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Biomedical subjects

M Levy

Publications and source records attributed to M Levy.

At least 55 records · Page 3Linked to original sources
PubMed2001

The exacerbation of pancreatic endocrine dysfunction by potent pancreatic exocrine supplements in patients with chronic pancreatitis.

BACKGROUND: Chronic pancreatitis often culminates in maldigestion and diabetes. Clinical management is complex as the correction of maldigestion often disturbs diabetic control. STUDY: In the following study, we examined the effects of a potent new commercial pancreatic enzyme on food absorption and blood glucose control. Enzymes were manufactured in enteric-coated mini-microsphere form (0.7--1.6 mm), designed to prevent gastric acid degradation and facilitate co-migration with food, and given in quantities calculated to cover normal digestion requirements (four capsules with meals, two with snacks; content/capsule: lipase 10,000 USP units, protease 37,500 units, amylase 33,200 units). Forty patients with chronic pancreatitis were screened during a run-in nonenzyme-supplemented phase; only those with stool fat excretion rates over 10 g/d (n = 29) were advanced to a 14-day parallel randomized placebo versus enzyme supplement group comparison. RESULTS: Of these, 62% were diabetic (50% insulin-dependent) and 52% were malnourished (body mass index less than 20 kg/m(2) ). After enzyme supplementation, stool fat and nitrogen excretion decreased, whereas fat absorption increased from 54.0 +/- 9.7% to 80.8 +/- 3.8% per day (p = 0.002) and protein from 80.5 +/- 3.4% to 86.8 +/- 2.2% per day (p = 0.004). Changing treatment from active enzyme supplementation to placebo (and vice versa) resulted in major problems with glucose control; blood glucose levels became abnormal in 28 of 29 patients, one patient required hospitalization for symptomatic hypoglycemia (0.9 mmol/L) during placebo treatment, and one developed diabetic ketoacidosis after recommencing active enzyme supplementation. CONCLUSIONS: In conclusion, high-dose pancreatin mini-microspheres improved, but did not normalize, fat absorption, possibly because of the residual influence of diabetes and malnutrition on absorptive function. In view of the brittle nature of blood glucose control in malnourished insulin-dependent patients, enzyme adjustment should be carefully supervised in-hospital.

Adult↗
PubMed2001

Thallium gated SPECT: relation between immediate post-stress evolution of ejection fraction and severity of perfusion pattern.

BACKGROUND AND AIMS: A significant decrease of left ventricular ejection fraction (LVEF) at stress has been reported with 99Tc(m) gated single-photon emission computed tomography (gSPECT) in severe myocardial stunning up to 1 h after exercise. This study was designed to show whether 201Tl gSPECT can measure LVEF evolution from rest to stress in routine examination and give additional information to perfusion interpretation since acquisition starts immediately after stress test. METHODS: Post-exercise and rest 201Tl gSPECT were performed in 187 patients with suspected coronary artery disease. Myocardial perfusion was quantified by 20-segment analysis. Patients were divided into four groups according to their summed perfusion score, reversibility rate and electrocardiographic findings, i.e. in order of severity: I = normal perfusion, II = fixed defect owing to a myocardial infarction, III = full reversible ischaemia, and IV = partial reversible ischaemia. LVEF was calculated by Germano's automatic algorithm. RESULTS: Normal subjects (n = 29) and infarcted patients (n = 34) showed a significant LVEF increase between rest and stress, +7 +/- 9% and +5 +/- 7% respectively. In full reversible ischaemic patients (n = 46), stress LVEF showed no increase (+1 +/- 8%) and this group was statistically different from both group I and group II. Furthermore, when ischaemia was partially reversible (n = 31), LVEF decreased significantly (-3 +/- 8%), particularly when exercise tests were abnormal (-4 +/- 8%). Group IV was statistically different from groups I and II. CONCLUSIONS: Good agreement exists between the severity of ischaemic perfusion pattern and LVEF degradation at stress, which is consistent with previously published data using 99Tc(m) gSPECT. Additionally, the use of 201Tl for immediate post-exercise imaging allows the observation of a physiological LVEF increase in normal and infarcted patients.

Adult↗
PubMed2001

Helicobacter pylori and gastric lymphoma: high seroprevalence of CagA in diffuse large B-cell lymphoma but not in low-grade lymphoma of mucosa-associated lymphoid tissue type.

OBJECTIVE: Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type is closely related to Helicobacter pylori (H. pylori) infection. In vitro studies have demonstrated H. pylori-induced B cell proliferation to be strain dependent. High prevalences of CagA protein and FldA protein have been reported in strains obtained from patients with gastric lymphoma of MALT type. The aims of the present study were to evaluate the prevalence of H. pylori infection and to search for antigenic particularities in 53 patients with primary gastric lymphoma in comparison with a group of infected patients with benign disease. METHODS: Of the 53 patients, 37 presented with low-grade lymphoma of MALT type (LGLM) and 16 with diffuse large B-cell lymphoma (DLBCL). They were compared to a group of 162 H. pylori-infected subjects comprising the control group: 111 had gastric or duodenal ulcer (GDU) and 51 nonulcer dyspepsia (NUD). Diagnosis of gastric lymphoma was established on histological examination of endoscopic specimens. Anti-H. pylori antibodies were assayed by third-generation ELISA. Western blot assay was used to detect antibodies against nine antigens (including CagA protein), which were recognized on the basis of their molecular weight. RESULTS: Of the 53 patients with gastric lymphoma, 45 were H. pylori-positive (85%): of these, 25 (56.5%) had anti-CagA antibodies. The prevalence of H. pylori seropositivity was 78% (29/37) in LGLM and 100% (16/16) in DLBCL. The prevalence of CagA seropositivity in H. pylori-positive patients was 44.8% (13/29) and 75% (12/16), respectively (p < 0.05). In comparison, the seroprevalence of CagA was 77.4% (86/111) in GDU patients and 43.1% (22/53) in NUD patients. The prevalence of antibodies to other antigenic proteins detected with Helicoblot 2.0 (19.5kd, 30kd, 35kd, VacA, HSPb, Urease A, and Urease B) did not differ among the groups except for 35kd protein, which was significantly higher (p < 0.01) in GDU than in NUD and in LGLM (76.6% vs 49% and 46.7%). CONCLUSION: These findings suggest that in patients who develop gastric lymphomas in response to H. pylori, virulent strains expressing CagA protein are preferentially associated with DLBCL.

Analysis of Variance↗
PubMed2001

Toward automated nucleic acid enzyme selection.

Methods for automation of nucleic acid selections are being developed. The selection of aptamers has been successfully automated using a Biomek 2000 workstation. Several binding species with nanomolar affinities were isolated from diverse populations. Automation of a deoxyribozyme ligase selection is in progress. The process requires eleven times more robotic manipulations than an aptamer selection. The random sequence pool contained a 5' iodine residue and the ligation substrate contained a 3' phosphorothioate. Initially, a manual deoxyribozyme ligase selection was performed. Thirteen rounds of selection yielded ligators with a 400-fold increase in activity over the initial pool. Several difficulties were encountered during the automation of DNA catalyst selection, including effectively washing bead-bound DNA, pipetting 50% glycerol solutions, purifying single strand DNA, and monitoring the progress of the selection as it is performed. Nonetheless, automated selection experiments for deoxyribozyme ligases were carried out starting from either a naive pool or round eight of the manually selected pool. In both instances, the first round of selection revealed an increase in ligase activity. However, this activity was lost in subsequent rounds. A possible cause could be mispriming during the unmonitored PCR reactions. Potential solutions include pool redesign, fewer PCR cycles, and integration of a fluorescence microtiter plate reader to allow robotic 'observation' of the selections as they progress.

Automation↗
PubMed2001

Intussusception due to Yersinia enterocolitica enterocolitis in a patient with beta-thalassemia.

Patients who are homozygous for thalassemia major are at risk for Yersinia enterocolitica infections. We present a case of a 4-year-old child with intussusception of the terminal ileum whose past medical history was significant for beta-thalassemia. His monthly blood transfusions for this condition may have put him at risk for Y enterocolitica enterocolitis. The pathogenesis of this disease relates to the role of iron as an essential growth factor for Yersinia, and this patient's transfusions left him in an iron-overloaded state, despite treatment with Desferal. Our patient's unusual presentation of intussusception was secondary to the mass effect caused by lymphoid hyperplasia, specifically hypertrophied Peyer's patches in the ileum caused by Y enterocolitica infection. To our knowledge, this is the first such case of intussusception caused by Yersinia to be reported.

Child, Preschool↗
PubMed2000

Debate: what constitutes 'terminality' and how does it relate to a living will?

A moribund and debilitated patient arrives in an emergency department and is placed on life support systems. Subsequently it is determined that she has a 'living will' proscribing aggressive measures should her condition be judged 'terminal' by her physicians. But, as our round table of authorities reveal, the concept of 'terminal' means different things to different people. The patient's surrogates are unable to agree on whether she would desire continuation of mechanical ventilation if there was a real chance of improvement or if she would want to have her living will enforced as soon it's terms were revealed. The problem of the potential ambiguity of a living will is explored.

Aged↗
PubMed2000

Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium.

Familial incontinentia pigmenti (IP; MIM 308310) is a genodermatosis that segregates as an X-linked dominant disorder and is usually lethal prenatally in males. In affected females it causes highly variable abnormalities of the skin, hair, nails, teeth, eyes and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring. Cells expressing the mutated X chromosome are eliminated selectively around the time of birth, so females with IP exhibit extremely skewed X-inactivation. The reasons for cell death in females and in utero lethality in males are unknown. The locus for IP has been linked genetically to the factor VIII gene in Xq28 (ref. 3). The gene for NEMO (NF-kappaB essential modulator)/IKKgamma (IkappaB kinase-gamma) has been mapped to a position 200 kilobases proximal to the factor VIII locus. NEMO is required for the activation of the transcription factor NF-kappaB and is therefore central to many immune, inflammatory and apoptotic pathways. Here we show that most cases of IP are due to mutations of this locus and that a new genomic rearrangement accounts for 80% of new mutations. As a consequence, NF-kappaB activation is defective in IP cells.

Exons↗
PubMed2000

Peptide nucleic acids rather than RNA may have been the first genetic molecule.

Numerous problems exist with the current thinking of RNA as the first genetic material. No plausible prebiotic processes have yet been demonstrated to produce the nucleosides or nucleotides or for efficient two-way nonenzymatic replication. Peptide nucleic acid (PNA) is a promising precursor to RNA, consisting of N-(2-aminoethyl)glycine (AEG) and the adenine, uracil, guanine, and cytosine-N-acetic acids. However, PNA has not yet been demonstrated to be prebiotic. We show here that AEG is produced directly in electric discharge reactions from CH(4), N(2), NH(3), and H(2)O. Electric discharges also produce ethylenediamine, as do NH(4)CN polymerizations. AEG is produced from the robust Strecker synthesis with ethylenediamine. The NH(4)CN polymerization in the presence of glycine leads to the adenine and guanine-N(9)-acetic acids, and the cytosine and uracil-N(1)-acetic acids are produced in high yield from the reaction of cyanoacetaldehyde with hydantoic acid, rather than urea. Preliminary experiments suggest that AEG may polymerize rapidly at 100 degrees C to give the polypeptide backbone of PNA. The ease of synthesis of the components of PNA and possibility of polymerization of AEG reinforce the possibility that PNA may have been the first genetic material.

Biopolymers↗
PubMed2000

Prebiotic synthesis of adenine and amino acids under Europa-like conditions.

In order to simulate prebiotic synthetic processes on Europa and other ice-covered planets and satellites, we have investigated the prebiotic synthesis of organic compounds from dilute solutions of NH4CN frozen for 25 years at -20 and -78 degrees C. In addition, the aqueous products of spark discharge reactions from a reducing atmosphere were frozen for 5 years at -20 degrees C. We find that both adenine and guanine, as well as a simple set of amino acids dominated by glycine, are produced in substantial yields under these conditions. These results indicate that some of the key components necessary for the origin of life may have been available on Europa throughout its history and suggest that the circumstellar zone where life might arise may be wider than previously thought.

Adenine↗
PubMed2000

Day 3 morphology is a poor predictor of blastocyst quality in extended culture.

OBJECTIVE: To determine how the quality of blastocysts formed on day 5/6 of extended culture compares with their morphology on day 3. DESIGN: Retrospective observational study of IVF laboratory records. SETTING: Private assisted reproduction clinic. PATIENT(S): 101 IVF cycles in which 5 to 25 embryos were produced. The average maternal age was 33.1 years. INTERVENTION(S): Embryos were individually cultured in vitro in sequential media for an extended time to enable use of blastocysts for fresh transfer or cryopreservation. MAIN OUTCOME MEASURE(S): Comparison of embryo quality for putative ET or cryopreservation on day 3 with quality of embryos used for actual ET and cryopreservation on day 5/6. RESULT(S): Of 1,263 cleaving embryos, 559 were judged to have been suitable for use on day 3; 355 would have been used for ET (average per ET, 3.5) and 204 would have been frozen (equivalent to 44% utilization). In actuality, 471 blastocysts were used on day 5/6, of which 234 were transferred (average per ET, 2.3), and 237 were frozen (equivalent to 37% utilization). Only 48% embryos that would have been chosen for ET and/or cryopreservation on day 3 were eventually used in such a manner at the blastocyst stage. Historically, the rate of viable pregnancy from day 3 transfers was 30.5% per transfer; this rate increased to 45% with routine day 5/6 transfers. CONCLUSION(S): Extended culture of human embryos seems to increase discrimination of potential embryonic viability. Criteria for embryo selection on day 3 seem to be inadequate. Extended in vitro culture may therefore be an effective means of optimizing IVF clinical success.

Adult↗
PubMed2000

Familial Mediterranean fever in the 'Chuetas' of Mallorca: a question of Jewish origin or genetic heterogeneity.

Familial Mediterranean fever (FMF) is a hereditary disease commonly found among Jews, Armenians, Turks and Arabs. Recently, FMF was found in the 'Chuetas', a unique community on the island of Mallorca (Spain). To address the question of their possible Jewish origin, we analysed markers known to be linked to the gene responsible for FMF in Jews (MEFV) in this population. We found that 1/3 of the 16p13.3 chromosomes of the 'Chuetas' FMF patients bore the major ancestral haplotypes (S,S2) and their corresponding M694V and E148Q mutations, displayed by Jews from North Africa. Furthermore, we also detected a novel mutation (L110P) in this community. Yet 2/3 of these patients bore S negative haplotypes and lack the mutations commonly known to cause FMF. These results confirm that at least some of the 'Chuetas' share a common origin with Jews. However, they also provide evidence for the possibility of genetic heterogeneity in this disorder.

Amino Acid Substitution↗
PubMed2000

Estimating prevalence in single-gene kidney diseases progressing to renal failure.

Incidence and prevalence, the measures of "frequency, " are often confused. While in a nonhereditary situation, the useful parameter is the incidence rate, evaluating the impact of an etiologic factor, it is prevalence that is considered useful in a hereditary disease. Prevalence may concern either the whole population or a fraction of this population, that is, males or females or individuals at a given age, for example, at birth. Pathologic phenotype and morbid genotype prevalences have to be clearly differentiated. In this article, we review the epidemiologic surveys allowing an estimation of the distribution of major single-gene kidney diseases progressing to renal failure in different populations. In order to compare their results, the geographic/ethnic composition of the population, the determination of its size, the choice and mode of calculation of the epidemiologic measure, the definition of the disease and modes of diagnosis, the inclusion of cases, the sources of ascertainment and the possible causes of underascertainment, and the period of time during which events were counted should be analyzed accurately. Although their impact in terms of morbidity, hospitalizations, mortality, and cost to society is high, this review shows that information on the prevalence of single-gene kidney diseases is far from complete. To date, the data essentially apply to large populations of European origin. A part of the variation among prevalence data may be due to methodological differences. Not representative are the small populations in which some rare diseases, especially recessive, are found with a high prevalence.

Genetic Predisposition to Disease↗