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Biomedical subjects

J Fuhrer

Publications and source records attributed to J Fuhrer.

At least 19 recordsLinked to original sources
PubMed2001

Diastolic dysfunction precedes myocardial hypertrophy in the development of hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy and impaired diastolic function may occur early in systemic hypertension, but longitudinal studies are missing. METHODS: We performed an echocardiographic follow-up study in young initially normotensive male offspring of hypertensive (OHyp) (n = 25) and normotensive (ONorm) (n = 17) parents. Blood pressure (BP), LV mass, and mitral inflow were determined at baseline and after 5 years. Pulmonary vein flow pattern assessment and septal myocardial Doppler imaging were additionally performed at follow-up. RESULTS: At follow-up, BP was not significantly different between the two groups (128 +/- 11/84 +/- 10 v 123 +/- 11/81 +/- 5 mm Hg, OHyp v ONorm) but five OHyp had developed mild hypertension. LV mass index remained unchanged and was not different between the two groups at follow-up (92 +/- 17 v 92 +/- 14 g/m2). Diastolic echocardiographic properties were similar at baseline, but, at follow-up, the following differences were found: mitral E deceleration time (209 +/- 32 v 185 +/- 36 msec, P < .05) and pulmonary vein reverse A wave duration (121 +/- 15 v 107 +/- 12 msec, P < .05) were prolonged in the OHyp as compared to the ONorm. Compared to the normotensive subjects, the five OHyp who developed hypertension had more pronounced alterations of LV diastolic function, that is, significantly higher mitral A (54 +/- 7 v 44 +/- 9 cm/sec, hypertensives v normotensives, P < .05), lower E/A ratio (1.31 +/- 0.14 v 1.82 +/- 0.48, P < .05), increased systolic-to-diastolic pulmonary vein flow ratio (1.11 +/- 0.3 v 0.81 +/- 0.16, P < .005), longer myocardial isovolumic relaxation time (57 +/- 7 v 46 +/- 12 msec, P < .05) as well as smaller myocardial E (10 +/- 1 v 13 +/- 2 cm/sec, P < .05) and E/A ratio (1.29 +/- 0.25 v 1.78 +/- 0.43, P < .05), despite similar LV mass (91 +/- 16 v 93 +/- 18 g/m2). CONCLUSIONS: Over a 5-year follow-up, initially lean, normotensive, young men with a moderate genetic risk for hypertension, developed Doppler echocardiographic alterations of LV diastolic function compared to matched offspring of normotensive parents. These alterations were more pronounced in the OHyp who developed mild hypertension and occurred without a distinct rise in LV mass.

Adult↗
PubMed2000

Association of severe insulin resistance with both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy.

HIV-lipodystrophy (HIV-LD) is characterized by the loss of body fat from the limbs and face, an increase in truncal fat, insulin resistance, and hyperlipidemia, factors placing affected patients at increased risk for vascular disease. This study evaluated insulin sensitivity and inflammatory status associated with HIV-LD and provides suggestions about its etiology. Insulin sensitivity and immune activation markers were assessed in 12 control subjects and 2 HIV-positive groups, 14 without and 15 with LD syndrome. Peripheral insulin sensitivity (mostly skeletal muscle) was determined with the hyperinsulinemic-euglycemic clamp. Circulating insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) and free fatty acid (FFA) levels, and their response to insulin infusion were indicative of insulin responsiveness of liver and adipose tissue, respectively. Serum levels of soluble type 2 tumor necrosis factor-alpha (TNF-alpha) receptor (sTNFR2) were used as an indicator of immune activation. HIV-LD study subjects had significantly reduced (twofold) peripheral insulin sensitivity, but normal levels of FFA and reduced levels of IGFBP-1, relative to the nonlipodystrophy groups, indicating that the loss of insulin sensitivity was more pronounced in skeletal muscle than in liver or fat. The significant loss of peripheral fat in the HIV-LD group (34%; p <.05) closely correlated with the reduced peripheral insulin sensitivity (p =. 0001). Levels of sTNFR2 were elevated in all HIV-infected study subjects, but they were significantly higher in those with lipodystrophy than without, and sTNFR2 levels strongly correlated with the reduction in insulin sensitivity (p =.0001). Loss of peripheral fat, normal levels of FFA, and reduced levels of IGFBP-1 indicate that insulin resistance in HIV-LD is distinct from type 2 diabetes and obesity. The relationship between the degree of insulin resistance and sTNFR2 levels suggests an inflammatory stimulus is contributing to the development of HIV-associated lipodystrophy.

Absorptiometry, Photon↗
PubMed1999

Insulin-like growth factor system in patients with HIV infection: effect of exogenous growth hormone administration.

The purpose of this study was to characterize changes in the levels of insulin-like growth factor-I (IGF-I) and IGF binding proteins (BP) 1, 2, and 3 in HIV-infected adults throughout the course of their disease, and to assess the responsiveness of the IGF system components to growth hormone (GH) administration (6 mg/day) for 2 weeks. Healthy control study subjects (n = 10) were compared with patients who were either HIV-positive (n = 9), had AIDS without weight loss (n = 13), or had AIDS with >10% weight loss (n = 6), all of whom had been free of acute illness for at least 3 months. Under basal conditions, fasting serum concentrations of epinephrine, norepinephrine, cortisol, glucagon, insulin, IGF-I, and IGFBP-3 were not significantly different among the four groups. The serum concentrations of IGFBP-1 and IGFBP-2 were significantly higher in AIDS patients with wasting than in the other three groups (p < .05). In addition, there was a statistically significant positive correlation between the levels of IGFBP- 1 (p = .004) and IGFBP-2 (p = .03) and the stage of disease. Following GH administration, the serum concentrations of insulin and IGF-I were increased in all groups (p < .05). In addition, the increases in insulin levels correlated with stage of disease (p = .004). The responses of the IGFBPs were more variable. GH administration significantly increased the levels of IGFBP-3 in all groups except the patients with AIDS wasting, whereas the levels of IGFBP-1 were significantly decreased in controls and AIDS patients. These results demonstrate that there is a continuum of both elevations in the IGFBPs and altered metabolic responsiveness in patients infected with HIV that increases with the severity of the disease. These data also demonstrate that AIDS patients, who are free from secondary infection, respond to administration of GH by significantly increasing hepatic IGF-I production.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Changing conditions and treatments in a dynamic cohort of ambulatory HIV patients: the HIV outpatient study (HOPS).

PURPOSE: Most HIV-infected persons are now treated as ambulatory patients. Obtaining continually updated data about these patients' changing conditions, therapies, and reimbursement is essential to health care provision and planning. The systematic tracking of patient medical and laboratory information in an ongoing commercial data collection program (The Health Research Network) allows clinicians to better understand health outcomes, practice patterns, and epidemiologic trends for their patients. METHODS: To evaluate trends in conditions and therapies of ambulatory HIV-infected patients, we analyzed such data electronically and prospectively collected in the HIV Outpatient Study (HOPS) from 1992 through 1996 from 1876 patients seen in 11,755 clinic visits to ten HIV clinical practices. RESULTS: Patients were as likely to be diagnosed with Mycobacterium avium complex ([MAC] 5.4 cases per 100 person-years) or wasting syndrome (7.8 cases per 100 person-years), as Pneumocystis carinii pneumonia ([PCP]; 7.6 cases per 100 person-years) or Kaposi sarcoma ([KS]; 6.9 cases per 100 person-years). A nested analysis showed that HIV-infected cigarette smokers were at substantially greater risk of pneumonia (relative hazard [RH] = 2.3), bronchitis (RH = 1.7) and hairy leukoplakia (RH = 1.9) than nonsmokers. By 1996, 35 (56%) of 62 patients with PCP, 9 (30%) of 30 patients with other pneumonias, 28 (90%) of 31 patients with KS, 35 (73%) of 48 patients with MAC, and 24 (63%) of 38 patients with cytomegalovirus retinitis were treated without hospitalization. CONCLUSIONS: The HOPS provides continually updated information on the changing characteristics, conditions, and therapy of ambulatory HIV-infected patients.

Adult↗
PubMed1998

Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators.

BACKGROUND AND METHODS: National surveillance data show recent, marked reductions in morbidity and mortality associated with the acquired immunodeficiency syndrome (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of whom had at least one CD4+ count below 100 cells per cubic millimeter, who were seen at nine clinics specializing in the treatment of human immunodeficiency virus (HIV) infection in eight U.S. cities from January 1994 through June 1997. RESULTS: Mortality among the patients declined from 29.4 per 100 person-years in the first quarter of 1995 to 8.8 per 100 in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in the intensity of antiretroviral therapy (classified as none, monotherapy, combination therapy without a protease inhibitor, and combination therapy with a protease inhibitor) were associated with stepwise reductions in morbidity and mortality. Combination antiretroviral therapy was associated with the most benefit; the inclusion of protease inhibitors in such regimens conferred additional benefit. Patients with private insurance were more often prescribed protease inhibitors and had lower mortality rates than those insured by Medicare or Medicaid. CONCLUSIONS: The recent declines in morbidity and mortality due to AIDS are attributable to the use of more intensive antiretroviral therapies.

AIDS-Related Opportunistic Infections↗
PubMed1998

The medial amygdaloid nucleus modifies social behavior in male rats.

Electrical stimulation of the medial amygdaloid nucleus (AME) produces a behavioral state in male rats that resembles the postejaculatory interval, but electrical recording from cells in the AME shows that they become active earlier in sexual behavior, around the time that the male first appears to become aware of estrus in the female. In an attempt to resolve which feature of sexual behavior was mediated by the AME, we stimulated the structure bilaterally in freely behaving males using voltage levels too low to produce the postejaculatory interval. We found that electrical activation of this kind facilitated sexual behavior when it would not otherwise occur (i.e., in the presence of a nonestrous female). However, the stimuli suppressed sexual behavior when it would normally occur (i.e., in the presence of a nonestrous female). We discuss alternative interpretations of the results in the context of a general model for the central organization of sexual behavior in males.

Amygdala↗
PubMed1998

Video-assisted thoracoscopic pericardial fenestration for loculated or recurrent effusions.

OBJECTIVE: The validity of video-assisted thoracoscopic pericardial fenestration was prospectively assessed for loculated effusions. effusions previously treated by percutaneous catheter manoeuvres and those with concurrent pleural diseases. METHODS: Inclusion criteria consisted of echocardiographically documented pericardial effusions requiring diagnosis or relief of symptoms and recurrent effusions after failed percutaneous drainage and balloon pericardiotomy. Pre-operative CT-scan was used to delineate additional pleural pathology and to determine the side of intervention. All patients were followed clinically and by echocardiographic examination 3 months post-operatively. RESULTS: Twenty-four patients underwent thoracoscopic pericardial fenestration with 11 patients (54%) being previously treated by percutaneous catheter drainage, balloon pericardiotomy or subxyphoidal fenestration. Pre-operative echocardiography revealed septation and loculation in 18 patients (72%). Additional pleural pathology was identified on CT scan in 12 patients (50%) and talc pleurodesis was performed in six patients, all suffering from malignant pleural effusion. The mean operation time was 45 min (range 30-60 min) with no complications being observed. All patients were followed 3 months post-operatively by clinical and echocardiographic examination; relief of symptoms was achieved in all patients but echocardiography showed a recurrence in one patient (4%). Another recurrence was found by echocardiography after a mean follow-up time of 33 months in the 12 patients suffering from a non-malignant pericardial effusion. No recurrence of pleural or pericardial effusion was observed in the subset of patients with talc pleurodesis. CONCLUSION: Video-assisted thoracoscopic pericardial fenestration is safe and effective for loculated pericardial effusions previously treated by percutaneous drainage manoeuvres and those with concomitant pleural disease.

Adolescent↗
PubMed1998

Albumin synthesis and bone collagen formation in human immunodeficiency virus-positive subjects: differential effects of growth hormone administration.

Loss of lean tissue often accompanies human immunodeficiency virus (HIV) infection. Exogenous human recombinant GH (hrGH) has been shown to be beneficial in reversing this wasting. However, catabolic effects of hrGH on muscle protein metabolism have also been reported. Therefore, the responsiveness of other GH-sensitive tissues, including bone formation and albumin synthesis, has been examined. Anabolic activity in bone, from serum levels of carboxy-terminal propeptide of type I collagen, was stimulated by 2 weeks of hrGH in controls (56 +/- 15%, P = 0.002), patients with asymptomatic HIV (24 +/- 10%, not significant), patients with AIDS (47 +/- 7%, P < 0.001), and patients with AIDS and > 10% weight loss (21 +/- 12%, P = 0.02). Albumin synthesis, determined from the incorporation of L-[2H5]phenylalanine, was increased in response to hrGH in controls (23 +/- 7%, P < 0.05), HIV+ subjects (39 +/- 16%, P < 0.05), and patients with AIDS (25 +/- 7%, P < 0.01). Patients with AIDS and weight loss, however, did not increase albumin synthesis (-0.6 +/- 12%) in response to hrGH. The results indicate variable anabolic responses to hrGH. Bone collagen synthesis remained sensitive to hrGH, whereas, the anabolic action of hrGH on the synthesis of albumin diminished with severity of disease. However unlike muscle protein synthesis, albumin synthesis was not depressed below basal levels by hrGH.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease.

This study was undertaken to determine if human recombinant growth hormone (hrGH, 6 mg/d for 2 wk) would stimulate muscle protein synthesis in AIDS wasting. Healthy controls were compared with patients who were HIV+, had AIDS without weight loss, and had AIDS with > 10% weight loss. Before hrGH, rates of skeletal muscle protein synthesis, measured with l-[2H5]phenylalanine, were the same in controls and in all stages of disease. Rates of myofibrillar protein degradation, however, assessed from urinary excretion of 3-methyl histidine, were higher in AIDS and AIDS wasting than in HIV+ or healthy individuals. The group with weight loss had significantly higher TNFalpha levels but not higher HIV viral loads. Muscle function, as determined by isokinetic knee extension and shoulder flexion, was significantly higher in controls than all infected individuals. After GH, rates of protein synthesis were stimulated 27% in controls, with a smaller increase (11%) in HIV+, and a significant depression (42%) in AIDS with weight loss, despite fourfold elevation in insulin-like growth factor-I in all groups. There was a significant correlation of hrGH-induced changes in muscle protein synthesis with severity of disease (P = 0.002). The results indicate increased basal muscle protein degradation and decreased responsiveness of muscle protein synthesis to GH in the later stages of disease.

Adult↗
PubMed1997

VATS-guided epicardial pacemaker implantation. Hand-sutured fixation of atrioventricular leads in an experimental setting.

BACKGROUND: In neonates and infants epicardial stimulation may be preferred to endocardial stimulation because of growth-associated lead problems and the risk of vascular complications associated with transvenous electrodes. This study analyzes the feasibility of atrioventricular implantation of a new epicardial lead using the video-assisted thoracic surgical (VATS) technique in an animal model. METHODS: Bipolar steroid-eluting epicardial leads were implanted in seven young white pigs. In five animals bipolar atrial and ventricular pacing leads (n = 10) were inserted and fixed by the VATS technique, while two animals served as controls and underwent implantation through anterolateral thoracotomy. Surgical feasibility, pacing, and sensing thresholds of the leads as well as hemodynamic parameters during pacing were studied. Histological changes beneath the electrodes were evaluated 1 week after the implantation. RESULTS: All animals survived the pacemaker lead implantation. One animal which underwent thoracotomy died because of irreversible ventricular fibrillation induced by rapid ventricular pacing. One animal in the VATS group exhibited intraoperative herniation of the heart through the pericardial window. All animals with left-sided VATS implantations demonstrated good individual pacing and sensing threshold values. The mean cardiac output was 1.6 times higher during AAI-mode pacing as compared to VVI-mode pacing at a heart rate of 140/min. One animal died postoperatively due to respiratory failure. No displacements of the pacemaker leads were observed in the survivors. CONCLUSION: While VATS-guided implantation of epicardial, atrial, and ventricular leads is feasible, technical improvements of the system are mandatory for safe clinical application.

Animals↗
PubMed1997

Isolated pulmonary microangiitis mimicking pneumonia in a patient infected with human immunodeficiency virus.

We describe the first case, to our knowledge, of apparently isolated pulmonary vasculitis mimicking bacterial pneumonia in a patient infected with human immunodeficiency virus (HIV). Patients presenting with fever, cough, and pulmonary infiltrates present a diagnostic challenge. As a result of severe T cell mediated immunosuppression and humoral dysregulation, the differential diagnosis is diverse. One must consider both noninfectious and infectious etiologies. Noninfectious etiologies such as pulmonary lymphoma, endobronchial Kaposi's sarcoma, and adverse drug reactions are common. Recent recognition of the paradoxical association between HIV and systemic vasculitis requires additional acknowledgment of this problem in diagnosis.

Adult↗
PubMed1996

[Implantable cardioverter-defibrillator].

In 1980, therapy with implantable cardioverter-defibrillators in survivors of cardiac arrest was introduced by Michael Mirowski. Over the last 15 years technology in these devices has dramatically improved. In this overview we give a short historical perspective and discuss, briefly aspects of generators, lead systems, sensing and detection algorithms as well as the main therapies of the ICD. Several studies have demonstrated that ICD therapy nearly eliminates sudden cardiac death and that device- and procedure-related mortality has become very low. Despite these impressive results, the overall benefit in terms of mortality has to be assessed; therefore, several randomized studies comparing ICD and competing pharmacological therapies have been started. Because of the rapid growth in popularity of these devices, guidelines for their use have been developed.

Bradycardia↗
PubMed1996

[Diagnostic electrophysiological studies].

Clinical cardiac electrophysiology has evolved over the last decades as a technique to study arrhythmias. Programmed stimulation is a potent tool in assessing the detailed mechanisms of most brady- and tachyarrhythmias as well as a method to judge the efficacy of antiarrhythmic therapy and to stratify patients at risk for the development of life-threatening sustained ventricular arrhythmias. We give an overview of the physiologic mechanisms responsible for paroxysmal supraventricular tachycardias, pre-excited tachycardias as well as sustained ventricular tachycardia in coronary artery disease. Benefit and limitations in assessing the risk for life-threatening tachyarrhythmias in clinically important situations are briefly discussed.

Atrial Flutter↗
PubMed1996

Wasting in the acquired immune deficiency syndrome is associated with multiple defects in the serum insulin-like growth factor system.

OBJECTIVE: The aim of this investigation was to characterize the GH-IGF axis of patients with AIDS associated wasting. A special emphasis was placed on determining whether IGF binding proteins (IGFBPs) of patients who have lost more than 10% of their ideal body mass are structurally different from the IGFBPs of patients with no weight loss. DESIGN AND PATIENTS: A cross-sectional study of 11 AIDS patients was performed to determine whether the IGF system is abnormal in AIDS patients with wasting. Seven additional AIDS patients were followed longitudinally to determine whether AIDS patients experience long-term changes to their IGF system. MEASUREMENTS: Serum levels of GH and IGF-I were measured by radioimmunoassay, IGF-II was measured by radioreceptor assay, and IGFBP-1 was measured by an enzyme linked immunoassay. IGFBP-3 and IGFBP-3 protease activity were measured by ligand blotting and a BP-3 protease assay, respectively. IGFBP-3 ternary complex formation and IGFBP-1 phosphovariants were analysed by non-denaturing PAGE. RESULTS: AIDS patients who had lost more than 10% of their ideal body mass demonstrated a 55% reduction in serum IGF-I (81 vs 179 micrograms/l) and a 70% reduction in IGF-II (226 vs 776 micrograms/l), compared to healthy HIV negative subjects. IGF-I levels were depressed, in some patients, despite high serum levels of GH. AIDS patients who had lost more than 10% of their ideal body mass had low levels of IGFBP-3 and a reduced ability to form the IGFBP-3 ternary complex. The IGFBP-3 ternary complex could be restored only upon addition of pure IGFBP-3 and acid labile subunit to serum. Serum IGFBP-1 was increased more than threefold compared to control subjects (90 vs 24 micrograms/l). IGFBP-1 was present as a free phosphoprotein in AIDS patients with low levels of IGF-I and in a bound form when serum IGF-I levels were normal. Changes in the GH-IGF axis were sustained for up to 25 months in AIDS patients with wasting. CONCLUSIONS: AIDS wasting is associated with a GH resistant state that results in low levels of serum IGF-I, IGF-II and IGFBP-3, elevated levels of phosphorylated IGFBP-1, and a reduced ability to form the IGFBP-3 ternary complex.

Acquired Immunodeficiency Syndrome↗