Reduced blood clearance and increased urinary excretion of N-nitrosodimethylamine in patas monkeys exposed to ethanol or isopropyl alcohol.

Low concentrations of N-nitrosodimethylamine are metabolized in rodent and human liver by cytochrome P450IIE1, an activity competitively inhibitable by ethanol. In rodents coadministration of ethanol with N-nitrosodimethylamine results in increased tumorigenicity in extrahepatic organs, probably as a result of reduced hepatic clearance. To test this concept in a primate, the effects of ethanol cotreatment on the pharmacokinetics of N-nitrosodimethylamine were measured in male patas monkeys. Ethanol, 1.2 g/kg given p.o. before i.v. N-nitrosodimethylamine (1 mg/kg) or concurrently with an intragastric dose resulted in a 10-50-fold increase in the area under the blood concentration versus time curves and a 4-13-fold increase in mean residence times for N-nitrosodimethylamine. Isopropyl alcohol, 3.2 g/kg 24 h before N-nitrosodimethylamine, also increased these parameters 7-10-fold; this effect was associated with persistence of isopropyl alcohol and its metabolic product acetone, both IIE1 inhibitors, in the blood. While no N-nitrosodimethylamine was detected in expired air, trace amounts were found in urine. Ethanol and isopropyl alcohol pretreatment increased the maximum urinary N-nitrosodimethylamine concentration 15-50-fold and the percentage of the dose excreted in the urine by 100-800-fold. Thus ethanol and isopropyl alcohol greatly increase systemic exposure of extrahepatic organs to N-nitrosodimethylamine in a primate.     

Listening to Silence

SUMMARY. I have examined the function of silence - its possible role and meanings - in the psychoanalytic encounter. I have argued that silence is complementary to words in general, and to analytic free-associations in particular, and that silence in the patient is often more than just the expression of his resistance.
It could be useful to consider the silent space within a session as a sort of container of words -words that, for complex, over-determined, unconscious reasons cannot be uttered. I have insisted on the significance of analytic silences and warned against responding to them either through a retaliatory silence or through a flood of premature interpretations. These inadequate reactions often stem from the analyst's own anxiety evoked in him by the patient's silence.
Anxiety and silence are closely connected. Each silence is a compromise formation, concealing the unconscious fantasy from which it originates, while expressing a conscious one, often related to the transference situation. It is the task of the analyst to listen to his patient's silences in order to help him understand their meanings.     

Taylor-type focal cortical dysplasia: is the epilepsy always resistant to medical treatment?

Patients with Taylor-type focal cortical dysplasia (TTFCD) generally present with medically intractable epilepsy and impaired neurological and/or intellectual functioning. Surgery usually proves to be the only treatment approach leading to control of seizures. We describe a 17-year-old girl with TTFCD who exhibited a very long period of seizure remission. Combined clinical and neuroimaging findings were compatible with a diagnosis of a balloon cell-subtype TTFCD. As for the clinical course, partial motor seizures began at one year of age and ceased at five: our patient has had no seizure recurrence over a 12-year-follow-up. Moreover, throughout the 15-year follow-up, neurological examinations and cognitive abilities always remained within normal limits. Neuropsychological assessment clearly showed no impairments in executive functions: planning abilities, working memory, attention and impulse control, or constructive aspects of motor coordination. The predominant deficits pertained to verbal abilities in the context of borderline intellectual performances. To our knowledge, this case report documents the longest duration of seizure remission in a patient with TTFCD, thus emphasizing the possible benign course of such dysplastic lesions which usually have a poor prognosis, leading to early surgical treatment.     

Effect of Managed Care Enrollment on Primary and Repeat Cesarean Rates Among U.S. Department of Defense Health Care Beneficiaries in Military and Civilian Hospitals Worldwide, 1999–2002

Abstract: Background : In response to rising cesarean rates, it is reasonable for health care organizations to look to a managed care model as a means of controlling further rate increases. However, little conclusive evidence exists to support this solution. We undertook a study of the Department of Defense health care beneficiary population to assess the impact of enrollment in TRICARE Prime, the Department's managed care health plan, on cesarean delivery rates. Methods : Pooled hospital discharge records from 1999–2002 for live, singleton births were analyzed to calculate primary and repeat cesarean rates for TRICARE Prime and non‐Prime beneficiaries in the military and civilian hospitals that comprise the Department of Defense health care network. Stepwise logistic regression was used to calculate adjusted odds ratios for clinical indicators for each combination of health plan and hospital setting using theχ²difference(p < 0.05)to eliminate nonsignificant variables from the model. Total primary and repeat cesarean rates were compared with primary and repeat cesarean rates for women with no reported clinical complications to account for differences in case mix across subgroups. Statistical significance of the differences calculated for subgroups was assessed usingχ². Results : Primary cesarean rates were significantly lower for TRICARE Prime enrollees relative to non‐Prime beneficiaries for all race subgroups and three of five age subgroups in military hospitals and four of five age subgroups in civilian hospitals. No significant differences in repeat cesarean rates were observed between Prime and non‐Prime beneficiaries within any race or age subgroup. Breech presentation followed by dystocia, fetal distress, and other complications were significant predictors for primary cesarean. Previous cesarean delivery was the leading predictor for repeat cesarean delivery. Primary and repeat cesarean rates observed for military hospitals were consistently lower than rates observed for civilian hospitals within each health plan type and age group. Conclusions : Enrollment in the managed care health plan was significantly associated with lower risk of primary cesarean delivery relative to membership in other health plans offered to Department of Defense health care beneficiaries. Repeat cesarean rates in this population varied independently of health plan type. Primary cesarean delivery was generally associated with clinical complications, whereas previous cesarean delivery was the strongest indictor for a repeat cesarean delivery. A clear explanation of reduced cesarean rates for Prime enrollees remains elusive, but it is likely that factors beyond individual practitioner decision‐making were at work.     

Leukocyte count and risk of major coronary heart disease events.

The association between leukocyte count and subsequent risk of major coronary heart disease events was examined using data from three prospective cohort studies--two from the United States and one from Great Britain. A total of 28,181 middle-aged men were followed for 6-12 years. A total of 1,768 men had a nonfatal myocardial infarction or died of coronary heart disease. In all three cohorts, there was a positive, statistically significant relation between baseline leukocyte count and risk of subsequent major coronary heart disease events after adjustment for age, serum total cholesterol, diastolic blood pressure, and number of cigarettes smoked per day (relative odds = 1.32 (p less than 0.0001), 1.15 (p = 0.0001), and 1.14 (p = 0.003), corresponding to a 2,000/mm3 difference in leukocyte count). The associations persisted when all nonsmokers (former smokers plus never smokers) and never smokers alone were considered and when those with evidence of preexisting coronary heart disease at baseline were excluded. Leukocyte count appears to be an indicator of a person's future risk of major coronary heart disease events.     

The role of infectious agents in the spondylarthropathies

The clinical similarities of the spondylarthropathies and their frequent association with both HLA B27 and microbial infections suggest common pathogenetic mechanisms. The latter may include deposition of immune complexes containing bacterial antigens. or cross-reactivity of such antigens with host target tissue or responding cell antigens. Enteric bacteria, chlamydia and mycoplasma are all candidate etiologic agents, but proof is difficult because they are often found as normal flora, although only genetically susceptible individuals may acquire disease, and many patients have been treated with antibiotics before they can be studied. Nonetheless, a role for endogenous bacteria in reactive arthritis at least seems certain, and should stimulate further investigation into similar pathogenetic mechanisms in other chronic arthritides.     

PRIMARY CARE FOR WOMEN: Comprehensive Assessment of the Head and Neck

This article reviews the pertinent anatomy of each body system involved in the assessment of the head and neck (including the eyes, ears, nose, and throat) and describes the basic elements of the comprehensive health assessment. Frequently encountered chief complaints are discussed. Aspects of the health assessment that will assist the primary care provider in making a differential diagnosis and determining the need for referral are presented. This article is the first of two articles on this topic; the subsequent article will address primary care management of common conditions of the head and neck.