Severely compromised quality of life in women and those of lower socioeconomic status waiting for joint replacement surgery

OBJECTIVE: To determine health-related quality of life (HRQOL), psychological distress, physical function, and self efficacy in persons waiting for lower-limb joint replacement surgery. METHODS: A total of 214 patients on a waiting list for unilateral primary total knee or hip replacement at a large Australian public teaching hospital completed questionnaires after entry to the list. HRQOL and psychological distress were compared with available population norms. RESULTS: Average HRQOL was extremely poor (mean +/- SD 0.39 +/- 0.24) and much lower (>2 SD) than the population norm. Near death-equivalent HRQOL or worse than death-equivalent HRQOL were reported by 15% of participants. High or very high psychological distress was up to 5 times more prevalent in the waiting list sample (relative risk 5.4 for participants ages 75 years and older; 95% confidence interval 3.3, 9.0). Women had significantly lower HRQOL, self efficacy, and physical function scores than men. After adjusting for age and sex, significant socioeconomic disparities were also found. Participants who received the lowest income had the poorest HRQOL; those with the least education or the lowest income had the highest psychological distress. Low self efficacy was moderately associated with poor HRQOL (r = 0.49, P < 0.001) and more strongly associated with high psychological distress (r = -0.55, P < 0.001). CONCLUSION: Patients waiting for joint replacement have very poor HRQOL and high psychological distress, especially women and those from lower socioeconomic backgrounds. Lengthy waiting lists mean patients can experience extended and potentially avoidable morbidity. Interventions to address psychological distress and self efficacy could reduce this burden and should target women and lower socioeconomic groups.     

p57Kip2 (cdkn1c): sequence, splice variants and unique temporal and spatial expression pattern in the rat pancreas

The cyclin-dependent kinase (CDK) inhibitor p57Kip2 (CDKN1C) is a negative regulator of cell proliferation, binding to a variety of cyclin-CDK complexes and inhibiting their kinase activities in vitro. The p57Kip2 gene is imprinted and the maternal allele is expressed in terminally differentiated cells, including human beta-cells. Somatic loss of p57Kip2 expression is associated with increased beta-cell proliferation in the focal form of Hyperinsulinism of Infancy. We cloned and sequenced the rat ortholog of p57Kip2, and demonstrate that it is highly homologous to the mouse gene. However, the human and rodent genes are quite divergent. Despite having highly homologous C- and N-terminal domains, the mid-portion of the human gene is entirely different from that of its rodent counterparts. Expression of p57Kip2 was evaluated during fetal and postnatal development, and a highly cell-specific, temporal and spatial expression profile was found. In contrast to other tissues, the expression pattern in rat pancreas was entirely opposite from that previously reported in man, with high levels of expression in rodent exocrine cells, but no expression in beta-cells during any stage of development. These findings demonstrate that p57Kip2 expression is highly regulated. In the pancreas, the functional significance of this gene appears to be quite different in humans when compared with rodents, suggesting that a better understanding of the function of this protein may provide new insights into the mechanisms involved in the control of human beta-cell mass.     

Prevalence of comorbid psychiatric illness and substance misuse in primary care in England and Wales

STUDY OBJECTIVE: To estimate the annual period prevalence of co-occurring psychiatric illness and substance misuse among patients in primary care. DESIGN: Analysis of the general practice research database. SETTING: England and Wales, 1993-1998. PARTICIPANTS: Registered patients at 230 general practices representing 3.1% of the population. A comorbid case was defined as one with both a psychiatric diagnosis and substance misuse diagnosis (not including alcohol or tobacco) within a calendar year. A potentially chronic comorbid case was one that met this definition and, in addition, was treated in subsequent years for either a psychiatric condition or substance misuse. MAIN RESULTS: The annual period prevalence of comorbidity increased from 50/100 000 patient years of exposure (PYE) to 80/100 000 PYE, an increase of 62% during the study period. Rates of comorbid psychoses, comorbid schizophrenia, and comorbid paranoia increased by 147%, 128%, and 144%. The average age of comorbid cases decreased from 38 years to 34 years. Over 80% of comorbid cases were newly diagnosed in each study year, although many are treated in subsequent years for either psychiatric illness or substance misuse. CONCLUSIONS: This study provides data on the nature and extent of comorbidity in primary care in England and Wales. As the comorbidity rate is increasing by about 10% each year, and as comorbid cases are becoming younger, it is probable that the comorbidity rate will have increased beyond the study end point.     

Long-term stability study of L-adrenaline injections: Kinetics of sulfonation and racemization pathways of drug degradation

Injectable formulations of L-adrenaline are commonly used in emergency medicine. Despite numerous studies, the comparative contribution and kinetics of the L-adrenaline inactivation pathways during storage have not been conclusively evaluated. We examined the kinetics of L-adrenaline degradation in a prospective study and determined the extent of drug inactivation by different pathways during and beyond the stipulated product shelf-life in 42 batches of adrenaline ampules stored under controlled conditions. The content of L-adrenaline and degradation products was determined with a chiral high-performance liquid chromatography (HPLC) assay, and the degradation products were identified by mass spectrometric detection as D-adrenaline and L- and D-adrenaline sulfonate. The kinetics of the content change with storage was analyzed simultaneously for L-adrenaline and the degradation products using kinetic modeling. The lower acceptable level of adrenaline content in the formulation stated by US Pharmacopoeia (90% as a sum of L- and D-isomers) was attained after 2.0 years of storage, at which time the content of the therapeutically active L-isomer amounted to as low as 85%. The modeling revealed significant differences in the degradation kinetics in the formulations produced before and after 1997, whose cause remained unidentified in this study.     

A volumetric study of parietal lobe subregions in Turner syndrome

Turner syndrome, a genetic disorder that results from the complete or partial absence of an X chromosome in females, has been associated with specific impairment in visuospatial cognition. Previous studies have demonstrated a relationship between parietal lobe abnormalities and visuospatial deficits in Turner syndrome. We used high-resolution magnetic resonance imaging to measure parietal lobe subdivisions in 14 participants with Turner syndrome (mean age 13 years 5 months, SD 5 years) and 14 age-matched controls (mean age 13 years 5 months, SD 4 years 7 months) to localize neuroanatomical variations more closely. Scans were acquired and analyzed for 14 females with Turner syndrome. Analyses of variance were used to investigate differences in regional parietal lobes. Females with Turner syndrome showed a bilateral parietal lobe reduction, specifically in the superior parietal and postcentral gyri. Full-scale IQ scores were significantly positively correlated with postcentral tissue volume in the Turner syndrome group. Structural differences in the parietal lobe are localized specifically to the anterior and superior parietal lobe and might be related to the visuospatial and visuomotor deficits associated with Turner syndrome.     

Continued parental attendance at a clinic for adult survivors of childhood cancer

PURPOSE: Adult survivors of childhood cancer have been an underserved and understudied population. Few clinics are available to take care of them, unlike the numerous ones that exist for children. The authors established a clinic that would take care of all survivors diagnosed before the age of 25 years, ensuring the participation of a significant number of adults. The authors observed that many adult patients came to their annual visits accompanied by one or both of their parents. The rate was almost three times as high compared with parents in either a primary care or subspecialty internal medicine clinic. METHODS: The authors investigated this phenomenon by asking parents of adult survivors to fill out a questionnaire that collected demographic information as well as reasons for parents accompanying their adult children to doctors' appointments. Open-ended comments were also solicited. RESULTS: Most parents who came with their adult survivor children did not accompany their other children to doctor visits and commented that they felt there was a unique bond created by the cancer experience that did not diminish with increasing age of their children. The rate of parental attendance was independent of diagnosis or demographic indicators. Many parents stated that they continued to be concerned about their child's diagnosis, overall health, and risk for cancer recurrence. DISCUSSION: Parents of adult survivors of childhood cancer may harbor deep feelings of protectiveness that continue well beyond the initial treatment and off-treatment periods when the threat of primary cancer recurrence is a realistic concern. This can be manifested in them by accompanying their adult children to doctors' appointments and deserves further study.     

Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization

OBJECTIVE: Exploration of the possibility that local injury of the endometrium increases the incidence of implantation. DESIGN: Prospective study. SETTING: Clinical IVF unit. PATIENT(S): A group of 134 patients, defined as good responders to hormonal stimulation, who failed to conceive during one or more cycles of IVF and embryo transfer (ET). INTERVENTION(S): The IVF treatment and ET were preceded by repeated endometrial biopsies, in a randomly selected 45 of a total of 134 patients. MAIN OUTCOME MEASURES: Outcome of IVF-ET treatments. RESULT(S): Transfer of a similar number of embryos (3.4 +/- 1.0 and 3.1 +/- 0.9 in the experimental and control patients, respectively) resulted in rates of implantation (27.7% vs. 14.2%, P =.00011), clinical pregnancy (66.7% vs. 30.3%, P =.00009), and live births per ET (48.9% vs. 22.5%, P =.016) that were more than twofold higher in the experimental group as compared to controls. CONCLUSION(S): These results suggest that IVF treatment that is preceded by endometrial biopsy doubles the chance for a take-home baby.