Polydrug Use in Adolescent Drinkers with and without DSM-IV Alcohol Abuse and Dependence

Alcohol and other substance use disorders are highly comorbid, but little is known about patterns of polydrug use in adolescents with different levels of alcohol involvement. This research examined patterns and correlates of polydrug use in 176 adolescent drinkers with DSM-IV alcohol dependence ( n = 61), alcohol abuse ( n = 57), and no alcohol diagnosis ( n = 58). Alcohol and other Substance Use Disorders were assessed using a modified version of the Structured Clinical Interview for the DSM. Lifetime histories of alcohol use and other drug use were assessed using a structured interview. Subjects also completed a questionnaire measure of the frequency of use of specific alcohol-drug combinations. The total number of illicit drugs ever used was greater in the alcohol dependence (mean = 3.8, SD = 2.1) and abuse groups (mean = 3.0, SD = 2.1), compared with the no-alcohol diagnosis group (mean = 1.9, SD = 1.3). Consistent with previous findings, there was a consistent pattern in the age of onset of psychoactive substance use: alcohol, followed by marijuana, followed by other drugs. The recent use of alcohol and other drugs in combination was reported by a greater percentage of subjects in the alcohol dependence (69%) and abuse groups (72%), compared with drinkers without an alcohol diagnosis (45%). The most common alcohol-drug combination was alcohol with marijuana (58% of the total sample), followed by alcohol-hallucinogens (16%). The frequency and extent of polydrug use was associated with being older and having higher levels of behavioral undercontrol and negative emotionality. Adolescent polydrug use, particularly the use of alcohol and other drugs in combination, is an important area for research, treatment, and prevention.     

Imaging Guidance for Transcatheter Mitral Valve Intervention on Prosthetic Valves,Rings, and Annular Calcification

Catheter-based interventions to improve mitral valve function are dependent on anatomic and functional information provided by noninvasive imaging to plan, perform, and evaluate each intervention. In this review we highlight the importance of imaging guidance for catheter-based interventions on prosthetic mitral valves, surgical rings, and native valve annular calcification. Both repair and replacement procedures are discussed. We review the general features common to this collection of procedures and discuss specific imaging issues and concerns for each procedure. Figures and intraprocedural videos emphasize central messages using case examples.     

Bone marrow transplantation from identical twins in the treatment of aplastic anaemia: implication for the pathogenesis of the disease

S ummary . Treatment of aplastic anaemia by bone marrow transplantation from a syngeneic (identical twin) donor has provided insights into the pathophysiology of the disease.
We report from patients with severe anaemia who were treated by syngeneic bone marrow transplantation. None of the patients had sustained recovery of peripheral blood counts. All four received second transplants from the same twin donor after immunosuppressive conditioning treatment. Each had prompt recovery of haematopoiesis. A review of the literature indicates that failure of syngeneic bone marrow transplantation in patients with aplastic anaemia is not uncommon. These data indicate that aplastic anaemia may be caused by a mechanism other than an absence or intrinsic abnormality of haematopoietic stem cells in many patients.     

Screening for colorectal cancer on the front line

OBJECTIVE: The aim of this study was to assess knowledge, beliefs, and practices of primary care clinicians regarding colorectal cancer screening. METHODS: We surveyed 77 primary care providers in six clinics in central Massachusetts to evaluate several factors related to colorectal cancer screening. RESULTS: Most agreed with guidelines for fecal occult blood test (97%) and sigmoidoscopy (87%), which were reported commonly as usual practice. Although the majority (86%) recommended colonoscopy as a colorectal cancer screening test, it was infrequently reported as usual practice. Also, 36% considered barium enema a colorectal cancer screening option, and it was rarely reported as usual practice. Despite lack of evidence supporting effectiveness, digital rectal examinations and in-office fecal occult blood test were commonly reported as usual practice. However, these were usually reported in combination with a guideline-endorsed testing option. Although only 10% reported that fecal occult blood test/home was frequently refused, 60% reported sigmoidoscopy was. Frequently cited patient barriers to sigmoidoscopy compliance included fear the procedure would hurt and that patients assume symptoms occur if there is a problem. Perceptions of health systems barriers to sigmoidoscopy were less strong. CONCLUSIONS: Most providers recommended guideline-endorsed colorectal cancer screening. However, patient refusal for sigmoidoscopy was common. Results indicate that multiple levels of intervention, including patient and provider education and systems strategies, may help increase prevalence.     

Concealed left atrial membrane: Pitfalls in the diagnosis of cor triatriatum and supravalve mitral ring

Cor triatriatum and supravalve mitral ring are forms of congenital left ventricular inflow obstruction produced by membranes within the left atrium. Typically, these defects occur as isolated anomalies with manifestations of pulmonary venous obstruction. Four children are presented whose left atrial membrane was associated with other significant cardiac defects, including, in one patient each, simple coarctation of the aorta, sinus venosus atrial septal defect, tricuspid atresia and complex coarctation of the aorta syndrome. The patient with the latter defect had undergone previous pulmonary arterial banding. None of these patients demonstrated significant pulmonary venous obstruction at cardiac catheterization. All patients had a normal value for either pulmonary arterial diastolic or pulmonary arterial wedge pressure. Three mechanisms explained the lack of pulmonary venous obstruction: (1) a large cross-sectional area of membrane openings, (2) an atrial septal defect that was confined to the pulmonary venous chamber and decompressed it by allowing blood to escape into the right atrium, and (3) decreased pulmonary blood flow. The diagnosis was facilitated by two dimensional echocardiography. Accurate diagnosis of left atrial membrane in the setting of other cardiac defects is of practical significance because pulmonary venous obstruction may occur after surgery for the associated defects.     

Gene targeting in the mouse: advances in introduction of transgenes into the genome by homologous recombination

The ability to stably introduce genes into the germline of animals provides a powerful means to address the genetic basis of physiology. Introduction of genes to generate transgenic animals has facilitated the development of complex genetic models of disease, as well as the in vivo study of gene function. However, one drawback of traditional transgenic technologies in which genes are microinjected into early-stage embryos is that there is little control over where and in how many copies genes are introduced into the genome. The development of animal transgenic technologies, which take advantage of homologous recombination mechanisms and the manipulation of embryonic stem (ES) cells, allows investigators to target and alter specific loci. In mouse transgenic systems, a plethora of sophisticated gene-targeting strategies now permit investigators to manipulate the genome in ways that essentially allow one to introduce virtually any desired change into the genome. Fur-thermore, when coupled with systems that allow for conditional gene expression, these gene-targeting strategies allow both temporal and tissue specific control of alterations to the genome. In the present review we briefly discuss some of the more recent gene-targeting strategies that have been developed to address the limitations of traditional animal transgenesis.     

Association of the human minK gene 38G allele with atrial fibrillation: evidence of possible genetic control on the pathogenesis of atrial fibrillation

Background Human minK protein is the β-subunit of I_Ks potassium channel and plays an important role in cardiac cellular electrophysiology. We investigated the association between human atrial fibrillation and the polymorphism of minK gene (38G or 38S) with a case-control study. Methods We included 108 patients with atrial fibrillation and 108 control subjects. The case patients and control subjects were matched regarding age, sex, presence of valvular heart disease, and presence of left ventricular dysfunction. The genotype of minK was determined with polymerase chain reaction and restriction fragment analysis. Results The results showed an association between the minK 38G allele and atrial fibrillation. The odds ratios for atrial fibrillation in patients with 1 and 2 minK 38G alleles were 2.16 (95% CI 0.81-5.74) and 3.58 (95% CI 1.38-9.27), respectively, when compared with patients without minK 38G allele. In a logistic regression model, the odds ratio for atrial fibrillation was 1.80 (95% CI 1.20-2.71, P < .0046) for patients with 1 more minK 38G allele. Conclusion We report the association between the minK 38G allele and clinical atrial fibrillation. Our findings suggest possible genetic control on the pathogenesis of atrial fibrillation. (Am Heart J 2002;144:485-90.)     

Diagnostic and prognostic factors in acute monocytic leukaemia: an analysis of 51 cases

Diagnostic features (cytochemistry, immunophenotyping and serum biochemistry) were examined in 51 cases of acute monocytic leukaemia (AMoL). Peroxidase, Sudan black B and alpha naphthyl acetate esterase (ANAE) cytochemical reactions were unrelated to morphological (FAB groups M5a and M5b) or immunological subtype. ANAE cytochemistry, however, indicated that AMoL cases could be subdivided into those with typical (M-type) reactions and those with insignificant staining or monocytic ANAE isoenzymes (defined by IEF). All cases were phenotypically CD13/CD33 positive and, with one exception, had greater than 30% HLA-DR positive cells. Membrane CD14 expression was insignificant or variable in 33% of M5a cases in contrast to 23/24 M5b cases which showed high proportions of CD14-staining cells with at least two monoclonal antibodies. Serum lysozyme, LDH and beta-2 microglobulin (beta 2m) were increased in 88%, 68% and 81% of cases respectively but, with the exception of statistically higher lysozyme levels in CD14+ cases, were unrelated to the morphological, cytochemical or immunological diagnostic subgroups. Clinical and diagnostic features were also examined as possible prognostic indicators. The morphological, cytochemical and immunological subgroups of AMoL were not found to be of prognostic relevance but age (P = 0.004), renal failure (P = 0.005) and serum beta 2m levels (P = 0.002) were related to patient survival. Moreover, renal failure and serum beta 2m remained significant (P = 0.012 respectively) when age was taken into account and were shown to be independent prognostic variables.     

A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection

BACKGROUND: We previously demonstrated that short-cycle structured intermittent therapy (SIT; 7 days without therapy followed by 7 days with antiretroviral therapy [ART]) with a ritonavir-boosted, indinavir-based, twice-daily regimen maintained suppression of plasma HIV viremia while reducing serum levels of lipids. Adherence to such a regimen may be problematic for certain patients. METHODS: Eight patients with a history of receiving combination ART that maintained suppression of plasma HIV RNA to <50 copies/mL received a once-daily SIT regimen of didanosine, lamivudine, and efavirenz. RESULTS: For 7 patients, suppression of plasma HIV RNA to <50 copies/mL was maintained for 60-84 weeks. Four patients with adequate samples had no evidence for an increase in plasma viremia for up to 72 weeks, by use of an assay with a limit of detection of <1 copy/mL. The lack of rebound viremia may be the result of the persistence of efavirenz in plasma on day 7 of the no-therapy period, as was detected in 7 of 7 patients. There was no significant change in CD4(+) T cell counts or serum hepatic transaminase or lipid levels. CONCLUSION: A once-daily short-cycle SIT regimen maintained suppression of plasma HIV RNA while preserving CD4(+) T cell counts. Such a regimen may have importance in resource-limited settings where the monetary cost of continuous ART is prohibitive.     

Angiotensin-converting enzyme inhibitors as adjunctive therapy in patients with persistent atrial fibrillation

Objectives

The purpose of the current study was to assess the effect of angiotensin-converting enzyme inhibitor (ACEI) therapy in facilitating cardioversion from persistent atrial fibrillation (AF) and maintaining sinus rhythm.

Background

Pharmacologic therapy and electrical cardioversion for AF are often unsuccessful in maintaining long-term sinus rhythm.

Methods

The current study, a 1-year, prospective follow-up, comprised 47 patients with persistent AF undergoing electrical cardioversion. Patients receiving ACEI were compared with those receiving other medications. The study end point was the number of defibrillation attempts required for atrial defibrillation and the number of hospital admissions. A secondary end point was change in signal-averaged P-wave duration (SAPD) 1 year after successful electrical cardioversion.

Results

Of those admitted and requiring electrical defibrillation, the number of defibrillation attempts required for successful cardioversion was significantly less in the ACEI group (P < .001). The incidence rate ratio for admissions comparing recipients of ACEI with others was 0.14 (P = .03). Patients receiving ACEI therapy had significantly lower SAPD at 1 year when compared with the no-ACEI group (135 ms ± 3 vs 150 ms ± 2, P = .002).

Conclusions

The use of long-term ACEI therapy facilitated electrical defibrillation in patients with persistent AF. ACEI therapy also reduced SAPD, suggesting amelioration of the arrhythmogenic substrate. Furthermore, we confirmed that SAPD is prolonged in patients with persistent AF.