Increased bladder permeability in interstitial cystitis/painful bladder syndrome

The definition of interstitial cystitis (IC) has evolved over the years from being a well-defined entity characterized by diagnostic lesion (Hunner’s ulcer) in the urothelium to a clinical diagnosis by exclusion [painful bladder syndrome (PBS)]. Although the etiology is unknown, a central theme has been an association with increased permeability of the bladder. This article reviews the evidence for increased permeability being important to the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBS) and in treating the disorder. Recent work showing cross-communication among visceral organs is also reviewed to provide a basis for understanding IC/PBS as a systemic disorder of a complex, interconnected system consisting of the bladder, bowel and other organs, nerves, cytokine-responding cells and the nervous system.     

Clinical and demographic factors associated with DSM-IV melancholic depression.

BACKGROUND: The purpose of this paper is to use demographic and clinical data from a large diverse group of outpatients diagnosed with non-psychotic major depression to investigate the validity of the DSM-IV concept of melancholic depression. METHODS: Baseline clinical and demographic data were collected on 1500 outpatients (1456 of whom melancholia could be determined) with non-psychotic major depressive disorder (MDD) participating in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Depressive symptom severity was assessed by clinical telephone interview using the 17-item Hamilton Rating Scale for Depression (HRS-D17) and the 30-item Inventory of Depressive Symptomatology (IDS-C30). The types and degrees of concurrent psychiatric symptoms were measured using a self report, the Psychiatric Diagnostic Screening Questionnaire (PDSQ), by recording the number of items relevant to each diagnostic category endorsed by study participants. RESULTS: Adjusting for severity of depression (as measured by the total HRS-D17 scores), no differences were found in the rate of melancholic depression by race, marital status, education, employment status, family history of depression, primary care versus specialty care, monthly income, and degree of psychiatric and medical co-morbidity. Melancholic depression was significantly more likely in men than women. Melancholic depression after adjustment for severity was associated with a slightly younger age at study entry, as well as with greater illness severity, and slightly shorter duration of current episode. Hispanic ethnicity was associated with lower melancholic depression rates at the .06 level of significance. CONCLUSIONS: Among outpatients with MDD, melancholic features were less likely in Hispanic patients, but more likely in slightly younger patients and in men. Melancholic features were also related to a slightly shorter current episode. These findings are consistent with the notion that external socio-demographic factors do not play an important role in the pathophysiology of melancholic depression.     

Long-Term implications of early onset in bipolar disorder: data from the first 1000 participants in the systematic treatment enhancement program for bipolar disorder (STEP-BD)

Background

Early onset of mood symptoms in bipolar disorder has been associated with poor outcome in many studies; however, the factors that might contribute to poor outcome have not been adequately investigated.

Methods

The first consecutive 1000 adult bipolar patients enrolled in the National Institute of Mental Health's Systematic Treatment Enhancement Program for Bipolar Disorder were assessed at study entry to determine details of their age of onset of mood symptoms. Clinical course, comorbidity, and functional status and quality of life were compared for groups with very early (age < 13 years), early (age 13-18 years), and adult (age > 18 years) onset of mood symptoms.

Results

Of 983 subjects in whom age of onset could be determined, 272 (27.7%) experienced very early onset, and 370 (37.6%) experienced early onset. Earlier onset was associated with greater rates of comorbid anxiety disorders and substance abuse, more recurrences, shorter periods of euthymia, greater likelihood of suicide attempts and violence, and greater likelihood of being in a mood episode at study entry.

Conclusions

Very early or early onset of bipolar disorder might herald a more severe disease course in terms of chronicity and comorbidity. Whether early intervention might modify this risk merits further investigation.     

Molecular targeting of Alzheimer's amyloid plaques for contrast-enhanced magnetic resonance imaging

Smart molecular probes for both diagnostic and therapeutic purposes are expected to provide significant advances in clinical medicine and biomedical research. We describe such a probe that targets beta-amyloid plaques of Alzheimer's disease and is detectable by magnetic resonance imaging (MRI) because of contrast imparted by gadolinium labeling. Three properties essential for contrast enhancement of beta-amyloid plaques on MRI exist in this smart molecular probe, putrescine-gadolinium-amyloid-beta peptide: (1) transport across the blood-brain barrier following intravenous injection conferred by the polyamine moiety, (2) binding to plaques with molecular specificity by putrescine-amyloid-beta, and (3) magnetic resonance imaging contrast by gadolinium. MRI was performed on ex vivo tissue specimens at 7 T at a spatial resolution approximating plaque size (62.5 microm(3)), in order to prove the concept that the probe, when administered intravenously, can selectively enhance plaques. The plaque-to-background tissue contrast-to-noise ratio, which was precisely correlated with histologically stained plaques, was enhanced more than nine-fold in regions of cortex and hippocampus following intravenous administration of this probe in AD transgenic mice. Continuing engineering efforts to improve spatial resolution are underway in MRI, which may enable in vivo imaging at the resolution of individual plaques with this or similar contrast probes. This could enable early diagnosis and also provide a direct measure of the efficacy of anti-amyloid therapies currently being developed.     

CLN -encoded proteins do not interact with each other

The lysosomal storage of lipofuscins is the common pathological feature that characterizes the infantile, late-infantile, juvenile (Batten's disease), and Finnish-variant neuronal ceroid lipofuscinosis (INCL, LINCL, JNCL and FNCL), which are due to mutations in the genes CLN1 , CLN2 , CLN3 , and CLN5 , respectively. The CLN1 and CLN2 genes encode lysosomal enzymes, but the CLN3 and CLN5 genes encode membrane-spanning proteins. Why deficiencies of lysosomal enzymes and membrane-spanning proteins produce similar clinical phenotypes and pathological changes is still unanswered. We hypothesize that CLN -encoded proteins may comprise a functional pathogenic pathway, in which protein associations may play important roles. To test this hypothesis, we studied protein-protein interactions among the CLN1 -, CLN2 -, and CLN3 -encoded proteins using a yeast two-hybrid system. Our results provided no evidence that CLN -encoded proteins interact with each other. This suggests there may be unidentified components in NCL pathogenesis. Received: December 1, 1999 / Accepted: February 2, 2000 / Published online: May 9, 2000     

Population-based outcomes after 28,246 in-hospital vasectomies and 1,902 vasovasostomies in Western Australia

OBJECTIVES: To examine trends in vasectomy and vasovasostomy, and the surgical complications and factors associated with reversal after vasectomy, and paternity after vasovasostomy. PATIENTS AND METHODS: Procedure rates were estimated from 1980 to 1996 in the population of Western Australia. Linked hospital morbidity records were used in the follow-up of men after vasectomy to estimate the risks of complications and reversals. Records of vasovasostomies were linked to the paternity field on birth registrations. Independent effects of the study factors were examined using Cox regression. RESULTS: There was little net change in vasectomy rates, whereas vasovasostomy rates increased in men aged 30-49 years. Risks of surgical complications were low and decreased for vasovasostomy. At 12-15 years after vasectomy, the risk of reversal levelled at 2. 4% in the total cohort and at 11.1% in men aged 20-24 years. The risk of vasovasostomy was 69% greater after vasectomy performed in 1994-96 than in 1980-84 (P = 0.011). The factors strongly associated with reversal were age < 30 years and being single, divorced or separated at the time of vasectomy. Paternity was achieved after an estimated 53% of vasovasostomies. Successful reversal was more likely if the man was younger at vasectomy and the time elapsed was comparatively short. Compared with vasovasostomies performed in 1980-84, the success rate of those in 1994-96 was almost four times higher. CONCLUSION: Population rates of vasectomy are stable but the risk of seeking a reversal has increased. Outcomes after vasovasostomy have improved. Care should be taken during the counselling of men before vasectomy, and especially in those aged <30 years.     

Cohort differences in the progression of developmental pathways: evidence for period effects on secular trends of violence in males

BACKGROUND: Rates of violence in the USA have fluctuated widely over the past few decades. Theorists have examined period and cohort effects, but there appear to be no studies examining these effects on progression in developmental pathways towards violence. OBJECTIVE: To assess whether differences in progression among individuals in the Pittsburgh Youth Study are consistent with period or cohort effects. DESIGN: Multivariate logistic regression was conducted to examine differences between cohorts in the odds of progressing through the developmental pathway towards violence. Adjusted and unadjusted odds ratios (ORs) and corresponding 95% CI are reported. SETTING: Pittsburgh Pennsylvania, from 1987 to 2000. SUBJECTS: Two cohorts of male adolescents from the Pittsburgh Youth Study. The youngest cohort (n = 503) was followed from median ages 7 to 20, and the oldest cohort (n = 506) was followed up from median ages 13 to 25. MAIN OUTCOME MEASURE: The odds of progression along a developmental pathway towards violence. RESULTS: There was no statistically significant difference between the cohorts in progression from minor aggression to physical fighting (OR = 1.13, 95% CI 0.77 to 1.65). However, after adjustment for major risk factors, the oldest cohort was significantly more likely to progress from physical fighting to violence (OR = 2.34, 95% CI 1.39 to 3.92). CONCLUSIONS: These results provide initial evidence that cohort effects, which would be present early in development, do not contribute significantly to later differences in reported violence and raises the possibility of whether period effects can explain these differences.     

Precocious aging and dementia in patients with Down's syndrome.

Fifty unselected institutionalized patients with Down's syndrome were studied to determine the clinical course of precocious aging and mental and neurological deterioration. In our studies we establish statistically significant differences in neurological and psychiatric abnormalities and mental deterioration in patients below and above age 35, indicating progressive changes in the central nervous system. We demonstrate higher incidence of recent memory loss, impairment of short-term visual retention, frontal release signs, hypertonia, hyperreflexia, long-tract signs, and psychiatric problems. We also note the presence of external features of precocious aging. Down's syndrome appears to be a human chromosomal abnormality in which genetically determined biochemical defects leading to precocious aging and dementia can be studied.