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Biomedical subjects

C Kelly

Publications and source records attributed to C Kelly.

At least 37 records · Page 2Linked to original sources
PubMed1997

Pseudomonas putida B2: a tod-lux bioluminescent reporter for toluene and trichloroethylene co-metabolism.

A tod-lux transcriptional fusion bioluminescent reporter strain, Pseudomonas putida B2, was developed to permit on-line analysis of trichloroethylene (TCE) transformation by toluene dioxygenase (todC1C2BA) in Pseudomonas putida F1. Strain B2 was exposed to toluene in growing and resting cell bioluminescence assays. The growing cells showed a direct correlation between bioluminescence and toluene concentration, while resting cells showed reproducible bioluminescence with repeated toluene exposures. In addition, P. putida B2 was encapsulated in alginate beads and used in a packed bed flow-through differential volume reactor. The TCE feed into the differential volume reactor was constant at 20 mg L-1 and toluene was pulsed in square-wave perturbations at 10 mg L-1. The system showed a direct correlation between the expression of the tod operon (as monitored by light output) and the co-metabolism of TCE. Approximately 20% of the TCE and 50% of the toluene was removed at a flow rate of 0.4 ml min-1. This approach allowed the on-line monitoring of tod gene expression and its relation to TCE biotransformation.

Alginates↗
PubMed1997

Thrombopoietin measurement in thrombocytosis: dysregulation and lack of feedback inhibition in essential thrombocythaemia.

Essential thrombocythaemia (ET), a myeloproliferative disorder (MPD) manifested by excessive platelet production, lacks a specific diagnostic test to facilitate differentiation from other thrombocytoses. We studied thrombopoietin (TPO) levels in 41 patients with thrombocytosis: 25 ET patients, eight with other MPD, and eight with reactive thrombocytosis. Mean age and platelet counts for these groups were comparable. TPO levels for 96 healthy individuals provided a reference range for normal. The majority of ET patients (19/25 or 76%) had normal TPO levels. No patient with ET had a TPO level below 75 pg/ml, compared with 57% of healthy donors and 8/16 (50%) patients with other thrombocytoses (P<0.05). TPO levels in ET are not appropriately down-regulated, as occurs with cytokines relevant to other MPD. In thrombocytosis, a TPO level <75 pg/ml indicates that ET is unlikely.

Adolescent↗
PubMed1997

Immunological and physiological responses to aortic surgery: effect of reperfusion on neutrophil and monocyte activation and pulmonary function.

BACKGROUND: The aims of this study were to evaluate the effects of aortic clamping and unclamping on neutrophil and monocyte activation and release of plasma mediators in 20 patients undergoing elective aortic aneurysm surgery, and to correlate these findings with pulmonary haemodynamics and gas exchange. METHODS: Simultaneous arterial and mixed venous samples were obtained during and after aortic clamping and unclamping. RESULTS: Neutrophil respiratory burst activity in mixed venous samples increased significantly during the period of aortic clamping. An initial increase in neutrophil CD11b expression in venous blood 5 min after clamp removal was followed by a significant decrease in level of expression. Plasma tumour necrosis factor levels increased at the end of the cross-clamp period and reached a maximum 60 min following reperfusion. There was a significant and sustained rise in plasma thromboxane B2 levels following clamp removal. This increase correlated with the development of increased pulmonary vascular resistance. CONCLUSION: This study confirms the central role played by activated neutrophils in the early stages of reperfusion injury and also suggests a role for plasma mediators in mediating cardiopulmonary dysfunction during major vascular surgery.

Aged↗
PubMed1996

Modeling nucleotide evolution: a heterogeneous rate analysis.

A new model of molecular evolution is introduced that allows for heterogeneous rates across the sequence positions. The development of this model was motivated by two issues: first, a number of studies have shown that the positions in a DNA sequence evolve at different rates, and second, it has been shown that not accounting for this heterogeneity can lead to biased estimates of evolutionary parameters. The authors generalize the Markovian model of molecular evolution to allow for heterogeneous rates and explore some of the consequences of such a model. In particular, they quantify the biases incurred by incorrectly assuming an equal-rate model and consider what can be learned about evolutionary parameters under a heterogeneous model.

Biological Evolution↗
PubMed1996

Reinnervation of the transplanted human heart as evidenced from heart rate variability studies.

This study evaluated heart rate variability (HRV) after cardiac transplantation in humans in an attempt to test the hypothesis that cardiac reinnervation occurs in the post-transplant period. HRV was measured using 24-hour Holter recordings performed on 37 ambulant patients 1 to 122 months after cardiac transplantation. All patients were free of histologic rejection and were taking no medication likely to influence HRV. Time and frequency domain were analyzed and circadian rhythm of hourly average heart rate was calculated. HRV increased with time after the transplant. Compared with patients in the early post-transplant period, patients > 36 months after transplant had lower 24-hour heart rates (86 vs 93 beats/min), an increased average of all 5-minute SDs of NN intervals (17.6 vs 11.3), and higher low-and high-frequency power. Ten of the 27 patients > 3 years after transplantation had evidence of functional cardiac reinnervation. Compared with patients who had no reinnervation, these patients had increased circadian variability with lower nocturnal heart rates (76 vs 91 beats/min) and greater sympathetic activity during daytime (natural logarithm sympathetic power -0.36 vs -1.45) and nighttime (natural logarithm sympathetic power -0.43 vs -1.98). Despite lower nocturnal heart rates, there was no HRV evidence for an increase in parasympathetic activity. Thus, patients late after cardiac transplantation have HRV evidence for an increase in sympathetic control of the heart.

Adult↗
PubMed1996

Public perceptions of a health visitor.

This paper outlines the views of a random sample of 175 members of the public on the role and function of the health visitor. Those who had previous contact with a health visitor were more likely to know her employer but not necessarily her qualifications. They also had a greater knowledge of the type of clients a health visitor may see and the advice she is able to give. Although many people were aware of the health visitor's work in health promotion, very few would contact a health visitor for health advice, the vast majority choosing to see their GP. Health visitors should be aware of this and the way in which their profession is viewed by those whose health they aim to influence and may also consider a change of name and/or direction if the profession is to continue to develop and be more responsive to the needs of the 90s.

Adolescent↗
PubMed1996

Postvitrectomy positioning complicated by ulnar nerve palsy.

PURPOSE: Ulnar nerve palsy is an unusual complication of postvitrectomy positioning. METHOD: We report two such cases. RESULTS: Both patients developed ulnar nerve palsy after maintaining a face-down position for 2 to 4 weeks after vitrectomy with intraocular perfluoro-octane. The neuropathy resolved in one patient after he was instructed to avoid prolonged pressure on his flexed elbows, whereas the other patient ultimately required surgical decompression of the nerve at the elbow. CONCLUSION: Ulnar nerve palsy can result from postvitrectomy positioning associated with prolonged direct pressure on the ulnar nerve or compression of the ulnar nerve via flexion of the elbow.

Adult↗
PubMed1996

High response rates with short infusional 2-chlorodeoxyadenosine in de novo and relapsed low-grade lymphoma. Australian and New Zealand Lymphoma Study Group.

Thirty-five patients (eight de novo, 27 relapsed disease) with low-grade non-Hodgkin's lymphoma (diffuse small lymphocytic, follicular small cleaved cell, follicular mixed cell, and lymphoplasmacytoid) were treated with 2-chlorodeoxyadenosine (2CdA) at a daily dose of 0.14 mg/kg for 5d (2 h infusion) for an average of three cycles. Minor treatment delays, generally due to haematological toxicities, occurred in nine of 105 cycles. Major toxicities were lymphopenia, neutropenia and thrombocytopenia. Opportunistic infections occurred in seven patients. Overall response rate was 69% (five complete, 19 partial) reaching 88% for de novo patients (two complete, five partial). Elevated beta 2-microglobulin level was negatively predictive of response (P = 0.0014). Eight of 24 responders relapsed, with a median follow-up of 13 months. 2CdA administered as an intermittent infusion shows considerable single-agent activity in low-grade lymphomas achieving high response rates of prolonged duration. Consideration of schedules where 2CdA is alternatively administered with combination chemotherapy appears warranted.

Adult↗
PubMed1996

Biases in amino acid replacement matrices and alignment scores due to rate heterogeneity.

Empirically derived amino acid replacement matrices are widely used in sequence comparison and database searches. We consider an extension of the usual Markov process model of protein evolution that admits site to site rate heterogeneity and demonstrates that rate heterogeneity can introduce a bias in estimated replacement probabilities and the corresponding alignment scores derived from these matrices. We suggest an approach to obtain unbiased estimates of replacement probabilities and alignment scores and derive the details for the case where rates are assumed to vary according to a gamma distribution.

Amino Acid Sequence↗
PubMed1996

Regulation and characterization of the interferon-alpha present in patients with advanced human immunodeficiency virus type 1 disease.

To examine a possible association between plasma viremia and interferon-alpha (IFN-alpha) in patients with the acquired immunodeficiency syndrome (AIDS), we performed IFN plasma immunoadsorption by apheresis (IFN-alpha apheresis) in four volunteers with AIDS who had sustained levels of endogenous plasma IFN-alpha. IFN-alpha apheresis with two plasma volume exchanges was performed daily for 5 days. Clinical signs and symptoms and hematologic, virologic, and immunologic parameters were monitored. Two subjects developed anemia from phlebotomy, and one had a catheter++-associated bacteremia. The IFN-alpha apheresis was effective only in transiently removing IFN-alpha: depletion of IFN-alpha led only to its rapid reconstitution. Cell-associated HIV-1 was unchanged, but three of four subjects had a modest decrease in culturable plasma virus burden following the procedures. The recovery of in vivo HIV-1-related IFN-alpha by apheresis allowed its biologic and biochemical characterization. The HIV-1 IFN-alpha showed characteristics on ELISA, western blot, and biologic assays similar to two subspecies of the natural protein. The natural, recombinant, and HIV-1-induced IFN-alpha s demonstrated nearly identical antiviral activities. The HIV-1 IFN-alpha eluted from the column was not acid labile. The inability of large amounts of plasma IFN-alpha found in some patients with AIDS to affect viral burden likely reflects properties of the virus or of host factors independent of IFN-alpha.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Use of pulsed-field gel electrophoresis typing to study an outbreak of infection due to Serratia marcescens in a neonatal intensive care unit.

Serratia marcescens is a well-known cause of nosocomial infections and outbreaks, particularly in critically ill neonates and immunocompromised patients. Numerous methods have been proposed for typing. We used pulsed-field gel electrophoresis (PFGE) typing to analyze an outbreak in a neonatal intensive care unit (NICU). We included 23 patient isolates from an outbreak (March to July 1995), and 10 patient isolates from different wards during the same time period. PFGE of whole-cell DNA digested by SpeI was used as a marker of strain identity. The most common presentation of the infection was sepsis in 18 of 23 (78%) neonates. Only four different biotypes were identified; biotype A8d accounted for 84% of the strains. PFGE typing revealed two clones responsible for two different clonal strain dissemination outbreaks from March to July, with 24 patient isolates being pattern A and 4 patient isolates being pattern E. PFGE typing suggests cross transmission between patients in the NICU and other wards. The isolates from 5 other patients showed distinct PFGE patterns. Extensive investigation and cultures failed to identify any environmental or staff reservoir of S. marcescens. This is one of the first reports applying PFGE to the study of S. marcescens, and this method was a useful marker of strain identity. PFGE typing distinguished strains which appeared to be the same by biotyping.

Bacterial Typing Techniques↗
PubMed1996

Evaluation of pulsed-field gel electrophoresis as a typing system for Candida rugosa: comparison of karyotype and restriction fragment length polymorphisms.

Nosocomial infections with Candida species have emerged as an increasingly important cause of morbidity and mortality in intensive care units. Ten Candida rugosa isolates from a previously documented cluster of C. rugosa infections in one hospital (nine burn unit isolates and one isolate from another hospital ward) and eight C. rugosa isolates recovered in a referral fungus testing laboratory (comparison isolates) from distinct geographic areas were investigated by molecular techniques. Isolates were from multiple anatomic sites. Pulsed-field gel electrophoresis (PFGE) of whole-cell DNA was performed with the 18 C. rugosa isolates as a marker of strain identity. The PFGE karyotypes of the C. rugosa isolates were demonstrated from four to seven chromosome bands. Karyotyping revealed the same PFGE pattern for the nine outbreak isolates from the burn unit, confirming clonal strain transmission. The isolate from the other hospital ward had a distinct karyotype. Distinct PFGE karyotype patterns were demonstrated for the eight comparison isolates. Restriction fragment length polymorphisms (RFLP) generated from whole-cell DNA digested with SfiI demonstrated the same RFLP pattern among outbreak isolates. Among comparison isolates, karyotyping distinguished some isolates that were indistinguishable by RFLP patterns. Karyotyping by PFGE appears to be the most useful molecular typing tool for discrimination among strains of C. rugosa and will be a useful marker for evaluating the epidemiology of future C. rugosa infections.

Candida↗
PubMed1996

Effect of long-term glycemic control on cognitive function.

OBJECTIVE: To investigate the relationship between recurrent hypoglycemia and cognitive impairment in insulin-dependent diabetic patients. RESEARCH DESIGN AND METHODS: Seventy patients who were diagnosed as diabetic at age 18 years or older, were under 55 years old, and had no condition likely to affect cognitive abilities were recruited from a diabetic register. Patients were interviewed to obtain information on the frequency of major and minor hypoglycemia. Their cognitive abilities were assessed on tests of premorbid intelligence, current intelligence, reaction time, concentration, memory, and information processing. RESULTS: There was a significant correlation between the apparent decline in intelligence, expressed as the discrepancy between the estimated premorbid and the actual performance intelligence quotient, and the frequency of major hypoglycemic attacks (rs = -0.30; P < 0.01). Comparison of patients with and without recurrent hypoglycemia showed few significant differences in cognitive ability. CONCLUSIONS: Results support previous work that suggests that major hypoglycemic attacks have a significant effect on some aspects of cognitive function, but the clinical importance of this finding remains to be determined.

Adult↗
PubMed1996

Tuberculosis infection in human immunodeficiency virus-positive adolescents and young adults: a New York City cohort.

OBJECTIVES: Adolescents with human immunodeficiency virus (HIV) infection are at increased risk for tuberculosis (TB), underscoring the importance of early identification of TB infection. The goals of this study were to assess the factors associated with the completion of evaluations for TB in a cohort of HIV-positive adolescents and young adults and to describe the prevalence of Mycobacterium tuberculosis infection and adherence to antituberculous treatment regimens. METHODS: A retrospective chart review was done for all HIV-positive adolescents and young adults, ages 13 to 21 years (n = 49), seen in a comprehensive care program from January 1991 through December 1992. Data collected included CD4 cell count, HIV clinical status, living situation, substance use history, and the completion of an annual evaluation for TB infection. The evaluation consisted of a tuberculin skin test (Mantoux test), using an intraepidermal injection of 0.1 mL of 5 tuberculin units of purified protein derivative (PPD) and a simultaneous Merieux multitest anergy panel. Chi-square analysis was used to assess the association between the completion of the evaluation for TB and both living status and substance use. RESULTS: Thirty-one (63%) of 49 patients completed evaluations for TB. Of the 31 completed evaluations, 18 were assessed by clinic staff on site, and 13 were assessed by other medical or trained nonmedical observers through community networking efforts. Neither homelessness nor illicit substance use were factors in the completion of the evaluation. Six (19%) of the 31 patients had positive PPD skin test results. Three had medical histories and chest radiographs suggesting active TB, and all were hospitalized for at least 2 weeks. Two had positive cultures for M tuberculosis, although the third also responded clinically to antituberculous therapy. All three were otherwise asymptomatic for HIV infection, with only moderately depressed CD4 cell counts. All three were homeless and used crack cocaine. After the initial treatment as inpatients, none completed treatment within the prescribed time period. CONCLUSIONS: The completions of the evaluations for TB were greatly facilitated by community networking, but innovative strategies to enhance both screening and treatment programs, such as training youth service providers in the community to read PPD skin tests, expansion of directly observed therapy services, and youth-centered programs for housing and substance use, need further development. The high prevalence of TB in the cohort underscores the need for providers to increase efforts to identify cases of TB infection among adolescents and young adults and to incorporate HIV risk assessment, counseling, and testing into their practices routinely.

Adolescent↗