Reversible myocardial dysfunction: an ubiquitous phenomenon in the critically ill?
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Biomedical subjects
Publications and source records attributed to Anand Kumar.
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The nature of myocardial dysfunction during sepsis and septic shock has been investigated for more than half a century. This review traces the evolution of scientific thought regarding this phenomenon during this period with particular emphasis on the current understanding of both the clinical manifestations and the molecular/cellular basis of septic myocardial dysfunction in critically ill patients. Current data suggest, contrary to older literature, that patients with septic shock develop a hyperdynamic circulatory state after fluid resuscitation and maintain this hyperdynamic circulatory state until death or recovery. Overt myocardial depression, as manifested by decreased cardiac output, is decidedly uncommon, even in the preterminal phase. Nonetheless, myocardial depression, as evidenced by biventricular dilation and depression of the ejection fraction, can be demonstrated in most patients with septic shock by using either radionuclide cineangiography or echocardiography. Depression is reversible over the course of 7 to 10 days in survivors. Available evidence suggests that myocardial hypoperfusion is not responsible for septic myocardial depression, because examination of humans with septic shock demonstrates increased myocardial perfusion, and animal models of septic shock appear to maintain myocardial high-energy phosphates. A circulating factor or factors, including the cytokines tumor necrosis factor alpha and interleukin-1beta, appear to have a significant role in the phenomenon. In addition, septic myocardial depression appears to be mediated in part through combinations of nitric oxide-dependent and -independent alterations of basal and catecholamine-stimulated cardiac myocyte contractility.
Psychiatric disorders are characterized by diverse clinical manifestations that include deficits in cognition, perception, mood and arousal. These complex processes are not mediated by any specific brain region but require the coordinated activity of several areas that are anatomically connected. Impairments in these neural circuits may therefore be expected to result in an attenuation of the functions regulated by them. The white matter provides the structural and physiological substrate of neural circuits in the central nervous system. We propose that injury to the white matter, from diverse biological sources, may compromise neural connectivity by associated axonal injury or impaired conductivity. Either mechanism could result in clusters of signs and symptoms that are currently recognized as psychiatric disorders. The role of white matter impairment in the pathophysiology of psychiatric illness is under-appreciated in the neurosciences. Focused translational research aimed at identifying the links between white matter compromise and specific behaviors are necessary for a more thorough understanding of the etiology of mental illness to emerge.
OBJECTIVE: Neuroanatomical abnormalities have been identified in patients with late-life mood disorders by using magnetic resonance imaging. This study examined the biochemical correlates of late-life major depression in the frontal gray and white matter by using single-voxel proton spectroscopy. METHOD: Twenty elderly patients with major depression and 18 comparison subjects similar in age and gender to the patients were scanned on a 1.5-T magnetic resonance scanner with head coil. Voxels were placed in the left dorsolateral white matter and bilaterally in the anterior cingulate gray matter. Absolute levels of N-acetylaspartate, choline, myo-inositol, and creatine were estimated with the LC-Model algorithm. Ratios of metabolite to creatine levels were computed from the absolute values. RESULTS: myo-Inositol/creatine and choline/creatine ratios were significantly higher in the frontal white matter in the major depression group than in the comparison group. The groups had no significant differences in the metabolite ratios in the gray matter. CONCLUSIONS: Biochemical changes in the white matter may provide some of the neurobiological substrates to late-life major depression.
Severe sepsis and septic shock is a common problem encountered in the critical care unit with an estimated incidence in the US of 750,000 cases/year and a mortality rate of 30-50%. Sepsis involves a complex interaction between bacterial factors and the host immune system producing a systemic inflammatory state that may progress to multiple organ failure and death. Endotoxin (a lipopolysaccharide) released from Gram-negative bacteria has been implicated as a potent, prototypical stimulus of the immune response to bacterial infection. Current antiendotoxin strategies utilise various approaches ranging from the prevention of binding to endotoxin receptors with antibodies (monoclonal or polyclonal) against endotoxin or endotoxin receptor/carrier molecules (antiCD14 or antilipopolysaccharide-binding protein antibodies), enhancing clearance or neutralisation (haemoperfusion, lipoproteins, lipopolysaccharide-neutralising proteins) or impairing cellular signalling (lipid A analogues, tyrosine kinase inhibitors). In the future, innovative therapies involving Toll-like receptors and their downstream signalling elements will be developed. This review discusses current knowledge regarding endotoxin signalling, antiendotoxin therapies currently under development, and future areas for research.
Sepsis and septic shock are a major cause of morbidity and mortality in patients admitted to the intensive care unit. Since the introduction of antibiotic therapy, the mortality associated with sepsis has remained within the 30- 50% range. Sepsis constitutes the systemic response to infection. This response encompasses both pro-inflammatory and anti-inflammatory phases that are marked by the sequential generation of pro- and anti-inflammatory cytokines. Among the most important pro-inflammatory cytokines are TNF-alpha and IL-1beta. The pro-inflammatory effects of such cytokines are inhibited by soluble receptors/receptor antagonists and anti-inflammatory cytokines including IL-10 and transforming growth factor-beta. Modulation of the activity of both pro- and anti-inflammatory cytokines to improve outcome in patients with sepsis has been subject of multiple clinical studies. This review will examine clinical trials evaluating several strategies for blocking or attenuating TNF-alpha and IL-1beta activity. This review will also survey the current state of experimental therapies involving IL-10, transforming growth factor-beta, granulocyte colony-stimulating factor and IFN-phi. Finally, newer developments related to less known cytokines such as macrophage migration inhibitory factor and high mobility group 1 protein will be evaluated.
The aim of this work is to promote the use of standard terminology for nursing documentation and for nurse protocols' description. We implemented an ICNP browser and we integrated it into two different systems: the nursing electronic patient record and the nursing protocols editor. The former allows nurses to choose ICNP terms for filling the clinical chart, while the latter allows computerising protocols using ICNP terms for the actions specification. Since, in a nursing information system, it should be worth to integrate protocols with the electronic patient record, sharing the same terminology is a crucial issue. We also show how we tailored the information system to the different wards. For each ward, we devised the most frequent patient needs and nursing actions. These lists are used to customise the different interfaces. Finally, by testing the prototype using real-world documents (clinical charts and protocols), we carried out an evaluation of the terminology itself, about its completeness and usability.
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OBJECTIVE: In an exploratory study, authors compared patients with late-life major depression (MDD) and age-matched control subjects to examine sex differences in frontal and orbito-frontal (OFC) regional brain volumes. METHODS: The study sample comprised 41 patients with MDD and 41 controls. Subjects underwent comprehensive neuropsychiatric examinations and magnetic resonance imaging (MRI) scans. Corrected frontal and OFC gray-matter volumes were compared among men and women in both groups. RESULTS: The depression group had lower MMSE scores, greater severity of medical burden, apathy, psychomotor retardation, and poor health-related quality of life than the controls. Men in both groups had a greater severity of medical burden, apathy, and psychomotor retardation than women. The depression group had smaller OFC total and gray-matter volumes than the controls after matching for age. Men had smaller frontal-matter volumes than women in both groups. The diagnosis x sex interaction in brain regional volumes was observed only after controlling for medical burden. CONCLUSIONS: Sex differences in brain neuroanatomy may be important in the pathophysiology of geriatric depression. Men may be susceptible to atrophy in frontal subregions. Medical burden may contribute to the diagnosis x sex interaction in brain regional volumes.
OBJECTIVES: Many groups are developing computer-interpretable clinical guidelines (CIGs) for use during clinical encounters. CIGs use "Task-Network Models" for representation but differ in their approaches to addressing particular modeling challenges. We have studied similarities and differences between CIGs in order to identify issues that must be resolved before a consensus on a set of common components can be developed. DESIGN: We compared six models: Asbru, EON, GLIF, GUIDE, PRODIGY, and PROforma. Collaborators from groups that created these models represented, in their own formalisms, portions of two guidelines: American College of Chest Physicians cough guidelines [correction] and the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. MEASUREMENTS: We compared the models according to eight components that capture the structure of CIGs. The components enable modelers to encode guidelines as plans that organize decision and action tasks in networks. They also enable the encoded guidelines to be linked with patient data-a key requirement for enabling patient-specific decision support. RESULTS: We found consensus on many components, including plan organization, expression language, conceptual medical record model, medical concept model, and data abstractions. Differences were most apparent in underlying decision models, goal representation, use of scenarios, and structured medical actions. CONCLUSION: We identified guideline components that the CIG community could adopt as standards. Some of the participants are pursuing standardization of these components under the auspices of HL7.
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Clinically significant non-major depression has been underinvestigated despite its high prevalence and public health impact. Although there is an increasing recognition of the importance of non-major forms of depression, their nosological boundaries and neurobiological mechanisms remain largely unknown. The authors discuss the literature pertaining to the current concepts, phenomenology, neurobiology, and treatment approaches to geriatric non-major clinically significant depression. They examine the similarities and differences between various subtypes of depressive disorders and compare non-major, clinically significant depression in elderly patients with non-geriatric adult populations. They draw conclusions from the published literature and propose clinical criteria for the diagnosis of clinically significant non-major depression in elderly persons.
Strokes following cardiac surgery occur in about 5% of patients. Intra-arterial thrombolysis is a good option in such a setting where intravenous thrombolysis is contraindicated, and when in-hospital strokes are detected well within the window for treatment and the chances of complete reperfusion are maximum. On postoperative day 4 after atrial septal defect correction, a 34-year-old woman with paroxysmal atrial fibrillation developed left middle cerebral artery stroke causing severe neurological deficits. Intra-arterial thrombolysis with urokinase led to remarkable recovery.
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The incidence of and mortality from prostatic cancer in the West is higher than that in Asian countries. Migrants from Asia to western countries, who maintain their traditional diet, do not have an increased risk of prostatic cancer. This has been attributed in part to 'phyto-oestrogens' in vegetarian Asian diets. Prostatic cancer is a hormone-dependent disease and oestrogens retard the growth of prostatic tumours by interfering with the action of testosterone. Oestrogen increases the level of sex hormone-binding globulin that binds testosterone, resulting in lower free testosterone levels, thereby decreasing androgenic stimulation of the prostate. Oestrogens used to retard the growth of prostatic cancer are associated with certain undesirable side-effects. Phyto-oestrogens have weak oestrogenic potency and anticancer effects. Thus, these phytochemicals have a possible role in the prevention of hormone-dependent diseases such as prostatic cancer. Although the relative potencies of various phyto-oestrogens compared with oestradiol are low, the oestrogen receptor (ER) complexes formed byoestradiol and isoflavones have functional similarities. Also, phyto-oestrogens have a higher affinity to bind to ER-beta than ER-alpha. They are antiproliferative and inhibit tyrosine and other protein kinases which play a key role in tumorigenesis, and also inhibit the production of the potent androgen 5alpha dihydrotestosterone in the prostate. Since prostatic cancer cells usually multiply slowly and the development of this cancer can take many years before symptoms appear, the latent period provides a chemopreventive opportunity for natural therapy with phyto-oestrogens. Although phyto-oestrogens have not yet been used in long-term trials to evaluate their ability to reduce the risk of prostate carcinoma, the evidence thus far suggests that they have a protective effect against the growth of prostate tumours.
A 27-year-old woman developed recurrent hydatid of liver. CT scan showed unilocular cysts in segments IV and VII. Intraoperatively, there was a fistulous communication between the gall bladder and the cyst in segment IV. Partial pericystectomy along with cholecystectomy was done for the segment IV cyst; percutaneous aspiration, instillation and re-aspiration using hypertonic saline was done for the cyst in segment VII. This was followed by albendazole treatment.
BACKGROUND: [corrected] Mifepristone is a synthetic antiprogestin which terminates early pregnancy. Since it interferes with the progesterone maintained decidua, we compared the effect of mifepristone on oestrogen and progesterone receptors, and on the biotransformation of these hormones in normal and deciduous uterus. METHODS: Ovariectomized rats were treated with an oestrogen-progesterone hormone regimen and deciduoma was induced by trauma in one horn of the rat uterus while the other served as a control under an identical hormonal milieu. Hormone receptor and biotransformation studies were done using radiolabelled oestradiol and progesterone with high specific activity. RESULTS: The artificially formed decidual tissue was comparable with that of early pregnancy. Mifepristone replenished oestrogen and progesterone receptors which were suppressed by progesterone in both the normal and decidualized uterine horns. Inhibition of oestrogen receptors by progesterone correlated with decreased oestradiol levels at the site of action. Metabolism of progesterone to less potent compounds was promoted by mifepristone. The enzymatic activities of 17beta-hydroxysteroid dehydrogenase (which metabolizes oestradiol), and 20alpha-hydroxysteroid dehydrogenase and 5alpha-reductase (which metabolize progesterone) were altered by mifepristone. CONCLUSION: The effect of mifepristone in varying the hormone receptor population and the availability of different levels of active metabolites of ovarian hormones have an Important role in the antiprogestin action of mifepristone.