Alcoholism and drug abuse in three groups — bipolar I, unipolars and their acquaintances

Objective: Previous work has shown that manic-depressive illness and alcohol abuse are linked. This study further explores the relationship of alcohol and drug abuse in bipolar I patients and unipolar depressives and a comparison group obtained through the acquaintance method. Method: Diagnosis was accomplished according to Research Diagnostic Criteria (RDC): controls=469; bipolars=277; unipolar depressives=678. Systematic data were gathered using the SADS on lifetime and current drug abuse and alcoholism. Both patients and comparison subjects were then followed prospectively for 10 years. First degree family members were interviewed using the RDC family history method. Results: The group of bipolar patients and the group of unipolar patients had higher rates of drug and alcohol abuse than the comparison group when primary and secondary affective disorder patients were combined. However, primary unipolar patients did not have higher rates of alcohol or drug abuse than the comparison group. In contrast, primary bipolar patients had higher rates of alcoholism, stimulant abuse, and ever having abused a drug than the primary unipolar group and the control group. In an evaluation of the bipolar patients, drug abusers were significantly younger at intake and had a significantly younger age of onset of bipolar disorder. There was a significant increase in family history of mania or schizoaffective mania in the drug-abusing bipolar patients as compared to the non-abusing bipolar patients. Limitation: As in all adult samples of patients with affective illness, the chronology of alcohol and substance problems vis-à-vis the onset of illness was determined retrospectively. Conclusions: (1) Alcoholism and drug abuse are more frequent in bipolar than unipolar patients. (2) The drug abuse of bipolar patients tends toward the abuse of stimulant drugs. (3) In a bipolar patient, familial diathesis for mania is significantly associated with the abuse of alcohol and drugs. (4) More provocatively, these findings suggest the hypothesis of a common familial-genetic diathesis for a subtype of bipolar I, alcohol and stimulant abuse. Clinical implications: The present analyses, coupled with two previous ones from the CDS, suggest that drug abuse may precipitate an earlier onset of bipolar I disorder in those who already have a familial predisposition for mania. Furthermore, in dually diagnosed patients with manic-depressive and alcohol/stimulant abuse history, mood stabilization of the bipolar disorder represents a rational approach to control concurrent alcohol and drug problems, and should be studied in systematic controlled trials.     

Initial evaluation of a continuous speech recognition program for radiology

The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant, and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed and sensitive manner.     

Egfl7 knockdown causes defects in the extension and junctional arrangements of endothelial cells during zebrafish vasculogenesis.

The endothelial cell (EC) -specific secreted protein EGFL7 is important for tubulogenesis in newly forming blood vessels. We studied its role in vascular tube formation by a quantitative ultrastructural analysis of Egfl7-knockdown zebrafish embryos. At 24 hours postfertilization, the endothelia of dorsal aorta (DA) and posterior cardinal vein (PCV) were correctly anchored to the hypochord and endoderm, respectively, but failed to expand into the vascular area. This resulted in vessels with reduced or split lumen and open sheets of ECs. Concomitantly, the organization of hematopoietic cells-identified by the presence of previously undescribed membrane tubules-between DA and PCV, and within the vessels, was severely disturbed. Strikingly, ectopic cell junctions occurred across the obstructed vessel lumen, on the luminal EC surfaces, which in control conditions never display junctions of any kind. These data suggest that Egfl7 provides ECs with a cue for their extension into the vascular area and in establishing EC cell polarity.     

Longer Term Outcomes Following High Tibial Osteotomy for Osteoarthritis: A Prospective,Multi-Centre Observational Study Comparing Tomofix and OPTY-LINE Devices

PurposeAssessing surgical accuracy and patient-recorded outcome measures for patients fitted with either the OPTY-LINE intramedullary realignment system or the Tomofix plate for medial opening wedge high tibial osteotomy (HTO).Patients and methodsTwo matched case series of patients with symptomatic medial compartment osteoarthritis without other significant knee pathology. One group comprised of 19 patients receiving the Tomofix plate, whereas another comprised of 12 patients receiving the OPTY-LINE intramedullary nail. Patella-centred long leg alignment radiographs were assessed to calculate surgical accuracy in all cases. Patients completed knee injury osteoarthritis outcome scores (KOOS) and osteotomy surgery patient satisfaction questionnaires pre-operatively and at 24 months post-surgery.ResultsAbsolute surgical accuracy at 2 years post-surgery was a mean 4.2 [standard deviation 3.7] for OPTY-LINE versus 9.2 [SD 7.8] for Tomofix (p = 0.11, Mann–Whitney U test). On average, patients in either the OPTY-LINE or Tomofix cohort reported at least a minimal perceptible clinical improvement—minimum average improvement of 15—for all five KOOS themes. No significant difference in change of KOOS scores over time or patient satisfaction levels were observed between the two cohorts.ConclusionThe OPTY-LINE device for HTO performs to a similar level as the Tomofix device. Surgical accuracy data are promising for OPTY-LINE, but does not seem to readily translate into difference in patient-reported outcomes compared to Tomofix. Even longer follow-up periods, to measure survival rates, and true randomised trials on larger samples can elucidate if there is a benefit for using one device over the other.     

Angiotensin-II stimulates nitric oxide release in isolated perfused renal resistance arteries

 Nitric oxide (NO) has been implicated as a modulator of the vascular effects of angiotensin II (ANG II) in the kidney. We used a NO-sensitive microelectrode to study the effect of ANG II on NO release, and to determine the effect of selective inhibition of the ANG II subtype I receptor (AT1) with losartan (LOS) and candesartan (CAN). NO release from isolated and perfused renal resistance arteries was measured with a porphyrin-electroplated, carbon fiber. The vessels were microdissected from isolated perfused rat kidneys and perfused at constant flow and pressure in vitro. The NO-electrode was placed inside the glass collection cannula to measure vessel effluent NO concentration. ANG II stimulated NO release in a dose-dependent fashion: 0.1 nM, 10 nM and 1000 nM ANG II increased NO-oxidation current by 85±18 pA (n = 11), 148±22 pA (n = 11), and 193±29 pA (n = 11), respectively. These currents correspond to changes in effluent NO concentration of 3.4±0.5 nM, 6.1±1.1 nM, and 8.2±1.3 nM, respectively. Neither LOS (1 μM) nor CAN (1 nM) significantly affected basal NO production, but both AT1-receptor blockers markedly blunted NO release in response to ANG II (10 nM): 77±6% inhibition with LOS (n = 8) and 63±9% with CAN (n = 8). These results are the first to demonstrate that ANG II stimulates NO release in isolated renal resistance arteries, and that ANG II-induced NO release is blunted by simultaneous AT1-receptor blockade. Our findings suggest that endothelium-dependent modulation of ANG II-induced vasoconstriction in renal resistance arteries is mediated, at least in part, by AT1-receptor-dependent NO release. Received: 24 September 1997 / Accepted: 20 October 1997     

Full and Abbreviated Courses of Maintenance Electroconvulsive Therapy

The authors describe their experience with maintenance electroconvulsive therapy administered to 10 patients, using an abbreviated or a full maintenance schedule. Recommendation for either form of treatment was made on clinical grounds. Patients with major depressive episodes with delusional features appear to respond best to maintenance ECT.     

Experimental down-regulation of intermediate biomarkers of carcinogenesis in mouse mammary epithelial cells

Summary The polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA) is a metabolism-dependent procarcinogen whose tumorigenicity is modified by dietary and endocrine manipulationsin vivo. DMBA initiates molecular and cellular alterations in the mammary tissue, while dietary components and estrogens affect the post-initiational phase of tumorigenic transformation. The mechanism(s) responsible for modulation of tumorigenic transformation remain unclear. This study examines the effects of selected tumor suppressing agents and estradiol (E₂) metabolites onin vitro DMBA carcinogenesis utilizing a newly established mouse mammary epithelial cell line C57/MG. Alteration in DNA repair synthesis, metabolism of E₂ via the C2- and C16-hydroxylation pathways, and acquisition of anchorage-independent growth were utilized as molecular, endocrine, and cellular biomarkers to quantitate the cellular transformation by DMBA and its modulation by tumor suppressing agents and E₂ metabolites. A single 24 hr exposure of 0.78 µM DMBA to C57/MG cells resulted in a 193.9% increase in DNA repair synthesis and a 73.1% decrease in C2/C16 hydroxylation of E₂. The DMBA treated C57/MG cells also exhibited increased anchorage-independencein vitro prior to tumorigenesisin vivo. A simultaneous treatment of cells with DMBA and with the highest non-cytotoxic doses of the tumor suppressing agents 5 µM N-(4-hydroxyphenyl) retinamide (HPR), 50 µM indole-3-carbinol (I3C), or 1 µM tamoxifen (TAM) resulted in a 35.6% to 63.9% decrease in DNA repair synthesis, a 23.8% to 1347.6% increase in C2/C16 hydroxylation of E₂, and a 53.8% to 72.4% decrease in anchorage-independent growth. The E₂ metabolites at the highest non-cytotoxic doses of 0.76 µM estrone (E₁), 0.69 µM 2-hydroxyestrone (2-OHE₁), and 0.66 µM 2-methoxyestrone (2-MeOHE₁) suppressed DMBA-induced DNA repair synthesis by 56.0% to 68.8%. These tumor suppressing agents and E₂ metabolites also effectively suppressed post-initiational, anchorage-independent growth by 24.9% to 72.4%. These results indicate that DMBA induces cellular transformation in part by causing DNA damage, altering C2/C16 hydroxylation in favor of C16-hydroxylation, and inducing anchorage-independent growth prior to tumor development. Effective downregulation of these genotoxic, endocrine and proliferative end points by prototypic tumor suppressing agents and by E₂ metabolites generated via the C2-hydroxylation pathway suggest that these agents may influence mammary tumorigenesis by inhibiting early occurring initiational and/or post initiational events.Abbreviations DMBA 7,12-dimethylbenz(a)anthracene - HPR N-(4-hydroxyphenyl) retinamide - I3C indole-3-carbinol - TAM tamoxifen - E₂ 17-estradiol - E₁ estrone - 2-OHE₁ 2-hydroxyestrone - 2-MeOHE₁ 2-methoxyestrone - 16-OHE₁ 16-hydroxyestrone - E₃ estriol - DME/F12 Dulbecco's modified Eagle's medium - F12 Ham's medium - HU hydroxyurea - PBS phosphate buffered saline - NaOH sodium hydroxide - SDS sodium dodecyl sulfate - TCA trichloroacetic acid - [C2-³H] E₂ estradiol labeled at C2 position - [C16-³H] E₂ estradiol labeled at C16 position - ANOVA analysis of variance     

Prevalence of recent cocaine use among motor vehicle fatalities in New York City

We determined the prevalence of recent cocaine and alcohol use among motor vehicle fatalities occurring in New York, NY, from 1984 through 1987. Recent cocaine use was detected at autopsy in 18.2% of the sample and no significant difference between drivers (20.0%) and passengers (13.9%) was found. Both alcohol and cocaine metabolites were found in 10.0% of cases tested. The prevalence of cocaine metabolites or alcohol detected in driver fatalities aged 16 through 45 years did not change significantly when the period prior to the widespread availability of "crack" cocaine (1984 through 1985) was compared with the period immediately following the introduction of crack cocaine (1986 through 1987). Additional studies are needed both to elucidate the association between cocaine use and these fatalities and to determine the value of screening persons seriously injured in traffic accidents in areas where such drug use is endemic.