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Biomedical subjects

Michael L Fisher

Publications and source records attributed to Michael L Fisher.

7 recordsLinked to original sources
PubMed2006

Intranasal inoculation of mice with Yersinia pseudotuberculosis causes a lethal lung infection that is dependent on Yersinia outer proteins and PhoP.

Yersinia pseudotuberculosis infects many mammals and birds including humans, livestock, and wild rodents and can be recovered from the lungs of infected animals. To determine the Y. pseudotuberculosis factors important for growth during lung infection, we developed an intranasal model of infection in mice. Following intranasal inoculation, we monitored both bacterial growth in lungs and dissemination to systemic tissues. Intranasal inoculation with as few as 18 CFU of Y. pseudotuberculosis caused a lethal lung infection in some mice. Over the course of 7 days, wild-type Y. pseudotuberculosis replicated to nearly 1 x 10(8) CFU/g of lung in BALB/c mice, induced histopathology in lungs consistent with pneumonia, but disseminated sporadically to other tissues. In contrast, a Delta yopB deletion strain was attenuated in this model, indicating that translocation of Yersinia outer proteins (Yops) is essential for virulence. Additionally, a Delta yopH null mutant failed to grow to wild-type levels by 4 days postintranasal inoculation, but deletions of any other single effector YOP did not attenuate lung colonization 4 days postinfection. Strains with deletions in yopH and any one of the other known effector yop genes were more attenuated that the Delta yopH strain, indicating a unique role for yopH in lungs. In summary, we have characterized the progression of a lung infection with an enteric Yersinia pathogen and shown that YopB and YopH are important in lung colonization and dissemination. Furthermore, this lung infection model with Y. pseudotuberculosis can be used to test potential therapeutics against Yersinia and other gram-negative infections in lungs.

Administration, Intranasal↗
PubMed2005

Effect of kidney transplantation on left ventricular systolic dysfunction and congestive heart failure in patients with end-stage renal disease.

OBJECTIVES: We examined the impact of kidney transplantation on left ventricular ejection fraction (LVEF) in end-stage renal disease (ESRD) patients with congestive heart failure (CHF). BACKGROUND: The ESRD patients with decreased LVEF and a poor New York Heart Association (NYHA) functional class are not usually referred for transplant evaluations, as they are considered to be at increased risk of cardiac and surgical complications. METHODS: Between June 1998 and November 2002, 103 recipients with LVEF < or =40% and CHF underwent kidney transplantation. The LVEF was re-assessed by radionuclide ventriculography gated-blood pool (MUGA) scan at six and 12 months and at the last follow-up during the post-transplant period. RESULTS: Mean pre-transplant LVEF% increased from 31.6 +/- 6.7 (95% confidence interval [CI] 30.3 to 32.9) to 52.2 +/- 12.0 (95% CI 49.9 to 54.6, p = 0.002) at 12 months after transplantation. There was no perioperative death. After transplantation, 69.9% of patients achieved LVEF > or =50% (normal LVEF). A longer duration of dialysis (in months) before transplantation decreased the likelihood of normalization of LVEF in the post-transplant period (odds ratio 0.82, 95% CI 0.74 to 0.91; p < 0.001). The NYHA functional class improved significantly in those with normalization of LVEF (p = 0.003). After transplantation, LVEF >50% was the only significant factor associated with a lower hazard for death or hospitalizations for CHF (relative risk 0.90, 95% CI 0.86 to 0.95; p < 0.0001). CONCLUSIONS: Kidney transplantation in ESRD patients with advanced systolic heart failure results in an increase in LVEF, improves functional status of CHF, and increases survival. To abrogate the adverse effects of prolonged dialysis on myocardial function, ESRD patients should be counseled for kidney transplantation as soon as the diagnosis of systolic heart failure is established.

Female↗
PubMed2004

Nesiritide does not improve renal function in patients with chronic heart failure and worsening serum creatinine.

BACKGROUND: Nesiritide (synthetic human brain natriuretic peptide) is approved for the treatment of symptomatic heart failure. However, studies of brain natriuretic peptide in patients with heart failure have come to conflicting conclusions about effects on glomerular filtration rate (GFR), effective renal plasma flow, natriuresis, and diuresis. METHODS AND RESULTS: To identify a population at high risk of renal dysfunction with conventional treatment, we selected patients with a creatinine level increased from baseline (within 6 months). We examined the effects of nesiritide on GFR (measured by iothalamate clearance), renal plasma flow (measured by para-amino hippurate clearance), urinary sodium excretion, and urine output in a double-blind, placebo-controlled, crossover study. Patients received nesiritide (2 microg/kg IV bolus followed by an infusion of 0.01 microg/kg per minute) or placebo for 24 hours on consecutive days. Nesiritide and placebo data were compared by repeated-measures analysis and Student t test. We studied 15 patients with a recent mean baseline creatinine of 1.5+/-0.4 mg/dL and serum creatinine of 1.8+/-0.8 mg/dL on admission to the study. There were no differences in GFR, effective renal plasma flow, urine output, or sodium excretion for any time interval or for the entire 24-hour period between the nesiritide and placebo study days. For 24 hours, urine output was 113+/-51 mL/h with placebo and 110+/-56 mL/h with nesiritide. GFR during placebo was 40.9+/-25.9 mL/min and with nesiritide was 40.9+/-25.8. CONCLUSIONS: Nesiritide did not improve renal function in patients with decompensated heart failure, mild chronic renal insufficiency, and renal function that had worsened compared with baseline. The lack of effect may be related to renal insufficiency, hemodynamic alterations, sodium balance, severity of heart failure, or drug dose. Understanding the importance of these issues will permit effective and appropriate use of nesiritide.

Adult↗
PubMed2004

The influence of age, gender, and race on the prevalence of depression in heart failure patients.

OBJECTIVES: The goal of this study was to determine the prevalence of depression in an out-patient heart failure (HF) population; its relationship to quality of life (QOL); and the impact of gender, race, and age. BACKGROUND: Most studies of depression in HF have evaluated hospitalized patients (a small percentage of the population) and have ignored the influence of various patient characteristics. Although reported depression rates among hospitalized patients range from 13% to 77.5%, out-patient studies have been small, have reported rates of 13% to 42%, and have not adequately accounted for the impact of age, race, or gender. METHODS: A total of 155 patients with stable New York Heart Association functional class II, III, and IV HF and an ejection fraction <40% were given questionnaires to assess QOL and depression. These included the Medical Outcomes Study Short Form, the Minnesota Living with Heart Failure questionnaire, and the Beck Depression Inventory (BDI). Depression was defined as a score on the BDI of > or =10. RESULTS: A total of 48% of the patients scored as depressed. Depressed patients tended to be younger than non-depressed patients. Women were more likely (64%) to be depressed than men (44%). Among men, blacks (34%) tended to have less depression than whites (54%). Depressed patients scored significantly worse than non-depressed patients on all components of both the questionnaires measuring QOL. However, they did not differ in ejection fraction or treatment, except that depressed patients were significantly less likely to be receiving beta-blockers. CONCLUSIONS: Depression is common in patients with HF, with age, gender, and race influencing its prevalence in ways similar to those observed in the general population. These data suggest that pharmacologic or non-pharmacologic treatment of depression might improve the QOL of HF patients.

Adrenergic beta-Antagonists↗
PubMed2002

Tolerability of beta-blocker initiation and titration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF).

BACKGROUND: beta-Blockade improves survival when administered over a long period of time to patients with heart failure. However, the time course of any possible deterioration during the titration phase has not been reported. METHODS AND RESULTS: We looked at evidence of clinical deterioration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) by analyzing events and symptoms during the first 90 days. During titration, the Kaplan-Meier curves for the combined end point of all-cause mortality/all-cause hospitalization were similar in all patients randomized, with no significant difference in favor of placebo at any visit or in any of the analyzed subgroups (New York Heart Association class II, III/IV, or III/IV with ejection fraction <0.25, heart rate less-than-or-equal 76 bpm, and systolic blood pressure less-than-or-equal 120 mm Hg). The curves started to diverge in favor of beta-blockade after 60 days. Low heart rate was the main factor that limited titration. In New York Heart Association class III/IV, 5.9% of the patients receiving placebo discontinued study medicine during the first 90 days compared with 8.1% of those receiving metoprolol CR/XL (P=0.037 unadjusted, P=NS adjusted); corresponding figures in those with New York Heart Association class III/IV and ejection fraction <0.25 were 7.1% and 8.0% (P=NS). From day 90 until the end of the study, more patients in the placebo group discontinued study medicine in all subgroups. There was no change in diuretic or ACE inhibitor dosing with beta-blocker titration. Most patients reported no change in symptoms of breathlessness or fatigue during the titration phase. CONCLUSIONS: When carefully titrated, metoprolol CR/XL can be given safely to the overwhelming majority of patients with stable mild to moderate heart failure, with minimal side effects or deterioration.

Adrenergic beta-Antagonists↗