Role of epithelial interleukin-8 (IL-8) and neutrophil IL-8 receptor A in Escherichia coli-induced transuroepithelial neutrophil migration.

Escherichia coli stimulates neutrophil migration across human uroepithelial cell layers. This study investigated the role of the neutrophil chemokine interleukin-8 (IL-8) in this process. E. coli and IL-1alpha stimulated urinary tract epithelial layers to secrete IL-8 and induced transepithelial neutrophil migration. Anti-IL-8 antibody reduced neutrophil migration across epithelial cell layers, indicating a central role for this chemokine in the migration process. Furthermore, addition of recombinant IL-8 to unstimulated cell layers was sufficient to induce migration. The IL-8 dependence of neutrophil migration was maintained after removal of soluble IL-8 by washing of the cell layers. Flow cytometry analysis with fluorescein isothiocyanate-labelled IL-8 confirmed IL-8's ability to bind to the epithelial cell surface. Indirect immunofluorescence with confocal laser scanning microscopy showed that IL-8 associated with the epithelial cell layers. Prior incubation of neutrophils with antibodies to IL-8 receptor A (IL-8RA) reduced neutrophil migration. Anti-IL-8 RB antibody had no effect on neutrophil migration. These results demonstrate that IL-8 plays a key role in E. coli- or IL-1alpha-induced transuroepithelial migration and suggest that epithelial cell-produced IL-8 interacts with IL-8RA on the neutrophil surface.     

Rates of bone loss in the appendicular and axial skeletons of women. Evidence of substantial vertebral bone loss before menopause

We made longitudinal measurements of bone mineral density (BMD) in 139 normal women (ages 20-88 yr) at midradius (99% cortical bone) and lumbar spine (approximately 70% trabecular bone) by single- and dual-photon absorptiometry. BMD was measured 2-6 (median, 3) times over an interval of 0.8-3.4 yr (median, 2.1 yr). For midradius, BMD did not change (+0.48%/yr, NS) before menopause but decreased (-1.01%/yr, P less than 0.001) after menopause. For lumbar spine, there was significant bone loss both before (-1.32%/yr, P less than 0.001) and after (-0.97%/yr, P = 0.006) menopause; these rates did not differ significantly from each other. Our data show that before menopause little, if any, bone is lost from the appendicular skeleton but substantial amounts are lost from the axial skeleton. Thus, factors in addition to estrogen deficiency must contribute to pathogenesis of involutional osteoporosis in women because about half of overall vertebral bone loss occurs premenopausally.     

PSM-R: Revised optimism-pessimism scale for the MMPI-2 and MMPI

The Revised Optimism-Pessimism (PSM-R) scale was developed for use with either the MMPI-2 or the MMPI. The scale measures explanatory style on a continuum from optimistic to pessimistic by using 263 MMPI items of the original 298–item Optimism-Pessimism (PSM) scale. These 263 items are common to both the MMPI-2 and MMPI. PSM-R norms are based on a random sample of 1,408 normal adults who also were used for developing norms for the original PSM scale. Reliability estimates (.93 for men; 0.94 for women) indicate that the PSM-R scale is as accurate as the original PSM scale.     

Anxiolytic-like activity of pregabalin in the Vogel conflict test in α2δ-1 (R217A) and α2δ-2 (R279A) mouse mutants

The α(2)δ auxiliary subunits (α(2)δ-1 and α(2)δ-2) of voltage-sensitive calcium channels are thought to be the site of action of pregabalin (Lyrica), a drug that has been shown to be anxiolytic in clinical trials for generalized anxiety disorder. Pregabalin and the chemically related drug gabapentin have similar binding and pharmacology profiles, demonstrating high-affinity, in vitro binding to both α(2)δ-1 and α(2)δ-2 subunits. Two independent point mutant mouse strains were generated in which either the α(2)δ-1 subunit (arginine-to-alanine mutation at amino acid 217; R217A) or the α(2)δ-2 subunit (arginine-to-alanine mutation at amino acid 279; R279A) were rendered insensitive to gabapentin or pregabalin binding. These strains were used to characterize the activity of pregabalin in the Vogel conflict test, a measure of anxiolytic-like activity. Pregabalin showed robust anticonflict activity in wild-type littermates from each strain at a dose of 10 mg/kg but was inactive in the α(2)δ-1 (R217A) mutants up to a dose of 320 mg/kg. In contrast, pregabalin was active in the α(2)δ-2 (R279A) point mutants at 10 and 32 mg/kg. The positive control phenobarbital was active in mice carrying either mutation. These data suggest that the anxiolytic-like effects of pregabalin are mediated by binding of the drug to the α(2)δ-1 subunit.     

Age, stage, and the MMPI: changes in response patterns over an 85-year age span.

Statistically significant and clinically relevant age-related changes in MMPI response patterns have long been known to clinicians. Graphic representations of mean scores that cover an 85-year age span, separately by sex, for each of the 13 basic MMPI validity and clinical scales support the use of adolescent norms and indicate that clinicians should give greater acknowledgement to age-related MMPI changes in adults and their interpretation, particularly among geriatric patients.     

Asymptomatic microhematuria and urologic disease. A population-based study

Asymptomatic microhematuria is a common finding, occurring in 13% of adult men and postmenopausal women in Rochester, Minn. Previous recommendations to perform cystoscopic and excretory urographic examinations on all patients with this finding were based on findings in referred patients. In the present population-based study, the frequency of serious urologic disease in patients with asymptomatic microhematuria was 2.3%; only 0.5% had bladder or renal cell carcinoma. Urologic malignant lesions occurred more frequently in the elderly. There was a trend toward more serious diseases in those with higher grades of hematuria. Complete urologic investigation of all patients with any degree of asymptomatic microhematuria cannot be recommended. The presence of other risk factors should be considered in opting for further evaluation.     

Ontario Child Health Study: correlates of disorder

Data from the Ontario Child Health Study were used to examine the prevalence and selected correlates of conduct disorder, hyperactivity, emotional disorder, and somatization in children 4 to 16 years of age by informant (parent and teacher for children 4 to 11, and parent and youth for children 12 to 16). The results indicate that the prevalence and pattern of correlates of the individual disorders differ in important ways by informant. This suggests that we need to understand the factors that influence assessments provided by informants from different contexts (e.g., parents and teachers) before combining information from them to arrive at singular classifications.     

Incidence of malignant bone and joint tumors in Olmsted County, Minnesota, 1935 through 1981

During the 47-year period 1935 through 1981, 30 cases of malignant bone and joint tumors (in 20 male and 10 female patients) were identified among Olmsted County, Minnesota, residents. The incidence rates per 100,000 population, age-adjusted to the 1970 US total white population, were 1.0 overall, 1.4 for male subjects, and 0.7 for female subjects. Mortality rates, likewise age-adjusted, were 0.7 overall and 1.1 and 0.3 for male and female subjects, respectively. These rates are similar to those from tumor registries, a finding that suggests that reporting of these tumors is relatively complete. The similarity of the incidence and the mortality rates is consistent with the high case-fatality rate. A comparison of the Olmsted County cases with Mayo Clinic referral cases provides some evidence for referral bias, as the referral patients were significantly younger and had significantly more high-grade tumors.     

Long-term outcome of renal transplantation in autosomal dominant polycystic kidney disease

This study was performed to determine the long-term outcome of renal transplantation in 54 patients with end-stage renal failure secondary to autosomal dominant polycystic kidney disease (ADPKD) and in 107 patients with renal diseases other than ADPKD or diabetes mellitus matched by gender, age, year of transplantation, and source of the allograft. The overall patient survival and patient survival with a functioning first renal allograft were similar in both groups. Infection and cardiovascular accidents were the leading causes of early and late death in both groups. No cause of death was greatly overrepresented in the ADPKD group. Serious complications from extrarenal manifestations of ADPKD following renal transplantation included a ruptured intracranial aneurysm in one patient, a dissection of the ascending thoracic aorta in one patient, and infected hepatic cysts in two patients. Neoplasia (other than skin or cervical) occurred in four ADPKD patients and in one control patient and included one lymphoma in each group. Two ADPKD and one control patient had monoclonal gammopathies of undetermined significance. No complications related to the retention of native kidneys were detected in 12 ADPKD patients with a mean follow-up of 3 years. Cysts were observed in the renal allografts of some patients in both groups at autopsy and in a prospective computed tomography (CT) study of the allograft. However, we failed to detect a significant difference in the occurrence and number of the cysts between ADPKD and control patients.