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Biomedical subjects

M Lesser

Publications and source records attributed to M Lesser.

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

Commitment to X inactivation precedes the twinning event in monochorionic MZ twins.

To gain insight into the timing of twinning, we have examined a closely related event, X-chromosome inactivation, in female MZ twin pairs. X-inactivation patterns in peripheral blood and buccal mucosa were compared between monochorionic MZ (MC-MZ) and dichorionic MZ (DC-MZ) twins. Overall, the MC-MZ twins displayed highly similar X-inactivation patterns, whereas DC-MZ twins frequently differed in their X-inactivation patterns, when both tissues were tested. Previous experimental data suggest that commitment to X inactivation occurs when there are 10-20 cells in the embryo. Simulation of embryo splitting after commitment to X inactivation suggests that MC-MZ twinning occurs three or four rounds of replication after X inactivation, whereas a DC-MZ twinning event occurs earlier, before or around the time of X inactivation. Finally, the overall degree of skewing in the MZ twins was not significantly different from that observed in singletons. This indicates that X inactivation does not play a direct role in the twinning process, and it further suggests that extreme unequal splitting is not a common mechanism of twin formation.

Adolescent↗
PubMed1998

Anticipation in Crohn's disease may be influenced by gender and ethnicity of the transmitting parent.

OBJECTIVE: We sought to examine whether anticipation (an earlier age of onset in succeeding generations) is observed in Crohn's disease (CD) patients within the New York metropolitan area, and whether there are differences in the degree of anticipation with respect to gender and ethnicity of the affected parent. METHODS: Sixty-one parent-child pairs both affected by CD were identified; about half of the pairs were of Ashkenazi Jewish descent. An additional 17 pairs of second-degree relatives with CD were also identified. The intergenerational difference in age at diagnosis (AAD) was used to perform regression analysis and the degree of anticipation among subsets of patients separated on the basis of gender and ethnicity of the transmitting parent was determined. RESULTS: The AAD was consistently (90% of the time) lower in the younger member of the 61 parent-child pairs (35.3+/-1.6 yr vs 20.8+/-1.1 yr, p = 0.0001). Furthermore, the degree of anticipation was significantly greater for father-child pairs (20.6+/-3.2 yr) than for mother-child pairs (11.7+/-2.1 yr). However, when the patient population where the parent had an AAD of < 28 was analyzed separately, there was a lack of clear-cut evidence of anticipation in the population as a whole. Only when the population was subdivided by ethnicity was there convincing evidence of anticipation in the Jewish population. CONCLUSION: Ascertainment bias may be responsible for the apparent anticipation observed in the CD population as a whole or in the nonJewish CD subgroup. However, the Jewish CD population displays strong evidence of anticipation even after correction for ascertainment bias.

Adult↗
PubMed1998

Neuropsychological testing in adult attention deficit hyperactivity disorder: a pilot study.

Diagnosing adult ADHD is frequently problematic because behavioral information from the patient's childhood, and multiple informants who can delineate the patient's current behavior, are often unavailable. This preliminary study was designed to explore whether objective neuropsychological testing may be a useful adjunct in the diagnosis of adult ADHD. Nineteen adults diagnosed with ADHD according to DSM-IV criteria, along with 10 controls, were assessed using a neuropsychological battery which comprised tests assessing linguistic, visual-spatial perceptual, academic, attentional and inhibitory control, mnestic and executive functions. Following preliminary analyses, designed to determine which variables best discriminated the groups, receiver operating characteristic (ROC) curves were constructed to determine the sensitivity and specificity of the best measures both alone and in combination. Only three measures significantly (p < 0.01) distinguished the groups; Digits Backwards from the WAIS-R and two reaction time measures from a computerized task modeled after Luria's Competing Motor Programs. ROC curve analyses indicated that in combination these measures had greater than 90% accuracy for classifying ADHD and non-ADHD patients. While further research is necessary these preliminary findings suggest that neuropsychological testing may be a useful adjunct in the differential diagnosis of adult ADHD.

Adolescent↗
PubMed1998

The effects of ipratropium bromide on histamine-induced bronchoconstriction in subjects with cervical spinal cord injury.

Previously, we reported that a majority of subjects with chronic cervical spinal cord injury (SCI) demonstrated airway hyperreactivity in response to inhaled methacholine. To further investigate mechanisms of airway hyperreactivity, 15 male subjects with cervical SCI were challenged with aerosolized histamine, and on a separate day responders were rechallenged 30 min after the inhalation of 72 micrograms of ipratropium bromide. Twelve of 15 subjects demonstrated airway hyperresponsiveness to histamine (geometric mean PC20 of 1.27 mg/ml), which was not blocked by pretreatment with ipratropium bromide (geometric mean PC20 1.50 mg/ml). Baseline forced vital capacity and forced expiratory volume in 1 sec were not significantly different between responders and nonresponders (2.8 +/- 0.6 vs. 3.0 +/- 0.4 L and 2.3 +/- 0.6 vs. 2.4 +/- 0.2 L, respectively). Findings that subjects with cervical SCI are hyperresponsive to methacholine and histamine, chemical agents with direct action through distinct receptor systems, suggest that bronchial hyperreactivity in these subjects represents a nonspecific process similar to that observed in patients with asthma.

Adult↗
PubMed1997

Prediction of fetal macrosomia using sonographically measured abdominal subcutaneous tissue thickness.

PURPOSE: We assessed the usefulness of sonographic measurement of abdominal subcutaneous tissue thickness in predicting fetal macrosomia (weight > 4,000 g). METHODS: Abdominal subcutaneous tissue thickness was measured sonographically in 133 term fetuses. All studied fetuses were delivered within 72 hours after the measurements were taken. RESULTS: One hundred thirteen fetuses were normal size, and 20 were macrosomic. The fetal abdominal subcutaneous tissue thickness ranged between 3 and 18 mm in all fetuses, with a mean measurement of 8.4 +/- 2.7 mm (standard deviation). The mean tissue thickness differed significantly between normal and macrosomic fetuses (7.0 mm versus 12.4 mm, respectively; p < 0.0001). There was a significant positive correlation between the abdominal subcutaneous tissue thickness and the birth weight (r = 0.67, p < 0.0001). The negative predictive value for a range of cut-off points between 8 and 13 mm varied between 84.3% and 100% (for prevalence rates of macrosomia of 5-25%). However, the positive predictive value was less than 50% for cut-off values below 11 mm. CONCLUSIONS: Sonographic measurement of the subcutaneous tissue thickness of the fetal abdomen is useful for ruling out macrosomia.

Abdominal Muscles↗
PubMed1997

Effects of GABA-B agonist baclofen on bronchial hyperreactivity to inhaled histamine in subjects with cervical spinal cord injury.

Bronchial provocation studies performed in our research center have consistently demonstrated airway hyperresponsiveness to both inhaled methacholine and histamine in subjects with chronic cervical spinal cord injury (SCI). More recently, we reported that the airways of such subjects maintained on chronic baclofen (gamma-aminobutyric acid) therapy were not hyperreactive to inhaled methacholine. In this study we determined whether baclofen also blocks the effects of the bronchoprovocative agent histamine in subjects with cervical SCI. Twenty-four male subjects with cervical SCI participated in this study; 14 were maintained on oral baclofen, and 10 served as age-matched controls. The subjects were challenged with increasing concentrations of aerosolized histamine until either a 20% fall in forced expiratory volume in 1 s (FEV1) from baseline (defined as PC20) was observed, or a maximum of 25 mg/ml histamine was administered. We found that 11 of the 14 baclofen subjects (78.5%) and 8 of the 10 control subjects (80%) responded (PC20 < 8 mg/ml) to the histamine challenge. Mean PC20 values among responders in the baclofen (PC20 = 2.91 +/- 2.3) and control (PC20 = 2.18 +/- 1.9) groups did not differ significantly. Because histamine acts directly on histamine receptors and indirectly on cholinergic pathways, our findings that baclofen blocks bronchoconstriction due to inhaled methacholine, but not that due to histamine, suggests that hyperresponsiveness in subjects with cervical SCI may be secondary to nonspecific airway hyperreactivity.

Adult↗
PubMed1997

rhuIL-2 adjunctive therapy in multidrug resistant tuberculosis: a comparison of two treatment regimens and placebo.

SETTING: Low-dose recombinant human interleukin 2 (rhuIL-2) adjunctive immunotherapy in multidrug resistant tuberculosis (MDR-TB) patients. OBJECTIVE: Evaluation of the effects of daily versus pulse-administered rhuIL-2 compared to placebo. DESIGN: MDR-TB patients on best available antituberculous chemotherapy received rhuIL-2 for 30 consecutive days (daily therapy), or for 5 days followed by a 9-day 'rest', for three cycles (pulse therapy). Placebo control patients received diluent. The cumulative total dose of rhuIL-2 given to each patient in either rhuIL-2 treatment group was the same. Patient immunologic, microbiologic, and radiologic responses were compared. RESULTS: The three treatment schedules induced different results. Immune activation was documented in patients receiving daily rhuIL-2 therapy. Numbers of CD25+ and CD56+ cells in the peripheral blood were increased in these patients, but not in patients receiving pulse rhuIL-2 or placebo. In addition, 5/8 (62%) patients receiving daily rhuIL-2 demonstrated reduced or cleared sputum bacterial load while only 2/7 (28%) pulse rhuIL-2 treated and 2/8 (25%) controls showed bacillary clearance. Chest radiographs of 7/12 (58%) patients receiving daily rhuIL-2 indicated significant improvement over 6 weeks. Only 2/9 (22%) pulse rhuIL-2-treated patients and 5/12(42%) placebo controls showed radiologic improvement. CONCLUSION: Daily low dose rhuIL-2 adjunctive treatment stimulates immune activation and may enhance the antimicrobial response in MDR-TB.

Adult↗
PubMed1997

Self-reported prevalence of pulmonary symptoms in subjects with spinal cord injury.

To determine the prevalence of respiratory symptoms in subjects with chronic spinal cord injury (SCI), 180 subjects completed a standard respiratory questionnaire modified for subjects with limited mobility. Subjects were categorized as high tetraplegia (HT:C5 and above not requiring mechanical ventilation), low tetraplegia (LT: C6-8), high paraplegia (HP: T1-7), or low paraplegia (LP: T8-L3). Overall, 68% of subjects reported one or more respiratory symptom. Breathlessness, the most prevalent complaint, was associated with level of lesion: HT = 73%, LT = 58%, HP = 43% and LP = 29%, whereas complaints of cough, phlegm, cough and phlegm, and wheeze did not differ significantly among subjects in the four groups. Breathlessness occurred significantly more often in the group with HT during rest or following exposure to hot air or passive smoke. Awareness of phlegm or wheeze was reported with increased prevalence among subjects with tetraplegia who had complete injuries. Among subjects with tetraplegia, respiratory complaints did not differ significantly in current smokers, former smokers, and non-smokers, whereas among subjects with paraplegia, phlegm and wheeze were reported more frequently, among current smokers.

Adult↗
PubMed1997

A pharmacodynamic study of morphine and its glucuronide metabolites after single morphine dosing in cancer patients with pain.

Eleven morphine naïve patients with cancer-related pain were given a single dose of either intravenous morphine (n = 5) or oral morphine (n = 6). Blood sampling was performed over a 24-hr period and serial pain assessments were made using a categorical scale. Plasma samples were analyzed for morphine, morphine-6-glucuronide (M-6-G), morphine-3-glucuronide (M-3-G), and normorphine using high-performance liquid chromatography. In neither the intravenous nor oral group was there a correlation between analgesia duration and the half-lives of morphine and M-6-G. There was no correlation between the time to peak analgesia and time to peak concentration for morphine or M-6-G. There was no significant difference in absolute concentrations of M-6-G or M-3-6 nor in the ratio of M-3-G to M-6-G at peak analgesia versus relapse.

Administration, Oral↗
PubMed1996

Peptidase inhibitors potentiate lysylbradykinin-induced bronchoconstriction in the rat.

To determine whether lysylbradykinin (LBK, kallidin) causes bronchoconstriction in animals and if peptidase inhibitors modulate the response, we studied the effects of LBK administered by aerosol in rats and assessed whether pretreatment with aerosolized solutions of enalaprilat, an inhibitor of angiotensin converting enzyme (ACE), or phosphoramidon, an inhibitor of endopeptidase 24.11 (EP 24.11, neutral endopeptidase), altered the response. Accordingly, LBK-induced bronchoconstriction was measured in anesthetized, mechanically ventilated, specific pathogen-free, Sprague-Dawley rats by body plethysmography and followed by continuous determination of lung resistance (RL) and maximal expiratory flow (MEF). Incremental doses of aerosolized LBK were administered by nebulization to obtain a concentration that caused a 5-15% increase in RL, which was designated the BC10 dose. We found that pretreatment with aerosolized enalaprilat (1 mM) 3 min prior to a BC10 dose of LBK significantly increased RL as compared to the BC10 dose alone (129 +/- 4.1% vs. 105 +/- 2.4%, P < 0.002, n = 4) and significantly decreased MEF (83 +/- 1.5% vs. 97 +/- 1.4%, P < 0.008, n = 4). Following pretreatment with aerosolized phosphoramidon (1 mM), significant increases in RL (113 +/- 1.4% vs. 106 +/- 1.6%, P < 0.019, n = 7) and decreases in MEF (92 +/- 0.9% vs. 95 +/- 0.9%, P < 0.035, n = 7) were observed (paired Student's t-test). The above findings demonstrate the effects of LBK on airway caliber for the first time in an animal model, and suggest that ACE and EP 24.11 contribute to degradation of the peptide in the airway.

Administration, Inhalation↗
PubMed1996

The practice of surgical staging and its impact on adjuvant treatment recommendations in patients with stage I endometrial carcinoma.

A survey of American gynecologic oncologists was undertaken to assess their compliance with current surgical staging criteria in patients with early endometrial carcinoma. One hundred forty-four members of the Society of Gynecologic Oncologists responded to the survey. Respondents treated an average of 22 new cases annually. Tumor grade and intraoperative determination of depth of myometrial invasion were demonstrated to influence the frequency of lymphatic dissection. In grade 1, 2, and 3 lesions, 76, 60, and 34% of responders, respectively, indicated that depth of invasion influenced their decision to perform lymphadenectomy. In addition, depth of invasion was important in determining type and extent of lymphatic resection. Further, the impact of pathologic lymph node status on postoperative adjuvant radiation therapy recommendations was evaluated for various stratifications of endometrial adenocarcinoma confined to the corpus. The greatest differences in treatment recommendations were noted in the 50-66% invasion category. For grade 1 and 2 cancers, adjuvant therapy recommendations were reduced by 23 and 16% respectively when comparing pelvic and combined therapy versus none and vaginal therapy. The effect of surgical staging data on clinical decisions is clearly evident. The knowledge of pathologically negative lymph node status reduces the recommendation for postoperative adjuvant radiotherapy in patients with adenocarcinoma otherwise confined to the uterine corpus.

Chemotherapy, Adjuvant↗
PubMed1996

Differentiation of sarcoidosis from tuberculosis by use of electron capture gas-liquid chromatography.

To explore further the possible etiologic role of mycobacteria in the development of sarcoidosis, we measured free, nonbound tuberculostearic acid (TSA, 10-methyloctadecanoic), a component of mycobacteria, in the sera of subjects with sarcoidosis or active untreated pulmonary tuberculosis and in healthy controls by use of frequency-pulsed electron capture gas-liquid chromatography (FPEC-GLC). The selective analytic system is capable of measuring as little as 15-fmol quantities of free, nonbound TSA in serum and cerebral spinal fluid. We found that TSA was present in the sera of all subjects with Mycobacterium tuberculosis (n = 10) but was undetectable in subjects with sarcoidosis (n = 15) and in healthy controls (n = 15), thereby suggesting that if sarcoidosis is caused by a mycobacterial organism, TSA is not produced or does not gain access to the systemic circulation in quantities sufficient for measurement. However, in the course of the studies we found that a peak, designated p11, was elevated in the sera of all subjects with acute sarcoidosis (n = 4). Also, a peak designated p3 was reduced significantly in all subjects with acute and chronic sarcoidosis and absent in subjects with M. tuberculosis compared with healthy controls. Both peaks were later shown by chemical analysis and mass spectral studies to be carboxylic acids not previously associated with specific disease entities. Follow-up detailed studies will be needed to determine if quantitation of these unique carboxylic acids will be useful in differentiating sarcoidosis from other disorders.

Carboxylic Acids↗
PubMed1996

Computed radiography in neonatal and pediatric intensive care units: a comparison of 2.5 K x 2 K soft-copy images vs digital hard-copy film.

OBJECTIVE: The goal of the study was to determine whether soft-copy images on high-resolution monitors (2.5 K x 2 K) are suitable for primary interpretation of images from pediatric and neonatal intensive care units. The hypotheses were that hard and soft images yield similar diagnostic information, and that both residents and faculty radiologists can use monitors effectively. Previous reports have produced conflicting results; the need for larger sample sizes has been emphasized. MATERIALS AND METHODS: One thousand one hundred and four images produced by computed radiography using the Kodak Ectascan Imagelink system were prospectively analyzed by two pediatric radiologists, one reading hard copy and the other soft copy of the same images. Bias was controlled by equal distribution of modalities between observers and by daily alternation of modality. Hard- and soft-copy observations of presence or absence of nine specific tubes and nine specific diagnostic findings were compared. Interobserver differences between pediatric radiologists and radiology residents were studied on additional images. The kappa statistic was used to evaluate the level of agreement for all observations. RESULTS: There was excellent agreement between hard and soft copy interpretation for each tube and diagnostic finding (kappa values 0.93-1.0) and excellent interobserver agreement between two pediatric radiologists (kappa values 0.84-1.0). The level of agreement between radiology residents and pediatric radiologist was excellent for the most objective findings. All results were statistically significant (p < 0.001). CONCLUSION: High resolution soft-copy images are suitable for primary interpretation in patients in pediatric and neonatal intensive care units.

Child↗
PubMed1996

Hydrolysis of N-formylmethionyl chemotactic peptides by endopeptidase 24.11 and endopeptidase 24.15.

Endopeptidase 24.11 (EP 24.11), a membrane-bound cell surface enzyme, modulates chemotactic responsiveness of neutrophils to f-Met-Leu-Phe. It is unknown if the enzyme degrades potent formylmethionyl tetrapeptides or if an enzyme with similar activities, endopeptidase 24.15 (EP 24.15), degrades formylated chemotactic peptides. In a study of five formylmethionyl tetrapeptides and f-Met-Leu-Phe, we found that EP 24.11 had high affinity for all peptides evaluated, although it did not effectively degrade f-Met-Ile-Leu-Phe. EP 24.15 had high affinity for three of the tetrapeptides, and for f-Met-Leu-Phe, although, for unclear reasons, it did not degrade f-Met-Ile-Leu-Phe or f-Met-Leu-Phe, the apparent natural products of Staphylococcus aureus and Escherichia coli, respectively.

Amino Acid Sequence↗
PubMed1996

Growth of acid fast L forms from the blood of patients with sarcoidosis.

BACKGROUND: Acid fast cell wall deficient forms (CWDF) of bacteria have been grown from blood, bronchial washings, and ocular anterior chamber fluid from patients with sarcoidosis. A monoclonal antibody raised against Mycobacterium tuberculosis whole cell antigen (H37RV) was used to characterise further CWDF grown from the blood of patients with sarcoidosis. METHODS: Blood from 20 patients with active sarcoidosis and from 20 controls was cultured using methods favourable for the growth of CWDF. Isolates were further characterised by indirect fluorescent antibody analysis using a monoclonal antibody highly reactive with M tuberculosis. RESULTS: CWDF were grown from the blood of 19 of 20 subjects with sarcoidosis. All isolates stained positively with the monoclonal antibody and with a modified Kinyoun stain. No organisms were grown from the blood of controls. CONCLUSIONS: These data demonstrate that CWDF can be grown from the blood of nearly all patients with active sarcoidosis. The results confirm that the organisms are mycobacterial in origin and are similar, if not identical, to M tuberculosis. Their role in the pathogenesis of sarcoidosis is unknown.

Fluorescent Antibody Technique, Indirect↗
PubMed1996

Proton MR spectroscopy of the basal ganglia in healthy children and children with AIDS.

PURPOSE: To evaluate proton magnetic resonance (MR) spectroscopy in children with the acquired immunodeficiency syndrome (AIDS) and to establish an age-dependent spectroscopic database of the normal basal ganglia in children. MATERIALS AND METHODS: Eighteen healthy children and 45 children with AIDS underwent both brain MR imaging and single-voxel MR spectroscopy with a long-echo-time point-resolved technique. A large part of the region of interest studied at MR spectroscopy included the basal ganglia. RESULTS: Seven patients with progressive encephalopathy and eight with static encephalopathy had significantly lower mean N-acetyl aspartate (NAA)/creatine (Cr) ratios than age-matched control subjects (P<.02). In determining the presence of progressive encephalopathy in children with AIDS, MR spectroscopy appears to be more sensitive and specific than MR imaging and immunologic testing. Thirty patients without encephalopathy had normal NAA/Cr ratios but significantly lower choline/Cr ratios than age-matched control subjects (P<.02). CONCLUSION: Proton MR spectroscopy may be a more sensitive diagnostic technique than MR imaging in childhood AIDS encephalopathy.

AIDS Dementia Complex↗