A review of post-trachelectomy isthmic and vaginal smear cytology.

Currently in the UK cervical cancer has a peak incidence in women aged 35-39. Fertility-conserving surgical treatment by radical trachelectomy is established in the management of early disease. This study aimed at establishing the value of cytology in follow-up after trachelectomy.

Predictors of short-term course of drinking in untreated rural and urban at-risk drinkers: effects of gender, illegal drug use and psychiatric comorbidity.

Objective: The purpose of this study was to examine predictors of changes in drinking and drinking consequences in untreated at-risk drinkers in a community sample.

Method: Four waves of telephone interviews were conducted at 6-month intervals with a probability sample of at-risk drinkers in the rural and urban South (initial N = 733). Participants were interviewed at each wave regarding concurrent drug use, psychopathology and social support, as well as alcohol service use.

Emergency department use of persons with comorbid psychiatric and substance abuse disorders.

Study Objective: This study assesses the relationship between substance abuse comorbidity and emergency department use among patients with psychiatric disorders in a large academic medical center.

Methods: Data were obtained from an administrative database including every patient visit to the ED of a large, academically affiliated county hospital from January 1994 through June 1998. This study focuses on 12,212 patients who were given a diagnosis of a primary psychiatric disorder in the ED.

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.

Depressive disorders and alcohol dependence in a community population.

This cross-sectional study examines sociodemographic, clinical and func tional correlates of comorbid depression in a community sample of 268 individuals with alcohol dependence. Results of analyses comparing drinkers with either current or past depression to never-depressed drinkers showed that respondents in the former two groups were more likely to be female and report more comorbid drug use disorders. In addition to marked functional impairment for currently depressed drinkers, we also found that respondents with past depression were significantly less likely to have health insurance coverage.

Depressive symptomatology and early attrition from intensive outpatient substance use treatment.

This study examines the relationship between depressive symptoms and attrition from outpatient treatment in a Veterans Affairs facility that had recently moved to intensive outpatient-only treatment for substance abuse. This article focuses on 126 consecutively admitted patients who were enrolled on their last day of a 3- to 4-day outpatient detoxification. Results indicate that severe depressive symptomatology presenting at treatment entry is a significant risk factor for early attrition from intensive outpatient substance use treatment but not later attrition.

Amyloid beta peptide as a vaccine for Alzheimer's disease involves receptor-mediated transport at the blood-brain barrier.

Much research is now focused on a potential vaccine for Alzheimer's disease (AD). Current studies involve administering the amyloid beta peptide (Abeta) in Freund's complete adjuvant, which cannot be used in humans. Our studies show that the immune complex of Abeta is taken up by a receptor-mediated process at the blood-brain barrier (BBB).

Short-term course of drinking in an untreated sample of at-risk drinkers.

Objective: We know little about the short-term course of drinking, particularly the stability or instability of at-risk drinking in untreated drinkers. Because few at-risk drinkers obtain help for their drinking, it is important to understand the short-term fluctuations between at-risk drinking and full-fledged alcohol use disorders, as well as remission of at-risk drinking.

Method: We used four waves of data (each 6 months apart) from a probability community sample of 733 at-risk drinkers in six states in the southern United States to determine variation in abstinence, drinking patterns and alcohol use disorders over a 2-year period.

Permeability of proteins at the blood-brain barrier in the normal adult mouse and double transgenic mouse model of Alzheimer's disease.

The permeability of albumin, insulin, and human A beta 1--40 at the blood-brain barrier (BBB) was determined in the normal adult mouse (B6/SJL) and in the double transgenic Alzheimer mouse (APP, PS1) by using an I.V. bolus injection technique to quantify the permeability coefficient-surface area (PS) product for each protein after correction for the residual plasma volume (V(p)) occupied by the protein in the blood vessels of different brain regions using a second aliquot of the same protein radiolabeled with a different isotope of iodine ((125)I vs (131)I) as a vascular space marker.

Therapeutic benefit of polyamine-modified catalase as a scavenger of hydrogen peroxide and nitric oxide in familial amyotrophic lateral sclerosis transgenics.

Continuous subcutaneous administration of polyamine-modified catalase that has increased permeability at the blood-brain barrier showed both a highly significant delay in onset and an increase in survival in a transgenic mouse model of familial amyotrophic lateral sclerosis having a point mutation in the gene encoding copper/zinc superoxide dismutase. These results suggest that hydrogen peroxide-mediated oxidative stress with subsequent free radical damage involving nitric oxide and possibly hydroxyl radicals in motor neurons may be the culprit in familial amyotrophic lateral sclerosis.

Quantitative histological analysis of amyloid deposition in Alzheimer's double transgenic mouse brain.

The development of transgenic mice has created new opportunities for the generation of animal models of human neurodegenerative diseases where previously there was no animal counterpart. The first successful transgenic mouse model of Alzheimer's disease expressed increased levels of mutant human amyloid precursor protein, exhibiting neuritic-type amyloid deposits and behavioral deficits at six to nine months of age. More recently, it was shown that transgenic mice expressing both mutant human amyloid precursor protein and presenilin 1 exhibit neuritic-type amyloid deposits and behavioral deficits in as little as 12 weeks.

Depression after alcohol treatment as a risk factor for relapse among male veterans.

We examined the association between relapse-to-drinking and depressive symptomatology measured during inpatient treatment for alcohol disorder and 3 months posttreatment. Data were obtained from 298 veterans who completed 21-day inpatient treatment. Follow-up interviews were conducted at 3, 6, 9, and 12 months posttreatment.

Targeting alzheimer amyloid plaques in vivo.

The only definitive diagnosis for Alzheimer disease (AD) at present is postmortem observation of neuritic plaques and neurofibrillary tangles in brain sections. Radiolabeled amyloid-beta peptide (Abeta), which has been shown to label neuritic plaques in vitro, therefore could provide a diagnostic tool if it also labels neuritic plaques in vivo following intravenous injection. In this study, we show that the permeability of Abeta at the blood-brain barrier can be increased by at least twofold through covalent modification with the naturally occurring polyamine, putrescine.

Obesity is associated with a decreased leptin transport across the blood-brain barrier in rats.

Leptin exerts important effects on the regulation of food intake and energy expenditure by acting in the brain. Leptin is secreted by adipocytes into the bloodstream and must gain access to specific regions in the brain involved in regulating energy balance. Its action is mediated by interaction with a receptor that is mainly expressed in the hypothalamus but is also present in other cerebral areas.

Quality Enhancement Research Initiative in Mental Health.

The Veterans Administration (VA) recently introduced its Quality Enhancement Research Initiative (QUERI) to facilitate the translation of best practices into usual clinical care. The Mental Health QUERI (MHQ) was charged with developing strategic plans for major depressive disorder (MDD) and schizophrenia. Twenty percent or more of VA service users are affected by 1 of these 2 disorders, disorders that often have a devastating impact on affected individuals.

Gender differences in the relationships among SES, family history of alcohol disorders and alcohol dependence.

Objective: Potential moderator and mediator roles of several measures of socioeconomic status (SES) were investigated for the relationship between a family history of alcoholism (FH) and alcohol dependence symptoms in adulthood.

Method: These analyses were performed with a sample of 931 men and 385 women participating in studies at the Alcohol Research Center, University of Michigan. Hierarchical multiple regression equations were used to assess whether SES mediated and moderated relationships between FH and alcohol dependence symptoms.

Plasma pharmacokinetics, nervous system biodistribution and biostability, and spinal cord permeability at the blood-brain barrier of putrescine-modified catalase in the adult rat.

Free radical-mediated oxidative damage has been proposed to be an underlying mechanism in several neurodegenerative disorders. Previous investigations in our laboratory have shown that putrescine-modified catalase (PUT-CAT) has increased permeability at the blood-brain (BBB) and blood-nerve barriers with retained enzymatic activity after parenteral administration when compared to native catalase (CAT). The goals of the present study were to examine the plasma stability, spinal cord BBB permeability, nervous system biodistribution, and spinal cord enzyme activity of CAT and PUT-CAT after parenteral administration in the adult rat.

Receptor-mediated transport of human amyloid beta-protein 1-40 and 1-42 at the blood-brain barrier.

Since amyloid beta-protein (A beta) is the primary component of both vascular and parenchymal amyloid deposits in Alzheimer's disease, information regarding its permeability at the blood-brain barrier (BBB) will help elucidate the contribution of circulating A beta to vascular and parenchymal A beta deposition in this disease and in brain aging. The permeability of the D- and L-enantiomers of A beta 1-40 and L-A beta 1-42 at the BBB was determined in the normal adult rat by quantifying the permeability coefficient-surface area product (PS) for each protein after correction for the residual plasma volume (Vp) occupied by the protein [labeled with a different isotope of iodine (125I vs 131I)] in blood vessels of different brain regions. After a single i.

Beta-sheet breaker peptide inhibitor of Alzheimer's amyloidogenesis with increased blood-brain barrier permeability and resistance to proteolytic degradation in plasma.

Short synthetic peptides homologous to the central region of Abeta but bearing proline residues as beta-sheet blockers have been shown in vitro to bind to Abeta with high affinity, partially inhibit Abeta fibrillogenesis, and redissolve preformed fibrils. While short peptides have been used extensively as therapeutic drugs in medicine, two important problems associated with their use in central nervous system diseases have to be addressed: (a) rapid proteolytic degradation in plasma, and (b) poor blood-brain barrier (BBB) permeability. Recently, we have demonstrated that the covalent modification of proteins with the naturally occurring polyamines significantly increases their permeability at the BBB.

Longitudinal changes in predictor profiles of abstinence from alcohol use among male veterans.

We examined variations in predictors of abstinence depending on the timing of follow-up after alcohol treatment using data from 298 males who completed inpatient treatment at a Midwestern VA Alcoholism Treatment Unit. Our findings indicate fluidity of abstinence and relapse across subjects in the 12 months posttreatment. We also found substantial shifts in the salience of predictors even across short periods of continued abstinence.

Do patients with alcohol dependence use more services? A comparative analysis with other chronic disorders.

Objective: The primary purpose of this research was to compare the service use of patients diagnosed with alcohol dependence to the service use of patients diagnosed with other chronic illnesses. The secondary purpose was to determine the impact of comorbid alcoholism on the service use of patients with chronic illnesses.

Methods: The sample included 67,878 veterans diagnosed with alcohol dependence, depression, or diabetes who were treated by the Department of Veterans Affairs in 1993.

Putrescine-modified nerve growth factor: bioactivity, plasma pharmacokinetics, blood-brain/nerve barrier permeability, and nervous system biodistribution.

Previous investigations from our laboratory have demonstrated that the covalent modification of a variety of proteins, including antioxidant enzymes, with the naturally occurring polyamines--putrescine (PUT), spermidine, and spermine--dramatically increases their permeability coefficient-surface area product (PS) at the blood-brain and blood-nerve barriers after parenteral administration. In the present study, we have covalently modified nerve growth factor (NGF) with PUT by targeting carboxylic groups for their graded modification by controlling the ionization of these groups with pH. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, western, and isoelectric focusing analyses demonstrated conversion of NGF to its polyamine-modified derivatives at different pH values.

Predicting problem drinking: a test of an interactive social learning model.

This study tested a social learning model and explored the direct and interactive relationships between personality and environment in predicting problem alcohol use. We used longitudinal data from a nonclinical sample of males and females first tested in adolescence and followed into young adulthood. Hierarchial regression analyses were used to test main effects and interaction models.

Putrescine-modified catalase with preserved enzymatic activity exhibits increased permeability at the blood-nerve and blood-brain barriers.

Much evidence exists in support of the hypothesis that free radicals contribute to the pathogenesis of several neurodegenerative disorders and that mechanisms of free radical generation occur both intracellularly and extracellularly. Previous studies in this laboratory have shown that covalent modification of growth factors and antioxidant enzymes with the naturally occurring polyamine, putrescine, increases their permeability at the blood-nerve and blood-brain barriers (BNB and BBB), but does not significantly inhibit bioactivity. Furthermore, putrescine-modified superoxide dismutase (SOD) was shown to reduce neurodegeneration in a rat model of global cerebral ischemia.