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S Segal

Publications and source records attributed to S Segal.

At least 55 records · Page 3Linked to original sources
PubMed2000

A mouse model of galactose-induced cataracts.

Galactokinase (GK; EC 2.7.1.6) is the first enzyme in the metabolism of galactose. In humans, GK deficiency results in congenital cataracts due to an accumulation of galactitol within the lens. In an attempt to make a galactosemic animal model, we cloned the mouse GK gene (Glk1) and disrupted it by gene targeting. As expected, galactose was very poorly metabolized in GK-deficient mice. In addition, both galactose and galactitol accumulated in tissues of GK-deficient mice. Surprisingly, the GK-deficient animals did not form cataracts even when fed a high galactose diet. However, the introduction of a human aldose reductase transgene into a GK-deficient background resulted in cataract formation within the first postnatal day. This mouse represents the first mouse model for congenital galactosemic cataract.

Aldehyde Reductase↗
PubMed2000

Determination of [(13)C]galactose enrichment in human plasma by gas chromatography/positive chemical ionization tandem mass spectrometry.

Galactosemia is a potentially fatal disease resulting from a deficiency of galactose-1-phosphate uridyl transferase. In order to perform mechanistic studies designed to elucidate further the etiology of the disease, we required a method to monitor (13)C enrichment in plasma galactose following a single oral dose or intravenous infusion of [1-(13)C]galactose. Determinations of plasma [(13)C]galactose enrichment requires methodology with extremely high specificity because of potential interference from other low molecular mass plasma constituents and from glucose, an isomer which is present in much higher concentrations. We have developed a method based on gas chromatography/positive chemical ionization tandem mass spectrometry (GC/PCI-MS/MS) for the precise and accurate determination of plasma [(13)C]galactose enrichment. The method employed a pentaacetylaldononitrile derivative of galactose in order to improve its GC and MS characteristics. Peak areas resulting from the transitions m/z 328 --> 106 and m/z 329 --> 107 were used to quantify the relative abundance of labeled and unlabeled galactose. Validation of the method was performed by determination of the precision and accuracy over a wide range of galactose concentrations and (13)C enrichments. The GC/PCI-MS/MS method was able to determine accurately enrichments at galactose concentrations down to 0.8 microM in the presence of 4 mM glucose, making it both highly selective and the most sensitive method currently available.

Calibration↗
PubMed2000

Apparent galactose appearance rate in human galactosemia based on plasma [(13)C]galactose isotopic enrichment.

Determination of endogenous galactose formation in galactosemic subjects provides important information in understanding the etiology of the long-term complications. To accomplish this task a sensitive method for measurement of isotopic enrichment of plasma galactose was developed. The aldononitrile pentaacetate derivative of galactose was utilized for gas chromatography/mass spectrometry analysis. Using a phenyl-methylsilicone capillary column, adequate separation of galactose from glucose was obtained by temperature programming of the chromatography. The specific fragmentation pattern of m/z 212, 225, 314 from d-[(12)C]galactose and m/z 213, 226, 315 from l-[(13)C]galactose was used for the galactose enrichment measurement by atom percent excess (APE). There was good correlation between expected enrichment and determined APEs at galactose concentrations of 1, 2, and 5 micromol/L with a coefficient of variation ranging from 0.22 to 7.17%. The method provides an accurate estimation of plasma [(13)C]galactose enrichment from which the galactose production rate can be calculated. The steady-state plasma l-[(13)C]galactose isotopic enrichment of three individuals with galactosemia, two males ages 33 and 13, and one female age 9, during constant infusion of l-[(13)C]galactose was 55, 41, and 55%, allowing the estimation of the apparent galactose appearance rate of 0.62, 1.09, and 0.82 mg/kg/h, respectively. The reanalysis of three previous studies by the present method found that APE values determined by the method then employed, butylboronate acetate derivatization, were systemically lower than those determined with aldononitrile pentaacetate derivatization, making for an overestimation of the apparent galactose appearance rate. The small plasma sample volumes needed make it feasible to perform these studies in infants and young children with galactosemia.

Carbon Isotopes↗
PubMed2000

Transcutaneous electrical nerve stimulation does not augment combined spinal epidural labour analgesia.

PURPOSE: The spinal portion of the combined spinal epidural technique (CSE) provides dramatic but limited labour analgesia. Transcutaneous Electrical Nerve Stimulation (TENS) has been noted to modulate pain, in part by the frequency of stimulation chosen. Because nerve action potentials are blocked by local anesthetics in a frequency dependent manner, we speculated that a TENS unit could increase the quality and duration of the spinal portion of a CSE. METHODS: Forty parturients in active spontaneous labour, with a singleton, vertex, term fetus, requesting analgesia were enrolled in a randomized, double blind fashion to receive a standardized CSE with either an active or inactive TENS unit. Prior to CSE placement, TENS intensity thresholds were determined with electrodes placed on the paraspinus muscles at T10-L1, and S2-4; TENS settings for mode, cycle, and pulse width were standardized. Data were collected at timed intervals on pain (VAS), sensory level (pinprick), motor blockade (Bromage), cervical dilatation, and duration of analgesia, and at delivery on fetal and neonatal outcome. RESULTS: The duration of the spinal portion of the CSE did not differ between groups (TENS off 91.1+/-33 [mean +/- SD] vs. TENS on 83.1+/-28 min, P = .42). Kaplan-Meier survival analysis and Mantel-Cox log rank analysis showed no difference between the two treatments (P = .28). Analgesia was comparable throughout the first hour of spinal analgesia. CONCLUSION: In healthy labouring parturients, the application of a TENS unit did not alter the quality or duration of labour analgesia provided by the spinal portion of CSE analgesia.

Adult↗
PubMed2000

The current clinical presentation of complete molar pregnancy.

OBJECTIVE: To study the current clinical presentation of complete molar pregnancy. METHOD: Retrospective study of the clinical and ultrasonographic records of 41 patients with complete hydatidiform mole. RESULTS: 17 (41%) patients were asymptomatic. 24 patients (58%) presented with vaginal bleeding, 6 (15%) had excessive uterine size, 1 (2%) had anemia and 1 (2%) had hyperemesis. Non of the patients had any other systemic manifestation. Pre-evacuation ultrasound was performed in all cases and molar pregnancy was diagnosed in 36 (88%). CONCLUSIONS: Currently with routine first trimester ultrasonography a significant proportion of patients with molar pregnancy are asymptomatic at the time of diagnosis.

Adult↗
PubMed2000

Thyroid hormone levels in cord blood of infants with acidemia at birth.

OBJECTIVE: To study the funic thyroid hormone levels in cases were fetal distress during labor resulted in acidemia at birth. MATERIAL AND METHODS: Arterial and venous levels of TSH, total T4, free T4 and total T3 obtained from cord blood at birth of twelve acidemic fetuses were compared with normal controls. RESULTS: Acidemic fetuses had a significanly higher TSH levels than controls (16.5+/-2. 1 microI/dl vs. 9.6+/-1.4 microI/dl, P=0.01). Total T3 levels were significantly lower in acidemic fetuses (49.2+/-2.9 ng/dl vs. 63+/-5. 5 ng/dl, P=0.04). Total and free T4 levels were similar and there was no difference between arterial and venous levels of the hormones. CONCLUSIONS: Birth acidemia from fetal distress during labor is associated with higher TSH levels and lower T3 levels.

Acidosis↗
PubMed2000

Hemodynamic effects of simultaneous administration of intravenous ephedrine and spinal anesthesia for cesarean delivery.

STUDY OBJECTIVE: To evaluate the hemodynamic effects of an intravenous (IV) ephedrine bolus given simultaneously with spinal anesthesia for cesarean delivery. DESIGN: Randomized, prospective, double-blind study. SETTING: Tertiary-care academic medical center. PATIENTS: 40 ASA physical status I and II nonlaboring women undergoing elective cesarean delivery of term, uncomplicated, singleton pregnancies. INTERVENTIONS: After a 10 mL/kg IV lactated Ringers bolus given over 15 minutes, patients simultaneously received an IV dose of 2 mL (10 mg) ephedrine or 2 mL saline, and an intrathecal dose of 12 mg (1.6 mL 0.75%) bupivacaine with 10 microg of fentanyl. Hypotension, defined as a 20% decrease in mean arterial pressure (MAP), was treated with 10-mg IV doses of ephedrine. MEASUREMENTS: Hemodynamic (heart rate and MAP) and non-invasive thoracic impedance (cardiac index, stroke index, and systemic vascular resistance index) measurements at baseline and at 1-minute intervals until the time of delivery. Total fluid, supplemental ephedrine, and Apgar scores were recorded. Data were evaluated using analysis of variance (ANOVA), ANOVA for repeated measures, and Mann-Whitney U-tests where appropriate, with p < 0.05 considered significant. MAIN RESULTS: Significant changes from baseline in MAP, systemic vascular resistance index, heart rate, and cardiac index were observed in both groups after spinal anesthesia. However, there were no differences between the ephedrine and saline groups in the incidence and severity of change from the baseline. The overall incidence of hypotension was 70% in both groups. No difference in total fluid or supplemental ephedrine use was observed. CONCLUSIONS: 10 mg of IV ephedrine given at the time of spinal anesthesia, and after a 10 mL/kg lactated Ringers fluid bolus, does not diminish the incidence or severity of hypotension in parturients undergoing cesarean delivery.

Adult↗
PubMed2000

Plasma galactose and galactitol concentration in patients with galactose-1-phosphate uridyltransferase deficiency galactosemia: determination by gas chromatography/mass spectrometry.

The plasma concentration of galactose and galactitol was measured in 27 patients with galactose-1-phosphate uridyltransferase (GALT) deficiency galactosemia on a lactose-restricted diet, 17 infants on lactose-free formula, and 21 infants and children on a normal diet, by a newly devised isotope dilution gas chromatograph/mass spectrometry (GC/MS) method. The method was linear in the range of 0.1 to 10 micromol/L for galactose and 1 to 20 micromol/L for galactitol with good reproducibility and a coefficient of variation less than 3%. The mean plasma galactose in 15 patients who were homozygous for the most common Q188R mutation of the GALT gene was 2.72 +/- 0.70 micromol/L (mean +/- SE) with a range of 0.58 to 3.98 in specimens obtained at regular clinic visits. In 12 patients with other GALT mutations, it was 2.45 +/- 0.75 micromol/L. The mean value in nongalactosemic subjects on lactose-free formula was 0.52 +/- 0.08 micromol/L, with a range of 0.12 to 1.25. The range in 21 normal subjects without diet restriction was 0.11 to 6.33 micromol/L, with a mean of 1.48 +/- 0.32. The plasma galactitol level was 11.63 +/- 0.46 and 10.85 +/- 1.38 micromol/L in the 2 galactosemic groups. There was no relationship between plasma galactose and galactitol levels, with variable ratios of the two substances in the galactosemic patients. Galactitol was not detectable in the plasma of normal subjects. The red blood cell galactose-1-phosphate level was also measured in the galactosemic patients, and no relationship between plasma galactose and red blood cell galactose-1-phosphate was found. The galactose-1-phosphate concentration was 28 to 54 times higher than the ambient galactose. The low galactose concentration in the plasma of galactosemics on galactose-restricted diets in relation to the higher plasma galactitol and red blood cell galactose-1-phosphate is a metabolic enigma. The ability to measure plasma galactose accurately presents a new way of characterizing the galactosemic patient and the levels monitored over time may provide insight into the development of long-term complications associated with the disorder.

Adolescent↗
PubMed2000

The effect of a rapid change in availability of epidural analgesia on the cesarean delivery rate: a meta-analysis.

OBJECTIVE: This study was undertaken to quantitatively estimate the effect of a rapid introduction or withdrawal of on-demand epidural analgesia on the cesarean delivery rate. STUDY DESIGN: MEDLINE and meeting abstracts were searched for studies reporting the cesarean delivery rate immediately before and after a rapid change in the availability of epidural analgesia. Nine studies reporting data on 37,753 patients were selected. Meta-analysis was performed to estimate the means and 95% confidence intervals for the changes in rates of total cesarean deliveries, cesarean deliveries among nulliparous women, cesarean deliveries for dystocia, and operative vaginal deliveries. RESULTS: There was no significant change in the overall cesarean delivery rate with an increase in the availability of epidural analgesia. Similarly, the rates of cesarean deliveries among nulliparous patients, of cesarean deliveries for dystocia, and of operative vaginal deliveries did not significantly differ between periods of high and low epidural analgesia availability. CONCLUSION: A rapid change in the availability of epidural analgesia is not associated with any increase in the cesarean delivery rate.

Analgesia, Epidural↗
PubMed2000

Alternative medicine use in presurgical patients.

BACKGROUND: A dramatic increase in the use of complementary and alternative medicines has been observed. The use of such remedies in the presurgical population has implications for the anesthesiologist because of the potential for drug interactions, side effects, and medical liability. This study was undertaken to quantify the use of herbal remedies and vitamins in the presurgical population of a large tertiary care center. METHODS: A one-page questionnaire was distributed to all patients presenting for evaluation in the preoperative clinic over an 11-week period. Patients answered questions regarding use of prescription and nonprescription medications, herbal remedies, and vitamins. RESULTS: Twenty-two percent of presurgical patients reported the use of herbal remedies, and 51% used vitamins. Women and patients aged 40-60 yr were more likely to use herbal medicines. Over-the-counter medication use was strongly associated with herbal preparation use. The most commonly used compounds, from highest to lowest, included echinacea, gingko biloba, St. John's wort, garlic, and ginseng. CONCLUSIONS: Alternative medicine use is common in the preoperative period.

Adult↗
PubMed2000

Cleft lip in the Talmud.

The authors address the problem of why the cleft lip anomalad is not mentioned even once in the Talmud, which contains detailed reports of numerous other forms of pathology and congenital anomalies. It also attempts to define the Sandal deformity, one of the most common congenital anomalies mentioned in the Talmud. It is assumed that cleft lip, the most common major facial defect, existed at the time of the Talmud. It is proposed that the Sandal deformity was actually made up of a number of entities grouped together because of a theorized common etiology, and that the cleft lip entity is included in the Sandal anomalad. This deformity, in its various forms, included, besides cleft lip, aborted tissue and products of gestation. They are all related to the common etiology of a twin gestation during which one fetus presses against the other causing the deformity. The Sandal was noted to look like the Sandal fish or sole, for which it is named. When photos of the Sandal fish and the cleft lip deformity are compared, a similarity is seen. In addition, this deformity apparently was thought to be fatal, and none of these babies survived. It is theorized that cleft lip babies were allowed to die because they were considered nonviable in the eyes of Jewish law. Supporting evidence for the ideas presented by the authors is derived from the talmudic texts and commentaries. If the Sandal does indeed include the cleft lip entity, the citation in the Mishnah (70-200 AD) makes it the earliest historical reference to the cleft lip deformity.

Bible↗
PubMed2000

Mad1 function is regulated through elements within the carboxy terminus.

Myc and Mad are basic helix-loop-helix leucine zipper (bHLH-LZ) proteins that heterodimerize with Max to bind DNA and thereby influence the transcription of Myc-responsive genes. Myc-Max dimers transactivate whereas Mad-Max-mSin3 complexes repress Myc-mediated transcriptional activation. We have previously shown that the N-terminal mSin3 binding domain and the centrally located bHLH-LZ are required for Mad1 to function during a molecular switch from proliferation to differentiation. Here we demonstrate that the carboxy terminus (CT) of Mad1 contains previously unidentified motifs necessary for the regulation of Mad1 function. We show that removal of the last 18 amino acids of Mad1 (region V) abolishes the growth-inhibitory function of the protein and the ability to reverse a Myc-imposed differentiation block. Moreover, deletion of region V results in a protein that binds DNA weakly and no longer represses Myc-dependent transcriptional activation. In contrast, deletion of the preceding 24 amino acids (region IV) together with region V restores DNA binding and transcriptional repression, suggesting a functional interplay between these two regions. Furthermore, phosphorylation within region IV appears to mediate this interplay. These findings indicate that novel regulatory elements are present in the Mad1 CT.

Amino Acid Sequence↗