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Biomedical subjects

L M Shulman

Publications and source records attributed to L M Shulman.

At least 37 records · Page 2Linked to original sources
PubMed1999

A new variant of echovirus 4 associated with a large outbreak of aseptic meningitis.

BACKGROUND: A large outbreak of aseptic meningitis which began in April 1997 involved hundreds of cases in all geographical regions of Israel and the Palestinian Authority, peaked between June and September, and lasted until December. OBJECTIVES: We have investigated the virus associated with the outbreak to determine its serotype and molecular type and to establish epidemiological links. DESIGN: Virus strains isolated from 210 clinical samples were serotyped by neutralization using LBM and WHO antiserum pools and two echovirus 4 (EV4)-specific antisera, and by immunofluorescence using a monoclonal antibody. RNA was extracted and a 435 base long fragment derived from the 5'UTR of the genome was amplified by RT-PCR using common primers, and sequenced. Sequences were compared to echoviruses 4, 6 and 7 prototypes from ATCC, and to other echoviruses sequences from the EMBL/Genbank data base. RESULTS: The outbreak isolates were identified by the EV4 type-specific antisera and the monoclonal antibody but not with the WHO pools. Very few isolates could be typed by the LBM pools. The EV4 isolates accounted for 68% of all enterovirus isolates in our laboratory in 1997. The age distribution of the patients was: 0-11 month, 11.2%; 1-4 years, 16.1%; 5-9 years, 31.8%; 10-14 years, 9.9%; 15-20 years, 9.5%; 21-44 years, 21.5%; and > 45 years, 0%. Males between 1 and 14 years of age were affected more frequently than females of the same age. The sequences of 25 of 28 EV4 isolates analyzed were closely related to each other (> 95% homology) and the remaining three isolates had < 95% homology to the others and to each other. Interestingly, the outbreak strains were less closely related to the EV4 prototype, than to several other echoviruses. Three closely related subgroups were identified which correlated with geographical distribution but the temporal distribution did not reveal links leading to the source of the outbreak. CONCLUSION: The outbreak was caused by a variant of EV4 which apparently did not circulate in the area before and thus was capable of causing a widespread infection.

Disease Outbreaks↗
PubMed1998

Asymmetric predominantly ipsilateral blepharospasm and contralateral parkinsonism in an elderly patient with a right mesencephalic cyst.

A 66-year-old woman presented with a 3-year history of predominantly right-sided blepharospasm and a 1-year history of progressive predominantly left-sided hemiparkinsonism manifested by a left upper extremity resting tremor and left-sided bradykinesia. Magnetic resonance imaging of the brain revealed a large right mesencephalic cyst with mass effect. Positron emission tomography revealed bilateral striatal hypometabolism consistent with nigrostriatal dopaminergic dysfunction. The association of predominantly ipsilateral blepharospasm and predominantly contralateral hemiparkinsonism is very rare, and its association with a posterior fossa space-occupying lesion has been reported only once. This is the second report of such an association and the first description of adult-onset symptomatology.

Aged↗
PubMed1998

Three forms of AU-1 like human rotaviruses differentiated by their overall genomic constellation and by the sequence of their VP8*.

Insight into the origin of human rotaviruses carrying the AU-1 VP4 allele was gained by examining their genomic RNA constellation using RNA-RNA hybridization and by sequencing the VP8* portion (nucleotides 1-750) of their gene 4. AU-1 like viruses isolated in Israel from children attending outpatient clinics were classified into three sub-genogroups based on RNA-RNA hybridization analysis: Subgenogroup 1 consists of two strains (Ro-5829 and Ro-5960) which belong to the AU-1 genogroup, since all their 11 segments hybridized to AU-1 segments. Subgenogroup 2 consists of one reassortant virus (Ro-5193) of which seven RNA segments hybridized to AU-1 segments and the remaining four segments hybridized to NCDV (bovine rotavirus). Subgenogroup 3 consists of four reassortant viruses (Ro-6460, Ro-6584, Ro-6784 and Ro-7044) which had a common genome constellation: only four of their RNA segments hybridized to AU-1 and the other seven segments hybridized to NCDV segments. Sequence analysis of the VP8* gene also revealed a three level pattern of homology with the AU-1 prototype and the local AU-1 like strains which was consistent with the overall genomic (RNA-RNA) constellation: Subgenogroup 1 had 98-98.1% homology with the AU-1 prototype; Subgenogroup 2 had 96.8% homology with the AU-1 prototype and 95.6-96.7% homology with Subgenogroup 1; Subgenogroup 3 had 95.3-95.6% homology with the prototype AU-1 and 93.4-94.3% homology with Subgenogroup 1. Possible evolutionary pathways are discussed.

Alleles↗
PubMed1998

Tolcapone in stable Parkinson's disease: efficacy and safety of long-term treatment. Tolcapone Stable Study Group.

In this double-blind, placebo-controlled trial, we investigated the effect of the catechol-O-methyltransferase inhibitor tolcapone 100 or 200 mg three times daily on activities of daily living and motor function in 298 patients with parkinsonism receiving levodopa but without motor fluctuations. At 6 months, both dosages of tolcapone produced significant reductions in the Unified Parkinson's Disease Rating Scale scores for activities of daily living (Subscale II) and motor function (Subscale III) and in the total score for Subscales I to III. These improvements were maintained up to the 12-month assessment. At 6 months, both tolcapone groups had changes in levodopa dosage that were significantly different from placebo: the tolcapone groups had decreases in mean total daily dose of levodopa, whereas the placebo group had a mean increase. Tolcapone was well tolerated. The principal adverse events were levodopa-related, but these were generally mild or moderate. Diarrhea was the most frequent nondopaminergic adverse event. Tolcapone appears to be beneficial in the treatment of patients with parkinsonism who have not yet developed motor fluctuations.

Aged↗
PubMed1997

Identification of a new strain of fastidious enterovirus 70 as the causative agent of an outbreak of hemorrhagic conjunctivitis.

A 1994 outbreak of acute hemorrhagic conjunctivitis in Israel was caused by an enterovirus 70 strain that was distinct from previously reported strains. Characterization was by electron microscopy (eye washes), reverse transcription-PCR (RT-PCR; eyewash, specimens, eye swabs, and tears), and sequence analysis of RT-PCR-amplified fragments from the 5' noncoding region and VP1.

Amino Acid Sequence↗
PubMed1997

Tolcapone in stable Parkinson's disease: efficacy and safety of long-term treatment. The Tolcapone Stable Study Group.

In this double-blind, placebo-controlled trial, we investigated the effect of the catechol-O-methyltransferase inhibitor tolcapone 100 or 200 mg three times daily on activities of daily living and motor function in 298 patients with parkinsonism receiving levodopa but without motor fluctuations. At 6 months, both dosages of tolcapone produced significant reductions in the Unified Parkinson's Disease Rating Scale scores for activities of daily living (Subscale II) and motor function (Subscale III) and in the total score for Subscales I to III. These improvements were maintained up to the 12-month assessment. At 6 months, both tolcapone groups had changes in levodopa dosage that were significantly different from placebo: the tolcapone groups had decreases in mean total daily dose of levodopa, whereas the placebo group had a mean increase. Tolcapone was well tolerated. The principal adverse events were levodopa-related, but these were generally mild or moderate. Diarrhea was the most frequent nondopaminergic adverse event. Tolcapone appears to be beneficial in the treatment of patients with parkinsonism who have not yet developed motor fluctuations.

Activities of Daily Living↗
PubMed1996

Dopamine inhibits mammalian photoreceptor Na+,K+-ATPase activity via a selective effect on the alpha3 isozyme.

The rat retina contains dopaminergic interplexiform cells that send processes to the outer plexiform layer where dopamine is released in a light-dependent manner. We report herein that physiologically relevant concentrations of dopamine inhibited ouabain-sensitive photoreceptor oxygen consumption in dark- and light-adapted rat retinas and inhibited Na+,K+-ATPase specific activity (EC 3.6.1.37) in a rat rod outer-inner segment preparation. Experiments with the selective D1 agonist fenoldopam or D2 agonist quinpirole and experiments with dopamine plus either the D1 antagonist SCH23390 or D2/D4 antagonist clozapine showed that the inhibition of oxygen consumption and enzyme activity were mediated by D2/D4-like receptors. The amphetamine-induced release of dopamine, monitored by the inhibition of oxygen consumption, was blocked by L-2-amino-4-phosphonobutyric acid and kynurenic acid. Pharmacological and biochemical experiments determined that the IC50 values of ouabain for the alpha1-low and alpha3-high ouabain affinity isozymes of photoreceptor Na+,K+-ATPase were approximately 10(-5) and approximately 10(-7) M, respectively, and that the D2/D4-like mediated inhibition of Na+,K+-ATPase was exclusively selective for the alpha3 isozyme. The dopamine-mediated inhibition of alpha3 first occurred at 5 nM, was maximal at 100 microM (-47%), had an IC50 value of 382 +/- 23 nM, and exhibited negative cooperativity (Hill coefficient, 0.27). Prior homogenization of the rod outer-inner segment completely prevented the long-lasting inhibition, suggesting that the effect was coupled to a second messenger. Although the physiological significance of our findings to photoreceptor function is unknown, we hypothesize that these results may have relevance for the temporal tuning properties of rods.

Aminobutyrates↗
PubMed1996

Internal tremor in patients with Parkinson's disease.

Although sensory symptoms were not originally described in Parkinson's disease (PD), in recent years it has been increasingly recognized that painful sensations and paresthesias occur in approximately 40% of patients. It has been our observation that PD patients often describe a sensation of internal tremor, a feeling of tremor inside the chest, abdomen, arms, or legs that cannot be seen. We investigated the prevalence and characteristics of internal tremor by administering a questionnaire to 100 consecutive patients with PD and 50 age-matched controls seen in our movement disorders center. A sensation of internal tremor was present in 44% of this sample of PD patients and in 6% of the control population (p < 0.0001). The presence of internal tremor was unrelated to Unified Parkinson's Disease Rating Scale score, Hoehn and Yahr stage, duration of disease, or the presence of observable tremor. The frequency of other sensory symptoms (aching, tingling, burning) was higher in the PD patients with internal tremor (73%) than in those without (45%; p = 0.005). Internal tremor is associated with anxiety in 64% of patients (p < 0.0001). It was described as uncomfortable and was unrelieved by antiparkinsonian medication in three quarters of patients. A sensation of internal tremor is commonly reported by PD patients and should be recognized as a useful diagnostic factor in PD.

Aged↗
PubMed1996

HIV encephalitis presenting with severe generalized chorea.

We report a case of rapidly progressive encephalopathy and generalized chorea due to HIV encephalitis. The patient was a 24-year-old man known to be HIV-seropositive for 4 years. The severity of the movement disorder resulted in rhabdomyolysis. Sepsis developed and he died after a 21-day hospitalization. Pathologic study revealed prominent neuronal loss and gliosis of subcortical regions. Acute encephalopathy with generalized chorea may be a rare consequence of HIV encephalitis.

Adult↗