High incidence of non-upper aerodigestive primary tumors in patients with esophageal cancer.

Earlier reports have described an association between esophageal cancer (EC) and high incidence of other primary tumors (OPTs) of the upper aerodigestive tract and breast cancer. We evaluated the incidence of non-upper aerodigestive OPTs among Israeli EC patients; 2328 EC patients were retrieved from the Israeli National Cancer Registry between 1980 and 2004. The relative risk of OPTs for EC patients was measured using standardized incidence ratio (SIR). Two cohorts, Israeli National Cancer Registry registered colorectal cancer (CRC) patients and the general Israeli population, were used for reference; 297 EC patients (12.7%) had OPTs, including breast (18.9%), CRC (16.2%), prostate (8.8%), and bladder (8.4%) cancers. Upper aerodigestive OPTs were less common. Most OPTs were identified before (74.4%) or simultaneously with (13.8%) EC diagnosis. The median time interval between OPTs diagnoses and EC development was 6.0 years. The incidence of OPTs was significantly higher among EC patients compared with CRC patients (SIR: 2.05, P < 0.01) or the general Israeli population (SIR: 3.90, 95% CI: 3.46-4.34, P < 0.01) regardless of gender or tumor histology. Patients with EC have high incidence of non-upper aerodigestive malignancies. Unlike previous reports, the distribution of OPTs in EC seems to represent the relative incidences of these cancers in the western populations.

Malpractice claims analysis yields widely applicable principles.

We received 50 claims of medical negligence in pediatric cardiology. From the analysis, patterns were identified and recommendations for improvement were found that apply generally to healthcare. Less than half (38%) of the claims were found to be medically meritorious. The impression of substandard care was often (7/50) created by an erroneous attribution of cause of death at autopsy. Both structured learning for caregivers and education of the public will reduce the frequency of malpractice forms-both valid and frivolous. Caregivers should document more effectively. The current tort system neither deters nor compensates as it was intended. The assignment of blame to a single individual is usually not in concert with the reality of modern medicine. Good health care is not a passive behavior; active participation by the public is required.

The doctor/patient relationship and immunity from malpractice.

The physician-patient relationship establishes a cause of action for malpractice should the physician breach his duty to the patient. Employer-contracted physical examinations create a professional relationship between physician and employee to the extent of the tests conducted. An Independent Medical Examination may create a professional relationship between the physician and subject of the Independent Medical Examination.

The pursuit of clinical truth: role of epidemiology/observation studies.

The need for evidence-based medicine as a foundation for optimal patient care requires application of the best scientific methods. Various methods used in the search for clinical truth are discussed. The most powerful method to test a clinical hypothesis is the randomized, controlled clinical trial. By contrast, epidemiology/observation studies (EOS) have inherent weaknesses that can lead to erroneous conclusions. Five such examples, two older and three very recent, are discussed to provide historical perspective and demonstrate potential problems with EOS. Each incident has produced widespread consternation or confusion among physicians. Types of bias leading to errors in EOS are discussed, and the need is emphasized for more rigorous evaluation of EOS by investigators, as well as editors, to avoid repetition of past mistakes and to ensure publication of correct medical information.

A crystallization-induced stereoselective glycosidation reaction in the synthesis of the anticancer drug etoposide.

The anticancer drug etoposide, 1, is prepared in 79% overall yield from readily available 4'-demethyl-4-epipodophyllotoxin, 3, and 4, 6-O-ethylidene-2,3-O-dibenzyl-D-glucose, 4, via a crystallization-induced stereoselective glycosidation reaction followed by catalytic hydrogenation.

Drug transport in the mammalian central nervous system: multiple complex systems. A critical analysis and commentary.

The rate of entry into and distribution of drugs and endogenous substances within the mammalian central nervous system (CNS) depend on the peculiar anatomy of the blood-brain and blood-cerebrospinal fluid barriers, the physicochemical nature of the substance or drug, and in many cases, multiple, complex specialized carriers. This review summarizes a systemic methodological and integrative approach to understanding the pharmacokinetic behavior of many drugs in the CNS in the context of the CNS barrier systems, focusing on recent data, several broad principles and selected examples. Standards of proof for valid conclusions are emphasized.

Cultural concepts of women's health and health-promoting behaviors.

Cultural diversity is the reality of the 1990s, and the United States is becoming the most ethnically diverse society in the world. The needs and responses of many different racial and ethnic groups are competing for recognition, and nurses must learn how to meet the health care needs of this multicultural society. This article explores cultural concepts relating to women's health and health-promoting behaviors in the context of this social change. It explores demographic change, concepts of heritage consistency, traditional health beliefs, and traditional health-promoting behaviors.

Vertical diplopia.

An accurate clinical evaluation of vertical diplopia is predicated upon meticulous history-taking, observations regarding the presence and pattern of an anomalous head position, and the analysis of several subjective and objective tests of extraocular muscle function. To reach a final diagnosis with minimum risk and expense to the patient the examiner must be familiar with the neuroanatomy of the supranuclear and infranuclear pathways which control the actions of the vertically-acting extraocular muscles, the clinical methods and pitfalls of a number of clinical techniques which are used to identify an underacting extraocular muscle, and the hallmark characteristics of a supranuclear, infranuclear and restrictive ophthalmopathy.

Lovastatin does not affect oral glucose tolerance in hypercholesterolemic patients.

In 15 non-diabetic Type II hypercholesterolemic patients, the effect of 80 mg lovastatin daily on oral glucose tolerance was investigated. Using a randomized, double-blind, two-panel, parallel design, patients on a low cholesterol diet received lovastatin (n = 7) or placebo (n = 8) for 6 weeks. After 6 weeks of treatment, patients receiving lovastatin had a significant reduction in total cholesterol (30%), LDL-cholesterol (36%), and triglycerides (26%). Time courses of plasma glucose and serum insulin changes from baseline after the oral glucose tolerance test were evaluated by AUC. No statistically significant differences were observed in the AUC of changes from baseline between treatment groups or within either treatment group at prestudy, 6 weeks, and poststudy. No patient had a clinically important laboratory or clinical drug-related adverse effect during the study. This study demonstrated that short-term administration of 80 mg lovastatin daily effectively lowers cholesterol without having adverse effects on oral glucose tolerance.

Oral leukotriene inhibitor (MK-886) blocks allergen-induced airway responses.

To elucidate the role of leukotrienes (LT) in allergic asthma in humans the effect of MK-886, an LT biosynthesis inhibitor, was evaluated on antigen-induced early (EAR) and late (LAR) asthmatic reactions and bronchial responsiveness to histamine. Eight atopic men participated in a two-part, double-blind, placebo-controlled, crossover trial. MK-886 was administered in two oral doses of 500 mg and 250 mg, 1 h before and 2 h after allergen inhalation, respectively. Biochemical effects of MK-886 were evaluated by the inhibition of urinary LTE4 excretion and calcium ionophore-stimulated LTB4 biosynthesis in whole blood ex vivo. MK-886 significantly inhibited the EAR by 58.4% (AUC0-3 h) and the LAR by 43.6% (AUC3-7 h) when compared with placebo (p < 0.01). There was no difference in PC20 histamine 30 h post allergen challenge between MK-886 and placebo (0.33 and 0.27 doubling doses, p > 0.1). MK-886 inhibited calcium ionophore-stimulated LTB4 production in whole blood (54.2 +/- 25.6%) for up to 6 h post allergen challenge. LTE4 excretion in urine was inhibited by 51.5% during the EAR by as much as 80% during the LAR. This indicates that LT play a role in allergen-induced asthmatic reactions in humans in vivo and that LT synthesis inhibitors such as MK-886 should be further explored for the treatment of asthma.

Acute respiratory failure due to Pneumocystis carinii pneumonia.

Pneumonia caused by Pneumocystis carinii is the most frequent indication for admission of AIDS patients to intensive care units. In this article, an approach to the diagnosis and management of this condition will be presented along with prognostic information. Differential diagnosis will be discussed, and characteristic responses to current standard and alternative chemotherapeutic agents and modes of ventilatory support will be reviewed.

Echographic diagnosis of dural carotid-cavernous sinus fistulas.

I used standardized ophthalmic echography to identify specific abnormalities in four patients with low-pressure, low-flow dural arteriovenous malformations. In all of the patients, B-scan ultrasonography showed engorgement of the ipsilateral vertical vein. A-scan ultrasonography dynamically imaged rapid blood flow through the superior ophthalmic vein and enlargement of the culpable ocular muscles in patients with restrictive ophthalmopathy. The 30-degree test distinguished between venous engorgement of the optic nerve sheath and apical compression of the optic nerve by enlarged ocular muscles.

Drug transport in the central nervous system: role of carriers.

The rate of entry into and distribution of many drugs in the mammalian brain cannot be explained by the physicochemical characteristics of these drugs taking into account the anatomy of the blood-brain barrier. Rather, specialized mechanisms (carriers) in the central nervous system have been sought after and characterized. These carriers explain the observed pharmacokinetic behavior of many drugs in brain. This review summarizes these data in the context of the blood-brain barrier and focuses on several broad principles and selected examples.

Advances in understanding the pharmacology of agents used to treat bacterial meningitis.

Recently, substantial progress has been made in the therapy of bacterial meningitis related in part to better understanding of and predictions about the pharmacokinetics of antibiotics in the central nervous system. This review summarizes new data on pertinent anatomy and physiology of penicillin and cephalosporin transport in the central nervous system, focusing on the choroid plexus, which transports many antibiotics out of the central nervous system. These new pharmacological data provide the scientific basis for understanding recent advances in therapy of meningitis.

Effect of dietary protein on renal tubular clearance of drugs in humans.

Diet is one of many factors that influence the pharmacokinetics of drugs. The level of protein intake has been found to significantly influence drug metabolism and glomerular filtration, both of which play an important role in the clearance of drugs. Recently, a marked change, resulting from restricted dietary protein intake, has been reported in the handling of several drugs which are reabsorbed and/or secreted by the renal tubules. In studies of healthy volunteers on protein-restricted diets the renal clearance and fractional excretion of model compounds have been altered, falling to 30% of values obtained on normal diets in the case of the weak acids oxipurinol and uric acid; the fractional excretion of the weak base cimetidine has been increased by 30%. These studies have also found that the change in the renal clearance of both acids is sustained with prolonged dietary protein-calorie restriction, and that, for oxipurinol, the magnitude of the change is directly related to the quantity of protein in the diet, the change is related specifically to the protein content in the diet (and not the total calories), the onset of change is rapid, and on a low-protein diet the renal clearance undergoes marked diurnal variation. The mechanism for the alteration in tubular function is not clear, but may be related to renal haemodynamic changes or competition for transport associated with protein intake. Regardless of the mechanism, these results have important implications for pharmacokinetic research and clinical practice.