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Biomedical subjects

M Barry

Publications and source records attributed to M Barry.

At least 91 records · Page 5Linked to original sources

The American Society of Tropical Medicine and Hygiene initiative to stimulate educational programs to enhance medical expertise in tropical diseases.

More than a decade ago, at a time when current and emerging tropical diseases posed growing threats to the United States, expert panels convened by the Institute of Medicine of the U.S. National Academy of Sciences concluded that medical expertise within the United States competent to address diseases of the tropics had declined. Recognizing a national need to encourage and enhance such, The American Society of Tropical Medicine and Hygiene developed a program to stimulate new postgraduate medical education in diseases of the tropics. The Society formally requested academic institutions within the United States and Canada to propose new postgraduate programs. To assure the quality of these new curricular offerings, the Society developed an outline of key areas of competency and agreed to offer an examination that would grant physicians a Certificate of Knowledge in Clinical Tropical Medicine and Travelers Health. The certifying examination was to be an integral component of a program to stimulate academic institutions to provide instructional programs in tropical diseases and to encourage physicians to become trained, evaluated, and recognized for their knowledge of clinical tropical diseases and travelers' health. The Society's initiative to stimulate educational programs in tropical medicine is reviewed.

Canada↗

[Cholera in Guinea: the 1994-1995 epidemic].

Since the first outbreak in 1970, cholera epidemics have occurred regularly in Guinea. Until 1994, epidemics recurred every 8 years and were confined to the capital and coastal areas. The first cases in every epidemic were observed in coastal lagoons near the Sierra Leone border. In 1994, the disease demonstrated its migratory ability as the first cases were reported in towns located in far eastern inland areas. Spread of the disease from war-torn Sierra Leone and Liberia where epidemics have also been reported cannot be ruled out. Control measures have gradually been implemented to deal with these outbreaks and a treatment facility was built at the University of Conakry in 1994. Bacteriological studies including antibiotic susceptibility tests carried out at this center showed that the offending bacteria was Vibrio cholerae El Tor of the Ogawa group. Although this strain is relatively sensitive to all antibiotics, analysis of epidemiological data revealed high mortality rates at the beginning of every outbreak probably due to delays in organizing appropriate care. A major effort is now being made to improve the response time particularly in remote inland areas.

Cholera↗

Cytotoxic T lymphocyte-assisted suicide. Caspase 3 activation is primarily the result of the direct action of granzyme B.

Cytototoxic T lymphocyte-induced apoptosis can occur either through the directed exocytosis of granzyme B and perforin or via ligation of Fas. Both pathways involve the activation of a family of cysteine proteinases, the caspases, that cleave substrates at aspartic acid and are themselves activated by cleavage at internal aspartate residues. Fas recruits caspase 8, which initiates the death program through the subsequent activation of caspase 3. Granzyme B can process both caspase 8 and 3 in vitro, suggesting that both Fas and granzyme B access the apoptotic program in the same way. Here we demonstrate that although the two mechanisms are similar, the events that lead to activation of caspase 3 can be distinguished in vivo on the basis of their sensitivities to both pharmacological and virus-encoded caspase inhibitors. In cytotoxic T lymphocytes-mediated death the initial cleavage event on caspase 3 is insensitive to benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (zVAD-fmk) inhibition in both mouse and human systems. During Fas-mediated death, however, activation of caspase 3 is completely inhibited to zVAD-fmk. In addition, the viral serpin SPI-2, a homologue of cytokine response modifier A (crmA), is an effective inhibitor of the Fas but not the granzyme pathway. Our results demonstrate that whereas Fas-mediated activation of caspase 3 requires an upstream caspase activity that is zVAD-fmk-sensitive, the initial cleavage of caspase 3 during granule-mediated cell death is insensitive to zVAD-fmk, suggesting that caspase 3 is cleaved directly by granzyme B in vivo.

Amino Acid Chloromethyl Ketones↗

Effects of human recombinant growth hormone (rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.

BACKGROUND: Human recombinant growth hormone (rhGH) has been shown to increase skeletal muscle protein synthesis and improve nitrogen balance in critically ill patients and those undergoing surgery. rhGH effects on hepatic protein turnover in critically ill patients are less clearly understood. OBJECTIVE: To examine rhGH effects on hepatic acute phase protein responses and inflammatory cytokine release in patients undergoing major surgery. DESIGN: Prospective double blind randomised trial. SETTING: Tertiary referral university teaching hospital. PATIENTS: Patients undergoing elective abdominal aortic aneurysm repair. INTERVENTION: Patients received rhGH (Genotropin, 0.3 IU/kg per day, n = 8) or placebo (n = 10) for 6 days prior to surgery. RESULTS: Blood levels of growth hormone (GH) and insulin-like growth factor (IGF-1) were measured following rhGH treatment and C-reactive protein (CRP), serum amyloid A (SAA) and the cytokines interleukin-6 (IL-6) and the IL-1 receptor antagonist (IL-1ra) were measured for up to 24 h following surgery. Significant increases in plasma rhGH (0.84 +/- 0.3, mean (sem) versus 52 +/- 20 mU/l, p < 0.0008) and IGF-1 levels (119 +/- 13 versus 644 +/- 110 ng/ml, p < 0.0001) were seen prior to surgery following rhGH administration. No differences in acute phase protein or cytokine levels were seen following surgery in patients receiving rhGH. CONCLUSIONS: These results indicate that pre-operative administration of rhGH does not alter acute phase protein or inflammatory cytokine release in response to major surgery.

Aged↗

Impact of a critical pathway on postoperative length of stay and outcomes after infrainguinal bypass.

PURPOSE: To determine the effect of a critical pathway on postoperative length of stay and outcomes after infrainguinal bypass. METHODS: A critical pathway for care of patients after infrainguinal bypass was introduced in December 1995 to coordinate postoperative care at our institution. We compared care of 67 consecutively treated patients before institution of the pathway with care of 69 consecutively treated patients with the critical pathway in place. Data collection was done by means of chart review. Univariate analyses were used to identify differences between prepathway and postpathway patients and to identify factors influencing postoperative length of stay. Multivariate analysis was used to identify factors that influenced length of stay and to examine the effect of use of the pathway after adjusting for other factors. RESULTS: Patients on the pathway were similar to prepathway controls with respect to comorbid illnesses, vascular risk factors, indications for surgical treatment, type of conduit, and type of operation. Factors associated with longer postoperative stays included distal anastomoses to tibial rather than popliteal vessels (p = 0.02), preexisting cardiac disease (p = 0.005), postoperative complications (p = 0.0003), lower preoperative hematocrit (p = 0.01), and elevated preoperative creatinine level (p = 0.006). Overall, pathway patients had somewhat shorter postoperative lengths of stay (median value 7 days; range 2 to 29 days) than prepathway patients (median value 6 days; range 2 to 35; p = 0.01), and the two groups had similar frequencies of postoperative complications, readmission, and 6-month mortality. However, patients on the pathway were more likely to be discharged to an intermediate-care facility rather than directly home. After 12 patients with extraordinarily prolonged postoperative stays were excluded, multivariate analysis indicated that pathway patients had significantly shorter postoperative stays (p = 0.001). However, the difference was not significant if patients with extraordinarily long postoperative stays were included in the analysis (p = 0.28). CONCLUSION: Use of a critical pathway was associated with a modest decrease in postoperative length of stay for most patients. This was accomplished without an adverse effect on readmission, complication, or mortality rates. However, the decrease in stay may have been achieved primarily by discharging more patients to intermediate-care facilities. The pathway did not appear to have any effect when the subset of patients with extraordinarily long stays because of complex medical problems was included.

Aged↗

The pregnant traveler.

The care of the pregnant traveler is both challenging and rewarding. It requires clinical information and skills that are derived from many disciplines. This article reviews preparatory guidelines for safe travel by the pregnant mother and her most important travel companion, the developing fetus. Issues considered are pretravel risk assessment, immunizations, and prevention of travelers' diarrhea and hepatitis. The safety and efficacy of malaria chemoprophylaxis in the present context of widespread multidrug-resistant malaria is discussed, and guidelines are offered for both prevention and treatment. A safety profile of commonly used travel medications, antibiotics, and antiparasitic drugs is reviewed.

Aircraft↗

Apoptosis regulators from DNA viruses.

The past year has seen an considerable expansion in knowledge about the field of apoptosis modulators expressed by DNA viruses. These diverse classes of virus-encoded regulators include caspase inhibitors, signal transduction effectors, Bcl-2 homologs, cell cycle control proteins, transcriptional regulators, reactive oxide scavengers, kinases, 'death factors' and novel host-range proteins.

Animals↗

The myxoma virus M-T4 gene encodes a novel RDEL-containing protein that is retained within the endoplasmic reticulum and is important for the productive infection of lymphocytes.

To investigate the contribution of the myxoma virus M-T4 gene to viral virulence, both copies of the M-T4 gene were inactivated by disruption and insertion of the Escherichia coli guanosine phosphoribosyltransferase gene. Infection of European rabbits with the recombinant M-T4-deleted virus, vMyxlacT4, resulted in disease attenuation. In contrast, infection of rabbits with vMyxlac elicited the classical features of lethal myxomatosis. A notable decrease in the number of secondary lesions in animals infected with vMyxlacT4 suggested an inability of the virus to disseminate in vivo. Infection of either a rabbit CD4+ T cell line, RL-5, or primary rabbit peripheral blood lymphocytes with vMyxlacT4- resulted in the rapid induction of apoptosis. Sequence analysis of M-T4 revealed both an N-terminal signal sequence and a C-terminal -RDEL sequence, suggesting that M-T4 resides in the endoplasmic reticulum. The M-T4 protein was found to be sensitive to endo H digestion and confocal fluorescence microscopy demonstrated that M-T4 colocalized with calreticulin, indicating that M-T4 is retained within the endoplasmic reticulum. Our results indicate that M-T4 is the first example of an intracellular virulence factor in myxoma virus that functions from within the endoplasmic reticulum and is necessary for the productive infection of lymphocytes.

Amino Acid Sequence↗

The T1/35kDa family of poxvirus-secreted proteins bind chemokines and modulate leukocyte influx into virus-infected tissues.

Immunomodulatory proteins encoded by the larger DNA viruses interact with a wide spectrum of immune effector molecules that regulate the antiviral response in the infected host. Here we show that certain poxviruses, including myxoma virus. Shope fibroma virus, rabbitpox virus, vaccinia virus (strain Lister), cowpox virus, and raccoonpox virus, express a new family of secreted proteins which interact with members of both the CC and CXC superfamilies of chemokines. However, swinepox virus and vaccinia virus (strain WR) do not express this activity Using a recombinant poxviruses, the myxoma M-T1 and rabbitpox virus 35kDa secreted proteins were identified as prototypic members of this family of chemokine binding proteins. Members of this T1/35kDa family of poxvirus-secreted proteins share multiple stretches of identical sequence motifs, including eight conserved cysteine residues, but are otherwise unrelated to any cellular genes in the database. The affinity of the CC chemokine RANTES interaction with M-T1 was assessed by Scatchard analysis and yielded a Kd of approximately 73 nM. In rabbits infected with a mutant rabbitpox virus, in which the 35kDa gene is deleted, there was an increased number of extravasating leukocytes in the deep dermis during the early phases of infection. These observations suggest that members of the T1/35kDa class of secreted viral proteins bind multiple members of the chemokine superfamily in vitro and modulate the influx of inflammatory cells into virus-infected tissues in vivo.

Amino Acid Sequence↗

Facet joint hypertrophy: the cross-sectional area of the superior articular process of L4 and L5.

With CT imaging, the lumbar facet joints are well visualised and enlargement secondary to degeneration may be noted. We measured the cross-sectional area of the superior articular process of the L5 facet joint in 100 consecutive CT scans and in 71 patients, the L4 process was also measured. We found that the mean cross-sectional area was significantly larger at L5 than at L4. Patient age and sex had no significant effect on the size at either L4 or L5. A review of the radiological reports revealed that the 13 patients with degenerative facet joints and radiologically normal discs did not have significantly larger facet joints than the 35 patients with disc disease and radiologically normal facet joints. In conclusion, the term "facet joint hypertrophy" should not be used when osteoarthritic changes are noted on CT scan, because these joints are not significantly larger than normal facet joints.

Adolescent↗

How is quality of life in prostate cancer patients influenced by modern treatment? The Wallenberg Symposium.

OBJECTIVES: To identify complications of various forms of treatments for prostate cancer and their influence on patients' quality of life with the ultimate goal of suggesting a Quality of Life Questionnaire specific for prostate cancer for further validation. METHODS: The literature was screened for reports on the more common complications following various forms of therapy for prostate cancer. Frequencies were summarized. The scarce literature reporting on quality of life in prostate cancer was reviewed and conflicting data were discussed and reassessed. Suggested questionnaires used in other studies were critically scrutinized and the various questions recorded. RESULTS: Following radical surgery, impotence and incontinence were the most common complications reducing patients' quality of life. The literature was not uniform with regard to whether loss of sexual function was regarded as a worse complication than loss of urinary control. Following radiotherapy, intestinal problems and sexual dysfunction were the dominating side effects. Quality of life was best preserved in surveillance-only series. Following endocrine therapy, not only impotence and hot flushes were focused upon, but also mental dysfunction and intestinal dysfunction from nonsteroidal antiandrogens, additionally, the importance of effective palliation was highlighted. A Quality of Life Questionnaire should contain general domains relevant to cancer patients, cancer-specific questions, and prostate-cancer-specific questions. The latter group includes: worry for prostate cancer and its prognosis, bone/pelvic pain, lower urinary tract symptoms, urinary incontinence, urinary diversion, bowel function, sexual function, endocrine effects, and satisfaction with medical care for prostate cancer. CONCLUSIONS: A modern trial of prostate cancer treatment should be regarded as insufficient without including a validated Quality of Life Questionnaire.

Costs and Cost Analysis↗

Virus encoded cytokines and cytokine receptors.

In order to replicate efficiently within the host, viruses have evolved multiple strategies to evade the host's immune system. In many cases viruses have actually hijacked various components of the host's immune system to ensure their own survival. One such strategy is the expression of virus encoded cytokines and cytokine receptors. Members of the poxvirus and herpesvirus families have been particularly successful with this strategy. The study of virus survival strategies provides important information regarding both virus biology as well as information about the immune system itself.

Animals↗

Public health expenditures: developing estimates for improved policy making.

The Public Health Foundation (PHF), under contract to the U.S. Department of Health and Human Services, Public Health Service (PHS), worked with federal, state, and local public health, mental health, substance abuse, and environmental agencies in nine states to develop and successfully test a methodology for estimating investments in essential public health services. Estimates from the nine-state sample revealed the predominance of personal health expenditures in the public health system. Of total state health care dollars, only 1 percent was spent on population-based health services by participating agencies. This pilot provides a rational starting point toward a uniform methodology for highlighting public health expenditures that may be critical in revealing the effects of a changing health care environment on the nation's health. In combination with other data, results are expected to lead to a more informed policy-making process.

Financing, Government↗

Management of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common cause of morbidity among older men. Primary care physicians need to develop expertise in its management. The causes of BPH are unknown; aging and the presence of male androgens are the dominant risk factors. Obtaining a medical history is a key step in assessing whether lower urinary tract symptoms are due to BPH or to some other process. A reliable and valid seven-item questionnaire has been developed to objectively assess symptom severity. A focused physical examination including a digital rectal exam should be performed, as well as a urinalysis and serum creatinine. Optional tests include uroflowmetry, post-void residual urine, and prostate-specific antigen measurements. BPH is treated primarily to improve the quality, rather than increase the quantity, of life. Optimal decisions about treatment are best made by a clinician and an informed patient working together.

Humans↗