mu and microsomal GST. GST pi has been implicated in the progression of carcinogenesis in both animal and human studies. This study examined constitutive GST isoenzyme expression in 60 primary epithelial tumors of the ovary, including benign, borderline and frankly malignant categories. GST pi was the predominant isoenzyme, being strongly expressed in all tumor types. The intensity of GST pi staining was independent of grade in all categories of carcinoma. Thus GST pi has no potential role as a marker of differentiation or tumor progression in epithelial ovarian tumors. GST alpha, which localizes to steroid-producing cells in normal ovary, was useful in demonstrating enzymatically active stromal cells in ovarian carcinomas with functioning stroma. GSTs, particularly the alpha and microsomal isoenzymes, have been implicated in both intrinsic and acquired resistance to cancer chemotherapy. Alpha, mu and microsomal GSTs displayed a heterogeneous staining pattern in all tumor types. This heterogeneity of expression may contribute to intrinsic drug resistance in ovarian carcinomas.     

The prognostic value of quantitative angiogenesis in breast cancer and role of adhesion molecule expression in tumor endothelium

Summary Angiogenesis is the formation of new capillaries from the existing vascular network and is essential for tumor growth and metastases. Increased microvessel density in breast cancer is associated with lymph node metastasis and reduced survival. We have assessed tumor vascularity in 211 breast carcinomas using a more rapid technique based on a Chalkley point eyepiece graticule. We confirmed using this method a significant reduction in overall survival between patients stratified by Chalkley count in both a univariate (p=0.02) and multivariate (p=0.05) analysis.Since studies have suggested that cell adhesion molecules (CAMs) might be important in the angiogenic process, and interaction of neoplastic cells with this neovasculature is a significant step in tumor metastasis, we have also examined the expression of CAMs in a subset of these tumors (n=64). Using immunohistochemistry we observed widespread and intense staining on the endothelium of tumor-associated vessels for PECAM (100%), ICAM 1 (69%), and E- and P-selectins (52% and 59% of cases respectively). Endothelial expression of the selectins was more prominent at the tumor periphery. Immunoreactivity of ICAM-1 (34%), PECAM (1.6%), and E- and P-selectins (7% and 37% of cases respectively) was also observed on the neoplastic element of the tumors.     

Transfer of telemedical support to Cornwall from a national telemedicine network during a solar eclipse

During late 1998 and early 1999, planning officers in Cornwall predicted a huge increase in summer visitors to the county to observe the August solar eclipse. There was the possibility that a mass gathering in Cornwall could overload existing arrangements for handling accident and emergency patients. We therefore set up a telemedicine system to support the county's minor injury units (MIUs) from hospitals throughout the UK. Six main hospital accident and emergency departments outside Cornwall with existing links to their own MIUs were twinned with 10 of the 11 MIUs in Cornwall before the expected date of the gathering. The network was live for nine days, starting four days before the eclipse, and 2045 patients were seen in the 10 MIUs. There were 93 telemedicine calls from the 10 MIUs, involving 91 patients. Overall, 4.6% of the patients required a telemedicine consultation. Fifty-seven calls were made during working hours. Thirty-four patients were referred for further management, of whom 18 were referred on the same day. The transfer of telemedical support to a national network was successful.