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N Smith

Publications and source records attributed to N Smith.

At least 19 recordsLinked to original sources

The isolation and partial characterization of trypsinogen, pancreatic secretory trypsin inhibitor and multiple forms of chymotrypsinogen and trypsin from the pancreas of the ostrich (Struthio camelus).

1. PSTI, two chymotrypsinogens and two trypsins were purified to homogeneity by acid extraction, salt fractionation, SP-Sephadex C-50 chromatography and RP-HPLC. 2. A third chymotrypsinogen, a trypsinogen and another trypsin were purified using an alkaline extraction procedure, followed by Trasylol- and Benzamidine-Sepharose affinity chromatography and hydroxylapatite chromatography. 3. The enzymes differed in amino acid composition as well as in specific activities towards synthetic amidase and esterase substrates. 4. N-terminal amino acid sequences were determined for one chymotrypsinogen and one trypsin.

Amino Acid Sequence

Disposition kinetics of orally administered enoximone in patients with moderate to severe heart failure.

Enoximone is a phosphodiesterase inhibitor, which has been studied extensively for use in the management of patients with moderate-to-severe heart failure. The authors have studied the absorption and disposition kinetics of enoximone and its primary metabolite, enoximone sulfoxide, after both single oral doses of enoximone and at steady-state after short-term chronic oral therapy. A total of ten patients (two female, eight male) with moderate-to-severe heart failure (NYHA class II-IV) were enrolled into the study after giving written informed consent. The plasma levels of enoximone sulfoxide were greater than those of enoximone at all sampling times. The peak enoximone sulfoxide plasma concentrations ranged from 3.5 to 17.3 times the peak enoximone plasma levels for individual patients. The average steady-state plasma concentrations for enoximone were 115 +/- 40 ng/mL and 190 +/- 78 ng/mL for 50 mg every 8 hours and 100 mg every 8 hours dosage regimens, respectively. The absorption and disposition kinetics of enoximone were found to be significantly variable between patients. The authors also evaluated the relationship between dose administered and steady-state plasma levels as well as the relationship between the observed and predicted steady-state plasma levels. The authors found a linear relationship between the dose that was administered and the accrued plasma levels, as well as a good correlation between the predicted and observed steady-state levels. Although these data confirm previous reports that the sulfide metabolite of enoximone accumulates extensively in the plasma during oral therapy, reaching levels much higher than those of enoximone, these data do not support previous suggestions that the disposition of enoximone is nonlinear.

Administration, Oral

Prenatal diagnosis for dystrophia myotonica using the polymerase chain reaction.

The polymerase chain reaction has been used to detect an abundant class of short repeat DNA families of the form (dC-dA)n.(dG-dT)n, known as microsatellites. These units are found throughout the human genome and have been characterized for several loci including APOC2 on chromosome 19q12-q13.2. The locus APOC2 is linked to the gene for dystrophia myotonica and a microsatellite within this locus was used to derive polymorphisms in a family to predict the inheritance of the disease. Chorionic villus sampling (CVS) was performed at 15 1/2 weeks' gestation. Following DNA extraction from the CVS material and parental blood samples, microsatellite analysis was carried out by the polymerase chain reaction.

Adult

Treatment of fetal supraventricular tachycardia with flecainide acetate after digoxin failure.

Transplacentally administered digoxin is the drug of choice for the treatment of fetal supraventricular tachycardia. We describe a case of fetal supraventricular tachycardia associated with fetal hydrops that did not respond to digoxin treatment because of a lack of transplacental passage. In contrast, flecainide acetate crossed the placenta and cured the fetus. The clinical implications of this new treatment are discussed.

Adult

Treating Type A behaviours and mild hypertension in middle-aged men.

Unmedicated mildly hypertensive Type A men were randomly allocated to one of three conditions: stress management intervention training (N = 15), Type A management (N = 15), and delayed Type A management intervention. Significantly greater reductions in blood pressure at rest and during the Type A structured interview were found following the active interventions than during the minimal treatment control period of the delayed intervention. Type A management was more successful in changing a number of Type A behaviours, including anger, hostility and global Type A behaviour. Changes on measures of anger-in, -out, hostility, and SI ratings of Type A behaviour were associated with changes in systolic and diastolic blood pressure reactivity during interview.

Adult

Using research-based interventions to decrease patient falls.

The purpose of this study was to decrease patient falls by applying relevant interventions found in the nursing research literature. Clinical nurse specialists assisted staff with the application of selected research-based patient fall program interventions on two adult medical-surgical specialty units in a tertiary care facility. The fall rate on these two units decreased during the study year, while the all-hospital patient fall rate increased. To encourage comparison of fall data among institutions, a standard method for calculating fall rate is presented.

Accidental Falls

Analysis of beta, gamma, and delta T-cell receptor genes in lymphomatoid papulosis: cellular basis of two distinct histologic subsets.

To investigate the histogenesis of lymphomatoid papulosis (LYP), we have analyzed the configuration of the beta, gamma, and delta T-cell receptor (TCR) and Ig genes in DNA from 31 biopsies of 18 patients with this condition and also from peripheral blood mononuclear cells of eight of these patients. Immunoglobulin genes were in a germ-line configuration in all patients, and TCR genes were in a germ-line configuration in six patients. In nine patients, one or two rearranged bands (RB) were detected with both beta and gamma TCR probes and in one patient with beta, gamma, and delta TCR probes. Two patients, in whom beta and delta TCR genes were in a germline configuration, had evidence of multiple discrete rearrangements of gamma TCR genes, consistent with a polyclonal T-cell population. Analysis of multiple biopsies revealed that RB, when present, were identical in different lesions from individual patients. All but one of the peripheral blood samples showed a germ-line configuration. The exception had evidence of a rearrangement of gamma and delta in peripheral blood and a beta and gamma rearrangement within tissue. This study has established that only a proportion of patients with LYP have a monoclonal T-cell proliferation. Correlation with the clinicopathologic and immunophenotypic data revealed that a T-cell clone was limited to patients with Willemze type B LYP or "mixed type" LYP, whereas patients with type A LYP consistently showed a germline configuration of TCR genes. This study indicates that in LYP the atypical hyperchromatic cerebriform mononuclear cells of type B invariably constitute a monoclonal T-cell population whereas the atypical CD30 positive type A cells represent a proliferation of cells of non-B, non-T-cell lineage.

Adult

Atypical Ph negative chronic myeloid leukaemia presenting as sudden profound deafness.

A patient with atypical Ph negative chronic myeloid leukaemia presented with the sudden onset of profound deafness. He survived only eight months. Detailed histological investigation performed at necropsy showed loss of ganglion cells and afferent nerve fibres in the cochlea and vestibule associated with extensive fibrosis and new bone formation in the labyrinthine spaces. Both leucophoresis and high dose chemotherapy capable of rapid cytoreduction are recommended in patients with chronic myeloid leukaemia with profound hearing loss, as conventional chemotherapy is rarely followed by recovery.

Deafness

Importance of insulin in subjective, cognitive, and hormonal responses to hypoglycemia in patients with IDDM.

Not all episodes of hypoglycemia are recognized as such by diabetic patients, suggesting that it is possible for them to adapt to a low blood glucose level, although the mechanism involved is not known. The aim of this study was to examine whether insulin has an effect, independent of blood glucose, on the subjective, cognitive, and hormonal responses to hypoglycemia. Nine patients with insulin-dependent diabetes mellitus (IDDM) participated in three hyperinsulinemic glucose-clamp studies. After 60 min at 4.5 mM, blood glucose was randomized to be 1) maintained at 4.5 mM for 240 min, 2) lowered to 2.8 mM for 180 min followed by 60 min at 2 mM with an insulin infusion rate of 40 mU.m-2.m-1, and 3) fitted to the same protocol as 2 but with an infusion rate of 120 mU.m-2.min-1. Symptoms and awareness of hypoglycemia (100-mm visual analogue scales), cognitive function, and counterregulatory hormone levels were assessed every 30 min. There were no subjective or cognitive changes during the euglycemic study. Awareness and hypoglycemic symptoms (hunger, facial flushing, trembling, and sweating) were attenuated by the higher insulin infusion rate (P less than 0.05 and P less than 0.01, respectively). Cognition was significantly impaired after 60 min at 2.8 mM (P less than 0.001) and deteriorated further when the blood glucose level was lowered to 2 mM (P less than 0.01). Levels of cortisol (P less than 0.01) and growth hormone (P less than 0.05) but not epinephrine were suppressed by the higher insulin infusion rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Kinetics of colonization of a porous vitreous carbon percutaneous implant.

Implants of porous vitreous carbon with pore diameters 200-500 microns were surgically placed in rabbits and pigs. Skin colonization experiments were carried out by topically inoculating concentrations of Staphylococcus aureus and Escherichia coli in a test area adjacent to the implant and to a remote control area. Subsequent swab cultures were taken at 6, 24, 48 and 72 h and one or more weeks. In vitro attachment studies were also performed using bacteria stained with FITC on 1 mm slices of the porous carbon. Proplast was used as a control. Results showed that despite a temporary high rate of colonization and obvious binding of the bacteria to the carbon, the skin-implant interface resists infection by both normal and pathogenic flora.

Animals

The effect of anti-Rho(D) and non-specific immunoglobulins on monocyte Fc receptor function: the role of high molecular weight IgG polymers and IgG subclasses.

Anti-Rho(D) immunoglobulin (anti-D) contained more high molecular weight (HMW) IgG polymers than intravenous non-specific immunoglobulin (i.v. Ig). The low-dose anti-D and high-dose i.v. Ig regimens used to treat idiopathic thrombocytopenic purpura (ITP) therefore contained similar total amounts of HMW IgG. In vitro, the HMW IgG polymers were more effective competitive inhibitors of monocyte phagocyte Fc receptors than monomeric IgG. The IgG subclass composition of anti-D and i.v. Ig were both similar to normal human plasma. We conclude that the HMW IgG content but not the IgG subclass composition of anti-D may explain its low-dose therapeutic efficacy in ITP.

Biopolymers

Post-transfusion thrombocytopenia: its duration in splenic and asplenic individuals.

Previous work in our department showed that after blood transfusion, the platelet count often falls to levels which are clinically significant. The probable site of platelet sequestration was identified as the spleen, and post-transfusion thrombocytopenia was prevented by blood filters which remove microaggregate debris from the donor blood. Since the duration of the thrombocytopenia has not been investigated, the purpose of the present study was to establish the rate of onset and duration of post-transfusion thrombocytopenia following packed red blood cell transfusions. In addition, the effect of spleen size, patients' diagnosis and post-transfusion history were examined. These observations provide interesting new data on the mechanisms involved in this phenomenon.

Humans

Relationship between expressed emotion and family burden in psychotic disorders: an exploratory study.

This study explored the relationship between level of expressed emotion (EE) and level of family burden in 20 families of individuals with psychotic disorder. Results indicated that a relationship between EE and family burden did exist, but it appeared to be strongly influenced by demographic and illness-related variables. The usefulness of the 5-min speech sample method of assessing EE was limited by the aversion of some family members to being videotaped and by denial of patient symptoms by some relatives. Other methodological weaknesses are discussed. The relationship between demographic and illness-related variables and level of EE needs further exploration.

Affective Disorders, Psychotic

Nonoxynol in condoms.

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Contraceptive Devices, Male

Invasive fungal disease in pediatric acute leukemia patients with fever and neutropenia during induction chemotherapy: a multivariate analysis of risk factors.

We evaluated the courses of 115 consecutive cases of pediatric acute leukemia treated with induction chemotherapy. Seventy-two patients developed fever associated with neutropenia; 15 developed systemic fungal infections. We reviewed multiple demographic and treatment characteristics of these patients in an attempt to identify potential risk factors for the development of invasive fungal disease (IFD). Risk factors identified in a univariate analysis included duration of neutropenia after first fever (P less than .0001), diagnosis of acute nonlymphocytic leukemia (ANLL) (P = .003), onset of fever and neutropenia within 5 days of starting induction chemotherapy (P = .009), and multiple (greater than one) surveillance culture sites positive for fungal organisms (P = .02). In a multiple logistic regression analysis, duration of neutropenia (P less than .001) remained a significant risk factor. The study group of patients had a significantly higher risk of fungal infections than a matched group of leukemia patients developing fever with neutropenia due to postremission consolidation chemotherapy (P = .003). In the first 48 patients, 14 (29%) developed IFD. In the subsequent patients (n = 24), intravenous miconazole (5 mg/kg every 8 hours) was begun at the time of the first fever. One of the 24 patients (4%) given miconazole developed IFD. The use of miconazole was a negative risk factor for the development of IFD in univariate (P = .01) and multivariate (P = .05) analysis. We conclude that pediatric leukemia patients who develop fever associated with neutropenia during induction chemotherapy are at high risk for developing IFD. The role of intravenous miconazole at the time of the first fever in this group deserves further study.

Adolescent