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Biomedical subjects

S Lowe

Publications and source records attributed to S Lowe.

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

1-Methoxy-agroclavine from Penicillium sp. WC75209, a novel inhibitor of the Lck tyrosine kinase.

A high-throughput screen was developed and implemented to identify inhibitors of the Lck tyrosine kinase. This report describes the identification of a specific inhibitor of this enzyme from the solid fermentation culture of the Penicillium sp., WC75209. The active compound was isolated and structurally characterized as 1-methoxy-5R, 10S-agroclavine, a new member of the ergot alkaloid family.

Enzyme Inhibitors↗
PubMed1997

Nicardipine versus nitroprusside for controlled hypotension during spinal surgery in adolescents.

Nicardipine or nitroprusside was used to induce controlled hypotension in healthy adolescents with idiopathic scoliosis undergoing spinal fusion. Twenty patients were randomly assigned to the nitroprusside (N) or nicardipine (C) group. All patients received a standardized anesthetic. A target mean arterial blood pressure (MAP) of 60 mm Hg was achieved by varying the vasoactive infusions only. Moderate hemodilution (PCV = 25) and intraoperative blood salvage were used in all cases. Hemodynamic variables, blood loss, occurrence of reflex tachycardia, and reversibility of the hypotensive state were compared between the two groups. Significant differences were observed between the two groups in the amount of blood loss and reversibility of the hypotensive state. Group C had less blood loss (761 +/- 199 mL) than Group N (1297.5 +/- 264, P < or = .05). Time to restoration of baseline MAP was longer with Group C (26.8 +/- 4.0 min) than Group N (7.3 +/- 1.1 min, P < or = 0.001). Both drugs rapidly achieved a stable, controlled hypotensive state and an acceptable operating field. There was no statistically significant difference between groups with respect to the amount of crystalloid administered or urine output. These results suggest that nicardipine is a safe, effective drug for controlled hypotension in this population and that it may offer the significant advantage of reduced blood loss in these patients.

Adolescent↗
PubMed1997

Accidental exposures to blood and body fluids among health care workers in dental teaching clinics: a prospective study.

The authors evaluated accidental exposures to blood and body fluids reported to a hotline or to health officials at four dental teaching clinics. The authors used a standard questionnaire to solicit and record data regarding each exposure. During a 63-month period, 428 parenteral exposures to blood or body fluids were documented. Dental students and dental assistants had the highest rates of exposure. Syringe needle injuries were the most common type of exposure, while giving injections, cleaning instruments after procedures and drilling were the activities most frequently associated with exposures.

Accidents, Occupational↗
PubMed1996

Uncoupling of stem cell inhibition from monocyte chemoattraction in MIP-1alpha by mutagenesis of the proteoglycan binding site.

We have studied the role of proteoglycans in the function of Macrophage Inflammatory Protein-1 alpha (MIP-1alpha), a member of the proteoglycan binding chemokine family. Sequence and peptide analysis has identified a basic region within MIP-1alpha which appears to be the major determinant of proteoglycan binding and we have now produced a mutant of MIP-1alpha lacking the basic charges on two of the amino acids within this proteoglycan binding site. This mutant (Hep Mut) appears to have lost the ability to bind to proteoglycans. Bioassay of Hep Mut indicates that it has retained stem cell inhibitory properties but has a compromised activity as a monocyte chemoattractant, thus suggesting uncoupling of these two properties of MIP-1alpha. Receptor studies have indicated that the inactivity of Hep Mut on human monocytes correlates with its inability to bind to CCR1, a cloned human MIP-1alpha receptor. In addition, studies using proteoglycan deficient cells transfected with CCR1 have indicated that the proteoglycan binding site in MIP-1alpha is a site that is also involved in the docking of MIP-1alpha to the monocyte receptor. The site for interaction with the stem cell receptor must therefore be distinct, suggesting that MIP-1alpha utilizes different receptors for these two different biological processes.

Amino Acid Sequence↗
PubMed1996

General anesthesia using the laryngeal mask airway during brief, laparoscopic inspection of the peritoneum in children.

The authors prospectively examined the cardiorespiratory changes seen with general anesthesia using the laryngeal mask with spontaneous ventilation during brief laparoscopic inspection of the peritoneum in children. Anesthesia consisted of halothane in 50% oxygen/air and a caudal epidural block. The patient was allowed to ventilate spontaneously without assistance. Baseline measurements of heart rate, systolic blood pressure (SBP), end-tidal CO2 (ETCO2), tidal volume, respiratory rate, and oxygen saturation were recorded every 1 min for 5 min prior to the start of laparoscopy and every minute during the laparoscopic procedure. A total of 15 patients were enrolled in the study ranging in age from 15 to 90 months (35.5 +/- 23.8 months) and in weight from 10 to 26.4 kg (14.9 +/- 4.9 kg). The length of the laparoscopy varied from 3 to 9 min (6.1 +/- 2.1 min). Although clinically insignificant, there was an increase in the heart rate from a baseline value of 141 +/- 9 to 148 +/- 9 beats/min (p = 0.0016) and in the SBP from a baseline value of 97 +/- 6 mm Hg to 101 +/- 7 mm Hg (p = 0.0087). The baseline tidal volume prior to the start of laparoscopy was 5.2 +/- 1.1 mL/kg and increased to 6.4 +/- 1.4 mL/kg during laparoscopy (p < 0.0001) while the respiratory rate increased from 32 +/- 4 to 40 +/- 6 breaths/min (p < 0.0001). ETCO2 increased from a baseline value of 47 +/- 6 to 53 +/- 6 torr (p = 0.0059). The maximum value of the ETCO2 was 55 torr or greater in 6 patients, exceeded 60 torr in 3 patients, with a maximum value of 63 torr. The increased ETCO2 returned to baseline within 2 to 7 min (4.7 +/- 1.5 min) following completion of the laparoscopy. There was no significant change in oxygen saturation. Our initial experience suggests that general anesthesia may be provided using the laryngeal mask during brief laparoscopic inspection of the peritoneum.

Anesthesia, General↗
PubMed1996

Harziphilone and fleephilone, two new HIV REV/RRE binding inhibitors produced by Trichoderma harzianum.

During the screening of the natural products for their ability to inhibit the binding of REV (regulation of virion expression) protein to [33P] labeled RRE (REV responsive element) RNA, two novel fungal metabolites, harziphilone and fleephilone, were isolated from the butanol-methanol (1:1) extract of the fermentation broth of Trichoderma harzianum by bioassay guided fractionation. The structures of these two new compounds were established by spectroscopic methods. Harziphilone and fleephilone showed inhibitory activity against the binding of REV-protein to RRE RNA with IC50 values of 2.0 microM and 7.6 microM, respectively. However both compounds did not protect CEM-SS cells from acute HIV infection at concentration levels up to 200 micrograms/ml using an XTT dye reduction assay. In addition, harziphilone demonstrated cytotoxicity at 38 microM against the murine tumor cell line M-109.

Anti-HIV Agents↗
PubMed1995

Cardiorespiratory changes in children during laparoscopy.

The authors prospectively examined the cardiorespiratory changes during brief laparoscopy (less than 15 minutes) in children. Intraoperative ventilatory management included a tidal volume of 12 mL/kg, with the rate adjusted to achieve an end-tidal CO2 (PETCO2) of 30 to 35 mm Hg. The initial rate and tidal volume were not changed during the procedure. Baseline measurements of heart rate, blood pressure, peak inflating pressure (PIP), PETCO2, and oxygen saturation were recorded every minute for 5 minutes before the start of the laparoscopic procedure, and every minute during the laparoscopic procedure. Fifty-five patients were enrolled in the study (age range, 1 month to 7 years; weight range, 5.2 to 31 kg). PIP increased from the baseline value of 20 +/- 2.5 to 23 +/- 3.2 cm H2O (P < .01) during laparoscopy. The increase in PIP was 5 or more in six patients, with a maximum of 7. PETCO2 increased from the baseline value of 32 +/- 3.1 to 35 +/- 4.8 mm Hg (P < .01). The PETCO2 returned to baseline within 10 minutes after completion of the laparoscopy. No increase in ventilatory parameters was required during the brief laparoscopic procedure.

Blood Pressure↗
PubMed1995

Analgesia after bilateral myringotomy and placement of pressure equalization tubes in children: acetaminophen versus acetaminophen with codeine.

Despite the brief nature of the procedure with limited tissue trauma, some form of analgesia is required in most children after bilateral myringotomy and placement of pressure equalization (PE) tubes. Previous studies have demonstrated the relative inefficacy of acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs), with 30%-55% of patients requiring supplemental postoperative analgesia. We undertook a prospective study evaluating the efficacy of the preoperative administration of oral acetaminophen (15 mg/kg) versus acetaminophen (10 mg/kg) and codeine (1 mg/kg). Fifty ASA grade I or II patients were randomized to receive oral midazolam premedication (0.7 mg/kg) mixed in either acetaminophen or acetaminophen with codeine elixir. Anesthesia was induced and maintained with halothane in nitrous oxide and oxygen. Postoperative pain was assessed at four times during the postoperative course using an objective pain scale. The two groups were similar with respect to age, weight, gender, duration of anesthesia, and duration of the surgical procedure. The patients who received acetaminophen with codeine had lower pain scores at all four points when compared with patients who received acetaminophen. None of the 25 patients who received acetaminophen with codeine required supplemental analgesics compared with 12 of 25 who received acetaminophen. No adverse effects were noted in either group. We conclude that the preoperative administration of acetaminophen with codeine provides superior analgesia after bilateral myringotomy and placement of PE tubes.

Acetaminophen↗
PubMed1995

Nicardipine: perioperative applications in children.

Nicardipine is the first intravenously administered dihydropyridine calcium channel blocker. Its primary physiological actions include vasodilatation with limited effects on the inotropic and dromotropic function of the myocardium. Several reports have documented its use in adult patients for pharmacological control of blood pressure. We present our experience with the perioperative use of nicardipine in children to treat intraoperative hypertension, as an agent for controlled hypotension during spinal fusion and LeFort I maxillary osteotomies and to treat postoperative hypertension. Dosing regimens and possible applications in paediatric anaesthesia are discussed.

Adolescent↗
PubMed1994

p53-dependent apoptosis suppresses tumor growth and progression in vivo.

To determine the contribution of p53 loss to tumor progression, we have induced abnormal proliferation in the brain choroid plexus epithelium of transgenic mice using a SV40 T antigen fragment that perturbs pRB family function but does not affect p53 function. Tumors induced by this mutant develop slowly compared with those induced by wild-type T antigen. Suppressed tumor growth is directly attributable to p53 function, since rapid tumor development occurs when the T antigen fragment is expressed in p53-null mice. In p53-heterozygous mice, stochastic loss of the wild-type p53 allele results in the focal emergence of aggressive tumor nodules characteristic of tumor progression. In each case, aggressive tumor development in the absence of p53 function corresponds to a decrease in the level of apoptosis. These results provide in vivo evidence that p53-dependent apoptosis, occurring in response to oncogenic events, is a critical regulator of tumorigenesis.

Animals↗
PubMed1994

Aggregation of the chemokine MIP-1 alpha is a dynamic and reversible phenomenon. Biochemical and biological analyses.

Macrophage inhibitory protein (MIP)-1 alpha is a potent inhibitor of hemopoietic stem cell proliferation and is a member of a family of pro-inflammatory mediators, the chemokine family. This molecule along with other members of the chemokine family exists as a peptide of 8 kDa but has a strong tendency for noncovalent extensive self-aggregation. As this aggregation may interfere with biological activity, we have produced nonaggregating variants of MIP-1 alpha which display a range of molecular sizes. The mutants, produced by sequential neutralization of carboxyl-terminal acidic residues, display native molecular masses representative of tetramers, dimers, and monomers. Intriguingly when these mutants are assessed in comparison with native MIP-1 alpha for bioactivity in vitro, they are seen to be equipotent in both stem cell assays and in monocyte shape-change assays, suggesting that there is no requirement for aggregation in either of these biological contexts. This indicates that the aggregated MIP-1 alpha and the aggregated mutants spontaneously disaggregate under assay conditions and ultimately function as monomers. We have further demonstrated the ability of MIP-1 alpha to disaggregate spontaneously in dilute solution by enzyme-linked immunosorbent assay analysis of fractions obtained from gel filtration of varying concentrations of MIP-1 alpha. The aggregation of MIP-1 alpha is therefore a dynamic and reversible phenomenon which has little, if any, impact on bioactivity in vitro.

Amino Acid Sequence↗
PubMed1994

Characterization of plasma lipids in genetically obese mice: the mutants obese, diabetes, fat, tubby, and lethal yellow.

Plasma lipid levels were measured in control strains C57BL/6J (B6) and C57BL/KsJ (BKs) and in the mutants obese (ob), diabetes (db), fat (fat), tubby (tub), and lethal yellow (Ay), which are considered models of non-insulin-dependent diabetes mellitus (NIDDM), to determine if perturbations in plasma lipids were similar to those observed in the obese or diabetic human population. Compared with control mice, obese, diabetes, tubby, and lethal yellow mice had triglyceride levels that were elevated 1.5-fold to twofold, but fat mice had triglyceride levels similar to those of controls. Elevated plasma cholesterol levels, which were also observed in most mutant mice, were mainly due to an increase in high-density lipoprotein cholesterol (HDL-C). The degree of hypercholesterolemia appeared to be related to the age of onset and severity of the obesity and diabetes phenotype, with the greatest elevations occurring in obese and diabetes, milder elevations in fat mice of both sexes, male tubby, and male yellow mice, and no apparent changes in female tubby or lethal yellow mice. Plasma HDL-C and glucose levels and body weight in B6-db/db mice and their normal littermates were measured at intervals between 2 and 12 weeks of age to determine when the changes in cholesterol occurred in relationship to hyperglycemia and obesity. An elevation in HDL-C in B6-db/db mice was apparent by 3 weeks of age, a time concurrent with the elevation in blood glucose but before any weight differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Caudal epidural block for analgesia following herniorrhaphy with laparoscopy in children.

This study prospectively evaluated the efficacy of caudal epidural block in providing analgesia following inguinal herniorrhaphy and laparoscopy. Laparoscopy was used only to inspect the contralateral side to determine if a second hernia was present. No surgical manipulation was performed through the telescope. Following mask induction with halothane in nitrous oxide and oxygen, a caudal epidural block was performed with 1.2 mL/kg of 0.25% bupivacaine. Pain scores were obtained at four points during the in-hospital postoperative course, and the need for supplemental analgesic agents was assessed. A total of 45 patients were studied. Caudal epidural block could not be performed in 1 patient, and this patient was excluded from further consideration. There were 34 boys and 10 girls, ranging in age from 2 to 84 months (mean +/- SD 37.4 +/- 18.2 months) and weighing from 3.4 to 34 kg (mean +/- SD 14.2 +/- 5.8 kg). Thirty-six of 44 patients (82%) did not require supplemental analgesic agents during their in-hospital postoperative course and had pain scores of 2 or less at all four evaluation points. Six of 8 patients required a single dose of intravenous fentanyl (0.5 microgram/kg) to maintain scores of 2 or less. No significant complications related to caudal epidural block were noted in any patient. Caudal epidural block provides effective analgesia following inguinal herniorrhaphy and laparoscopy in children.

Analgesia, Epidural↗
PubMed1994

General anesthesia by mask with spontaneous ventilation during brief laparoscopic inspection of the peritoneum in children.

We prospectively examined the cardiorespiratory changes seen with general anesthesia by mask with spontaneous ventilation during brief laparoscopic inspection of the peritoneum in children. Anesthesia consisted of isoflurane in 50% oxygen/air and a caudal epidural block. The patient was allowed to ventilate spontaneously without assistance. Baseline measurements of heart rate, systolic/diastolic blood pressure (BP), end-tidal CO2 (PETCO2), tidal volume, respiratory rate, and oxygen saturation were recorded every 1 min for 5 min before the start of laparoscopy and every minute during the laparoscopic procedure. A total of 20 patients were enrolled in the study, ranging in age from 15 to 80 months (mean 40.8 months) and in weight from 10.5 to 27 kg (mean 15.9 kg). The length of the laparoscopy varied from 3 to 18 min (mean 6.9 min). No significant changes (increase or decrease of 20% from baseline) of heart rate or BP occurred. Oxygen saturation remained at 98%-100% throughout the procedure in all patients. The baseline tidal volume before the start of laparoscopy was 6.27 +/- 1.9 mL/kg and increased to 7.3 +/- 2.2 mL/kg during laparoscopy (p = 0.01). The baseline respiratory rate was 27.7 +/- 7.0 breaths/min and increased to 33.5 +/- 7.2 breaths/min during laparoscopy (p = 0.0001). PETCO2 increased from a baseline value of 37.5 +/- 6.5 to 44.6 +/- 6.8 mm Hg (p = 0.0001). The increase in PETCO2 was 10 or greater in 3 patients and exceeded 50 mm Hg in 3 patients, with a maximum value of 66 torr.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1994

Validation of the low dose short insulin tolerance test for evaluation of insulin sensitivity.

OBJECTIVE: The assessment of insulin sensitivity requires an accurate and reproducible technique. The short insulin tolerance test is a simple and rapid method for screening large numbers of subjects when the fasting glucose level is normal. Conventionally, an insulin dose of 0.1 units/kg is used, but this may result in symptomatic hypoglycaemia in healthy thin subjects who are insulin sensitive. In order to overcome this problem we have employed a lower dose of insulin and have studied the reproducibility of this modified technique comparing it with the euglycaemic hyperinsulinaemic clamp. DESIGN: Subjects were studied on two separate occasions, once by a short insulin tolerance test and on a second occasion by either a euglycaemic hyperinsulinaemic clamp (insulin infusion of 40 mU/m2/min) or a repeat short insulin tolerance test. PATIENTS: Eleven healthy subjects were studied twice with a short insulin tolerance test. A further 10 healthy subjects received a short insulin tolerance test on one day and a euglycaemic hyperinsulinaemic clamp study on another occasion. MEASUREMENTS: Insulin sensitivity was measured in the short insulin tolerance test using the slope of arterialized blood glucose concentration from 3 to 15 minutes after an intravenous bolus of short-acting insulin, 0.05 units/kg body weight. In the clamp study, insulin sensitivity was derived from the average amount of glucose infused at steady state (M) and the mean plasma insulin level (I). RESULTS: In the short insulin tolerance test no subject developed symptomatic or biochemical hypoglycaemia, defined as a blood glucose < 2.2 mmol/l. The (mean +/- SEM) insulin sensitivities for the 11 subjects studied twice were 174 +/- 10 and 179 +/- 11 mumol/l/min with a coefficient of variation of 6.9 +/- 2.6%. There was a close correlation between insulin sensitivity derived from the short insulin tolerance test and that obtained from the euglycaemic clamp studies (so-called M/I ratio) in the same subjects (r = 0.81; P < 0.005). CONCLUSION: The short insulin tolerance test employing 0.05 units/kg insulin is a safe, valid and reproducible method for the assessment of insulin sensitivity.

Adult↗