Reopening of the ductus arteriosus after closure with indomethacin: importance of sustained effective indomethacin serum concentrations.
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Ductus Arteriosus↗
Biomedical subjects
M S Smith
Publications and source records attributed to M S Smith.
Comparison of the polymerase chain reaction and serology for the diagnosis of HTLV-I infection.
Human T-lymphotropic virus type I (HTLV-I) is associated with tropical spastic paraparesis (TSP) and adult T-cell leukaemia/ lymphoma (ATL). HTLV-I seroconversion may not take place for many years after infection and some patients develop relatively low concentrations of antibodies that are difficult to detect by means of conventional assays. Some serologic tests also yield high rates of false-positive results. We therefore decided to determine whether the polymerase chain reaction (PCR) might be more sensitive than serology for the diagnosis of HTLV-I infection. Samples of serum and of peripheral blood mononuclear cells were obtained from 50 patients with spastic myelopathy and nine with T-cell neoplasia. The serum samples of serum were tested for the presence of HTLV-I antibodies by means of an enzyme-linked immunosorbent assay (ELISA). Positive results were confirmed by Western blot (WB) assay. DNA was extracted from the peripheral blood mononuclear cells and a PCR performed by use of two primer pairs from the env and pol regions of the proviral genome. Seven of the 50 patients with myelopathy and none of those with T-cell neoplasia had detectable antibodies to HTLV-I and all seven were PCR positive. One patient with an indeterminate WB result and one who was HTLV-I antibody-negative, both with myelopathy, were also PCR-positive. In this study, PCR was found to be more sensitive than serology for the diagnosis of HTLV-I infection. PCR should therefore be considered for selected HTLV-I antibody-negative patients with unexplained spastic myelopathy or T-cell neoplasia.
Adolescent↗
A novel method of preparing PLGA microcapsules utilizing methylethyl ketone.
PURPOSE: To substitute dichloromethane with a safer solvent, a solvent extraction process using methylethyl ketone (MEK) was developed to prepare poly(d,l-lactide-co-glycolide) microcapsules. METHODS: The MEK dispersed phase containing PLGA and progesterone was emulsified in the MEK-saturated aqueous phase (W1) to make a transient oil-in-water (O/W1) emulsion. It was then transferred to a sufficient amount of water (W2) so that MEK residing in polymeric droplets could be extracted effectively into the continuous phase. RESULTS: This solvent extraction process provided the encapsulation efficiency for progesterone ranging from 77 to 60%. The amount of MEK predissolved in W1, as well as the degree of progesterone payload, influenced the encapsulation efficiency. The leaching profile of MEK analyzed by GC substantiated that, upon dispersion of O/W1, to W2, MEK quickly diffused into the continuous phase. Such a rapid diffusion of MEK from and the ingression of water into polymeric droplets produced hollow microcapsules, as evidenced by their SEM micrographs. CONCLUSIONS: When solvent extraction/evaporation techniques are employed for preparing PLGA microcapsules, water-immiscibility of a dispersed phase is not an absolute prerequisite to the successful microencapsulation. Adjustment of an initial extraction rate of MEK and formation of a primary transient O/W1 emulsion are found to be very crucial not only for the success of microencapsulation but also for the determination of microcapsule morphology.
Butanones↗
Morning versus evening dosing of lansoprazole 30 mg daily on twenty-four-hour intragastric acidity in healthy subjects.
BACKGROUND: Morning dosing is usually recommended with proton pump inhibitors, but there are few data from 24-h intragastric acidity studies comparing times of dosing. METHODS: A double-blind, placebo-controlled study was performed on the seventh day of dosing to compare the effects of lansoprazole 30 mg given either in the morning or evening on 24-h intragastric acidity in 32 healthy volunteers. RESULTS: The median integrated 24-h intragastric acidity on the seventh day of morning dosing with lansoprazole 30 mg was decreased to 36% of the placebo value, compared with 42% for evening dosing. For each daytime meal-related interval, morning dosing was significantly more effective for controlling acidity, but there was no significant difference between the regimens during the night interval (23.00-08.00 h). CONCLUSIONS: These data favour morning dosing of lansoprazole 30 mg for routine use, but patients with mainly nocturnal symptoms may be best treated by evening dosing.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Thrombotic vascular risk factors in inflammatory bowel disease.
BACKGROUND: Thrombosis may be an important effector mechanism in the pathogenesis of Crohn's disease. METHODS: This study therefore investigated the prevalence of independent thrombotic risk factors (factor VII coagulant activity, lipoprotein (a), fibrinogen, plasma triglycerides, and smoking) in patients with Crohn's disease, ulcerative colitis, and normal controls. RESULTS: In Crohn's disease (n = 75), the mean plasma VII:C, lipoprotein (a) and fibrinogen concentrations were significantly greater than in the normal population (n = 85). In ulcerative colitis (n = 35), only the mean factor VII:C concentration was significantly higher than normal. Ninety three per cent of patients with Crohn's disease and 86% of those with ulcerative colitis had at least one risk factor for thrombotic vascular disease, compared with 61% of the normal population (p < 0.001). CONCLUSIONS: In many young patients with inflammatory bowel disease, plasma concentrations of these prothrombotic factors were in excess of the limits that are regarded as posing an increased risk for the development of occlusive vascular disease.
Adult↗
Measles viral genomic sequences in intestinal tissue.
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Humans↗
Perioperative management of drug therapy, clinical considerations.
The objectives for the provision of a safe anaesthetic include rendering the patient analgesic for the procedure (amnesic if appropriate), with control of adverse haemodynamic perturbations, and muscle relaxation to facilitate surgery as necessary. This must be done with an understanding of the patient's pre-existing pathophysiology and drug therapy. This article focuses on the management of medications in the perioperative period from the practitioner's perspective. Areas of drug therapy examined include drugs affecting the cardiovascular, central nervous, haemostatic and endocrine systems. Review of the limited data available suggests that the safest course of action for the preoperative management of the vast majority of drug therapy is to continue such therapy until the time of surgery, particularly agents in which a withdrawal syndrome has been described, e.g. beta-adrenoceptor blocking agents, alpha 2-adrenoceptor agonists. Exceptions to this generalisation might include discontinuing ACE inhibitors prior to surgery as these agents may be associated with adverse haemodynamic changes during surgery. The management of drug therapy for patients receiving monoamine oxidase inhibitors (MAOIs) continues to be challenging due to the potential for drug interactions, e.g. severe hypertension with use of indirect-acting vasopressors and excitatory/depressive reactions with administration of pethidine (meperidine) or dextromethorphan. However, recent clinical experience has demonstrated the relative safety of continuing MAOIs prior to surgery by use of specific 'MAOI safe' anaesthetic techniques and/or substitution of short-acting MAOIs which do not irreversibly inhibit the enzyme. For drugs affecting the coagulation system, such as heparin and warfarin, prudence dictates discontinuing these agents whenever possible prior to surgery where it can be anticipated that haemorrhage will occur, e.g. vascular surgery, or where the consequences of even minor bleeding could be catastrophic, e.g. eye surgery. Controversy exists as to the management of patients receiving prophylactic low dose heparin for deep vein thrombosis prophylaxis or in whom intraoperative or postoperative anticoagulation is planned, e.g. aortic surgery, and in whom a regional anaesthetic technique is planned as part of the anaesthetic management. The data available suggest that, where prophylactic use of heparin is concerned, and provided the administration of the last dose of heparin and the institution of a regional anaesthetic nerve block does not occur at the same time, use of regional anaesthesia is not contraindicated in such circumstances. Where therapeutic anticoagulation is planned as part of the surgical management, there is a very small risk of the development of epidural or spinal haematoma when major central conduction nerve block is employed for anaesthesia, with resultant spinal cord compression and paralysis. These precautions do not apply to patients receiving aspirin or other nonsteroidal anti-inflammatory agents as there is a large clinical and published experience of the safety of regional anaesthesia in this group of patients. Patients treated with fibrinolytic agents are at increased risk for bleeding should surgery be required. For these patients, pre- and intraoperative use of agents with antifibrinolytic activity, e.g. aprotinin, has been demonstrated in case reports to be beneficial. Finally, recommendations for the management of patients who have received or are receiving glucocorticoids are given. Throughout the review, areas of uncertainty where further research is required are identified.
Animals↗
HTLV-I infection in the Free State region of South Africa: a sero-epidemiologic study.
Human T-lymphotropic virus type I (HTLV-1) is associated with tropical spastic paraparesis (TSP) and adult T-cell leukemia/lymphoma. HTLV-I infection is endemic in certain parts of the Natal/KwaZulu region of South Africa. No studies on the seroprevalence of HTLV-I infection in the Free State (FS) have been published. This study was designed to determine the prevalence of HTLV-I antibodies among different patient groups in the FS. Sera from 863 patients were analyzed. There were: 178 asymptomatic rural Blacks, 200 asymptomatic urban Blacks, 50 asymptomatic Whites, 60 patients with spastic myelopathy, 70 patients with other neurologic disorders, 12 patients with T-cell haematologic malignancies and 293 human immunodeficiency virus (HIV) seropositive patients. Sera were tested for the presence of HTLV-I/II antibodies using an enzyme linked immunosorbent assay (ELISA). Positive results were confirmed using a modified Western blot assay. None of the asymptomatic Whites were HTLV-I antibody positive (95 pc confidence interval (CI): 0 to 7 pc), while 2 pc (95 CI: 0.5 to 5 pc) of asymptomatic urban Blacks and 1.1 pc (95 pc CI: 0.14 to 4 pc) of asymptomatic rural Blacks had HTLV-I antibodies. Of the group of patients with spastic myelopathy 33.3 pc (95 pc CI: 21.7 to 46.7 pc had HTLV-I antibodies, while none of the patients with T-cell haematologic malignancies (95 pc CI: 0 to 26.5 pc) or other neurologic disorders (95 pc CI: 0 to 5 pc) had HTLV-I antibodies. Of the HIV seropositive patients 6.1 (95 pc CI: 4 to 9.5) were co-infected with HTLV-I. HTLV-I infection is present in the Free State. It is strongly associated with spastic myelopathy in this region. HIV seropositive patients have a high rate of HTLV-I co-infection.
Adult↗
Disposition and excretion of 6-methoxy-2-naphthylacetic acid, the active metabolite of nabumetone in horses.
OBJECTIVE: To examine, in horses, the disposition and excretion of the active metabolite 6-methoxy-2-naphthylacetic acid (6MNA) of the nonsteroidal anti-inflammatory prodrug nabumetone. DESIGN: Pharmacokinetic analysis of 6MNA after oral administration of nabumetone and IV administration of 6MNA. PROCEDURE: Using a crossover design, 5 horses were orally administered 3.7 mg of nabumetone/kg of body weight. After a 3-week washout period, 4 horses were administered 2.5 mg of 6MNA/kg, IV. RESULTS: Absorption of nabumetone from the gastrointestinal tract and its metabolism to 6MNA had a median appearance half-life of 0.88 hour. The elimination half-life was 11 hours. Area under the plasma concentration time curve for 6MNA after oral administration of nabumetone was 120.6 mg/h/L. A dose of 2.5 mg/kg of 6MNA administered IV resulted in plasma concentration nearly equivalent to that induced by the orally administered dose. Disposition of 6MNA was modeled as a one-compartment, first-order elimination. The area under the plasma concentration time curve for IV administration of 6MNA was 117.0 mg/h/L, and the specific volume of distribution was 0.247 L/kg. The distribution half-life and the elimination half-life were 0.56 and 7.90 hours, respectively. Percentage of total dose recovered in urine for the 36-hour collection period after the oral and IV administrations was 7.4 and 5.3%, respectively. CONCLUSIONS: Metabolism of nabumetone to 6MNA, as reported in other species, also occurs in horses. There were a number of additional metabolites of nabumetone in urine that could not be fully identified and characterized.
Administration, Oral↗
alpha 2-Adrenergic receptors in human spinal cord: specific localized expression of mRNA encoding alpha 2-adrenergic receptor subtypes at four distinct levels.
alpha 2-Adrenergic receptor (AR) subtype mRNA (alpha 2a, alpha 2b, alpha 2c) neuronal localization in human spinal cord has not been described. We therefore performed in situ hybridization to identify cell bodies at four levels of human spinal cord (cervical, thoracic, lumbar, sacral) containing alpha 2AR subtype specific mRNA. alpha 2AR mRNA is present in gray matter only (ventral > dorsal; sacral > cervical > thoracic = lumbar). In addition to alpha 2AR mRNA in cell bodies in thoracic and lumbar intermediolateral (sympathetic) and sacral intermediate (parasympathetic) cell columns (lamina VII), all levels in dorsal horn laminae I, II, V, and ventral horn lamina IX, we demonstrate alpha 2AR mRNA in dorsal horn laminae III and IV, and dorsal nucleus of Clarke, where alpha 2ARs have not been described. Previously unreported heterogeneity in alpha 2AR subtype distribution (alpha 2a and alpha 2bAR mRNA present, alpha 2cAR mRNA virtually absent) is found at all sites of alpha 2AR mRNA expression in human spinal cord, including locations known to mediate effects of alpha 2AR agonist drugs on nociception, autonomic function and motor tone. Cervical spinal cord demonstrates a predominance of alpha 2a mRNA signal, while thoracic, lumbar, and sacral spinal cord demonstrate an increasing predominance of alpha 2bAR mRNA. If confirmed at a protein level, these findings have profound implications for therapeutic strategies in managing human pain.
Autoradiography↗
Do GnRH neurons express the gene for the NMDA receptor?
Previous studies have revealed that in several animal models, N-methyl-D,L-Aspartate (NMA) stimulates LH secretion by acting at a suprapituitary site. In addition, NMDA receptor antagonists appear to block GnRH neuronal activation on the afternoon of proestrous as evidenced by the lack of c-Fos expression in the neurons and by the absence of an ovulatory LH surge. However, administration of NMA does not induce c-Fos or c-Jun expression in GnRH neurons. To better understand the effects of NMDA receptor activation on GnRH neuronal function, we examined whether GnRH neurons express the NMDA receptor in male rats, and in female rats during diestrus and proestrus, by performing double label in situ hybridization. An 35S-labeled cRNA probe for the NMDA receptor subunit (NMDAR1) was used to quantify NMDAR1 mRNA and a digoxigenin-labeled cRNA probe for GnRH was used to identify GnRH neurons. The data were quantified and expressed as grains/average cell area. In male and female rats, less than 5% of GnRH neurons expressed grain levels twice the minimum detectable level and were considered double-labeled. However, many non-GnRH neurons in the same areas as GnRH neurons expressed high levels of NMDAR1 mRNA. These results suggest that the effects of NMA on GnRH secretion are unlikely to be mediated solely by the activation of NMDA receptors on GnRH neurons. Given the widespread expression of NMDAR1 mRNA in the hypothalamus, it is possible that the stimulatory effects of NMA on GnRH neurons are indirect through activation of other neurons.
Animals↗
Serum concentrations of von Willebrand factor and soluble thrombomodulin indicate alteration of endothelial function in inflammatory bowel diseases.
Serum concentrations of immunoreactive von Willebrand factor (vWF) and soluble thrombomodulin (TM), and vWF multimer patterns were measured to assess endothelial function in patients with inflammatory intestinal diseases. In Crohn's disease and acute infective diarrhea, vWF concentrations were significantly higher than in normal controls. In all patient groups, multimeric analysis of vWF and the concentration of serum TM were not different from normal controls. The results indicate alteration of endothelial function in inflammatory intestinal disorders. They may be compatible with the presence of localized vasculitis, but indicate that systemic endothelial destruction does not occur in inflammatory bowel disease.
Colitis, Ulcerative↗
Orthotopic liver transplantation for chronic hepatitis in two patients with common variable immunodeficiency.
Two patients with common variable immunodeficiency underwent orthotopic liver transplantation for chronic hepatitis, unequivocally caused by hepatitis C virus in one case. Although one patient had pneumonia 8 days after surgery and the other developed hepatic venular stenosis in the transplanted liver, both had a reasonably good quality of life for at least 15 months. However, both subsequently died of recurrent hepatitis C virus hepatitis or hemorrhage after splenectomy for hypersplenism. This shows that severe infection is not a major problem in patients with common variable immunodeficiency after liver transplantation provided they undergo prophylactic antimicrobial and immunoglobulin therapy. The longer term prognosis must be regarded as poor until more data are available following transplantation in similar patients.
Adolescent↗
The development and validation of the Perceived Health Competence Scale.
A sense of competence or self-efficacy is associated with many positive outcomes, particularly in the area of health behavior. A measure of a sense of competence in the domain of health behavior has not been developed. Most measures are either general measures of a general sense of self-efficacy or are very specific to a particular health behavior. The Perceived Health Competence Scale (PHCS), a domain-specific measure of the degree to which an individual feels capable of effectively managing his or her health outcomes, was developed to provide a measure of perceived competence at an intermediate level of specificity. Five studies using three different types of samples (students, adults and persons with a chronic illness) provide evidence for the reliability and validity of the PHCS. The eight items of the PHCS combine both outcome and behavioral expectancies. Results from the five studies indicate that the scale has good internal consistency and test-retest reliability. The construct validity of the scale is demonstrated through the support obtained for substantive hypotheses regarding the correlates of perceived health competence, such as health behavior intentions, general sense of competence and health locus of control.
Adaptation, Psychological↗
Sickness absence in male Royal Naval medical and dental branch ratings: 1981-1989.
Sickness episodes for the male members of the medical and dental branch of the Royal Navy were compared with those for a control group consisting of other male naval ratings over the period 1981-1989. Age-corrected statistical analysis showed the study group to have had a significantly higher (P < 0.001) number of sickness episodes. An estimate of under-reporting was carried out by taking a sample of weekly sick lists and establishing which cases should have been reported and which actually had been reported. In the sample from a naval hospital, 67.8% (120/177) of cases that should have been reported were actually reported. This figure dropped to 46.8% (171/365) for a naval shore establishment. From this information, correction factors were derived and applied to the sickness episode data. The resulting difference in episodes was not statistically significant between groups. When the study group was compared with male NHS workers, both the observed rates and the estimated rates for the study group were much lower than those for the NHS groups. Bias due to under-reporting was probably a major factor in the overall difference originally observed.
Absenteeism↗
Perceived anxiety of pediatric patients to magnetic resonance.
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Adolescent↗
Increased GnRH mRNA in the GnRH neurons expressing cFos during the proestrous LH surge.
GnRH neuronal activity is increased during the proestrous LH surge as assessed by the expression of cFos. Whether there is an increase in GnRH mRNA concomitant with GnRH neuronal activation is still controversial. In the present study we have compared GnRH mRNA levels in GnRH neurons expressing cFos (activated) with those not expressing cFos during the proestrous LH surge. Brain tissue was obtained from adult female rats perfused on proestrus before (1100-1300 hr) or during (1500-1900 hr) the LH surge. Twenty-five microns free-floating brain sections were subjected to double labeling of cFos by immunocytochemistry and of GnRH mRNA by in situ hybridization using an 35S-labeled cRNA probe. Another series of sections were stained by double-label immunocytochemistry for cFos and GnRH. Serum LH concentrations and cFos expression in GnRH neurons indicated that rats sacrificed at or before 1300 hr had basal levels of LH secretion, and no cFos activity was detected in GnRH neurons. In animals sacrificed between 1500 and 1900 hr, LH concentrations were at levels indicative of the ascending phase of the LH surge. A significant positive correlation between plasma LH values and the proportion of GnRH mRNA-containing neurons expressing cFos was observed. The average cellular GnRH mRNA content (silver grain numbers per cell) during the LH surge was not different from that before the surge. However, if GnRH neurons during the surge were further divided into cFos-positive and cFos-negative neurons, GnRH mRNA levels in the cFos-positive GnRH neurons were significantly increased by 28% when compared with GnRH neurons without cFos expression. These data suggest that cFos expression in GnRH neurons during the proestrous LH surge identifies transcriptionally more active GnRH neurons.
Animals↗
"I have a future" comprehensive adolescent health promotion: cultural considerations in program implementation and design.
"I Have a Future" Adolescent Health Promotion Program is a life options program. The program uses the Nguzo Saba (seven principles) and African philosophy to systematically address violence and attitudes reinforcing the use of violence. The Nguzo Saba promotes self-respect, and commitment to and support for developing a positive community. Data was collected from four public housing developments--two served as match control sites. Adolescents residing in neighborhoods in which the program operated had greater acceptance of the Nguzo Saba than those in matched communities. Those who perceived themselves as having life options engaged in fewer delinquent/violent acts. There was a strong negative correlation between the acceptance of the Nguzo Saba and the number of reported delinquent/violent behaviors. There was a positive relationship between the acceptance of the Nguzo Saba and positive self-concept, psychosocial maturity, and clarity of goals.
Adolescent↗