Physician beliefs and practice regarding end-of-life care in India.

BACKGROUND AND AIMS: Physician beliefs and practices largely determine the withdrawal of life support in intensive care units. No information exists regarding beliefs regarding the withdrawal of life support among physicians in India. MATERIALS AND METHODS: We performed a questionnaire at the NAPCON conference in Jaipur. RESULTS: One hundred and twenty-two questionnaires were completed and returned. The majority of respondents did not apply do not resuscitate orders. Most physicians stated withdrawal of life support was not allowed or practiced at their institution. Thirty-five percent of physicians stated they performed life-support withdrawal. Barriers to good end-of-life care were primarily legal but also included hospital policy and social constraints. CONCLUSIONS: Pulmonary and critical care physicians in India have a lower rate of withdrawal of life support than western physicians. The reasons seem to be primarily legal and policy related. Culture and religion were not identified as barriers. Clarification of the legal and policy status of withdrawal of life support is needed.

Use of thrombolytic therapy to treat heparin-refractory pulmonary embolism in a menstruating patient.

A 26-year-old woman developed an acute pulmonary embolism at the beginning of her menstrual cycle and was admitted to the hospital. When she failed initial standard treatment with heparin, the only other therapeutic option was a thrombolytic agent such as recombinant tissue plasma activator (rt-PA). Use of these agents, however, carries a large risk of major bleeding complications and brings concern of increased menstrual blood flow and duration. A literature search of the use of thrombolytic agents in menstruating patients found only limited reports. Our patient responded well to rt-PA therapy Her hemoglobin levels remained stable, and she experienced no bleeding complications. Careful monitoring and caution are recommended when administering thrombolytic agents to menstruating patients.

Cross-bridge cooperativity during isometric contraction and unloaded shortening of skeletal muscle.

Whether the two heads of skeletal muscle myosin work independently or cooperatively remains an open question in muscle biophysics. While individual myosin heads are sufficient for ATPase activity (Reisler (1980) J Mol Biol 138: 93-107) and force production (Harada et al. (1987) Nature 326: 805-808), it has also been reported that in situ, the two heads of a myosin molecule work cooperatively (Chaen et al. (1986) J Biol Chem 261(29): 13,632-13,636). To examine the role of cross-bridge cooperativity on isometric contraction and unloaded shortening we progressively inactivated myosin cross-bridges via titration with para-phenylenedimaleimide. The resting fiber ATPase was measured to provide an estimate of the fraction of active cross-bridges remaining during the titration. Isometric force and unloaded shortening velocity decline more rapidly than the resting ATPase as the titration proceeds. This is inconsistent with models for independent force generation and suggests cooperative action of myosin cross-bridges when muscle is isometrically contracting or shortening under zero load. However the degree of cooperativity depends on the type of muscle activity. While isometric force declines in a manner consistent with pair-wise cooperative action of myosin heads, unloaded shortening velocity declines more rapidly (greater cooperativity). Therefore, myosin cross-bridges in situ may be capable of at least two types of cooperative interactions, pair-wise cooperativity (when isometric) and another form of cooperativity that is sensitive to longer range interactions transmitted from other cross-bridges in the ensemble (during unloaded shortening).

Methods to improve diagnostic accuracy in a community mental health setting.

OBJECTIVE: This study determined the extent to which adding structured procedures improved diagnostic accuracy for outpatients with severe mental illness in a community mental health setting. METHOD: The Structured Clinical Interview for DSM-III-R (SCID) was used to interview 200 psychiatric outpatients. A research nurse reviewed medical records and amended the SCID diagnoses accordingly. A research psychiatrist or psychologist reviewed the diagnostic data and interviewed each patient to verify or further modify the previous findings. Diagnostic outcomes at each step of the procedure were compared to determine whether adding additional data improved diagnostic accuracy. The additional time required for each element of the diagnostic procedure was also assessed. RESULTS: Kappa comparisons of the different diagnostic levels showed that adding additional data significantly improved accuracy. Diagnoses rendered by combining the SCID and review of the medical record were the most accurate, followed by the SCID alone, and then diagnoses made by psychiatrists during routine care. In addition, the SCID alone identified five times as many current and past secondary diagnoses as were documented routinely in patients' charts. CONCLUSIONS: Combining structured interviewing with a review of the medical record appears to produce more accurate primary diagnoses and to identify more secondary diagnoses than routine clinical methods. The patients' knowledge of their diagnoses was limited, suggesting a need for patient education in this setting. Whether use of structured interviewing in routine practice improves patient outcomes deserves further study.

Disseminated Pseudallescheria boydii infection in a nonimmunocompromised host.

We present a highly unusual case of pulmonary Pseudallescheria boydii infection in a nonimmunocompromised host with a cavitating mass lesion. The diagnosis was confirmed by open lung biopsy. The patient was treated at another institution with course of amphotericin B, considered an ineffective therapy for this infection, and presented to us with direct extension and invasion of the left atrial appendage and the pulmonary artery, followed by massive pulmonary embolization and hematogenous dissemination to the liver, spleen, kidney, pancreas, and brain.

Wegener's granulomatosis and alpha1-antitrypsin-deficiency emphysema: proteinase-related diseases.

Wegener's granulomatosis (WG) and alpha1-antitrypsin (alpha1-AT)-deficiency emphysema are both uncommon disorders. A relationship may exist between these diseases involving the proteinase and antiproteinase balance in the lung. A case is presented of WG and alpha1-AT-deficiency emphysema occurring in the same patient. Previous studies concerning the correlation between abnormal alpha1-AT alleles and WG are discussed. Potential mechanisms for the relationship and recommendations for screening are given.

Graphical evaluation of alkylation of myosin's SH1 and SH2: the N-phenylmaleimide reaction.

Previous assertions about the effect of alkylation of SH1 and SH2 on the myosin high-salt calcium and EDTA ATPases have been summarized, and a simple procedure for obtaining the fractional labeling of SH1 and SH2 after treatment of myosin with alkylating agents has been derived. A simple graphical procedure for illustrating the degree of preference of a particular alkylating agent for SH1 over SH2 has also been developed. The procedures we developed were validated by applying them to two previously studied compounds, 4-(2-iodoacetamido)-TEMPO and 2,4-dinitrofluorobenzine, and then were used to determine a procedure for maximizing the extent of labeling of SH1 alone by N-phenylmaleimide, a compound not previously studied in this manner. It was found that approximately 80% of the SH1 sites could be alkylated without significant alkylation of SH2.

Predicting wheat yields: the search for valid and precise models.

Interest in predicting wheat yield in terms of physiological, cultural and meteorological variables is more than a century old. Early attempts involved statistical analyses of relationships between yield and observational data on precipitation, temperature, radiation, etc., and scientific study of physiological and cultural influences such as dates of sowing or anthesis, farming procedures and soil treatments. More recently these have been augmented by large-scale mechanistic models of phenological development, such as AFRCWHEAT, CERES and SIRIUS, incorporating some simulation facilities. All approaches implicitly involve fitting models of some sort: statistical, mechanistic or (preferably) a hybrid of these forms. Levels of success on this important matter are highly variable. After reviewing the field, we consider the results of recent efforts to contrast and evaluate the (large-scale) mechanistic approaches, using spatial/temporal methods for interpolating the required climatological input variables. The work employs a substantial database of wheat yields assembled for this purpose. After assessing the validity of the large-scale mechanistic models (with some intriguing conclusions), we then consider some results from a current approach to parsimonious hybrid modelling, based on statistical study of accessible climatological data interpreted in terms of physiological knowledge of key influences on plant development.

The site and stoichiometry of the N-phenylmaleimide reaction with myosin when weakly-binding crossbridges are formed in skinned rabbit psoas fibers.

Treatment of relaxed skinned rabbit psoas muscle fibers with 0.1 mM N-phenylmaleimide (NPM) for 1 h locks all of the crossbridges in a weakly-binding state resembling that of the myosin.ATP crossbridge. Under these conditions, NPM reacts mainly with myosin heavy chain (Barnett et al. (1992) Biophys. J. 61, 358-367). Here the specific sites for that reaction are explored. Small bundles of rabbit psoas muscle fibers were treated with Triton X-100 to make the fiber sarcolemmas permeable. The bundles were treated with 0.1 mM [14C]NPM for 1 h, and homogenized for SDS-PAGE. 43 +/- 2.2% of the muscle fiber protein ran in the myosin heavy chain band, the same as for untreated fibers. An alkylating stoichiometry of 2.2 +/- 0.33 moles NPM per mole myosin heavy chain was determined. Exhaustive trypsin digestion followed by two-dimensional thin-layer chromatography and reverse-phase HPLC revealed two major sites on myosin heavy chain for NPM binding. The sites contained about the same amount of linked NPM, suggesting that the reaction stoichiometry of each site under the conditions studied is approx. 1 mol NPM/mol myosin heavy chain. Comparison of the labeled tryptic peptides with NPM-reacted synthetic SH1 and SH2 tryptic peptides and analysis of the treated fiber bundles' ATPase activity suggested that the sites for NPM reaction on myosin heavy chain when it locks crossbridges in a weakly-binding state are Cys-697 (SH2) and Cys-707 (SH1).

Resolution of three structural states of spin-labeled myosin in contracting muscle.

We have used electron paramagnetic resonance (EPR) spectroscopy to detect ATP- and calcium-induced changes in the structure of spin-labeled myosin heads in glycerinated rabbit psoas muscle fibers in key physiological states. The probe was a nitroxide iodoacetamide derivative attached selectively to myosin SH1 (Cys 707), the conventional EPR spectra of which have been shown to resolve several conformational states of the myosin ATPase cycle, on the basis of nanosecond rotational motion within the protein. Spectra were acquired in rigor and during the steady-state phases of relaxation and isometric contraction. Spectral components corresponding to specific conformational states and biochemical intermediates were detected and assigned by reference to EPR spectra of trapped kinetic intermediates. In the absence of ATP, all of the myosin heads were rigidly attached to the thin filament, and only a single conformation was detected, in which there was no sub-microsecond probe motion. In relaxation, the EPR spectrum resolved two conformations of the myosin head that are distinct from rigor. These structural states were virtually identical to those observed previously for isolated myosin and were assigned to the populations of the M*.ATP and M**.ADP.Pi states. During isometric contraction, the EPR spectrum resolves the same two conformations observed in relaxation, plus a small fraction (20-30%) of heads in the oriented actin-bound conformation that is observed in rigor. This rigor-like component is a calcium-dependent, actin-bound state that may represent force-generating cross-bridges. As the spin label is located near the nucleotide-binding pocket in a region proposed to be pivotal for large-scale force-generating structural changes in myosin, we propose that the observed spectroscopic changes indicate directly the key steps in energy transduction in the molecular motor of contracting muscle.

Ethical considerations in the management of individuals with severe neuromuscular disorders.

There have been many recent advances in improving the quality of life and prolonging life for individuals with advanced neuromuscular disease. These include the use of physical medicine techniques to balance extremity muscle strength and improve range of motion and noninvasive techniques to provide inspiratory and expiratory muscle assistance to prolong life without resort to tracheostomy. Such advances help eliminate the "crisis" decision making about "going on a respirator" and sophisticated assistive equipment and robotic aids. Physicians and society in general use quality of life issues inappropriately derived by questioning physically able individuals to justify withholding or implementing life-sustaining therapeutic interventions for these individuals. Informed decisions about ethically and financially complex matters such as long-term ventilator use should be made by examining the life satisfaction of competent individuals who have already chosen these options. The great majority of severely disabled ventilator-assisted individuals with neuromuscular disease are satisfied with their lives despite the inability to achieve many of the "usual" goals associated with quality of life in the physically able population. Their principle life satisfaction derives from social relationships, the reorganization of goals and from their immediate environment. Although the Americans with Disabilities Act is seen as an important step to prevent discrimination against disabled individuals, it does little or nothing for the self-directed disabled individual who is not informed by his/her physicians regarding potentially vital therapeutic options nor does it help those who are warehoused in institutions because of lack of a national personal assistance services policy.(ABSTRACT TRUNCATED AT 250 WORDS)