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Biomedical subjects

M Estes

Publications and source records attributed to M Estes.

At least 19 recordsLinked to original sources
PubMed2001

Cardiac conduction abnormalities in a mouse model of Lyme borreliosis.

BACKGROUND: Borrelia Burgdorferi (BB) induces cardiac conduction abnormalities in infected humans. Mice models of Lyme disease have been developed, however their electrophysiologic (EP) properties of conduction are unknown. METHODS: Seventy-six C3H/J mice (BB infected and age- and gender-matched controls) underwent blinded in vivo EP studies. In a first phase of the study, 40 male C3H/J mice were divided into 2 groups: Group (A) mice were infected at age 3 (weeks) and studied at 5, and Group (B) mice were infected at 9 and studied at 11. In a second phase, 36 female mice were divided into 2 groups: Group (C) mice were infected at 3 weeks and studied at 5, and Group (D) mice were infected at 3 and studied at 11. RESULTS: Infected mice of group (A) and (C) had wider QRS complexes (21.0+/-1.6 versus 17.3+/-1.3ms, p< or =0.0001 and 20.3+/-2.1 versus 18.5+/-1.7, p = 0.05, respectively) compared to the healthy controls (HC). Infected mice of group (B) and group (D) were similar to the HC. In all groups, the presence of conduction abnormalities correlated very closely with the amount of inflammation on pathology. CONCLUSION: This study describes the first EP mouse model of Lyme carditis. C3H/J mice exhibit conduction abnormalities that are reversible 8 weeks after inoculation, closely paralleling the resolution of inflammation on pathology. This model can be a valuable tool in the developing and testing of new modalities for the prevention and treatment of Lyme carditis.

Animals↗
PubMed2001

Jail inmates and HIV care: provision of antiretroviral therapy and Pneumocystis carinii pneumonia prophylaxis.

The objective of this study was to examine prescription and acceptance of antiretroviral therapy (ART) and Pneumocystis carinii pneumonia (PCP) prophylaxis in jail and at release. A retrospective cross sectional design was used, by record review, of 77 inmates receiving HIV-related care in the San Francisco City and County Jail and released to the community in 1997. Average CD4 cell count was 335/microl. Fifteen had undectable HIV RNA, and average viral load was 19,826 copies/ml. Fifty-eight per cent were put on ART in jail. Lower CD4 cell count was associated with ART (P=0.017). All inmates with CD4 cell counts less than 200/microl received PCP prophylaxis. According to 1996 guidelines, 72% of those eligible for ART were on therapy. Of 24 inmates released on ART, 71% followed medical advice and picked up medication at release. HIV care in the San Francisco Jail met high standards and exceeded levels reported in other populations.

Adult↗
PubMed2000

Distinct epidemiological patterns of Norwalk-like virus infection.

Norwalk-like viruses (NLV) are important economically as a cause of both sporadic gastroenteritis in the community and large outbreaks in hospitals and other institutional settings. Despite the description of several antigenic types relatively little is known about the epidemiology of these individual types. NLVs were detected by electron microscopy in faecal specimens from 706 outbreaks of gastroenteritis that represented 68% of all outbreaks of non-bacterial gastroenteritis. These outbreaks took place in the counties of West and North Yorkshire and Humberside during six winter seasons between July 1992 and June 1998. NLV strains from 671 outbreaks were typed by antigen capture enzyme linked immunosorbent assays (ELISA) based on antisera made to recombinant virus-like particles of three antigenically distinct NLVs; Norwalk (NV), Mexico (MXV) and Grimsby (GRV) viruses. GRV was the predominant strain for five of the six winter seasons and overall was associated with 61% of NLV outbreaks. MXV was responsible for a single epidemic peak in the winter of 1993/94 but was also observed at other times throughout the study period. NV was only associated with two outbreaks in 1994 that were epidemiologically linked. Strains from the remaining 32% of outbreaks were non-reactive in all three ELISA. Thus, a single NLV antigenic type seems to have predominated during the period 1992 to 1998 in the UK.

Adult↗
PubMed2000

Defibrillators in nonischemic cardiomyopathy treatment evaluation.

The Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE) is a multicenter randomized trial. Patients will have nonischemic cardiomyopathy (LVEF < or = 35%), a history of symptomatic heart failure and spontaneous arrhythmia (> 10 PVCs/hour or nonsustained ventricular tachycardia defined as 3-15 beats at a rate of > 120 beats/min) on Holter monitor or telemetry within the past 6 months. Patients will be randomized to an implantable cardioverter defibrillator (ICD) versus no ICD. All patients will receive standard oral medical therapy for heart failure including angiotensin converting enzyme inhibitors and beta-blockers (if tolerated). Patients will be followed for 2-3 years. The primary endpoint will be total mortality. Quality-of-life and pharmacoeconomics analyses will also be performed. A registry will track patients who meet basic inclusion criteria but are not randomized. We estimate an annual total mortality of 15% at 2 years in the treatment arm that does not receive an ICD. The ICD is expected to reduce mortality by 50%. Approximately 204 patients will be required in each treatment group. Twenty-five centers will be included in a trial designed to last an estimated 4 years.

Cardiomyopathy, Dilated↗
PubMed1999

Correlation waveform analysis to discriminate monomorphic ventricular tachycardia from sinus rhythm using stored electrograms from implantable defibrillators.

In order to examine whether a template-matching program utilizing correlation waveform analysis (CWA) might be used to discriminate monomorphic ventricular tachycardia (MMVT) from sinus rhythm (SR) in patients with implantable cardioverter defibrillators (ICDs), we studied stored episodes of induced MMVT in 25 patients and compared them to corresponding stored SR electrograms. We calculated mean correlation coefficients for SR beats against an SR template chosen within each sinus episode, induced MMVT beats against an induced MMVT template within each ventricular tachycardia episode, and induced MMVT beats against the original SR template. For each patient, the 99.5% lower confidence limit for the mean correlation coefficient of SR beats versus an SR template (patient-specific method) or the empirical correlation coefficient value 0.9 were selected as threshold values to discriminate induced MMVT from SR. The mean correlation coefficient for induced MMVT beats versus the original SR template for each patient was subtracted from both threshold values. A positive value is defined as accurate discrimination of induced MMVT from SR. Using 0.9 for a threshold cut off, 21 of 25 episodes of induced MMVT were accurately labeled with a sensitivity of 84%. Using the patient-specific method, we were able to correctly distinguish 23 of 25 episodes of induced MMVT from SR with a sensitivity of 92%. There was no statistically significant difference between the patient-specific or empirical methods in detecting MMVT (P 50.4). This is the first demonstration using stored intracardiac electrograms from ICDs that CWA is able to discriminate MMVT from SR with high sensitivity. Such a template-matching system may be used for off-line analysis or real-time rhythm discrimination.

Aged↗
PubMed1999

Analysis of ankle deflection during a forward fall in snowboarding.

Toward the general goal of preventing ankle injuries in snowboarding accidents, the objective of this project to develop a dynamic system model of a snowboarder and assess which model parameters, particularly those attributed to the boot, most strongly influenced ankle deflections during a forward fall. To satisfy this objective, a system model was created that included the rider, the boots, the snowboard, and the snow as components. Through dynamic simulations, peak ankle deflections were computed over realistic ranges of input parameter values for each of the model components. Defining sensitivity as the total change in peak ankle deflection over the range of a particular parameter studied, results indicated that the peak ankle deflection was most sensitive to the boot stiffness. Although lower, the sensitivity of the peak ankle deflection to the snow model parameters was still significant, being roughly half of the boot sensitivity. Increases in both snow stiffness and snow damping caused higher ankle deflections. Variations in both snowboard stiffness and anthropometric parameters had little effect. Due to the strong dependence of ankle deflection on boot stiffness, the potential exists for mitigating the ankle injury problem through judicious design of the boot.

Accidental Falls↗
PubMed1999

Humoral and cell-mediated immune responses in humans to the NSP4 enterotoxin of rotavirus.

Rotavirus nonstructural protein NSP4 has recently been suggested to function as a viral enterotoxin and play a role in the pathophysiological mechanism whereby rotaviruses induce diarrhea. The ability of rotavirus NSP4 to stimulate a humoral immune response was examined in naturally infected children and adults, rotavirus vaccinated children, as well as a cellular immune response in adults. In this study, 10 of 10 naturally infected children and 9 of 10 rotavirus-vaccinated children showed a weak humoral IgG immune response to recombinant NSP4 (rNSP4) and/or a synthetic peptide corresponding to residues 114-134 of NSP4. Modest serum IgG antibody responses were detected in 20 of 20 adults. A cellular immune response to rNSP4 and/or NSP4(114-134) were detected in 8 of 10 adults measured either as a T-cell proliferative response (7 of 10), an increased production of IL-2 (6 of 10), or increased production of interferon-gamma (8 of 10). These results indicate that NSP4 induces a humoral immune response in humans and show for the first time that NSP4 stimulates a cellular immune response, possibly including cytolytic T-cells.

Adult↗
PubMed1997

Interference with cardiac pacemakers by cellular telephones.

BACKGROUND: A growing body of evidence suggests that electromagnetic interference may occur between cardiac pacemakers and wireless hand-held (cellular) telephones, posing a potential public health problem. Electromagnetic interference may occur when the pacemaker is exposed to an electromagnetic field generated by the cellular telephone. METHODS: In this multicenter, prospective, crossover study, we tested 980 patients with cardiac pacemakers with five types of telephones (one analogue and four digital) to assess the potential for interference. Telephones were tested in a test mode and were programmed to transmit at the maximal power, simulating the worst-case scenario; in addition, one telephone was tested during actual transmission to simulate actual use. Patients were electrocardiographically monitored while the telephones were tested at the ipsilateral ear and in a series of maneuvers directly over the pacemaker. Interference was classified according to the type and clinical significance of the effect. RESULTS: The incidence of any type of interference was 20 percent in the 5533 tests, and the incidence of symptoms was 7.2 percent. The incidence of clinically significant interference was 6.6 percent. There was no clinically significant interference when the telephone was placed in the normal position over the ear. Interference that was definitely clinically significant occurred in only 1.7 percent of tests, and only when the telephone was held over the pacemaker. Interference was more frequent with dual-chamber pacemakers (25.3 percent) than with single-chamber pacemakers (6.8 percent, P<0.001) and more frequent with pacemakers without feed-through filters (28.9 to 55.8 percent) than with those with such filters (0.4 to 0.8 percent, P=0.01). CONCLUSIONS: Cellular telephones can interfere with the function of implanted cardiac pacemakers. However, when telephones are placed over the ear, the normal position, this interference does not pose a health risk.

Adolescent↗
PubMed1997

Transthyretin amyloidosis: a new mutation associated with dementia.

Familial transthyretin (TTR) amyloidosis commonly presents with peripheral neuropathy and involvement of visceral organs. In contrast, signs of central nervous system (CNS) involvement are exceptional. We report that members of a kindred affected by a slowly progressive dementia, seizures, ataxia, hemiparesis, and decreased vision without neuropathy have TTR amyloid deposits in the leptomeninges, the brain parenchyma, and the eye. This condition, previously labeled oculoleptomeningeal amyloidosis, is linked to a mutation at codon 30 of TTR gene, resulting in the substitution of valine with glycine in this family, TTR amyloid deposits were present in the leptomeninges, especially the leptomeningeal vessels, and in the subependymal regions of the ventricular system where they disrupted the ependymal lining and resulted in amyloid-glial formations protruding into and narrowing the ventricular system. Hydrocephalus and atrophy and infarction of cerebral and cerebellar cortexes were also present. Review of the literature shows that amyloid deposition in the leptomeninges is not uncommon in TTR amyloidoses clinically characterized by peripheral neuropathy and lack of CNS signs. The present kindred, which presented exclusively with signs of CNS involvement, expands the phenotype of TTR amyloidosis and raises questions concerning the mechanisms determining phenotypic expression in TTR familial amyloidosis.

Amyloid Neuropathies↗
PubMed1997

Pharmacokinetics and cardiovascular effects of ma-huang (Ephedra sinica) in normotensive adults.

The purpose of this study was to evaluate heart rate and blood pressure responses to a commercially available source of ma-haung, a natural source of the sympathomimetic substance, ephedrine, and to evaluate the pharmacokinetic properties of the product in normotensive, healthy adults. On day 1, twelve study participants were monitored with an ambulatory blood pressure device between hours 7 and 20. On day 2, they ingested four capsules of powdered ma-huang at hours 8 and 17 while again wearing the monitor between hours 7 and 20. Serial plasma samples were obtained and concentrations of ephedrine were analyzed by high-performance liquid chromatography. Pharmacokinetic parameters of ephedrine were determined from plasma concentration-time profiles. The ephedrine alkaloid content of each capsule was also determined by high-performance liquid chromatography. Six participants experienced a statistically significant increase in heart rate, but the effects on blood pressure were variable. The half-life, volume of distribution, clearance, and maximum concentration in plasma of ephedrine in the ma-huang product were similar to values previously reported for a 20 mg, immediate-release ephedrine tablet. Values for the absorption rate were considerably lower and time to reach maximum concentration was longer for the capsules, compared with the standard tablet. Variability in alkaloid content of ephedrine was low and yielded a mean dose of ephedrine at 19.4 mg; pseudoephedrine at 4.9 mg; and methylephedrine at 1.2 mg for a four-capsule dose. In summary, ma-haung had variable effects on blood pressure and increased heart rate in healthy, normotensive adults. Pharmacokinetic parameters for ephedrine were in agreement with those previously reported; however, the absorption rate was much slower after ingestion of ma-huang.

Adult↗
PubMed1997

Extrahepatic ischemia-reperfusion injury reduces hepatic oxidative drug metabolism as determined by serial antipyrine clearance.

PURPOSE: All transplanted solid organs experience some degree of ischemia-reperfusion (I-R) injury. This I-R injury can contribute to graft dysfunction which stems in part from the acute phase response and a resultant host of cytokines. Recent evidence suggests that organs remote to the site of I-R injury can be affected by circulating cytokines originating from these I-R injuries. Since many of these acute phase cytokines inhibit hepatic cytochrome P-450 (CYP) enzymes, we chose to investigate whether extrahepatic I-R injuries could influence hepatic oxidative drug metabolism. METHODS: Fifteen dogs were divided into three surgical groups: (I) sham I-R; (II) bilateral normothermic renal I-R; and (III) normothermic intestinal I-R. Antipyrine (AP) was selected as a model substrate and administered intravenously at a dose of 10 mg/kg. AP serum concentrations were determined by HPLC and cytokine activity (IL-1, IL-6, and TNFalpha) was measured via bioassay. Serial AP clearance and serum cytokine concentrations were determined 3 days prior to and at 4 hr, 24 hr, 3 days and 7 days after surgery. Hematology and blood chemistries were monitored throughout the study period. RESULTS: AP clearance was significantly reduced in groups II and III at 4 and 24 hrs post-l-R injury, while AP binding and apparent volume of distribution were unaffected. Peak levels of TNF and IL-6 activity occurred at 1 and 4 hours, respectively. IL-I activity was not detected in any group. AP clearance correlated strongly to circulating levels of IL-6 (r = -0.789, p = 0.0002). CONCLUSIONS: Our findings indicate that extrahepatic I-R injury can affect hepatic oxidative drug metabolism and this effect is mediated in part by circulating cytokines.

Animals↗
PubMed1996

Prevalence of serum antibodies to Norwalk virus among Norwegian military recruits.

The prevalence of serum antibodies against Norwalk virus among military recruits in Norway was investigated using an enzyme-linked immunosorbent assay (ELISA). A total of 1017 sera were assayed for anti-Norwalk virus total antibodies (ig), of which 300 (29.5%) were positive. Of 227 positive sera, 10.6 and 15.4% were positive for IgA and IgM, respectively, while 2.2% were positive for both. The prevalence of antibodies against Norwalk virus in south-east Norway was significantly higher than that in northern Norway.

Adult↗
PubMed1993

Efficacy of a recombinant Norwalk virus protein enzyme immunoassay for the diagnosis of infections with Norwalk virus and other human "candidate" caliciviruses.

A recombinant Norwalk virus antigen enzyme immunoassay (rNV EIA) for the detection fo Norwalk virus (NV) antibodies was evaluated using sera from volunteers and patients infected with Norwalk, Hawaii, Snow Mountain Agent, small round structured viruses (SRSV), and human calicivirus (HuCV) strains. The results for NV antibodies correlated well with previous results obtained using a NV radioimmunoassay. The test rNV EIA was found to be highly specific for NV. The results of tests on sera obtained from patients involved in confirmed outbreaks of SRSV in the UK showed that only 1/12 was due to Norwalk virus. Further evidence is presented that SRSV strain UK2 is antigenically related to NV.

Adult↗
PubMed1993

Activation of distinct multidrug-resistance (P-glycoprotein) genes during rat liver regeneration and hepatocarcinogenesis.

The multidrug transporter P-glycoproteins are encoded by three multidrug-resistance (mdr) genes in rodents, designated mdr1a (mdr3), mdr1b (mdr1), and mdr2. Only the first two genes are functionally related to multidrug resistance. Activation of rodent mdr genes during liver regeneration and hepatocarcinogenesis has been reported. In mice, mdr1a is activated in hepatocellular carcinomas (HCCs) produced by various carcinogenic protocols, whereas both mdr1a and mdr2 are activated during liver regeneration. In this communication, we report isolating three gene-specific probes for the rat mdr homologues, which were used as probes in an RNase protection assay to demonstrate that mdr1b mRNA was expressed in HCCs induced by two different protocols. Furthermore, high levels of hepatic mdr1b mRNA but only moderate levels of mdr1a and mdr2 mRNA were seen in preneoplastic lesions in rats treated with 2-acetylaminofluorene. Likewise, highly elevated levels of hepatic mdr1b mRNA but only moderately increased levels of mdr1a and mdr2 mRNA were seen after partial hepatectomy. Nevertheless, the general patterns of tissue-specific expression of these three mdr genes were similar in rats and mice. These results reveal a complex hepatic gene expression pattern during hepatocarcinogenesis and hepatic proliferation for this conserved gene family in rodents.

2-Acetylaminofluorene↗
PubMed1991

Serum enzyme alterations in chronic muscle disease. A biopsy-based diagnostic assessment.

The results of interpretation of muscle biopsies were compared retrospectively to activities of serum enzymes and isoenzymes. A total of 137 patients seen at the Cleveland Clinic Foundation in 1986 and 1987 were included in this study. Serum enzymes evaluated were CK, AST, LD, and aldolase (ALS), as well as the percentage CK-MB isoenzyme. The units of CK-MB and the ratios of CK to AST, LD, and ALS were calculated. Descriptive statistics, Kruskal-Wallis one-way analysis of variance, and stepwise logistic regression were performed. A diagnostic algorithm was constructed using a computer-assisted rule generation program. Myopathic diseases yielded a greater mean increase in serum enzyme activity than atrophic diseases. By multivariate stepwise logistic regression, increases in serum AST and CK activity were independently associated with the presence of inflammation in a muscle biopsy specimen. The diagnostic algorithm allowed for the separation of myopathies from atrophies and could identify cases of Duchenne's muscular dystrophy and polymyositis.

Algorithms↗
PubMed1989

Systemic vasculitis in association with human immunodeficiency virus infection.

Fourteen cases of vasculitis associated with human immunodeficiency virus infection have thus far been described. Five of these cases may be classified as angiocentric immunoproliferative disorders, including benign lymphocytic angiitis, lymphomatoid granulomatosis, and angiocentric lymphoma. We report a case of benign lymphocytic angiitis of T cell lineage. Extensive studies found no evidence of viral antigens in the inflammatory infiltrates, and immunologic evaluation of the pathologic lesions revealed the infiltrating cells to be predominantly CD3+, CD8+, CD4-. A significant number of these lymphocytes demonstrated a deletion of T cell antigen receptor determinants. We believe that in certain cases of human immunodeficiency virus disease, there occurs a spectrum of lymphoproliferative disorders with angiocentric features that lead to the clinical picture of systemic necrotizing vasculitis. Clinicians should be aware of this association.

Acquired Immunodeficiency Syndrome↗