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Biomedical subjects

D Wolfe

Publications and source records attributed to D Wolfe.

At least 37 records · Page 2Linked to original sources
PubMed1998

Volatile anesthetic additivity and specificity in Saccharomyces cerevisiae: implications for yeast as a model system to study mechanisms of anestheitc action.

BACKGROUND: In animals, combinations of volatile anesthetics are additive for inducing anesthesia. Furthermore, although there is a correlation between lipophilicity and anesthetic potency, not all volatile lipophilic compounds are anesthetic. Previously the authors demonstrated the effects of volatile anesthetics on the eukaryote Saccharomyces cerevisiae (yeast). To further relate anesthetic action in this organism to mammals, anesthetic additivity and effects of volatile, lipophilic nonanesthetics were studied. In addition, yeast pleiotropic drug-resistance (Pdr) mutants, which confer resistance to various lipophilic compounds, were tested to determine if they are involved in anesthetic response. METHODS: Yeast strains were grown to saturation in liquid culture, diluted, plated on various solid media, incubated, and scored for growth. RESULTS: Combinations of volatile anesthetics inhibit growth of wild-type (Zzz+) but not anesthetic-resistant (Zzz-) strains when additive concentrations equal 1 minimum inhibitory concentration (MIC). Two volatile, lipophilic compounds that are nonanesthetic in mammals do not inhibit yeast growth. Zzz- mutants remain sensitive to drugs used to identify yeast PDR genes. Conversely Pdr strains, which are resistant to various lipophilic compounds, remain sensitive to volatile anesthetics. CONCLUSIONS: Yeast growth is inhibited in an additive manner by volatile anesthetics. Volatile, lipophilic compounds devoid of anesthetic activity in mammals do not inhibit yeast growth. Zzz- mutants appear to be specifically resistant to volatile anesthetics and distinct from known Pdr mutants. These results suggest that volatile anesthetics behave in a parallel manner in yeast and mammals, making yeast a useful model to investigate the molecular effects of these compounds in living cells.

Anesthetics, Inhalation↗
PubMed1998

Cerebral syncope: loss of consciousness associated with cerebral vasoconstriction in the absence of systemic hypotension.

Transcranial Doppler (TCD) ultrasonography done during head-upright tilt induced neurocardiogenic syncope has demonstrated that cerebral vasoconstriction occurs concomitant with (or precedes) loss of consciousness. This article demonstrates evidence that cerebral blood flow changes alone (vasoconstriction), in the absence of systemic hypotension, may result in syncope. Five patients (4 men, 1 woman; mean age 41 +/- 17 years) with recurrent unexplained syncope were evaluated by use of an upright tilt table test for 45 minutes with or without an infusion of low dose isoproterenol. TCDoppler ultrasonography was used to assess middle cerebral artery systolic velocity (Vs); diastolic velocity (Vd); mean velocity (Vm); and pulsatility index (PI = Vs = Vd/Vmean). Syncope occurred in five patients during the baseline tilt and in one patient during isoproterenol infusion. During tilt induced syncope, at an average mean arterial pressure of 89 +/- 16 mmHg, TCD sonography showed a 2% +/- 10% increase in systolic velocity; a 51% +/- 27% decrease in diastolic velocity; and a 131% +/- 87% increase in pulsatility index. One patient underwent continuous electroencephalographic recording during tilt, which demonstrated diffuse slow wave activity (indicating cerebral hypoxia) at the time of syncope concomitant with the aforementioned TCD changes in the absence of systemic hypotension. These findings reflect an increase in cerebrovascular resistance secondary to arteriolar vasoconstriction distal to the insonation point of the middle cerebral artery, that occurred concomitant with loss of consciousness and in the absence of systemic hypotension. We conclude that in some individuals abnormal baroreceptor responses triggered during orthostatic stress may result in a derangement of cerebral autoregulation leading to cerebral vasoconstriction with resultant cerebral hypoxia in the absence of systemic hypotension.

Adolescent↗
PubMed1998

An epidemiologic and entomologic investigation of a cluster of Rocky Mountain spotted fever cases in Delaware.

BACKGROUND: Rocky Mountain spotted fever (RMSF) continues to be the most common fatal tick-borne illness in the United States. In August of 1996, four children attending a summer camp in Delaware were diagnosed with RMSF. This report summarizes the results of the epidemiologic and entomologic investigation conducted by the Delaware Division of Public Health and the Centers for Disease Control and Prevention regarding this cluster of RMSF cases. Epidemiologic and clinical aspects of RMSF, as well as previously reported clusters of the disease, are also reviewed. METHODS: A questionnaire regarding symptoms and activities was administered via telephone to 163 (73 percent) of the 223 attendees. A suspected case was defined as an illness in a person attending the camp between August 11 and 17 that occurred during the two-week period following the session, characterized by either 1) fever with one or more symptoms (i.e., headache, rash, myalgia, or fatigue) or 2) no fever with two or more symptoms. Cases of RMSF were confirmed by serologic evaluation. RESULTS: Seven of 13 patients with suspected RMSF submitted sera for testing. Four patients had confirmed RMSF; three were males, and the median age was 12.5 years compared with 12 years for all attendees. All confirmed patients reported fever, headache, fatigue, and rash. An increased risk of becoming ill was associated with overnight camping at site A (Odds Ratio (OR) undefined, p = 0.02), visiting or overnight camping at site B (OR undefined, p = 0.003 and 0.002), and leaving the trails when hiking (OR undefined, p = 0.02). CONCLUSIONS: These data suggest that development of RMSF was associated with visiting or camping at specific sites and behavior likely to increase contact with ticks. Camp supervisors were advised to educate campers regarding tick bite prevention measures, reduce underbrush around campsites, and encourage campers to remain on the trails. Health care providers should remain aware of the increased risk for RMSF during the spring, summer, and fall months.

Animals↗
PubMed1997

Loss of heterozygosity in the retinoblastoma tumor suppressor gene in skull base chordomas and chondrosarcomas.

BACKGROUND: The retinoblastoma (Rb) gene is a well characterized tumor suppressor gene in which loss of heterozygosity has been implicated in a number of malignancies including osteosarcoma and breast carcinoma. Chordomas and chondrosarcomas are rare skull base neoplasms with a propensity for local recurrences, resistance to conventional radiotherapy, and a 5%-30% incidence of metastases. Except for the so called "chondroid chordoma," histologic features do not correlate with the clinical behavior or growth patterns of these tumors. No study to date has investigated what role tumor suppressor genes or oncogenes play in the development and continued growth of these rare neoplasms. METHODS: In order to evaluate the role of the retinoblastoma tumor suppressor gene in chordomas and chondrosarcomas we screened seven chordomas and two chondrosarcomas located at the skull base for loss of heterozygosity (LOH) of the Rb gene. Genomic DNA was extracted from tumor specimens as well as matched control tissue and utilizing a polymerase chain reaction technique, intron 17 and 20 were amplified from each specimen. The intron 17 product was then digested with the restriction endonuclease X ba1 followed by electrophoresis on a 1% agrose gel. The intron 20 amplified products were electrophoresed on a nondenaturing 6% polyacrylamide gel. RESULTS: We demonstrated LOH at intron 17 of the retinoblastoma gene in 2/7 chordomas and in 0/2 chondrosarcomas. The two chordomas possessing LOH were particularly aggressive tumors demonstrating extensive involvement of the skull base and rapid recurrences following radical resections. CONCLUSIONS: Alterations of the Rb gene may play a role in the growth of skull base chordomas with LOH of the Rb gene serving as a marker for more aggressive tumors. This report represents the first study evaluating the Rb gene in chordomas or chondrosarcomas and is the first report of allelic loss of the Rb gene in skull base chordomas.

Adolescent↗
PubMed1996

Molecular genetic analysis of volatile-anesthetic action.

The mechanism(s) and site(s) of action of volatile inhaled anesthetics are unknown in spite of the clinical use of these agents for more than 150 years. In the present study, the model eukaryote Saccharomyces cerevisiae was used to investigate the action of anesthetic agents because of its powerful molecular genetics. It was found that growth of yeast cells is inhibited by the five common volatile anesthetics tested (isoflurane, halothane, enflurane, sevoflurane, and methoxyflurane). Growth inhibition by the agents is relatively rapid and reversible. The potency of these compounds as yeast growth inhibitors directly correlates with their lipophilicity as is predicted by the Meyer-Overton relationship, which directly correlates anesthetic potency of agents and their lipophilicity. The effects of isoflurane on yeast cells were characterized in the most detail. Yeast cells survive at least 48 h in a concentration of isoflurane that inhibits colony formation. Mutants resistant to the growth-inhibitory effects of isoflurane are readily selected. The gene identified by one of these mutations, zzz4-1, has been cloned and characterized. The predicted ZZZ4 gene product has extensive homology to phospholipase A2-activating protein, a GO effector protein of mice. Both zzz4-1 and a deletion of ZZZ4 confer resistance to all five of the agents tested, suggesting that signal transduction may be involved in the response of these cells to volatile anesthetics.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Progressive multifocal leukoencephalopathy after orthotopic liver transplantation.

Six weeks after liver transplantation, a 51-year-old man developed a slowly progressive hemiparesis with deteriorating mental status and seizures. Successive computed tomography (CT) scans of the brain revealed unilateral nonenhancing white matter lucencies that gradually coalesced and progressed to both hemispheres. Brain biopsy results were consistent with progressive multifocal leukoencephalopathy (PML). We believe this is the first antemortem description of PML after liver transplantation. Herein, we describe the case and review the literature on PML after solid organ transplantation. Early recognition of this central nervous system disease may be important with new advances in therapy of this viral infection of the immunocompromised patient.

Biopsy↗
PubMed1995

Mitochondrial abnormalities in human immunodeficiency virus-associated myopathy.

There is controversy as to whether zidovudine (ZDV) induces a mitochondrial myopathy that is distinguishable from human immunodeficiency virus (HIV)-associated myopathy in ZDV-naive patients. Mitochondrial abnormalities were evaluated in skeletal muscle obtained from 18 HIV-positive, ZDV-exposed patients, and 9 who were drug naive. All patients had clinical myopathy, and underwent neuromuscular evaluation with information recorded on timing and dosage of ZDV. All underwent muscle biopsies and samples were examined without knowledge of clinical history or ZDV status. Biopsy samples were evaluated by light and electron microscopy. Mitochondrial abnormalities were seen in ZDV-treated and -naive groups, and did not correlate with ZDV exposure or cumulative ZDV dosage. Mitochondrial abnormalities displayed significant correlation with the presence and severity of myofiber degeneration on biopsy, regardless of ZDV status. As mitochondrial abnormalities reflect myofiber degeneration, present in both patient groups, they may not be used as evidence of primary mitochondrial dysfunction. The etiology of myofiber degeneration in patients with HIV infection, whether ZDV-exposed or -naive, remains unclear.

Adult↗
PubMed1995

Eosinophilic temporal and systemic arteritis.

We describe a 39-year-old patient with an unusual type of bilateral temporal arteritis characterized histologically by inflammation, diffuse eosinophilic infiltration, destruction of elastic tissue, and fibrosis. In addition, the patient had a history of systemic vasculitis, peripheral eosinophilia, eosinophilic lymphadenitis, and membranous glomerulonephritis. The patient has been followed up for 14 years and is well controlled on moderate doses of steroids. We propose that this patient suffers from an immune reaction to an unknown, possibly infectious, antigen.

Adult↗
PubMed1995

The effect of retrograde cerebral perfusion after particulate embolization to the brain.

Neurologic injury as a consequence of cerebral embolism of either air or atherosclerotic debris during cardiac or aortic surgery is still a major cause of postoperative morbidity and mortality. While exploring various means of improving cerebral protection during complex cardiothoracic procedures, we have developed a chronic porcine model to study retrograde cerebral perfusion. We have previously demonstrated that retrograde perfusion results in a small amount of nutritive flow and provides cerebral protection that appears to be superior to simple prolonged hypothermic circulatory arrest. The current study was designed to evaluate the efficacy of retrograde cerebral perfusion in mitigating the effects of particulate cerebral embolism occurring during cardiac surgery. Four groups of pigs (19 to 28 kg) underwent cardiopulmonary bypass with deep hypothermia at an esophageal temperature of 20 degrees C: an antegrade control group (AC, n = 5), an antegrade embolism group (AE, n = 10), a retrograde control group (RC, n = 5), and a retrograde embolism group (RE, n = 10). In addition, because of extreme heterogeneity in outcome in the initial RE group, an additional group of 10 animals underwent embolism and retrograde perfusion at a later time. Embolization was accomplished by injection of 200 mg of polystyrene microspheres (250 to 750 micrograms in diameter) via the aortic cannula into an isolated aortic arch preparation in the AE and RE groups; the control groups received injections of 10 ml of saline solution. After infusion of the microspheres or saline solution, conventional perfusion, with the aortic arch pressure maintained at 50 mm Hg, was continued for a total of 30 minutes in the antegrade groups; in the retrograde groups, retrograde flow was initiated via a cannula positioned in the superior vena cava, and was continued for 25 minutes. Superior vena caval flow was regulated to maintain a sagittal sinus pressure of approximately 30 mm Hg in the retrograde groups, and blood returning to the isolated aortic arch was collected and measured. All animals were allowed to recover and were evaluated daily according to a quantitative behavioral score in which 9 indicates apparently complete normalcy, with lower numbers indicating various degrees of cerebral injury. At the time of planned death on day 6, half of the brain was used for recovery of embolized microspheres after digestion with 10N sodium hydroxide. The other half was submitted for histologic study. Neurologic recovery in both the antegrade and retrograde control groups appeared to be complete, although mild evidence of histologic damage was present in some animals in the retrograde control group.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Type II collagen in mixed tumors of the skin. An immunohistochemical study and new speculations concerning histogenesis.

We studied 11 cases of mixed tumor of the skin with a polyclonal antibody against human type II collagen. Two of the cases were of the eccrine type, six were apocine, and three were malignant. In all of the benign cases of mixed tumor and in some of the malignant type, "chondroid" and mucinous portions stained. The clearly epithelial portions of the tumor stained as well, and staining was most intense in the eccrine types and least intense in the malignant types. The positive staining in mixed tumors may help elucidate the histogenesis of these unusual tumors as well as help differentiate among the various subtypes.

Adenoma, Pleomorphic↗
PubMed1994

Leigh syndrome and hypertrophic cardiomyopathy in an infant with a mitochondrial DNA point mutation (T8993G).

Mutation of mitochondrial (mt) DNA at nucleotide (nt) 8993 has been reported to cause neurogenic weakness, ataxia, retinitis pigmentosa (NARP), or Leigh syndrome (LS). We report a family in whom the mutation was expressed clinically as LS and hypertrophic cardiomyopathy (CMP) in a boy who presented with a history of developmental delay and hypotonia, and who had recurrent lactic acidosis. The mother's first pregnancy resulted in the birth of a stillborn female; an apparently healthy older brother had died suddenly (SIDS) at age 2 months. MtDNA analysis identified the presence of the T8993G point mutation, which was found to be heteroplasmic in the patient's skeletal muscle (90%) and fibroblasts (90%). The identical mutation was present in leukocytes (38%) isolated from the mother, but not from the father or maternal grandmother. Our findings expand the clinical phenotype of the nt 8993 mtDNA mutation to include hypertrophic cardiomyopathy and confirm its cause of LS.

Acidosis, Lactic↗
PubMed1994

Fluoxetine hydrochloride for the treatment of severe refractory orthostatic hypotension.

OBJECTIVE: To evaluate the usefulness of fluoxetine hydrochloride in the treatment of patients with severe refractory orthostatic hypotension. DESIGN: Prospective, nonrandomized study. PATIENTS: Five patients (3 men, 2 women with a mean age of 67 +/- 7 years with chronic symptomatic orthostatic hypotension resistant to or intolerant of other therapies. METHODS: Symptoms and orthostatic responses were recorded in the baseline state. Fluoxetine hydrochloride 20 mg orally once daily was started and patients were reevaluated after 6 to 8 weeks of therapy. RESULTS: All patients demonstrated orthostatic hypotension (20 mm Hg or greater decline in systolic blood pressure) associated with symptoms (eg, dizziness, vertigo, near syncope) in the baseline state. After 6 to 8 weeks of fluoxetine therapy, 2 patients reported resolution of all symptoms, 2 had a marked reduction in symptoms, and 1 patient experienced no effect. Orthostatic responses were attenuated in 4 of the 5 patients (80%). CONCLUSION: Fluoxetine hydrochloride may be an effective therapy for some patients with recurrent severe orthostatic hypotension refractory to other forms of therapy.

Aged↗