Biomedical subjects

M Lesser

Publications and source records attributed to M Lesser.

At least 19 recordsLinked to original sources

PubMed2001

Immunophenotypic analysis of HIV-infected children: alterations within the first year of life, changes with disease progression, and longitudinal analyses of lymphocyte subsets.

Perinatal infection with human immunodeficiency virus (HIV) results in tremendous activation of the pediatric immune system. An important component of understanding the pathogenesis of this disease is to characterize and quantify antigenic indicators of activation within the peripheral lymphocyte population. We measured T-lymphocyte activation and maturation antigens in a cohort of 112 HIV-infected children treated with antiretroviral therapy according to the current standard of care. Changes in expression of CD95, HLA-DR, and CD45RO were evident in 22 HIV-infected children younger than 1 year of age. A comparison of phenotypic profiles of children in mild, moderate, and severe immune categories revealed perturbations of CD28, CD38, CD45RA, CD45RO, CD95, and HLA-DR. Finally, a novel analysis of 56 HIV-infected children based on the repeated collection of data over time (median of seven observations over 33 months) demonstrated a strong negative correlation between the percentage CD4 and the percentage of CD45RO, CD95, and HLA-DR on both CD4 and CD8 cells. Our data implicate persistent immune activation, beginning within the first year of life, as a major driving force in the pathogenesis of perinatally acquired HIV disease.

ADP-ribosyl Cyclase↗

PubMed2001

Lack of postprandial leptin peaks in patients with type 2 diabetes mellitus.

Leptin production by the adipocyte is acutely stimulated by insulin in vitro. In normal individuals, postprandial insulin peaks are not accompanied by corresponding changes in circulating leptin. Postprandial regulation of leptin in individuals with type 2 diabetes, to our knowledge, has not been previously examined in detail. We examined the effect of meals on circulating leptin levels in six patients with type 2 diabetes who were not treated with insulin and in seven normal individuals. After informed consent was obtained, all subjects were admitted to the General Clinical Research Center for 6 days. They consumed four meals daily (breakfast, lunch, dinner and snack). Eighteen blood samples were drawn between 7.40 a.m. and midnight for the determination of serum leptin, insulin and glucose levels. Postprandial peaks were clearly identifiable for glucose and insulin levels both in normal subjects and in those with type 2 diabetes. However, no postprandial peaks of leptin levels were present. Correlation analysis demonstrated a lack of correlation between leptin levels and the levels of glucose or insulin. We conclude that, in spite of the presence of postprandial insulin peaks, there are no acute changes in circulating leptin levels postprandially in patients with type 2 diabetes who are not on insulin therapy. In this regard, in-vivo regulation of leptin by meals in patients with type 2 diabetes is similar to that in normal individuals.

Adult↗

PubMed2001

An open-label study of the treatment efficacy of olanzapine for Tourette's disorder.

BACKGROUND: An open-label trial was performed to explore efficacy and safety of olanzapine, an atypical neuroleptic with diverse receptor activity including both dopamine-2 and serotonin-2A and -2C antagonism, for treatment of Tourette's disorder. METHOD: Ten adult patients aged 20 to 44 years with Tourette's disorder were treated using an open-label, flexible dosing schedule for 8 weeks. Three patients who continued olanzapine were reevaluated after 6 months. Three subjects were psychotropic medication naive, 5 patients experienced intolerable side effects with conventional neuroleptics, and 2 patients had remote (> or = 10 years) successful response to conventional neuroleptics. Tic severity was rated by the Yale Global Tic Severity Scale; weight, vital signs, and adverse effects were assessed weekly. Electrocardiogram, laboratory studies, and comorbid symptoms, assessed by the Yale-Brown Obsessive Compulsive Scale and ADHD Behavior Checklist for Adults, were measured at baseline and at week 8. RESULTS: Two of 10 patients prematurely discontinued olanzapine owing to excessive sedation. Of 8 patients who completed the 8-week trial, 4 (50%) demonstrated reduction of global tic severity scores by > or = 20 points, and 6 (75%) demonstrated reductions by > or = 10 points. No significant changes in comorbid symptoms were demonstrated. Sedation, weight gain, increased appetite, dry mouth, and transient asymptomatic hypoglycemia were the most common side effects. Tic improvements were maintained in 3 patients reassessed 6 months later. Final olanzapine dosages ranged from 2.5 mg to 20 mg daily (mean = 10.9 mg/day). CONCLUSION: This open-label study suggests that olanzapine should be explored as a potential alternative to conventional neuroleptic medications for treatment of motor tics and Tourette's disorder.

Adult↗

PubMed2000

Is chemiluminescent immunoassay an appropriate substitution for radioimmunoassay in monitoring estradiol levels?

OBJECTIVE: To determine the correlation between serum estradiol measurements by chemiluminescent immunoassay (CIA) vs. radioimmunoassay (RIA) in two groups: patients treated with gonadotropins and patients treated with oral estrogen. DESIGN: Prospective study. SETTING: Assisted Reproductive Technology (ART) program based in a university-affiliated hospital in Manhasset, New York. PATIENT(S): Three hundred forty-eight patients undergoing gonadotropin stimulation and 63 patients receiving oral estrogen between July and December, 1997. INTERVENTION(S): Estradiol levels were measured concomitantly on all patients undergoing gonadotropin stimulation for IVF and all patients receiving oral estrogen for a frozen-thaw cycle. MAIN OUTCOME MEASURE(S): RIA:CIA ratio. RESULT(S): In the group undergoing gonadotropin stimulation, the median RIA:CIA ratio was 0.92, RIA = 1.26 x CIA(0.96), r = 0.98. In the group receiving oral estrogen, the median ratio was 3.93, RIA = 2.9 x CIA(1.05), r = 0.89. CONCLUSION(S): Estradiol levels determined by CIA correlate closely with RIA results for patients being treated with gonadotropins. Conversely, for patients receiving oral estrogen, CIA levels are one-third or less of the RIA level.

Administration, Oral↗

PubMed2000

Baclofen-induced cough suppression in cervical spinal cord injury.

OBJECTIVE: To determine the effect of the GABA-agonist baclofen on cough reflex sensitivity in subjects with cervical spinal cord injury (C-SCI). Baclofen has been shown to inhibit the cough reflex in able-bodied volunteers. DESIGN: Prospective, nonrandomized control trial. SETTING: Veterans Affairs medical center with large outpatient SCI population. PARTICIPANTS: Twelve adult males (11 outpatients) with C-SCI chronically maintained on oral baclofen for the treatment of muscle spasm. INTERVENTION: Subjects underwent cough challenge testing with inhaled capsaicin. The concentrations (microM) of capsaicin inducing 2 or more (C2) and 5 or more (C5) coughs were determined. Mean values for log C2 and log C5 were compared with a control group of outpatients with C-SCI not receiving baclofen. RESULTS: Subjects treated with baclofen had a significantly higher cough threshold (diminished cough reflex sensitivity) than control subjects. Mean (+/- standard error of the mean) values for log C2 in study subjects and controls were 1.28 +/- .16 and .65 +/- .15, respectively (p = .009). Mean values for log C5 in subjects receiving baclofen and in control subjects were 2.20 +/- .22 and 1.43 +/- .23, respectively (p = .024). Subjects and controls did not differ in terms of age, spirometric parameters, or duration of injury. CONCLUSIONS: The results suggest that chronic therapy with baclofen diminishes cough reflex sensitivity in subjects with C-SCI. The clinical significance of this finding remains to be elucidated.

Adult↗

PubMed2000

A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease.

BACKGROUND & AIMS: Clinical experience suggests that 6-mercaptopurine (6-MP) is effective therapy for children with active steroid-dependent Crohn's disease (CD). We report the results of a prospective, placebo-controlled, multicenter trial evaluating the combination of 6-MP and prednisone as therapy for children with newly diagnosed moderate-to-severe CD. METHODS: Fifty-five children (age, 13+/-2 years) were randomized to treatment with 6-MP (1.5 mg x kg(-1) x day(-1)) or placebo within 8 weeks of initial diagnosis. Both groups also received prednisone (40 mg/day). Prednisone dosage adjustments were based on a defined schedule determined by the change in a subject's disease activity score, and steroid administration was discontinued as remission was achieved. Study treatment with 6-MP or placebo continued for 18 months. RESULTS: Groups were comparable for age, sex, and site and activity of disease. In the 6-MP group, the duration of steroid use was shorter (P<0.001) and the cumulative steroid dose lower at 6, 12, and 18 months (P<0.01). Although remission was induced in 89% of both groups, only 9% of the remitters in the 6-MP group relapsed compared with 47% of controls (P = 0.007). Growth was comparable in both groups. No clinically significant adverse events occurred, although mild leukopenia and increases in aminotransferase activity were noted in the 6-MP group. CONCLUSIONS: Addition of 6-MP to a regimen of corticosteroids significantly lessens the need for prednisone and improves maintenance of remission. 6-MP should be part of the initial treatment regimen for children with newly diagnosed moderate-to-severe CD.

Adolescent↗

PubMed2000

Explosive outbursts in children with Tourette's disorder.

OBJECTIVE: Sudden, explosive outbursts of behavior occur in some children with Tourette's disorder (TD). The etiology of these symptoms is unknown. This study investigated the relationship between explosive outbursts, TD, and its comorbid disorders. METHOD: Tic type and severity and the presence of specific comorbid disorders were compared in 37 children with TD and explosive outbursts and 31 children with TD who did not have such symptoms. RESULTS: Children with TD and explosive outbursts were more likely to demonstrate significant comorbid conditions, particularly attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and oppositional defiant disorder. Tic type and severity did not appear related to the presence of explosive outbursts. A highly significant relationship was demonstrated between the number of comorbid psychiatric diagnoses and explosive outbursts. CONCLUSIONS: Explosive outbursts in children with TD resemble intermittent explosive disorder and may reflect dysregulation of diverse domains of brain function. The presence of such symptoms should alert the clinician to underlying comorbid conditions.

Adolescent↗

PubMed2000

Airway hyperreactivity in subjects with tetraplegia is associated with reduced baseline airway caliber.

OBJECTIVES: We administered aerosolized histamine to 32 subjects with tetraplegia to determine whether there were differences in spirometric and/or lung volume parameters between responders and nonresponders. RESULTS: Baseline pulmonary function parameters revealed mild to moderate restrictive dysfunction. We found that 25 subjects (78%) were hyperreactive to histamine (mean provocative concentration of a substance causing a 20% fall in FEV(1) [PC(20)], 1.77 mg/mL). Responders (PC(20), < 8 mg/mL) had significantly lower values for forced expiratory flow between 25% and 75% of the outflow curve (FEF(25-75)), FEF(25-75) percent predicted, and FEF(25-75)/FVC ratio. Among all 32 subjects, the natural logarithmic transformation performed on PC(20) values (lnPC(20)) correlated with FEF(25-75) percent predicted, FEV(1) percent predicted, and FEF(25-75)/FVC ratio but not with FVC percent predicted. Responders with PC(20) values < 2 mg/mL (n = 13) had significantly reduced values for FVC, FVC percent predicted, FEV(1), and FEV(1) percent predicted compared to those with PC(20) values between 2 mg/mL and 8 mg/mL. In addition, among responders, there was a significant correlation between lnPC(20) and FVC percent predicted. A significant relationship was found between maximal inspiratory pressure (PImax) and both FEV(1) percent predicted and FEF(25-75) percent predicted, but not between lnPC(20) and either PImax or maximal expiratory pressure (PEmax). CONCLUSIONS: These findings demonstrate that subjects with tetraplegia who exhibit airway hyperreactivity (AHR) have reduced baseline airway caliber and that lower values for lnPC(20) are associated with parallel reductions in surrogate spirometric indexes of airway size (FEV(1) percent predicted and FEF(25-75) percent predicted) and airway size relative to lung size (FEF(25-75)/FVC ratio). The absence of an association between lnPC(20) and FVC percent predicted for the entire group or between lnPC(20) and either PImax or PEmax indicates that reduced lung volumes secondary to respiratory muscle weakness cannot explain the mechanism(s) underlying AHR. Among responders, however, a possible role for reduction in lung volume, as it pertains to increasing AHR, cannot be excluded. Proposed mechanisms for reduced baseline airway caliber relative to lung size in subjects with tetraplegia include unopposed parasympathetic activity secondary to the loss of sympathetic innervation to the lungs and/or the inability to stretch airway smooth muscle with deep inhalation.

Adult↗

PubMed2000

Mitochondrial damage in Alzheimer's disease varies with apolipoprotein E genotype.

Brain metabolism and the activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), a mitochondrial enzyme, are diminished in brains from patients with Alzheimer's disease (AD). In 109 subjects, the Clinical Dementia Rating (CDR) score was highly correlated with brain KGDHC activity. In AD patients who carried the epsilon 4 allele of the apolipoprotein E gene (ApoE4), the CDR score correlated better with KGDHC activity than with the densities of neuritic plaques or neuritic tangles. In contrast, in patients without ApoE4, the CDR score correlated significantly better with tangles and plaques than with KGDHC activity. The results suggest that mitochondrial/oxidative damage may be more important for the cognitive dysfunction in AD patients who carry ApoE4 than in those who do not.

Aged↗

PubMed1999

A new method for estimating the axis of rotation and the center of rotation.

A new method is presented for estimating the parameters of two different models of a joint. The two models are: (1) A rotational joint with a fixed axis of rotation, also referred to as a hinge joint and (2) a ball and socket model, corresponding to a spherical joint. Given the motion of a set of markers, it is shown how the parameters can be estimated, utilizing the whole data set. The parameters are estimated from motion data by minimizing two objective functions. The method does not assume a rigid body motion, but only that each marker rotates around the same fixed axis of rotation or center of rotation. Simulation results indicate that in situations where the rigid body assumption is valid and when measurement noise is present, the proposed method is inferior to methods that utilize the rigid body assumption. However, when there are large skin movement artefacts, simulation results show the proposed method to be more robust.

Artifacts↗

PubMed1999

Inhibition of airway hyperreactivity by oxybutynin chloride in subjects with cervical spinal cord injury.

OBJECTIVE: To further investigate mechanisms of airway hyperreactivity among subjects with chronic cervical spinal cord injury (SCI), we assessed airway responsiveness to aerosolized methacholine and histamine in subjects receiving chronic oxybutynin chloride therapy, and compared the findings with those not receiving the agent. METHODS: Twenty-five male subjects with cervical SCI participated in this study; 12 were maintained on oral oxybutynin chloride and 13 served as age-matched controls. Six of the 12 subjects receiving oxybutynin were challenged with aerosolized methacholine, and six with histamine; seven of the 13 control subjects were challenged with aerosolized methacholine and the remaining six with histamine. RESULTS: All 13 control subjects and all six oxybutynin/histamine subjects exhibited a significant bronchoconstrictor response (PC20 < 8 mg/ml), whereas mean PC20 values for the oxybutynin/methacholine group were > or =25 mg/ml. CONCLUSION: Our finding that the bronchoconstrictor effects of methacholine were blocked by oxybutynin chloride while those of histamine were not suggests that oxybutynin acts primarily through anticholinergic pathways rather than by causing generalized airway smooth muscle relaxation.

Adult↗

PubMed1999

The utility of quantitative body surface isoarea mapping for predicting ventricular tachyarrhythmias.

Noninvasive techniques, such as the signal averaged ECG, have been used to assess risk of ventricular tachyarrhythmias (VT). However, these methods produce false positive and negative results. The purpose of this study was to develop body surface map algorithms which would enhance prediction of susceptibility to VT. Fifty-three patients referred for programmed electrical stimulation were enrolled in this study. All patients underwent signal averaged ECG, body surface map, programmed electrical stimulation. Group I patients had no sustained inducible VT and group II patients had either inducible sustained VT at electrophysiology study or previously documented spontaneous, sustained VT. For body surface map analysis, the difference between extrema on isoarea maps was calculated and defined as the gradient range. An abnormal body surface map was defined as a QRST gradient range < or = 109 mv.ms. The mean QRST gradient range in group II was significantly < that in group I (P < 0.05). By logistic regression analysis, the presence of coronary artery disease, a QRST gradient range < or = 109 mv.ms, an EF < 40% and a signal averaged ECG QRS duration > 114 ms predicted VT. The sensitivity, specificity, positive and negative predictive values for predicting VT susceptibility of an algorithm which combines the signal averaged ECG QRS duration and the QRST gradients were 0.93, 0.76, 0.79, and 0.91, respectively, while those for the signal averaged ECG alone were 0.52, 0.69, 0.63, and 0.59 for VT susceptibility. A combined body surface map-signal averaged ECG algorithm was more sensitive in detecting susceptibility to VT than the signal averaged ECG alone.

Adolescent↗

PubMed1999

Why don't emergency department patients have advance directives?

OBJECTIVES: In 1997 the authors determined that only 27% of their adult ED patients had advance directives (ADs). The purpose of this follow-up study was to determine the reasons why their adult ED patients do not have ADs. METHODS: This prospective study enrolled patients from a convenience sample of representative shifts in the ED selected over a three-month period. Survey questions included demographic information, whether the patients had a life-threatening medical problem, whether they had an AD, with whom they had discussed their ADs, and the reasons why they did not have an AD. We excluded those who refused participation or who were incapacitated (i.e., any patient with a condition that precluded him or her from answering the questionnaire himself or herself, such as an altered level of consciousness, dementia, mental retardation, or inability to understand English). RESULTS: Four hundred seventy-six subjects were enrolled during the study period from an ED census of 816 adult patients. Three hundred forty patients were not included in the study for the following reasons: inability to complete the survey, refusal to participate, or not being approached by the interviewers. Of those enrolled, 77% of the patients did not have an AD (females, 73%; males, 80%). The most frequent reasons given for not having an AD were: 40% never thought about it, 24% preferred family to make the decision, and 23% were procrastinating. Factors jointly predictive of having an AD were older age, having a specialist, having a life-threatening medical problem, and not being Catholic. Patients who had ADs were discussing their ADs with their primary care physicians (PCPs) only 5% of the time. CONCLUSION: Many patients, even when they have life-threatening medical problems, do not have an AD, and several reasons for this have been identified. Few of these ED patients who had ADs had discussed them with their physicians. Further studies should assess whether more physician intervention would increase the percentage of patients who have ADs.

Adolescent↗

PubMed1999

Airway hyperresponsiveness to ultrasonically nebulized distilled water in subjects with tetraplegia.

The majority of otherwise healthy subjects with chronic cervical spinal cord injury (SCI) demonstrate airway hyperresponsiveness to aerosolized methacholine or histamine. The present study was performed to determine whether ultrasonically nebulized distilled water (UNDW) induces airway hyperresponsiveness and to further elucidate potential mechanisms in this population. Fifteen subjects with SCI, nine with tetraplegia (C4-7) and six with paraplegia (T9-L1), were initially exposed to UNDW for 30 s; spirometry was performed immediately and again 2 min after exposure. The challenge continued by progressively increasing exposure time until the forced expiratory volume in 1 s decreased 20% or more from baseline (PD20) or the maximal exposure time was reached. Five subjects responding to UNDW returned for a second challenge 30 min after inhalation of aerosolized ipratropium bromide (2.5 ml of a 0.6% solution). Eight of nine subjects with tetraplegia had significant bronchoconstrictor responses to UNDW (geometric mean PD20 = 7.76 +/- 7.67 ml), whereas none with paraplegia demonstrated a response (geometric mean PD20 = 24 ml). Five of the subjects with tetraplegia who initially responded to distilled water (geometric mean PD20 = 5.99 +/- 4.47 ml) were not responsive after pretreatment with ipratropium bromide (geometric mean PD20 = 24 ml). Findings that subjects with tetraplegia are hyperreactive to UNDW, a physicochemical agent, combined with previous observations of hyperreactivity to methacholine and histamine, suggest that overall airway hyperresponsiveness in these individuals is a nonspecific phenomenon similar to that observed in patients with asthma. The ability of ipratropium bromide to completely block UNDW-induced bronchoconstriction suggests that, in part, airway hyperresponsiveness in subjects with tetraplegia represents unopposed parasympathetic activity.

Adult↗

PubMed1999

Cough reflex sensitivity in subjects with cervical spinal cord injury.

An effective cough requires an intact cough reflex as well as adequate respiratory muscle function to generate elevated intrathoracic pressures. Since the major muscles of expiration are innervated by the first thoracic segment and below, transection of the cervical spinal cord results in severely compromised expiratory function and cough. To investigate the effects of cervical spinal cord injury (C-SCI) on cough reflex sensitivity, we measured responsiveness to inhaled capsaicin in 12 male subjects with chronic C-SCI and compared findings to those from a control group of 50 able-bodied men. The concentrations (microM) of capsaicin inducing two or more (C2) and five or more coughs (C5) did not significantly differ between the two groups. Mean (+/- SEM) values for log C2 in subjects with C-SCI and control subjects were 0.65 +/- 0.15 and 0.87 +/- 0.07, respectively (p = 0.15). Mean values for log C5 in subjects with C-SCI and control subjects were 1.43 +/- 0.23 and 1.41 +/- 0.08, respectively (p = 0.94). We conclude that cough reflex sensitivity is preserved after C-SCI, and that ineffective cough in this population results primarily from the loss of innervation of respiratory muscles.

Adult↗

PubMed1999

Effects of a beta2-agonist on airway hyperreactivity in subjects with cervical spinal cord injury.

STUDY OBJECTIVE: Aerosolized ipratropium bromide or orally administered baclofen or oxybutynin chloride (Ditropan) block methacholine-associated airway hyperreactivity in subjects with chronic cervical spinal cord injury (SCI), whereas these agents do not inhibit airway hyperreactivity associated with the inhalation of histamine. The present study was performed to determine whether pretreatment with a beta2-agonist attenuates airway hyperresponsiveness in these subjects. PARTICIPANTS: Subjects with chronic cervical SCI previously demonstrating airway hyperreactivity were challenged with methacholine (n = 9) or histamine (n = 16) alone and, on a separate day, 25 min following inhalation of nebulized metaproterenol sulfate. RESULTS: Inhalation of the beta2-agonist was associated with an increase in provocative concentration causing a 20% decrease in FEV1 (PC20) values (geometric mean) from 1.01+/-2.76 to 20.54+/-6.24 mg/mL for methacholine and from 2.29+/-2.26 to 19.82+/-5.93 mg/mL for histamine. No correlation was found between specific PC20 values for individual subjects and percentage improvement in FEV1 (liter) following inhalation of metaproterenol sulfate and between PC20 values and baseline FEV1 percent. CONCLUSION: These data, combined with findings that patients with chronic high cervical SCI experience increased breathlessness following exposure to exogenous agents, suggest that long-term prophylactic beta2-agonist therapy may reduce respiratory symptoms associated with airway hyperreactivity in these patients.

Administration, Inhalation↗

PubMed1999

Cytotoxicity of 2-chlorodeoxadenosine (cladribine, 2-cdA) in combination with other chemotherapy drugs against two lymphoma cell lines.

Cladribine is a purine analog with impressive activity in patients with low-grade lymphoproliferative disorders. We studied the combination of cladribine with other antineoplastic drugs against two human-derived B-cell lymphoma cell lines in vitro. Cladribine was combined with cisplatin, daunorubicin, chlorambucil, paclitaxel or etoposide. Under the experimental conditions studied, only the combination of cladribine and cisplatin showed significantly increased cytotoxicity compared to the effect of either drug alone.

Antineoplastic Agents↗

PubMed1999

Modulation by DLST of the genetic risk of Alzheimer's disease in a very elderly population.

The mitochondrial alpha-ketoglutarate dehydrogenase complex (KGDHC) is deficient in Alzheimer's disease (AD). The DLST gene encodes the core, dihydrolipoyl succinyltransferase (DLST) component of KGDHC, and recent reports indicate an association between polymorphisms of DLST and AD in both white and Japanese patients. We therefore examined the relationship between AD and the DLST and apolipoprotein E (APOE) genes in elderly (89 +/- 7 years) AD patients, in whom the epsilon4 allele of APOE (APOE4) is a weak risk factor for AD. Polymorphisms of DLST (A19,117G and T19,183C), shown to be of interest in previous studies, were analyzed by restriction fragment length polymorphism analysis after polymerase chain reaction amplification. In a series of 429 white subjects from two Jewish nursing homes, an association of APOE4 with AD was found only in patients homozygous for the G,C allele of DLST. Similar relationships occurred in the "very elderly" (> or =85 years, n = 302) subgroup of this series, and also in an autopsy series (n = 225) that included white subjects from the Jewish nursing homes as well as other white subjects. These findings suggest a relationship between APOE4 and a DLST locus in the pathogenesis of AD in very elderly subjects.

Acyltransferases↗