Treating nondementia illnesses in patients with dementia

Physicians increasingly are called on to provide primary care for the growing population of people with Alzheimer-type dementia. However, little attention has been paid to the care of nondementia illnesses in this group of patients. To illustrate how presence of dementia can alter the risk-benefit ratio of treatment of a common medical problem, we present a case study in which a patient with dementia developed disastrous adverse effects to a drug commonly used to treat osteoporosis. This case and 2 composite vignettes illuminate how presence of dementia should influence the decision-making process for treatment of nondementia illnesses. We address issues such as decreased decision-making capacity, problems with reporting adverse effects, decreased cognition leading to problems with treatment adherence, and the role of screening and basic questions about acceptable burdens of treatments in patients with limited prognosis. We suggest ways to improve communication with patients with dementia in an effort to minimize complications and improve care, as well as policy changes to include patients with dementia in clinical trials. JAMA. 2000;283:3230-3235     

Underprediction of visibly complex chromosome aberrations by a recombinational-repair ('one-hit') model

PURPOSE: Published low-LET FISH data were used to test two models of chromosome aberration production based on breakage-and-reunion or recombinational repair. MATERIALS AND METHODS: Randomness of DNA double strand break induction and misrejoining is analyzed comprehensively and adopted as a working hypothesis. Proximity effects are approximated by using interaction sites. Model results are calculated using CAS (chromosome aberration simulator) Monte Carlo computer software with two adjustable parameters. CAS can emulate the specifics of any experimental painting protocol, allowing very detailed tests of the models. RESULTS: To reasonable approximation, breakage-and-reunion model predictions are consistent with low-LET FISH results, including two large, elaborate, one-paint data sets. An explicitly specified version of the recombinational-repair model severely underpredicts the frequency of the visibly complex aberration patterns most commonly observed with one-paint FISH, and is inconsistent with some observed multi-paint patterns. When high-dose effects (distortion and saturation) are taken into account quantitatively, a dose-response relation for apparently simple interchanges slightly favours the breakage-and-reunion model over the recombinational-repair model, despite being approximately linear over the dose range 2-6 Gy. CONCLUSIONS: The random breakage-and-reunion model gives comprehensive baseline predictions that are sufficiently accurate for the organization of experimental results. The data speak against complex aberrations being formed by the random recombinational repair pathway discussed here.     

Dysphoria from a transnosological perspective

The objective of our psychopathological analyses is to shed light on the position of irritable mood (dysphoria) in psychiatric diagnostics and nosology. In today's most commonly applied classification systems, the ICD-10 and the DSM-IV, dysphoria is mentioned mostly in the context of diagnostic criteria of personality and affective disorders. Other authors have emphasized the importance of dysphoric states in organic psychoses and delusional disorders. Summarizing the various publications on the nosological position, dysphoria is a nosological nonspecific syndrome which may occur in the course of all psychiatric disorders and illnesses. According to the results of our psychopathological analyses, the pathogenesis of dysphoria has to be considered as a multidimensional circular process in which various mental, physical and social factors act as predisposing, triggering and disorder-maintaining factors. Stressors induced by particular experiences and perceptions and by impaired health may lead to a dysphoric state if adequate coping mechanisms are missing. Dysphoria itself usually leads to a deterioration in the mental and physical state of the patient, and shows a clear impact on the patient's social network. The reactions of people close to the patient combined with the impaired mental and physical conditions of the patient cause the circle to restart. As contemporary diagnostic entities do not refer to pathogenesis, classical categorical diagnostics cannot provide the basis for effective pathogenesis-oriented therapy. A change of paradigm in diagnostics from a categorical to a dimensional approach thus becomes necessary. Following a dimensional diagnostic approach based on a dynamic model of vulnerability, a precise differential diagnosis of the complex constellation of conditions and their interactions becomes necessary in order to develop effective treatment strategies. Disorder-maintaining factors determine the treatment of the acute symptomatology, whereas predisposing and triggering factors serve as the basis for the prophylactic treatment.     

The role of the anesthesiologist in the care of the parturient with cardiac disease

Women with cardiac disease constitute a growing percentage of parturients, and in many series cardiac disease is the leading cause of maternal mortality. Involvement of anesthesiologists in the planning for and management of delivery in these women can improve the experience and potentially the outcome of these patients. Communication with the anesthesiology team about particularly complex cases is essential to avoid both medical complications and inter-disciplinary disagreements. The specific role and contributions of the anesthesiology team will depend significantly on the nature of the institution and the organization of the (obstetric) anesthesiology service.     

A simple automated stimulator of mechanically induced arrhythmias in the isolated rat heart

Transient stretching of the ventricle can trigger arrhythmias and evoke ventricular fibrillation, especially when the stimulation occurs in the vulnerable period. To explore the sensitivity of small hearts we used a commercial pressure servo to study the kinetic relationship of left ventricular pressure to excitability and arrhythmias in the rat heart. Stimulation protocols were readily composed on the computer and programmed to vary the stimulus amplitude and timing relative to pacing. The pressure-induced premature ventricular excitations were similar to those observed in larger hearts, but the convenience of using small hearts allows the use of inexpensive transgenic animals to explore the molecular basis of transduction.     

INTERACTION OF THE CARBOHYDRATE-BINDING PROTEIN CONCANAVALIN A WITH NORMAL AND TRANSFORMED CELLS

It has been shown that the carbohydrate-binding protein concanavalin A (ConA) can agglutinate leukemic cells and cells transformed by polyoma virus, simian virus 40, chemical carcinogens, and X-irradiation. This protein did not agglutinate normal cells under the same conditions. The agglutination was reversed by competition with α-methyl-D-glucopyranoside (α-MG), a carbohydrate that strongly binds to ConA, but not by the carbohydrates α-methyl-L-fucopyranoside or N-acetylglucosamine, with no binding or weak binding to ConA. Destruction of the α-MG binding sites of the native protein by removal of bivalent metal ions abolished the agglutination produced by the native protein. The treatment of cells with trypsin resulted in the agglutination of normal cells by ConA and a decrease of agglutinability of transformed cells. When nonagglutinating untransformed 3T3 cells were infected with simian virus 40 and normal rat cells were infected with polyoma virus, the infected cells became agglutinable several days after virus infection. The percentage of cells agglutinated, about 50 per cent, was much higher than the percentage of cells hereditarily transformed. The results indicate that the surface membrane of transformed cells contains sites that interact with the α-MG binding sites of ConA, that such sites can be found on the surface membrane of normal cells after treatment with trypsin, and that the change in the surface structure from normal to transformed occurs in cells that are abortively transformed.