Search PubMed⌕ Search

Biomedical subjects

S Fink

Publications and source records attributed to S Fink.

At least 19 recordsLinked to original sources
PubMed1999

Screen for MAOA mutations in target human groups.

Brunner et al. [1993: Am J Hum Genet 52: 1032-1039; 1993: Science 262:578-580] described males with an MAO-A deficiency state resulting from a premature stop codon in the coding region of the MAOA gene. This deficiency state was associated with abnormal levels of amines and amine metabolites in urine and plasma of affected males, as well as low normal intelligence and apparent difficulty in impulse control, including inappropriate sexual behavior. In the present study, disruption of the MAOA gene was evaluated in males with mental retardation with and without a history of sexually deviant behavior, as well as normal controls, healthy males, and patients with other diseases (Parkinson disease, Lesch-Nyhan syndrome). When available, plasma samples were evaluated first for levels of 3-methoxy, 4-hydroxyphenolglycol (MHPG), a metabolite of norepinephrine which serves as the most sensitive index of MAO-A activity in humans. Blood DNA from individuals with abnormally low MHPG, and from other individuals for whom metabolite levels were not available, were screened for nucleotide variations in the coding region of the MAOA gene by single-strand conformational polymorphism (SSCP) analysis across all 15 exons and splice junctions, and by sequencing, when indicated by either altered metabolites or SSCP shifts. No evidence for mutations disrupting the MAOA gene was found in 398 samples from the target populations, including institutionalized mentally retarded males (N = 352) and males participating in a sexual disorders clinic (N = 46), as well as control groups (N = 75). These studies indicate that MAOA deficiency states are not common in humans.

Adult↗
PubMed1999

Clinical use of continuous arterial blood gas monitoring in the pediatric intensive care unit.

CONTEXT: Continuous arterial blood gas monitoring is a new technology based on the combination of opto-chemical and fiber-optic detectors that can measure pH, PCO2, PO2, and temperature on a continuous basis via a sensor placed in an artery. OBJECTIVE: To evaluate this technology in pediatric patients who would normally require frequent arterial blood gas sampling. DESIGN: A criterion standard study in which the results of arterial blood gas samples measured by the laboratory analyzer were compared with the sensor readings. SETTING: A pediatric intensive care unit of a tertiary referral center. PATIENTS: Children with severe respiratory failure who required frequent arterial blood gas sampling and who had a 20-gauge arterial line in either a radial or femoral site. RESULTS: Twenty-four patients with a mean age of 6.4 years (range 1-21 years) had a sensor placed. Sensors were in place for a mean of 101 +/- 62 hours. Eighteen patients underwent continuous monitoring for at least 24 hours or until no longer clinically necessary. There were 414 pairs of blood gas samples obtained. The bias/precision for pH was 0.005/0.030; for PCO2, -1.8/6.3 mm Hg; and for PO2, 1.2/24 mm Hg. The correlation (r value) between the sensor readings and the blood gases were pH 0. 960, PCO2 0.927, PO2 0.813 (P <.01 for all values). The bias and precision for PO2 levels < 70 mm Hg were 0.057/9.34 mm Hg. There were no complications from sensor placement. Continuous blood gas monitoring allowed immediate recognition of clinical changes. CONCLUSION: The continuous arterial blood gas sensor is capable of clinically accurate blood gas measurements. This technology provides the clinician with immediate data that can allow rapid interventions in unstable patients.

Adolescent↗
PubMed1998

Role of radionuclide phallogram in therapeutic decision-making for erectile dysfunction.

OBJECTIVE: The purpose of this study is to evaluate the role of radionuclide phallograms in therapeutic decision-making for erectile dysfunction. METHOD: Forty-eight impotent men being considered for pharmacologically-induced penile erection therapy (PIPE) had radionuclide phallograms (RP) as part of their evaluation. RP were performed using 99mTc-labeled autologous red blood cells and provided a measurement of penile blood volume (PBV) change following the intracorporeal injection of 0.25 to 0.3 mL of a papaverine/phentolamine mixture. RESULTS: Thirty-eight patients showed a good response with a mean PBV increase 2.6 times baseline (range 1.2 to 8.9). Ten patients had significantly lower PBV changes (P = 0.001) than the first group, with a mean PBV increase of 1.6 times baseline (range 1.1 to 2.4). These ten patients were dissatisfied with pharmacologically induced penile erection (PIPE) therapy after an unsuccessful treatment trial. CONCLUSION: We conclude that the RP can help to discriminate between patients who will benefit from PIPE therapy and those who will not.

Adult↗
PubMed1998

Interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are necessary in the early stages of induction of CD4 and CD8 cytotoxic T cells by Mycobacterium leprae heat shock protein (hsp) 65 kD.

Cytotoxic T cells (CTL) may play an important role in host defence against mycobacterial infections. CD4 CTL are preferentially induced by mycobacteria, but both CD4 and CD8 CTL may be necessary components of a protective immune response. The 65-kD mycobacterium heat shock protein (hsp65) is a poor inducer of CTL in multibacillary leprosy (MB) patients. In this study we evaluate the possible role of cytokines in modulating the cytotoxic activity of CTL from leprosy patients and normal individuals (N) against autologous macrophages presenting Mycobacterium leprae hsp65. Our results show that hsp65-specific CTL were generated from both CD4 and CD8 lymphocytes. In N, individual cytokines as well as the combination of them were able to modify the hsp65-induced cytotoxic activity. The effect of cytokines on leprosy patients' lymphocytes was different in MB and paucibacillary (PB) patients. Thus, IL-6, IL-2, IFN-gamma or TNF-alpha did not modify the generation of hsp65-CTL from either MB (with or without an erythema nodosum episode (ENL)) or PB. In all the patients the simultaneous addition of two cytokines was required in order to increase CTL generation. In MB, IL-6 plus IFN-gamma or IL-2 increased both CD4 and CD8 CTL, while TNF-alpha plus IFN-gamma up-regulated only CD4 CTL. In PB, CD8 CTL were prominent with IL-6 plus IFN-gamma, while the increase was significant in CD4 CTL with IL-6 plus IL-2. Down-regulation of CTL was observed by addition of IL-4, IL-10, anti-IFN-gamma or anti-TNF-alpha in N controls. Our data demonstrate that IFN-gamma and TNF-alpha must be present for at least the first 60 h of the induction stage in order to generate full hsp65 CTL. Hence, IFN-gamma and TNF-alpha would be key factors in the generation of hsp65 CTL.

Adolescent↗
PubMed1998

Pulmonary embolism and malpractice claims.

BACKGROUND: Deep venous thrombosis (DVT) with pulmonary embolization (PE) often occurs as an unexpected event with fatal consequences. This provides a setting for malpractice claims. METHODS: We reviewed 160 consecutive malpractice claims submitted by attorneys for medical expert review during the 11-year period ending in 1997. Seven cases involved DVT with PE. RESULTS: Alleged failure to anticipate and reduce the chance of PE was the basis for six of the claims. All six patients were at risk for lower extremity DVT, and one had a history of DVT 6 months earlier. The PE was manifested by sudden death in three cases. The seventh case represented a complication of heparin therapy for PE. CONCLUSIONS: We conclude that risk management for PE should focus primarily on DVT. Physicians should perform and document an examination for DVT whenever there is a history of lower extremity stasis or it is likely to occur. They should also consider documenting a concurring second opinion when making anticoagulant-related decisions.

Adult↗
PubMed1997

Iatrogenic hypoglycemia and malpractice claims.

Iatrogenic neuroglycopenia represents a medical emergency for which accepted and usually effective treatment exists. Treating physicians face a malpractice risk if there is permanent neurologic damage and there is a perception of failure to act prudently both before and after the damaging episode. We report two cases to illustrate the medical and legal issues that may be raised in such claims.

Aged↗
PubMed1997

Stroke and malpractice claims.

We describe 15 malpractice claims that were filed after the patients had strokes. Both embolic and thrombotic, sterile and infected strokes led to claims. Ten of the claims alleged physician failure to protect the patient, two alleged physician failure to react as called for by symptoms, and three were related to medication. We conclude that physicians should advise patients of the possibility of stroke when circumstances warrant it, as well as documenting their judgment and suggested preventive practices. These cases further suggest that treatment decisions supported by documented second opinions may reduce the number of malpractice claims for strokes.

Anti-Bacterial Agents↗
PubMed1997

Differential development of CD4 and CD8 cytotoxic T cells (CTL) in PBMC across the leprosy spectrum; IL-6 with IFN-gamma or IL-2 generate CTL in multibacillary patients.

In the present study we evaluated the contribution of CD4 and CD8 T cells on the antigen-specific cytotoxic activity induced by whole Mycobacterium leprae in leprosy patients and normal controls (N) as well as the modulation of this activity by some cytokines. Peripheral blood mononuclear cells (PBMC) from N or from leprosy patients were stimulated with antigen in the presence or absence of cytokines for 7 days. M. leprae-stimulated PBMC were depleted of CD4 or CD8 antigen-bearing cells and employed as effector cells in a 4-hr [31Cr]-release assay against autologous M. leprae-pulsed macrophages. Our results demonstrate that both CD4 and CD8 T cells contribute to M. leprae-induced cytotoxic activity, with differences observed in paucibacillary (PB) and multibacillary (MB) patients. CD8-mediated cytotoxic activity is higher than that of CD4 cells in PB patients, while in MB patients CD4 cytotoxicity is predominant. Our data also demonstrate that the generation of CD4 and CD8 cytotoxic T lymphocytes (CTL) can be modulated differentially by interleukin-4 (IL-4), IL-6, gamma interferon (IFN-gamma), or IL-2. Although MB patients developed the lowest CTL response, cytokines such as IL-6 plus IL-2 or IFN-gamma were able to generate both CD4 and CD8 cytotoxic T cells from MB patients. In PB patients, IL-6 plus IFN-gamma displayed the highest stimulation on CD8 effector cells. Thus, an important role may be assigned to IL-6, together with IL-2 or IFN-gamma, in the differentiation of M. leprae-specific CTL effector cells.

Adolescent↗
PubMed1996

T-lymphocyte subsets in patients with abnormal body weight: longitudinal studies. in anorexia nervosa and obesity.

OBJECTIVE: In contrast to other types of starvation which are characterized by low CD4+ counts and increased susceptibility to infection, anorexia nervosa is not associated with an increase in infectious complications. To determine why infection risk of anorectics differs from that of other starving populations, we studied T-lymphocytes, including CD4+ and CD8+ phenotypes, in patients with anorexia nervosa, and for comparison, in dieting obese subjects. METHODS: T-lymphocyte phenotypes were determined by flow cytometric analysis of monoclonal antibody-labeled cells obtained from patients with anorexia nervosa before and after successful therapy and weight gain, and in obese subjects before and after weight loss on a very-low-calorie diet. RESULTS: Weight loss in anorectics and obese dieters was associated with normal CD4+ counts. Unexpectedly, CD8+ counts were low in anorectics, both before and after weight gain, and in obese subjects after (but not before) dieting. DISCUSSION: Normal CD4+ counts in anorectics and obese dieters, despite marked weight loss, may explain the lack of increased infection risk in these eating-disordered patients, in contrast to other starving populations. The observation that CD8+ counts are low in anorectics with low and restored body weight and in obese patients after dieting has not been previously reported. The persistence of low CD8+ counts in anorectics even after weight gain suggests that some factors other than weight loss per se may be involved, possibly including effects due to stress, comorbid psychiatric conditions, or unidentified aspects of dysregulated pathophysiology secondary to disordered eating.

Adolescent↗
PubMed1996

Continuous arterial gas monitoring: initial experience with the Paratrend 7 in children.

OBJECTIVE: To describe clinical usage of the Paratrend 7 continuous arterial blood gas monitor in children. DESIGN: Children older than 24 months of age who required significant ventilatory intervention were eligible for sensor placement. INTERVENTIONS: The sensor was placed via the arterial catheter to measure pH, PCO2, PO2, and temperature. The simultaneous arterial blood gas value was recorded along with the sensor reading. RESULTS: The sensor functioned for as long as seven days and provided the clinicians with data on the patient's respiratory status. The statistical validity of the device when compared to the arterial blood gas showed that the bias/precision for pH was 0.006/0.024, for PCO2 -0.78/4.68 mmHg, and for PO2 1.9%/17.1% (mmHg). CONCLUSIONS: This report demonstrates actual clinical use of continuous blood gas monitoring in children. The information obtained is a major asset to the management of critically ill children in the intensive care unit.

Age Factors↗
PubMed1996

Clinical evaluation of a multiparameter intra-arterial blood-gas sensor.

OBJECTIVE: To evaluate the in vivo performance of a continuous, intra-arterial, multiparameter blood-gas sensor containing a thermocouple, miniaturized polarographic oxygen electrode, as well as fiberoptic pH and pCO2 sensors. DESIGN: Prospective, multicenter study comparing pH, PaCO2, and PaO2 measurements from the intraarterial sensor with those obtained from a conventional, laboratory blood-gas monitor. SETTING: Intensive care units in three academic medical centers. PATIENTS: Adult ICU patients (n = 26) with a clinical need for a radial artery catheter and frequent monitoring of arterial blood gases for > or = 3 days. INTERVENTIONS: All patients had the multiparameter intra-arterial sensor placed through a 20-gauge catheter into the radial artery. Every 4 h, or more frequently if clinically indicated, a blood-gas sample was withdrawn from the radial artery catheter and sent to the laboratory for analysis using a conventional laboratory blood-gas analyzer. Immediately prior to withdrawal of the arterial blood, values for pH, PaCO2, and PaO2 from the multiparameter intra-arterial sensor were recorded. MEASUREMENTS AND MAIN RESULTS: The multiparameter sensor was placed into 26 patients. In 7 of the patients, premature discontinuation of monitoring was necessary because of dampening of the pressure tracing, difficulty in withdrawing blood from the arterial catheter, or bending of the extra-arterial fiberoptic channel owing to the cable being inadequately secured (mean monitoring time in these 7 patients: 40.6 +/- 25.7 h). In the other 19 patients, monitoring was continued until no longer clinically indicated. In these patients, a total of 341 data sets was collected, with the average length of monitoring being 69.9 +/- 37.9 h (range 22.0 to 57.9 h). Comparison of the sensor values with those from the blood-gas analyzer showed bias and precision values of 0.006 and 0.026 for arterial pH - 1.19% and 12.54% for PaO2, and 1.28 mmHg and 2.48 mmHg for PaCO2, respectively. No complications were associated with the intra-arterial sensor. CONCLUSIONS: Clinical performance of this intra-arterial, multiparameter blood-gas sensor demonstrated stability, consistency, and accuracy comparable to laboratory blood-gas analyzers. The present multiparameter, intravascular blood-gas sensor, when inserted in the radial artery, can provide stable and accurate monitoring of pH, PaCO2, and PaO2 over clinically relevant periods of as long as 6 days in the critical care setting.

Adult↗
PubMed1996

[Evaluation of cytokine production in leprosy patients].

The aim of the present study was to evaluate the cytokine production by peripheral blood mononuclear cells (PBMC) of leprosy patients when the cells were stimulated in culture by ConA, PPD or M.leprae. We measured IL-2, IL-4, IFN-gamma and IL-6 in cell-free supernatants by enzyme linked immunoassays. Our results do not suggest a clear association of a clinical form of leprosy with either Th1 or Th2 cytokine secretion profile in PBMC of leprosy patients.

Adolescent↗
PubMed1995

Every-other-week methotrexate in patients with rheumatoid arthritis. A double-blind, placebo-controlled prospective study.

OBJECTIVE: To determine if patients with rheumatoid arthritis (RA) that is stable with weekly methotrexate (MTX) therapy could be switched to an every-other-week regimen of MTX. METHODS: Forty-seven patients with classic or definite RA who had received MTX for at least 8 months were studied. Clinical measurements consisted of the number of tender and swollen joints, physician and patient global evaluation of disease activity on a 5-point scale, grip strength, patient evaluation of pain, morning stiffness, and the interval to onset of fatigue from time of awakening. Laboratory measures included the erythrocyte sedimentation rate (ESR), rheumatoid factor, C-reactive protein (CRP), and baseline serum folate levels. Uptake of MTX was measured with tritiated thymidine from peripheral blood mononuclear cells (PBMC) from patients ex vivo. Serum measures of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF alpha) were performed in sera, and TNF alpha was also measured on PBMC supernatants. RESULTS: Twelve of the 23 patients receiving every-other-week MTX (52%) were able to complete 6 months of this treatment without experiencing a disease flare. Eleven of the 23 patients receiving every-other-week MTX (48%) withdrew from the study before completing 6 months of treatment, because of a flare. No significant differences in clinical or laboratory parameters were seen when the 24 patients receiving weekly MTX were compared with the 12 patients in the every-other-week MTX group who successfully completed 6 months of the study. None of the changes in serum cytokine levels were significantly different between the patients receiving MTX weekly versus those receiving it every other week, and changes in ESR and CRP did not differ between groups. Age, sex, RA disease duration, MTX weekly dose or duration, baseline joint counts, or serum folate status did not predict a flare. Tritiated MTX uptake did not differ between groups. CONCLUSION: Some patients with RA that is stable on weekly dosing are able to change to every-other-week dosing without experiencing a flare in their disease activity.

Aged↗
PubMed1995

Medical characteristics of 61 unwarranted malpractice claims.

We describe malpractice claims closed by plaintiff attorneys after initial medical expert (ME) review. This retrospective study includes 61 cases, of which 33 originated in hospitals, 18 in physicians' offices, and 10 in nursing homes. No claims were against state or federal agencies. The reviews were done between 1987 and 1994 for 29 attorneys from 11 states. The cases fell into 12 diagnostic groups, and leading causes for action were late diagnosis (13 cases), drug administration (11 cases), sepsis (6 cases), and strokes (5 cases). We conclude that internists are particularly liable to unwarranted malpractice claims when unexpected complications occur and when treatment fails to cure infectious disease. However, such claims may be terminated following the initial ME review.

Accidental Falls↗