Complexities of morality

This letter is sharply critical of an article by Dr. Holmes (Annals of Iternal Medicine 72: 123-127, 1970). The dilemma of 18 to 21-year-olds requesting birth control pills is not simply a question of "aesthetic bias." The pressures on these young women to have sexual relations is intense and the author has found these women grateful to hear an adult decidely opposed to premarital intercourse. The author is amazed at Dr. Holmes' characterization of a marriage between gentile and Jew as an act of morality. "Intermarriage as an act of agression against the parents is in my opinion as likely as intermarriage an an act of social justice," he writes. Finally, he feels that in talking with young patients, adults in general and psychiatrists in particular should not feel guilty because the world is not perfect. Children have a right to "enough healthy cynicism to avoid exploitation by those who would deceive them in the name of morality."     

ACE Inhibitors in Heart Failure: Prospects and Limitations

ACE inhibitors have been shown to be effective in reducing the morbidity and mortality of patients with left ventricular systolic dysfunction, but their application to clinical practice in this situation is still limited. In part, the failure to prescribe an ACE inhibitor to a patient with left ventricular systolic dysfunction is due to perceptions regarding their side effects, such as cough and renal dysfunction. Relatively few patients with left ventricular systolic dysfunction and a serum creatinine ≥2 mg/dl receive an ACE inhibitor in clinical practice. In this situation one should consider an agent such as fosinopril, which is metabolized by the liver as well as secreted by the kidney. In patients with moderate renal dysfunction, fosinopril has been well tolerated without an increase in serum creatinine. In patients who develope cough due to an ACE inhibitor, consideration should be given to an angiotensin II type 1 receptor blocking agent, such as losartan. The relative safety and efficacy of an ACE inhibitor compared with an angiotensin II type 1 receptor blocking agent is being explored in a prospective randomized trial (Evaluation of Losartan In The Elderly [ELITE]), as well as the safety and pharmacological effectiveness of adding an angiotensin II receptor antagonist to an ACE inhibitor (Randomized Angiotensin receptor antagonists–ACE-inhibitor Study [RAAS]). There may also be a role for the combination of an aldosterone receptor antagonists and an ACE inhibitor in patients with left ventricular systolic dysfunction. Once an ACE inhibitor is administered to a patient with left ventricular systolic dysfunction it should be continued indefinitely. ACE inhibitors may be of value not only in preventing the progression of heart failure but also in reversing endothelial dysfunction and preventing the development of atherosclerosis and its consequences, such as myocardial infarction.     

Therapie und Prophylaxe der infektiösen Endokarditis

Infective endocarditis is an infection of cardiovascular structures which is typically caused by bacteria. Despite recent medical advances mortality ranges from 20 to 25%. Without treatment, IE is a lethal disease. The mortality rate depends on several clinical factors including the causative microorganism, the time of diagnosis, and the initiation of an adequate therapeutic regimen. The diagnosis is based on positive blood culture results with identical microorganisms and the demonstration of endocardial involvement. Negative blood cultures represent a diagnostic challenge which may increase the importance of diagnostic tools such as serology and PCR. An early and targeted initiation of an antibiotic therapy after microbiologic testing is crucial for therapeutic success. The immediate cooperation of Cardiologists, Microbiologists, Infectious Disease Specialists and Cardiac Surgeons is highly recommended to allow an adequate medical and surgical treatment in complex cases. Prophylaxis appears reasonable due to the inherent high mortality. The efficacy of an antibiotic prophylaxis is, nevertheless, not rigorously proven. Even if a high efficacy is assumed, the number needed to treat is extremely high due to the low individual risk. Thus, current guidelines recommend an antibiotic prophylaxis only in patients with a high risk for an adverse outcome.     

Effect of Electrode Position on the Outcome of Cardioversion

Acute termination of atrial fibrillation is the starting point of any therapy aimed at preventing atrial fibrillation and improves cardiac output in patients with hemodynamic compromise due to the arrhythmia. External electrical cardioversion is a simple procedure to terminate persistent atrial fibrillation in the majority of cases. Initially, Lown et al. used an anterior-lateral position of electrodes to apply a cardioversion shock. Recent pathophysiological studies have shown that atrial fibrillation is maintained by functional re-entry circuits anchored in the left atrium. As the left atrium is located posteriorly in the thorax, an anterior-posterior electrode position may be more efficient for external cardioversion of atrial fibrillation than the commonly used anterior-lateral electrode position. Several recent studies have confirmed that an anterior-posterior electrode position is superior to an anterior-lateral electrode position for external cardioversion of atrial fibrillation. There are no indications that an anterior-posterior electrode position is less safe than an anterior-lateral electrode position. We therefore suggest that an anterior-posterior electrode position should initially be used for external cardioversion of atrial fibrillation.     

Therapy and prophylaxis of infective endocarditis

Infective endocarditis is an infection of cardiovascular structures which is typically caused by bacteria. Despite recent medical advances mortality ranges from 20 to 25%. Without treatment, IE is a lethal disease. The mortality rate depends on several clinical factors including the causative microorganism, the time of diagnosis, and the initiation of an adequate therapeutic regimen. The diagnosis is based on positive blood culture results with identical microorganisms and the demonstration of endocardial involvement. Negative blood cultures represent a diagnostic challenge which may increase the importance of diagnostic tools such as serology and PCR. An early and targeted initiation of an antibiotic therapy after microbiologic testing is crucial for therapeutic success. The immediate cooperation of Cardiologists, Microbiologists, Infectious Disease Specialists and Cardiac Surgeons is highly recommended to allow an adequate medical and surgical treatment in complex cases.Prophylaxis appears reasonable due to the inherent high mortality. The efficacy of an antibiotic prophylaxis is, nevertheless, not rigorously proven. Even if a high efficacy is assumed, the number needed to treat is extremely high due to the low individual risk. Thus, current guidelines recommend an antibiotic prophylaxis only in patients with a high risk for an adverse outcome.     

Changes in mitochondrial redox state following an oral glucose load

Summary Changes in cytosol and mitochondrial redox state after an oral glucose load were studied in the liver of rats. The [NAD⁺]/[NADH] ratios increased 4-fold in the cytoplasm and 1.5-fold in the mitochondria 60 min after an oral glucose load, when serum IRI was maximally increased. It is suggested that an increase in mitochondrial redox state following an oral glucose load is due to an enhanced rate of removal of NADH by the respiratory chain, possibly due to an elevated level of insulin available to hepatocytes, and that an increase in cytosol redox state depends on an enhancement in mitochondrial oxidation of cytosol reducing equivalent.     

Indications for and techniques of tracheotomy

Although the operation has been practiced for centuries, the modern technique of tracheotomy was introduced and popularized in the beginning of the 20th century. The initial indication for tracheotomy was limited to impending airway obstruction resulting from trauma, but current indications are broader. Tracheotomy is one of four methods available to intubate the trachea and is associated with physiologic changes that are dependent on the duration of tracheotomy. Although surgical in nature, it is employed to relieve or prevent airway obstruction and to offer ventilatory support. Tracheotomy may be performed as an elective or an emergency procedure. Ideally, it is done in a controlled situation. However, when performed in an emergency setting, variations of the procedure, such as minitracheotomy or cricothyroidotomy, may be temporarily substituted. Preferably, tracheotomy is performed in an operating room; however, it may be carried out successfully in an intensive care unit as well.     

Consequences of localized frustration for the folding mechanism of the IM7 protein

In the laboratory, IM7 has been found to have an unusual folding mechanism in which an "on-pathway" intermediate with nonnative interactions is formed. We show that this intermediate is a consequence of an unusual cluster of highly frustrated interactions in the native structure. This cluster is involved in the binding of IM7 to its target, Colicin E7. Redesign of residues in this cluster to eliminate frustration is predicted by simulations to lead to faster folding without the population of an intermediate ensemble.     

洪涝灾害后疟疾流行早期预测的探讨

通过对 1989～ 1997年湖北省汉川市和老河口市的疟疾疫情资料分析 ,求出逐月及年疟疾病例之总合 ,并分别计算出逐月发病均数和标准差 ,以均数加标准差为标准绘出曲线 ,以此双曲线作为标准曲线与既往各年逐月的实际发病曲线相比较 ,找出各月疟疾上升的突破点。结果显示 ,平均数加两个标准差是疟疾上升的预警指标 ,此指标的准确性为 95 %。一般而言 ,湖北省回升预警点出现在每年的 4～ 5月 ,出现突破预警后需立即进行流行病学分析 ,并制定出针对性的防治对策 ,将疟疾控制在回升之初     

Airway smooth muscle in asthma

Abstract One of the factors that may contribute to the exaggerated airway narrowing in asthma is an abnormality of the airway smooth muscle. This abnormality could take the form of an increase in the amount of muscle or an alteration in its pharmacological reactivity. The former could be due to either hypertrophy (an increase in individual muscle cell size) or hyperplasia (an increase in cell number). Changes in pharmacological reactivity that could be relevant to altered airway calibre could result from an increase in contraction or alternatively, a decrease in relaxation. Based on available evidence, the increase in smooth muscle bulk is probably the consequence of both hyperplasia and hypertrophy and several growth factors, inflammatory mediators and cytokines have been implicated. Asthmatic airway tissue is rarely available for in vitro pharmacological studies and evidence for enhanced contraction is limited. Recent evidence suggests that an abnormality in beta adrencoceptor function may contribute to impairment of relaxation, but further work needs to be done. Passive sensitization of non-asthmatic airways in vitro provides a good model for the study of the mechanisms underlying airway hyperresponsiveness, and will be the subject of more intensive study in the future.     

Radiation therapy for Cushing's disease: a review

Because patients with Cushing's disease have an increased morbidity and an age-corrected mortality, treatment is generally started as soon as possible. The goal of treatment in these patients is to induce remission. Although a variety of treatments are available, pituitary radiation is a good option for aggressive Cushing's disease that fails to respond to surgery, disease that invades the cavernous sinus, and disease that relapses following an initial remission. Conventional radiation therapy, stereotactic radiosurgery, fractionated stereotactic radiation therapy, and brachytherapy with Yttrium-90 (Y 90) and Gold-198 (Au 198) have been used successfully to treat ACTH-secreting pituitary adenomas in specialized centers. Conventional radiation therapy is the most frequently used method of radiation therapy for Cushing's disease. Stereotactic radiosurgery may be used as an alternative in patients with adenomas that are smaller than 30 mm and located at least 3 to 5 mm from the optic chiasm. Fractionated stereotactic radiation therapy is an alternative to radiosurgery while interstitial pituitary irradiation is an alternative to surgical resection in invasive tumors. Hypopituitarism is the most common side effect of pituitary irradiation. This article will review the role of radiation in the primary and secondary treatment in patients with Cushing's disease caused by pituitary adenomas.     

Surgical treatment of unicompartmental degenerative arthritis of the knee

The number of patients with unicompartmental osteoarthritis is increasing with the average age of our population. Good surgical techniques are available to improve pain and increase motion in the knee with degenerative disease. It is important to make early accurate diagnoses in arthritic patients so that the least surgically ablative procedure can be performed that will maximally benefit each patient. Total knee replacement is an extremely effective operation for relieving pain, but its major drawback is the large amount of bone stock that must be sacrificed during the procedure. Unicondylar knee replacement has proven itself to be an excellent alternative to total knee replacement in more limited arthritic disease. High tibial osteotomy still plays a major role as treatment for unicompartmental arthritis in younger and more active patients. McKeever interpositional hemiarthroplasty is an alternative in young patients when osteotomy is contraindicated. Arthroscopy is playing an increasing role in both diagnosis and treatment of unicompartmental osteoarthritis. The decision to perform unicompartmental arthroplasty, osteotomy, or total knee replacement is made on an individual basis. The extent of cartilage degeneration in the knee as well as the age, weight, and activity demands of the patient help to guide that decision.     

The X prime descent in jugular contour nomenclature and recognition

To help prevent the inspection of jugular contours from falling into disuse due to an irrational nomenclature tradition, the historical back-ground for the development of a bewildering jugular nomenclature is presented. The term “X prime” is revived in an attempt to bring order into the labeling of the systolic venous collapse. The descent of the base is shown to produce an X prime descent even in the presence of atrial fibrillation. Labeling troughs rather than descents is examined in an attempt to discourage this firmly entrenched tradition. Finally, an audiovisual method of recognizing the normal jugular contour is presented, utilizing the observation that the X prime descent falls on to the second heart sound.     

Modulation of transcription factor NF-kappa B binding activity by oxidation-reduction in vitro.

NF-kappa B is a widely used regulator of inducible and tissue-specific gene control. In the cytosol, when complexed to an inhibitory molecule, I kappa B, NF-kappa B is in an inactive form and cannot bind DNA. Activation of cells with appropriate stimuli results in the dissociation of NF-kappa B from I kappa B and its translocation to the nucleus as an active binding protein. We now demonstrate that NF-kappa B binding in vitro can be inhibited by agents that modify free sulfhydryls. Binding is eliminated after treatment with N-ethylmaleimide, an alkylating agent, and diamide, an oxidizing agent. The diamide effect can be reversed by 2-mercaptoethanol. Further, 2-mercaptoethanol acts synergistically with deoxycholate plus Nonidet P-40 in converting inactive cytosolic NF-kappa B to an active DNA-binding form. It is therefore possible that modulation of the redox state of NF-kappa B could represent a post-translational control mechanism for this factor.     

Biophysics of aging and therapeutic interventions by entropy-variation systems

The cell is thermodynamically an open system and aging is characterized by an increasingly higher structural disorder (increase of entropy) and functional loss. If a variation of negative entropy is introduced by an external source, an anti-clockwise effect leading to regenerative processes and/or increase of the functional reserve supporting regenerative tissue changes is theoretically expected. The achievement of a negative variation of entropy is the main principle of a new technology which implies an exogenous delivery of energy with higher performance than the physiological production. Promising clinical experiences in liver cirrhosis and in long-standing scarring lesions seem to confirm the clinical applicability of the theoretical model.     

Pathophysiology of exercise hypertension

The blood pressure is not a fixed entity but rather a parameter subject to substantial situational fluctuations. Studies based on ambulatory blood pressure measurement as well as exercise testing have shown that the highest blood pressure values in an individual can be recorded during physical exercise. During exercise in healthy subjects, in association with an increase in cardiac output and decrease in peripheral resistance, there is an increase in systolic arterial pressure with nearly constant diastolic pressure. In contrast to normotensive individuals, during dynamic exercise hypertensive patients demonstrate excessive pressure increases due to impaired vasodilatation. The mechanism responsible may be structural changes in the arteriolar walls but age is also an important determinant. The extent of blood pressure increase is more dependent on the mass of contracting muscle than on the mode of contraction. During isometric exercise, there is an increase in both systolic and diastolic blood pressure, predominantly reflex-induced, which is more marked in patients with manifest hypertension at rest than in those with borderline hypertension or in normotensive subjects. During dynamic exercise in a subgroup of patients with coronary artery disease, in contrast to normal subjects in whom the diastolic pressure remains constant, an increase in up to 15 mm Hg in this parameter may be found as a result of ischemia induction with left ventricular dysfunction, inadequately increased cardiac output and reflex vasoconstriction. During dynamic exercise, there is an increase in norepinephrine, more marked in hypertensive than normotensive subjects together with an increase in plasma renin activity; plasma aldosterone changes are in parallel with those of renin activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Equivalence trials in SLE research: issues to consider

In contrast to the objective of most clinical trials, which is to demonstrate superiority of an experimental treatment over a standard or placebo, the aim of an equivalence trial is to show that two treatments are equivalent in outcome or only marginally different. This would be of interest when an experimental treatment offers advantages such as reduced toxicity, ease of administration, or cost relative to the standard. Demonstrating equivalence may also be a goal when evaluating the safety of certain drugs because similarity in the risks of an adverse event in subjects exposed and unexposed to the drug is an indication of its safety. The classical formulation of the null hypothesis of treatment equality that is used in superiority trials is not applicable to equivalence trials because absolute equivalence between treatment groups cannot be proven. The strategy in equivalence trials is to define a maximum difference between treatment groups that is clinically acceptable and then assess whether there is sufficient evidence from the trial to conclude that the true treatment difference is within this acceptable range. In this paper, we discuss issues surrounding the planning, conduct, and analysis of equivalence trials in the context of SLE, with examples from the SELENA study.     

Metabolic aspects of alcoholic liver damage: 1984/1985 update. 2: Microsomal enzyme induction and hypermetabolism

In the second part of this review, the effect of ethanol on hepatic microsomal enzymes is primarily discussed. Since ethanol is metabolized via a cytochrome P-450 dependent biotransformation system (MEOS) in hepatic microsomes, the microsomal enzyme induction in the smooth endoplasmic reticulum has to be considered as an adaptive response. This enzyme induction results in an accelerated metabolism of ethanol. However, subsequently, the negative consequences of such a microsomal enzyme induction are predominant. Acetaldehyde production increases and oxygen consumption is enhanced leading to pericentral (perivenular) hypoxia. In addition, microsomal enzyme induction results in an enhanced metabolism of drugs, xenobiotics and hepatotoxins and thus to an increased production of toxic intermediates. Also procarcinogens are activated to a higher degree in microsomes following chronic ethanol consumption. Subsequently, an enhanced microsomal metabolism of vitamin A may explain the low serum concentrations of this vitamin in the alcoholic and may lead to toxic metabolites of retinol. The quantitative role of an enhanced reoxidation of NADH responsible for an increased oxidation of alcohol following chronic ethanol ingestion has still to be determined. However, according to recent investigations, a thyroid hormone induced hypermetabolism seems unlikely.     

Incarceration of a colonoscope in an inguinal hernia: Case report and literature review

Incarceration of an endoscope in an inguinal hernia may occur during the course of routine colonoscopy. The incarceration may occur on insertion or withdrawal and frequently the hernia is not suspected prior to the colonoscopy. Most commonly, a left sided inguinal hernia is involved, however right inguinal hernias may be implicated in subjects with altered anatomy post abdominal surgery. Incarceration of an endoscope in an inguinal hernia has been seldom reported in the literature which is likely to be related to under reporting. A range of techniques have been suggested by various authors over the last four decades to manage this unusual complication of colonoscopy. These techniques include utilizing fluoroscopy, manual external pressure and/or the fitting of a cap onto the tip of the colonoscope to facilitate colonoscopic navigation. The authors present a case report of incarceration of the colonoscope on withdrawal in an unsuspected left inguinal hernia with a review of the literature on the management of this colonoscopic complication. A management strategy is suggested.