Biomedical subjects

L F Smith

Publications and source records attributed to L F Smith.

At least 73 records · Page 4Linked to original sources

PubMed1991

Contribution of general practitioners to hospital intrapartum care in maternity units in England and Wales in 1988.

OBJECTIVE: To ascertain the contribution of general practitioners to hospital intrapartum care in 1988. DESIGN: Confidential postal questionnaire. SETTING: All maternity units in England and Wales. MAIN OUTCOME MEASURES: Type of general practitioner unit (if any); number of bookings, transfers, and deliveries by general practitioners; participation of general practitioners in the policy and audit of the unit. RESULTS: 277 (93%) of 297 units replied. Of 611,644 deliveries, 36,043 (5.9%) were under general practitioner care. In all, 228 units permitted general practitioners to book women under their sole care: 65 were isolated, 29 alongside, and 134 integrated general practitioner units. Alongside units had significantly more bookings (568), antenatal transfers (69), intrapartum transfers (86), and deliveries (387) compared with isolated units (185, 18, 16, and 125, respectively) and integrated units (106, 18, 18, and 52) (p less than 0.001 for all differences). The percentage of women booked by general practitioners transferred either before or during labour was independent of both the type of unit and the number of general practitioner bookings. General practitioners in consultant units were significantly less likely to attend meetings reviewing perinatal mortality (p less than 0.01), and these units were less likely to have any form of general practitioner-consultant liaison committee (p less than 0.001) compared with general practitioner units as a whole. Compared with those in isolated and alongside units, general practitioners in integrated units were less likely to have taken part in deciding the unit's booking policy (p less than 0.01) and consultants more likely to be the final determinant of whether a general practitioner should be permitted to practice within the unit (p less than 0.001). CONCLUSIONS: Both the number of deliveries booked by general practitioners and the number of isolated general practitioner units have fallen. Transfer from general practitioner to consultant care was independent of the general practitioner unit's caseload or the type of unit. General practitioner units differ from consultant units in important ways and differ among themselves as well. Except in remote areas, alongside units may be the ideal type of unit to encourage general practitioners to continue to provide intrapartum care.

Delivery Rooms↗

PubMed1991

Medical and social outcome in adolescents with end-stage renal failure.

Clinical information was collected on 118 adolescents who developed ESRF at age 143 months or older and were treated between 1966 and 1986 at the Toronto Hospital for Sick Children. The cumulative survival rate in transplanted patients (N = 109) was 80.1% after 15 years. Survival rates after four years were 93.9% in transplanted and 46.9% in nontransplanted patients (P less than 0.001). No patient receiving dialysis alone (N = 9) was followed longer than four years. Nine patients received three transplants and had an 89% survival rate. Six of these had a functioning graft at end of the follow-up. The cumulative survival of the entire group was 76.4% at eighteen years. Forty-two (35.6%) patients had a height below the third percentile. Functional status obtained by a structure telephone interview with a member of the present treating nephrology service was good (G) or excellent (E) for 66.7% of all patients (73.5% of transplant patients (N = 68) and 45% of dialysis patients (N = 20). Hemodialysis patients functioned less well [25% G/E (N = 12)] than peritoneal dialysis patients [75% G/E (N = 8)]. Most patients achieved an appropriate level of formal education although more slowly than normal adolescents. Only 11 patients were neither enrolled in an educational institution nor employed. We conclude that aggressive treatment for adolescents with ESRF is an appropriate application of health care resources.

Adolescent↗

PubMed1991

Antigenic differences between the endometrium of women with and without endometriosis.

Serum and peritoneal fluid from 12 women with endometriosis, 4 women with uterine leiomyomata and 6 fertile women without endometriosis (controls) and serum from 4 women with adenomyosis were tested with a passive hemagglutination assay for antibodies against endometrium from all the controls, 8 patients with endometriosis and all patients with uterine leiomyomata and from implants from 8 patients with endometriosis. Serum antibody titers in patients with endometriosis or leiomyomata were significantly higher against endometrial or implant antigens from patients with endometriosis and 2 patients with leiomyomata than those against the controls' endometrium. Peritoneal fluid endometrial antibody titers failed to reflect these antigenic differences. Controls and patients with adenomyosis had low titers of endometrial antibodies in their serum or peritoneal fluid. Antigenic differences appear to exist between the endometrium of patients with endometriosis and that of controls.

Adult↗

PubMed1990

Intraoperative phototherapy (PDT) and surgical resection in a mouse neuroblastoma model.

This study evaluates the effect of intraoperative photodynamic therapy (PDT) using the multiline argon laser (488-514 nm) or the argon-dye laser (630 nm) combined with surgical resection compared with surgical resection alone in reducing the incidence of C1300 neuroblastoma recurrence in mice. In the control groups, surgical resection alone resulted in 86% +/- 12% tumor recurrence. Surgical resection and intraoperative lasing without photosensitizer resulted in 75% +/- 27% tumor recurrence with the argon-dye laser and 55% +/- 18% recurrence with the multiline argon laser. In the treatment groups, surgical resection and intraoperative PDT at 630 nm resulted in 56% +/- 19% tumor recurrence whereas surgical resection and intraoperative PDT at 488-514 nm resulted in 21% +/- 7% tumor recurrence. The cause for the decrease in local recurrence in the control group using the multiline argon laser is unknown, but could it be due in part to hyperthermic effects. Intraoperative PDT was an effective adjunct to surgical resection in preventing local recurrence in this tumor model.

Animals↗

PubMed1990

Endometrial autoantigens eliciting immunoglobulin (Ig)G, IgA, and IgM responses in endometriosis.

Endometrial antigens from patients with endometriosis and fertile controls were tested against immunoglobulin (Ig)G, IgA, or IgM in endometrium, serum, and peritoneal fluid (PF) of the patients and controls by Western blot analysis. Endogenous IgG was detected in 78% of the endometria or endometriosis implants from the patients and 22% of the endometria from the controls. Endometrial IgA and IgM were detected in few controls and patients. Immunoglobulin G in the serum and/or PF of patients with endometriosis was specifically directed against antigens with molecular weights of 34, 42, 82, 94, 110, 120, and 140 kd found in the patients' endometrium or endometriosis implants. Immunoglobulin A and IgM in the serum or PF of the patients and controls were nonspecific in their reactivity. Endometrial antigens found in endometrium or implants of patients with endometriosis, and eliciting IgG responses, may be relevant to autoimmunity in endometriosis.

Adult↗

PubMed1989

Proteosome-hydrophobic 'foot' malaria peptide vaccines for Plasmodium falciparum and P. vivax.

The immunogenicity of synthetic peptides representing the repeating portions of circumsporozoite proteins of Plasmodium sporozoites was greatly increased by complexing them to proteosomes via hydrophobic moieties added to their amino termini. Proteosomes have been used safely in people in the development of meningococcal vaccines and therefore proteosome-peptide vaccines are prime candidates for use against malaria.

Adjuvants, Immunologic↗

PubMed1988

Blood lead and associated risk factors in Ontario children.

The purpose of this study was to determine blood levels in Ontario children and to identify those risk factors associated with higher blood lead levels. A random sample of 1315 children aged 7 and younger from urban, suburban and rural Ontario was selected. Blood lead concentration was determined in finger prick blood samples by graphite furnace atomic absorption spectrophotometry. Measurements of lead in air, tap water, soil, and gasoline were also established. Traffic pattern were determined in each area. A questionnaire was administered to a random sample of 800 families of the children tested to assess the presence of other risk factors. Urban children had higher geometric mean blood lead levels (12.02, S.D. = 4.4 micrograms/dl) than suburban children (9.95, S.D. = 3.5 micrograms/dl), and they, in turn, had higher blood lead levels than rural children (8.91, S.D. = 3.9 micrograms/dl). Each of these differences is statistically significant (p less than 0.001). Fifty four (4.3%) of all children were at or above the alert level of 20 micrograms/dl. The proportion above the alert level did not differ significantly between urban, suburban and rural children. Blood lead levels were slightly higher for males than females and for pre-schoolers aged 3 and 4, compared to school age children aged 5 and 6. The blood lead levels of these children were significantly lower than that of children surveyed near a point source of industrial emissions. Multivariate statistical modelling resulted in a set of characteristics which best explained the differences in children's blood lead levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1988

Proteosome-lipopeptide vaccines: enhancement of immunogenicity for malaria CS peptides.

Proteosomes are hydrophobic, membranous, multimolecular preparations of meningococcal outer membrane proteins that are also B cell mitogens. These characteristics suggested that proteosomes may serve as carrier proteins and adjuvants to enhance peptide immunogenicity. Although high titers of malaria circumsporozoite (CS) antibodies protect against malaria, vaccines thus far tested in humans have been insufficiently immunogenic to be clinically useful. Here it is shown that synthetic CS peptides hydrophobically complexed to proteosomes by way of lauroyl-cysteine become highly immunogenic in mice without other adjuvants. The high titers of antibodies produced and the safety of proteosomes in humans suggest that this novel system is widely applicable for the development of peptide vaccines to protect against many diseases.

Adjuvants, Immunologic↗

PubMed1988

Peptides bound to proteosomes via hydrophobic feet become highly immunogenic without adjuvants.

Addition of either a lauroyl or a pentapeptide (FLLAV) hydrophobic foot to the NH2 terminus of a small, synthetic peptide allowed the peptide to hydrophobically complex to meningococcal outer membrane protein proteosomes by simple dialysis. Both conventional and LPS-hyporesponsive mice immunized with these complexes without any adjuvants developed high-titered and persistent anti-peptide IgG. Since proteosomes have been safely given to many people and since important antigenic determinants are generally hydrophilic, this system should be widely applicable to the development of peptide vaccines for human use.

Adjuvants, Immunologic↗

PubMed1987

Characterization of a protein C activator from Agkistrodon contortrix contortrix venom.

The protease from Southern Copperhead venom that activates protein C was purified to homogeneity by sulfopropyl (SP)-Sephadex C-50 ion-exchange chromatography, Sephadex G-150 gel filtration, and Mono-S fast protein liquid chromatography. The purified enzyme is a glycoprotein containing 16% carbohydrate, and migrated as a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular mass of 40,000 kDa. The enzyme is composed of a single polypeptide chain possessing an NH2-terminal sequence of Val-Ile-Gly-Gly-Asp-Glu-Cys-Asn-Ile-Asn-Glu-His. The purified venom protein C activator hydrolyzed several tripeptide p-nitroanilides. The amidolytic and proteolytic activities of the enzyme were readily inhibited by phenylmethanesulfonyl fluoride, p-amidinophenylmethanesulfonyl fluoride, chloromethyl ketones, and human antithrombin III. Covalent binding of diisopropyl fluorophosphate to the enzyme was confirmed using a tritium-labeled preparation of the inhibitor. The venom protease readily activated human and bovine protein C at 1:1000 enzyme:substrate weight ratio. The protease also cleaved human prothrombin, factor X, factor IX, factor VII, and fibrinogen. Prothrombin coagulant activity decreased upon incubation with the venom protease, and the rate of this reaction was reduced in the presence of calcium. Factor X and factor IX coagulant activity increased upon incubation with the venom protease in the presence of calcium, and decreased in the absence of calcium. Human factor VII clotting activity decreased slightly upon incubation with the venom protease. Although the venom protease did not clot human fibrinogen, it nonetheless cleaved the A alpha chain of fibrinogen, and this cleavage appeared to be associated with a measurable increase in the clottability of the protease-treated fibrinogen by thrombin. These data demonstrate that the protein C activator from Southern Copperhead venom is a typical serine protease with a relatively broad specificity.

Amino Acid Sequence↗

PubMed1987

Factor IX metal ion-dependent antigen assays for measurement of warfarin effect.

Factor IX metal ion-dependent antigen was assayed using monoclonal antibodies in 521 samples obtained after prothrombin time testing in patients treated with warfarin. Factor IX metal ion-dependent antigen was less than measured Factor IX clotting activity and less than total Factor IX antigen adsorbable to aluminium hydroxide, suggesting that the metal ion-dependent antigen assay measures a subpopulation of circulating Factor IX in patients treated with oral anticoagulants. There was a graded decrease of Factor IX metal ion-dependent antigen as prothrombin times increased in patient samples. In two hospitals, the median prothrombin times and Factor IX antigen levels were 19 and 20 seconds and 0.10 and 0.11 U/mL (kU/L), respectively. This study shows that immunoassays measure the biologic effect of warfarin and provide information that may supplement the prothrombin time test for patient monitoring. Factor IX metal ion-dependent antigen assays may be useful in efforts to standardize laboratory tests for warfarin effect.

Anticoagulants↗

PubMed1987

Carrier testing in hemophilia B with an immunoassay that distinguishes a prevalent factor IX dimorphism.

Immunoassays with a monoclonal antibody (A-1) detect a prevalent dimorphism in plasma coagulation factor IX. The antibody was shown to react with a dimorphic segment of the normal factor IX sequence as follows. First, A-1 bound to isolated activation peptide (residues 146 through 180) prepared from activated factor IX from a normal plasma pool. Second, binding of recombinant factor IXs with A-1 or factor IX from normal individuals was strong only when they had Threonine (Thr) at position 148; factor IXs with the Alanine (Ala) allele at that position were far less reactive. Third, immunoblot reactivity of Escherichia coli fusion proteins containing known segments of the factor IX sequence restricted the epitope to residues 147 through 153. In 120 hemophilia B pedigrees, the Ala immunoassay allele frequency was 0.19 and did not differ from the Ala frequency in normal males. In 22 of 49 families, immunoassay testing was informative for classification of obligate or possible carriers. In one large family, 4 obligate carriers were heterozygous for the dimorphism and 3 of their 7 daughters were classified as carriers. In other families, when the affected member had less than 1 nmol/L factor IX antigen, heterozygosity for Thr/Ala alleles excluded the carrier state even when DNA studies were not informative. Strong linkage disequilibrium of Thr/Ala alleles with the common TaqI DNA polymorphism was found. Nineteen of 75 normal and hemophilic factor IX genes had the 1.3-kilobase (kb) fragment and coded for the Ala allele; the rest had the 1.8-kb fragment and coded for Thr. In selected families, the A-1 immunoassay is an inexpensive and rapid method to confirm and supplement restriction fragment length polymorphism analyses of DNA for carrier testing.

Alleles↗

PubMed1986

Intravenous infusion of magnesium sulphate after acute myocardial infarction: effects on arrhythmias and mortality.

Two hundred patients with acute myocardial infarction were entered into a randomised double-blind trial where they received either intravenous magnesium sulphate or saline for 24 hours after admission to hospital. The incidence of ventricular arrhythmias necessitating treatment was reduced by more than half in the group receiving magnesium sulphate. There were two deaths in the group receiving magnesium sulphate and seven receiving saline placebo. Total cardiac events were significantly reduced in the magnesium treated group. These reductions cannot be attributed to differences in risk factors or therapy between the two groups, either before or during the period of study. These results suggest that magnesium administration reduces the incidence of serious tachyarrhythmias and death after acute myocardial infarction and that this simple regime warrants further study.

Arrhythmias, Cardiac↗

PubMed1985

Unexplained deaths in a children's hospital. An epidemiologic assessment.

During a nine-month period, July 1980 through March 1981, the mortality rate for patients on the cardiology ward of a children's hospital was 43.1 deaths per 10,000 patient-days, as compared with 11.0 deaths per 10,000 patient-days during the preceding 54 months. Twenty-five (76 per cent) of 33 infant deaths during this nine-month period occurred between midnight and 6:00 a.m., as compared with 1 of 10 infant deaths during a separate 27-month period (P less than 0.001). Although nearly all deaths occurred in patients with serious congenital heart disease, epidemic-period deaths were more likely to have an unexpected timing and a clinical pattern consistent with digoxin toxicity. In four patients, forensic and clinical digoxin measurements suggested that an intravenous overdose of digoxin had been administered shortly before death. Although a review of nursing schedules revealed a strong association (relative risk, 64.6) between infant deaths and the duty times of a particular nurse, the cause of the epidemic remains unclear. The study led to suggestions that the hospital strengthen central control over procedures for dispensing medicines and implement a system for monitoring the occurrence of deaths by time and place within the hospital.

Digoxin↗

PubMed1983

Interactions of dopamine and the release of [3H]-taurine and [3H]-glycine from the isolated retina of the rat.

1 The dose-related, calcium-dependent, potassium-stimulated release of preloaded [(3)H]-dopamine from the superfused rat retina has been demonstrated.2 A high-affinity uptake system for dopamine exists in rat retina in vitro; K(m) value was calculated as 1.89 muM, V(max) value as 1.4 nmol g(-1) tissue h(-1).3 Dopamine (0.8 and 4 mM) inhibited the spontaneous release of [(3)H]-glycine from retina, and in the case of 0.8 mM dopamine this inhibitory effect was antagonized by 10 muM (+)-butaclamol but not by 10 muM (-)-butaclamol.4 The potassium-evoked (25 mM) release of [(3)H]-glycine from rat retina was similarly inhibited by dopamine (0.4-4 mM) in a dose-related manner when added to the superfusate with the potassium. The effect of 0.8 mM dopamine was antagonized by 10 muM (+)-butaclamol but not by 10 muM (-)-butaclamol.5 Dopamine (4 mM) significantly reduced the spontaneous release of [(3)H]-taurine from rat retina.6 The potassium-stimulated (25 mM) release of [(3)H]-taurine occurred after the cessation of the depolarizing stimulus. This delayed release of [(3)H]-taurine was unaffected if dopamine was applied to the superfusate at the same time as the potassium, but it was significantly reduced if dopamine (0.8 and 4 mM) was applied after the depolarizing stimulus had been removed and during the actual amino acid release phase.7 The inhibition of K(+)-stimulated (25 mM) delayed release of [(3)H]-taurine by applying dopamine (0.8 mM) after the depolarizing stimulus was blocked by 10 muM (+)-butaclamol but not by 10 muM (-)-butaclamol.8 The results are discussed with respect to the possible neurotransmitter role for dopamine within the rat retina, and its possible interaction with glycine and taurine.

Animals↗

PubMed1982

Potassium-stimulated release of radiolabelled taurine and glycine from the isolated rat retina.

The release of preloaded [3H]glycine and [3H]taurine in response to a depolarising stimulus (12.5-50 mM KCl) has been studied in the superfused rat retina. High external potassium concentration immediately increased the spontaneous efflux of [3H]glycine, the effect of 50 mM K+ apparently being abolished by omitting calcium from the superfusing medium. In contrast, although high potassium concentrations increased the spontaneous efflux of [3H]taurine from the superfused rat retina, this release was not evident until the depolarising stimulus was removed from the superfusing medium. The magnitude of this "late" release of [3H]taurine was dependent on external K+ concentrations, and appeared immediately after cessation of the stimulus irrespective of whether it was applied for 4, 8, or 12 min. Potassium (50 mM)-induced release of taurine appeared partially calcium-dependent, being significantly reduced (p less than 0.01) but not abolished by replacing calcium with 1 mM EDTA in the superfusate. High-affinity uptake systems for both [3H]glycine and [3H]taurine were demonstrated in the rat retina in vitro (Km values, 1.67 microM and 2.97 microM; Vmax values, 19.3 and 23.1 nmol/g wet weight tissue/h, respectively). The results are discussed with respect to the possible neurotransmitter roles of both amino acids in the rat retina.

Animals↗

PubMed1980

IgA-dependent, monocyte-mediated, antibacterial activity.

IgA purified from the sera of patients convalescing from disseminated group C meningococcal disease induced human monocyte-mediated anti-meningococcal activity in vitro in the absence of complement. Both IgA- and IgG-dependent activity were directed against the group C meningococcal polysaccharide (Csss) capsule. The amount of IgA that was effective bound less than 1 ng of Csss. Antibacterial activity was dependent upon the length and the temperature of the test incubation and on the concentration of monocytes. The implications of this mechanism for local cell-mediated antibacterial immunity are discussed.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1980

Antibody-dependent cell-mediated antibacterial activity of human mononuclear cells. II. Immune specificity of antimeningococcal activity.

Antibody-dependent activity against group C meningococci mediated by human mononuclear cells or purified lymphocytes was inhibited when sera from adults immunized with group C meningococcal polysaccharide were preincubated with that polysaccharide. Likewise, activity against group A meningococci induced by heat-inactivated sera from adults immunized with group A meningococcal polysaccharide was inhibited by preincubation with that polysaccharide. Neither heterologous polysaccharide nor homologous protein or lipopolysaccharide meningococcal antigens inhibited the activity of either of these sera. The data indicate that immune specificity in this cell-mediated antibacterial system is dependent upon antibodies to the specific polysaccharide antigen with which the serum donor had been immunized.

Adult↗