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Biomedical subjects

M Connolly

Publications and source records attributed to M Connolly.

At least 55 records · Page 3Linked to original sources
PubMed1998

Cardiac operations in patients with cirrhosis.

BACKGROUND: A retrospective review was performed to determine the outcome after cardiac operations in patients with a documented history of noncardiac cirrhosis. METHODS: The charts of patients admitted to the cardiothoracic surgical service between 1990 and 1996 were reviewed, and 13 patients with a preoperative history of cirrhosis were identified. The severity of preoperative liver disease was graded according to the criteria of Child. RESULTS: Most of the cases of cirrhosis were alcohol-related. Eight patients were classified as having Child class A and 5 as having Child class B cirrhosis. One hundred percent of patients with Child class B and 25% of those with Child class A cirrhosis had major complications. The postoperative chest tube output and transfusion requirements of these patients were approximately three times higher than average. The overall perioperative mortality rate was 31%. In patients with Child class B cirrhosis, the mortality rate was 80%. No patient with Child class A cirrhosis died. Deaths were related to gastrointestinal and septic complications, and not to cardiovascular failure. CONCLUSIONS: These findings suggest that patients with minimal clinical evidence of cirrhosis can tolerate cardiopulmonary bypass and cardiac surgical procedures, whereas those with more advanced liver disease should not be offered operation.

Aged↗
PubMed1998

Synthesis of isomeric 3-piperidinyl and 3-pyrrolidinyl benzo[5,6]cyclohepta[1,2-b]pyridines: sulfonamido derivatives as inhibitors of Ras prenylation.

Blocking farnesylation of oncogenic Ras proteins is a mechanism based therapeutic approach that is of current interest for the development of antitumor agents to treat ras associated tumors. As part of a SAR study on the lead farnesyl protein transferase (FPT) inhibitor I, we report here the synthesis of novel geometric isomers II and III and the FPT inhibition activity of their N-acyl and N-sulfonamido derivatives 15-65. The N-acyl derivatives are markedly less active than the lead inhibitor I thereby demonstrating that the spatial location of the N-acyl group in I is critical for binding of the compound to FPT. In contrast to I, the N-sulfonamido-II series is a novel lead of non-sulfhydryl, nonpeptidic compounds that are dual FPT/GGPT inhibitors. In light of recent reports on the alternative prenylation of N- and K-Ras, dual FPT/GGPT inhibitors may be required to control cell proliferation in tumors containing activated Ras.

Alkyl and Aryl Transferases↗
PubMed1998

Tuberculosis control in refugee populations: a challenge to both relief agencies and national programs.

Today's worldwide tuberculosis epidemic and the movement of a growing number of refugees overlap geographically and have made tuberculosis control in refugee populations an issue of increasing importance. However, in developing countries, where both of these problems are concentrated, tuberculosis control in refugee populations remains a largely unmet need. Experience shows that despite difficult field conditions, tuberculosis control programs can be managed successfully in this setting. The range of outcome results reported for treatment completion and defaulting is, however, wide. Analyzing possible determinants for observed variation in treatment outcome results, this paper outlines prerequisites for establishing a tuberculosis control program in a refugee setting. An attempt is made to formulate a general strategy for the main policies which, if applied consistently, will reduce morbidity, mortality and transmission of tuberculosis among refugee populations living in camps. Criteria for the evaluation and monitoring of such a program are discussed.

Communicable Disease Control↗
PubMed1997

[Control of tuberculosis in refugees and displaced].

As a result of national and international conflicts, the number of refugees and displaced persons in various countries of the world is increasing. The complex and protracted nature of these conflicts often forces refugees to remain away from their countries for long periods, living in refugee camps. Many refugees come from countries where tuberculosis is endemic and, once the immediate problems of establishing a camp are overcome, this disease becomes the principal problem affecting refugee camps. In order to advise the persons in charge of refugee camps on how to set up tuberculosis control programs, this document details the general requirements and specific recommendations of WHO for the implementation of such programs, as well as guidelines for their evaluation and monitoring, including criteria that would justify camp closure.

Humans↗
PubMed1996

The N terminus of bradykinin when bound to the human bradykinin B2 receptor is adjacent to extracellular Cys20 and Cys277 in the receptor.

Chemical cross-linking combined with site-directed mutagenesis was used to evaluate the role of extracellular cysteines and their positions relative to the binding site for the agonist bradykinin (BK) in the human BK B2 receptor. All extracellular cysteines, Cys20, Cys103, Cys184, and Cys277, in the receptor were mutated to serines, and single and double mutants were transfected into COS-7 cells. The Ser20 and Ser277 single mutants and the Ser20/Ser277 double mutant bound [3H]BK and the antagonist [3H]NPC17731 with pharmacological profiles identical to the wild-type B2 receptor. In contrast, the Ser103 and Ser184 single mutants were unable to bind either of the two radioligands. However, these mutants were still expressed as determined by immunoblotting with anti-B2 receptor antibodies. Previous studies on the bovine B2 receptor showed that bifunctional reagents, which are reactive to amines at one end and to free sulfhydryls in the opposite end, cross-link the N terminus of receptor-bound BK to a sulfhydryl in the receptor (Herzig, M. C. S., and Leeb-Lundberg, L. M. F. (1995) J. Biol. Chem. 270, 20591-20598). Here, we show that m-maleimidobenzoyl-N-hydroxysuccinimide ester and 1,5-difluoro-2, 4-dinitrobenzene cross-linked BK to the wild-type human B2 receptor and the Ser20 and Ser277 single mutant receptors, whereas these reagents were unable to cross-link BK to the Ser20/Ser277 double mutant. These results show that Cys103 and Cys184 are both required for expression of high affinity agonist and antagonist binding sites in the human B2 receptor, while Cys20 and Cys277 are not required. Furthermore, the results provide direct biochemical evidence that the N terminus of BK, when bound to the B2 receptor, is adjacent to Cys277 in extracellular domain 4 and Cys20 in extracellular domain 1 of the receptor.

Animals↗
PubMed1996

Synthesis and characterization of pseudopeptide bradykinin B2 receptor antagonists containing the 1,3,8-triazaspiro[4.5]decan-4-one ring system.

A series of pseudopeptides containing alkyl-, cycloalkyl-, aryl-, and aralkyl-substituted 1,3,8-triazaspiro[4.5]decan-4-one-3-acetic acids as amino acid surrogates to replace the Pro2-Pro3-Gly4-Phe5 section of the peptide bradykinin B2 receptor antagonist [Pro3, Phe5]HOE 140 (D-Arg0-Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-D-Tic7+ ++-Oic8-Arg9) were prepared. These psuedopeptides were examined in vitro for their B2 receptor affinities as well as for their ability to block bradykinin mediated actions in vivo. Two compounds in particular, NPC 18521 (I) and NPC 18688 (V) were quite potent in these latter assays, indicating that a significant portion of this prototypical second generation decapeptide antagonist can be replaced with a more compact nonpeptide molecule.

Amino Acid Sequence↗
PubMed1996

Tuberculosis in Siberia: 1. An epidemiological and microbiological assessment.

SETTING: Siberia, Russian Federation. OBJECTIVE: To assess the situation regarding tuberculosis as a paradigm for the Russian Federation. DESIGN: Data was obtained from official sources and through visits to dispensaries and hospitals in 1994. RESULTS: The downward trend in notifications of tuberculosis throughout Russia reversed in 1990/91, the rate increasing from 34/100,000 to 42.9/100,000 in 1993. Incidence rates are higher in Siberia, varying from approximately 43 to 108/100,000; prevalence is 250-300/100,000. The tuberculosis service is centralized and based on specialized polyclinics and dispensaries. An extensive surveillance system employs regular fluorography and tuberculin testing: half of the cases diagnosed are detected by fluorography, against 1% through contact tracing. Patients are classified principally on clinical and radiological grounds. Bacille Calmette-Guérin immunisation is performed at birth and at age 7, and again at 13, 21, and 28 years if Mantoux test is negative. Microscopy and culture services are organisationally separate, and direct comparison of smear and culture data is not possible. Drug resistance to isoniazid and streptomycin is probably high and resistance to rifampicin low, but data on susceptibility of isolates from new cases are not available. CONCLUSION: Tuberculosis is increasing in Siberia. Homelessness, unemployment and alcoholism are important factors, but concurrent human immunodeficiency virus (HIV) infection appears to be uncommon. Prisons probably form a significant reservoir of infectious cases.

Adult↗
PubMed1996

Tuberculosis in Siberia: 2. Diagnosis, chemoprophylaxis and treatment.

OBJECTIVE: To assess tuberculosis diagnosis, chemoprophylaxis and therapy in Siberia as a paradigm for the Russian Federation. DESIGN: Data was obtained from official sources and through visits to dispensaries and hospitals in 1994. RESULTS: Tuberculosis disease and cure is classified according to a Dispensary Group Register based principally on clinical and radiological criteria. Isoniazid is widely used for chemoprophylaxis and post-therapy and may be linked to high levels of isoniazid resistance. Combination drug therapy is individualized, frequently changed, and given orally, parenterally or intra-bronchially. Galvanization, autotransfusion of ultra-violet irradiated blood, antioxidants and steroids are used as adjunct treatment. Ambulatory treatment is uncommon. Surgical treatments including lobectomy and pneumonectomy are used in 5-10% of patients. CONCLUSION: Tuberculosis is increasing in Siberia. An improved drug supply using short course standardized regimens is required supported by high quality co-ordinated bacteriological services. Surgery retains a useful role, but many adjunct therapies should be abandoned.

Adult↗
PubMed1996

Freeze crystallization of imipenem.

This work is a study of the freeze crystallization process developed for the production of a rapidly soluble and stable crystalline form of imipenem, an antibiotic. The objective is to understand the relationship between process conditions and the product crystallinity during the freeze crystallization. Solutions of imipenem and sodium bicarbonate, a drug stabilizer, were crystallized in acetone-water solvent systems at various ratios and temperatures. The degree of crystallinity of the resulting products was measured using an X-ray powder diffraction analysis technique. The acetone-water S-L phase diagram was used to correlate the resulting degrees of crystallinity of imipenem products and equilibrium properties of the system. It was discovered that the conversion of amorphous imipenem to crystalline products was directly related to the percentage of equilibrium liquid during the freeze crystallization. Solubility data indicated that imipenem is virtually insoluble in these equilibrium liquid phases. This suggests that the phase transition from the amorphous state to the crystalline state is mediated by the presence of the liquid phase.

Crystallization↗
PubMed1996

Visual memory skills in Japanese and Caucasians.

Two visual memory tasks were administered to 80 subjects, 48 Japanese and 32 Caucasian, 49 female and 31 male. Japanese subjects were divided into 2 groups, those brought up in Japan with knowledge of kanji and Americans of Japanese ancestry with no kanji experience. The Caucasian subjects were subdivided into two groups, those who had learned kanji as adults, and others without knowledge of kanji. The purpose of the experiment was to examine the possible influence of kanji on the finding that Japanese children and adults score higher than their Caucasian peers in tests of visual ability. A knowledge of kanji did not appear to influence the scoring pattern.

Adult↗
PubMed1996

Women and tuberculosis.

Tuberculosis is the leading infectious cause of death in women worldwide. The disease poses a major threat to women's health security. Population growth, the HIV epidemic, increasing poverty and rising levels of drug resistance will inevitably increase the burden of this disease in women. Women are at increased risk of progression to disease during their reproductive years. However, in most low-income countries, twice as many men are notified with tuberculosis as women. Biological mechanisms may account for most of this difference but socioeconomic and cultural factors leading to barriers in accessing health care may cause under-notification in women. Tuberculosis control programmes should be sensitive to the constraints faced by women in accessing health care, in order to empower women to commence and complete treatment. The fear and stigma associated with tuberculosis have a greater impact on women than on men, often leaving them in a more precarious social and economic position. Tuberculosis in women creates orphans, impoverished families and reduces the economic development of society. Tuberculosis is a major cause of preventable suffering and death in women. WHO's recommended tuberculosis control strategy, DOTS, represents a cost-effective response to the problem of tuberculosis in women. Tuberculosis is a major women's health issue. It is a global health priority that tuberculosis treatment be made available to women, particularly to those in low-income countries who are bearing the brunt of this epidemic.

AIDS-Related Opportunistic Infections↗
PubMed1995

Factors associated with healing leg ulceration with high compression.

To investigate factors relevant to the healing of leg ulceration by high compression, patients were interviewed using a standard questionnaire prior to treatment with a four-layer bandage high-compression system in six community ulcer clinics. We explored the relation of size, ulcer duration and medical history to healing. Cumulative healing rates were high using this method, being 69% after 12 weeks and 83% after 24 weeks. Twelve-week healing rates varied slightly between clinics, ranging from 62% to 83%. Univariate analysis of the total group showed that male sex (RR = 0.77, p = 0.023), poor limb joint mobility (RR = 0.39, p < 0.001), poor general mobility (RR = 0.49, p = 0.015), treatment at home (RR = 0.52, p < 0.001), ulcer size > 10 cm2 (RR = 0.37, p < 0.001), history of deep vein thrombosis (RR = 0.67, p = 0.016) and ulcer duration >6 months (RR = 0.35, p < 0.001) were significantly inversely associated with healing, Ulcer size, duration, limb joint mobility and general mobility were significant independent factors in multivariate analysis.

Adult↗
PubMed1995

Venous ulcer healing: effect of socioeconomic factors in London.

OBJECTIVE: To determine which social and clinical factors are associated with healing in patients with venous ulceration. DESIGN: Patients were questioned about social factors at their first visit to a community ulcer clinic. They were treated by high compression bandage system and were interviewed again after 12 weeks. SETTING: Community leg ulcer clinics held in health centres throughout Riverside Health Authority in London. PATIENTS: All patients referred to five community leg ulcer clinics with venous ulceration over a six month period. MAIN OUTCOME MEASURES: These were factors significantly associated with healing within 12 weeks of beginning treatment, measured by odds ratio (OR) given by logistic regression analysis. MAIN RESULTS: Of 168 patients with venous ulceration, 87 (52%) healed after 12 weeks of treatment. Univariate analysis showed that low social class (OR = 3.44, 95% CI 1.17, 10.14), lack of central heating (OR = 2.22, 95% CI 1.18, 4.18), and being single (OR = 2.77, 95% CI 1.15, 6.69) were all significantly associated with delayed healing. After adjustment for the known risk factors of ulcer size, ulcer duration, and general mobility only lack of central heating was still significant (OR = 2.27, 95% CI 1.11, 4.55). The remaining factors failing to achieve statistical significance because of their inter-relationship with the known risk factors. CONCLUSIONS: Clinical features of the ulcer seem to determine the progress of healing in patients with leg ulceration. Although there were associations between socio-economic factors and poor healing, adjustment for clinical risk factors generally led to lower non-significant associations. Only lack of central heating retained its association and may play a part in prolonging healing of venous ulceration.

Aged↗
PubMed1995

Characteristics of state hospital patients arrested for offenses committed during hospitalization.

OBJECTIVE: The study was a preliminary exploration of the relatively new phenomenon of arresting psychiatric inpatients for offenses committed in the hospital. METHODS: A retrospective record review at two New York state hospitals identified all 73 inpatients arrested over a 30-month period for an offense committed while they were hospitalized. Logistic regression was used to compare arrestees with a control group of 1,438 non-arrested inpatients. RESULTS: The number of arrests at the two hospitals significantly increased over the study period. Seventy-nine percent of arrests resulted from a violent incident. At least 68 percent of arrestees had been arrested previously. Compared with the control group, arrestees were more likely to be young, male, and black and to have a shorter length of stay. Axis I diagnoses did not differentiate arrestees from control patients. Ninety percent of arrestees had a diagnosis of substance use or personality disorder or both. The sample more closely resembled the population of criminal offenders in the community than the psychiatric inpatient population. Prosecution resulted in jail or prison terms for 11 percent of arrestees. CONCLUSIONS: This descriptive preliminary study was limited by its retrospective nature and reliance on records of varying quality. Although the increase in arrests is clear, the cause of the increase and the impact of arrests on arrestees and hospitals remain to be clarified.

Adult↗