Studies on the Acute Hepatic Porphyrias

This thesis consists of three sections. The first section is a general description of porphyrins and biochemical control of haem biosynthesis followed by an up-to-date review of the acute hepatic porphyrias and their clinical management, with particular emphasis on acute intermittent porphyria (AIP). The second section addresses itself to the pathogenesis of the neuropathy of AIP. Following a critical review of the histopathological and biochemical work on the subject the results of a study on the cardiovascular autonomic function in AIP are discussed. Objective evidence for parasympathetic and sympathetic dysfunction during an acute attack is provided. Moreover, there is suggestion of parasympathetic involvement both in patients who have fully recovered from the acute episodes and asymptomatic latent cases. These findings support the electrophysiological results of Mustajoki and Seppalainen (1975). Using two different histochemical techniques, cytochrome oxidase activity was found to be markedly depressed in muscle biopsies taken from AIP patients during an acute attack. Since cytochrome oxidase plays a vital role in the terminal oxidative phosphorylation pathway, the possibility of a myopathic component in the muscle weakness, hitherto attributed to the neuropathy, is considered. But more significantly, depression of cytochrome oxidase activity in muscle tissue suggests that this might be the case in nerve cells. Further support for this concept comes from other workers who have shown that the activity of the cytochrome-P450-dependent mixed-function oxidase system is also depressed in porphyric patients. The cytochrome oxidase study is followed by a clinico-pathological discussion on the autopsy findings of a 31-year old AIP patient who died of the disease. Detailed documentation of the patient's clinical course and the purposeful neuropathological autopsy carried out provided us with a rare opportunity to investigate further the relative roles of demyelination and axonal degeneration in the pathogenesis of the disease. It was indeed surprising when independent review of the autopsy material by two experienced neuropathologists failed to reveal any of the characteristic morphological changes previously described. The newly discovered association between early-onset chronic renal disease and AIP is discussed along three main possibilities: analgesic-induced nephropathy, hypertension-related renal disease and cytotoxic effects of porphyrin precursors on the kidneys. Analgesic-induced nephropathy could be satisfactorily excluded. On balance evidence is in favour of hypertension-related renal disease although a local toxic effect by porphyrin precursors cannot be entirely excluded. A strong case can be made for the porphyria-associated hypertension to the neurogenic in type. Many AIP patients with severe abdominal pain fail to respond to large dosages of opiate analgesics. A study was performed to determine whether the porphyric pain was truly resistant to opiates. It was found that if the patient failed to respond to the usual therapeutic dosage of one of three opiates: pethidine, morphine and buprenorphine, increasing the amount of drug administered did not improve the response rate. In 1981, I observed that the pupils of a porphyric patient in a severe attack failed to undergo miosis after parenteral administration of large doses of morphine; yet they retained a normal response to accommodation and light stimulation. The significance of this finding, only recently appreciated, indicate the possibility of either dysfunction or depletion of the mu-opioid receptors in the optic nervous system. (Abstract shortened by ProQuest.)

Effects of Qigong on Depression: A Systemic Review

Physical exercises and relaxation have been found to be beneficial for depression. However, there is little evidence on the use of Qigong, a mind-body practice integrating gentle exercise and relaxation, in the management of depression. The aim of this paper is to evaluate the effects of Qigong on depression. The paper examined clinical trials measuring the effect of Qigong on depression within six large-scale medical research databases (PubMed, Medline, ProQuest, Science Direct, EMBASE, and PsycInfo) till October 2011. Key words “Qigong,” “depression,” and “mood” were used. Ten studies were identified as original randomized controlled trial (RCT) studies investigating the effect of Qigong on depression as primary (n = 2) or secondary outcome (n = 8). Four studies reported positive results of the Qigong treatment on depression; two reported that Qigong effect on depression was as effective as physical exercise. One study reported that Qigong was comparable to a conventional rehabilitation program, but the remaining three studies found no benefits of Qigong on depression. While the evidence suggests the potential effects of Qigong in the treatment of depression, the review of the literature shows inconclusive results. Further research using rigorous study designs is necessary to investigate the effectiveness of Qigong in depression

Towards Vision-Based Smart Hospitals: A System for Tracking and Monitoring Hand Hygiene Compliance

One in twenty-five patients admitted to a hospital will suffer from a hospital acquired infection. If we can intelligently track healthcare staff, patients, and visitors, we can better understand the sources of such infections. We envision a smart hospital capable of increasing operational efficiency and improving patient care with less spending. In this paper, we propose a non-intrusive vision-based system for tracking people's activity in hospitals. We evaluate our method for the problem of measuring hand hygiene compliance. Empirically, our method outperforms existing solutions such as proximity-based techniques and covert in-person observational studies. We present intuitive, qualitative results that analyze human movement patterns and conduct spatial analytics which convey our method's interpretability. This work is a step towards a computer-vision based smart hospital and demonstrates promising results for reducing hospital acquired infections.Comment: Machine Learning for Healthcare Conference (MLHC

A study of the effectiveness of telepsychiatry-based culturally sensitive collaborative treatment of depressed Chinese Americans

<p>Abstract</p> <p>Background</p> <p>Chinese American patients with Major Depressive Disorder (MDD) tend to underutilize mental health services and are more likely to seek help in primary care settings than from mental health specialists. Our team has reported that Culturally Sensitive Collaborative Treatment (CSCT) is effective in improving recognition and treatment engagement of depressed Chinese Americans in primary care. The current study builds on this prior research by incorporating telemedicine technology into the CSCT model.</p> <p>Methods/Design</p> <p>We propose a randomized controlled trial to evaluate the acceptability and effectiveness of a telepsychiatry-based culturally sensitive collaborative treatment (T-CSCT) intervention targeted toward Chinese Americans. Patients meeting the study's eligibility criteria will receive either treatment as usual or the intervention under investigation. The six-month intervention involves: 1) an initial psychiatric interview using a culturally sensitive protocol via videoconference; 2) eight scheduled phone visits with a care manager assigned to the patient, who will monitor the patient's progress, as well as medication side effects and dosage if applicable; and 3) collaboration between the patient's PCP, psychiatrist, and care manager. Outcome measures include depressive symptom severity as well as patient and PCP satisfaction with the telepsychiatry-based care management service.</p> <p>Discussion</p> <p>The study investigates the T-CSCT model, which we believe will increase the feasibility and practicality of the CSCT model by adopting telemedicine technology. We anticipate that this model will expand access to culturally competent psychiatrists fluent in patients' native languages to improve treatment of depressed minority patients in primary care settings.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00854542">NCT00854542</a></p

Large-scale inference and graph theoretical analysis of gene-regulatory networks in B. stubtilis

We present the methods and results of a two-stage modeling process that generates candidate gene-regulatory networks of the bacterium B. subtilis from experimentally obtained, yet mathematically underdetermined microchip array data. By employing a computational, linear correlative procedure to generate these networks, and by analyzing the networks from a graph theoretical perspective, we are able to verify the biological viability of our inferred networks, and we demonstrate that our networks' graph theoretical properties are remarkably similar to those of other biological systems. In addition, by comparing our inferred networks to those of a previous, noisier implementation of the linear inference process [17], we are able to identify trends in graph theoretical behavior that occur both in our networks as well as in their perturbed counterparts. These commonalities in behavior at multiple levels of complexity allow us to ascertain the level of complexity to which our process is robust to noise.Comment: 22 pages, 4 figures, accepted for publication in Physica A (2006

Dr1 (NC2) is present at tRNA genes and represses their transcription in human cells

Dr1 (also known as NC2{beta}) was identified as a repressor of RNA polymerase (pol) II transcription. It was subsequently shown to inhibit pol III transcription when expressed at high levels in vitro or in yeast cells. However, endogenous Dr1 was not detected at pol III-transcribed genes in growing yeast. In contrast, we demonstrate that endogenous Dr1 is present at pol III templates in human cells, as is its dimerization partner DRAP1 (also called NC2{alpha}). Expression of tRNA by pol III is selectively enhanced by RNAi-mediated depletion of endogenous human Dr1, but we found no evidence that DRAP1 influences pol III output in vivo. A stable association was detected between endogenous Dr1 and the pol III-specific transcription factor Brf1. This interaction may recruit Dr1 to pol III templates in vivo, as crosslinking to these sites increases following Brf1 induction. On the basis of these data, we conclude that the physiological functions of human Dr1 include regulation of pol III transcription