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Biomedical subjects

C C Grant

Publications and source records attributed to C C Grant.

At least 37 records · Page 2Linked to original sources
PubMed1997

Primary care and health reform in New Zealand.

AIMS: (1) To describe New Zealand's primary care system (2) to compare New Zealand to other Anglo-American members of the OECD with respect to the adequacy of primary care, and (3) to assess the cost-efficiency and effectiveness of New Zealand's system by comparing health spending and health indicators relevant to primary care. METHOD: A cross-national comparison of primary care, health spending and health indicators in New Zealand, Australia, Canada, the United Kingdom and the United States of America. Main outcome measures were health spending measured in purchasing power parties. Health indicators: mean life expectancy in years, years of potential life lost and infant mortality rates. RESULTS: New Zealand's primary care system ranked below the UK, above the USA and similar to Canada and Australia. Favourable characteristics of New Zealand's primary care system were the use of generalists as the predominant type of practitioner and the low proportion of active physicians who were specialists. Compared to the other countries, New Zealand scored poorly for financial that are necessary for the practise of good primary care. New Zealand and the UK had the lowest spending per capita on health care. New Zealand and the USA scored lowest for all three of the health care indicators. CONCLUSIONS: The quality of primary care in New Zealand is limited by barriers to access to care and the intermediate level of practise characteristics essential to primary care. Compared to other AngloAmerican OECD nations, New Zealand has relatively low levels of national health expenditure. In order to improve the quality of primary care, future reform should aim to facilitate access to care, increase the gatekeeping role of primary care physicians, and promote the practise characteristics essential to primary care.

Australia↗
PubMed1997

The father's role during infancy. Factors that influence maternal expectations.

OBJECTIVE: To describe factors that influence maternal expectations of the father's role during infancy. RESEARCH DESIGN: Cross-sectional survey. SETTING: Postpartum obstetric ward of an inner-city teaching hospital. SUBJECTS: Mothers who were residents in the inner-city communities that surround the hospital and who were recently delivered of a newborn. SELECTION PROCEDURE: Consecutive sampling from March to May 1992. MEASUREMENTS: Through structured maternal interviews, the father's expected role was measured in terms of accessibility, engagement in child care tasks, and decision-making responsibility. Influences included demographics, the mother's desire for the father's involvement, and her perceptions of his motivation, prenatal support, and ability to parent. RESULTS: Of 226 eligible mothers, 197 (87%) were interviewed. Expectations varied widely. Concerning accessibility, 48% and 18% of the mothers expected to see the father daily and less than weekly, respectively. Concerning engagement, 81% of the mothers expected some paternal involvement; the average mother assumed that the father would participate in one third of child care tasks. Concerning decision-making responsibility, 34% of the mothers expected to share all decisions; 30% expected to share none. In all areas, expectations were positively associated with the mother's desires, the strength of the parents' relationship, and the mother's perceptions of the father's motivation and ability to parent and the father's prenatal involvement (all, P < .001). Expected accessibility and engagement were greater for fathers who worked; expected engagement and decision-making responsibility were greater for fathers without children from other relationships (all, P < .03). CONCLUSIONS: The maternal desire for the father's participation, the strength of the parents' relationship, the mother's perception of the father as a parent, and the father's prenatal involvement are all consistently associated with the maternal expectations of the father's role. The demographic characteristics of either parent are not as strongly or consistently associated with the maternal expectations.

Adult↗
PubMed1996

Oral prednisone as a risk factor for infections in children with asthma.

OBJECTIVE: To determine whether the frequency of acute infections in children with asthma is associated with the number of doses of prednisone received for asthma attacks. DESIGN: A cohort study. SETTING: Primary care clinic and emergency department of an inner-city teaching hospital from March 31, 1992, to May 31, 1993. PATIENTS: Convenience sample of clinic enrollees aged 2 to 14 years who had made two or more outpatient visits for acute asthma in the preceding year. Eighty-six children were enrolled. Seventy-eight (91%) completed the study. MAIN OUTCOME MEASURES: The independent variable was cumulative prednisone dose received during the study period. Outcome variables were episodes of acute infections. RESULTS: The mean (+/-SD) number of doses of prednisone (2 mg/kg to a maximum of 60 mg) received was 9.5 +/- 11.8 doses (range, 0 to 57 doses). Ninety-four episodes of acute infection occurred in 50 children. No difference was observed in the mean number of doses of prednisone received by those with the infection compared with those without the infection. No correlation was observed between the number of doses of prednisone received and the number of episodes of each infection. CONCLUSIONS: The administration of prednisone as short courses for acute asthma is not associated with an increase in the number of episodes of common acute infections.

Acute Disease↗
PubMed1996

Demarcation of potentially mineral-deficient areas in central and northern Namibia by means of natural classification systems.

Mineral deficiencies that lead to production losses often occur concurrently with climatic and management changes. To diagnose these deficiencies in time to prevent production losses, long-term monitoring of mineral status is advisable. Different classification systems were examined to determine whether areas of possible mineral deficiencies could be identified, so that those which were promising could then be selected for further monitoring purposes. The classification systems addressed differences in soil, vegetation and geology, and were used to define the cattle-ranching areas in the central and northern districts of Namibia. Copper (Cu), Iron (Fe), zinc (Zn), manganese (Mn) and cobalt (Co) concentrations were determined in cattle livers collected at abattoirs. Pooled faecal grab samples and milk samples were collected by farmers, and used to determine phosphorus (P) and calcium (Ca), and iodine (I) status, respectively. Areas of low P concentrations could be identified by all classification systems. The lowest P concentrations were recorded in samples from the Kalahari-sand area, whereas faecal samples collected from cattle on farms in the more arid areas, where the harder soils are mostly found, rarely showed low P concentrations. In the north of the country, low iodine levels were found in milk samples collected from cows grazing on farms in the northern Kalahari broad-leaved woodland. Areas supporting animals with marginal Cu status, could be effectively identified by the detailed soil-classification system of irrigation potential. Copper concentrations were lowest in areas of arid soils, but no indication of Co, Fe, Zn, or Mn deficiencies were found. For most minerals, the geological classification was the best single indicator of areas of lower concentrations. Significant monthly variation for all minerals could also be detected within the classification system. It is concluded that specific classification systems can be useful as indicators of areas with lower mineral concentrations or possible deficiencies.

Analysis of Variance↗
PubMed1996

The usefulness of faecal phosphorus and nitrogen in interpreting differences in live-mass gain and the response to P supplementation in grazing cattle in arid regions.

The average daily gains of heifers and oxen on commercial and experimental farms in Namibia were used to indicate production differences in several areas and at different rates of phosphorus and protein supplementation. Faecal concentrations of phosphorus and nitrogen were used to indicate concentrations of these nutrients in grazing. Areas with high concentrations of nitrogen in faeces proved to support high levels of average daily gain. Animals responded positively to phosphorus supplementation only when faecal nitrogen concentrations were above 12 g/kg DM. Nitrogen concentrations in faeces were directly related to average daily gain of heifers, but protein supplementation did not have a significantly positive effect on average daily gain.

Animal Nutritional Physiological Phenomena↗
PubMed1995

Site-directed mutagenic alteration of potential active-site residues of the A subunit of Escherichia coli heat-labile enterotoxin. Evidence for a catalytic role for glutamic acid 112.

Escherichia coli heat-labile enterotoxin (LT) and the related cholera toxin exert their effects on eukaryotic cells through the ADP-ribosylation of guanine nucleotide-binding proteins of the adenylate cyclase complex. The availability of the crystal structure for LT has permitted the tentative identification of residues that lie within or are vicinal to a presumptive NAD(+)-binding site and thus may play a role in substrate binding or catalysis. Using a plasmid clone encoding the A subunit of LT, we have introduced substitutions at such potential active-site residues and analyzed the enzymatic properties of the resultant mutant analogs. Enzymatic analyses, employing both transducin and agmatine as acceptor substrates, revealed that substitutions at serine 61, glutamic acid 110, and glutamic acid 112 resulted in reduction of enzyme activity to < 10% of wild-type levels. Kinetic analyses indicated that alteration of these sites affected the catalytic rate of the enzyme and had little or no effect on the binding of either NAD+ or agmatine. Of the mutant analogs analyzed, only glutamic acid 112 appeared to represent an essential catalytic residue as judged by the relative effects on kcat and kcat/Km. The results provide formal evidence that glutamic acid 112 of the A subunit of LT represents a functional homolog or analog of catalytic glutamic acid residues that have been identified in several other bacterial ADP-ribosylating toxins and that it may play an essential role in rendering NAD+ susceptible to nucleophilic attack by an incoming acceptor substrate.

Amino Acid Sequence↗
PubMed1995

Economic impact of immunization against rotavirus gastroenteritis. Evidence from a clinical trial.

OBJECTIVE: To estimate the economic impact of immunization against rotavirus gastroenteritis in an infant population in the United States. DESIGN: Cost identification and break-even analyses from the perspective of society, nested within a phase 3, randomized, double-blind, placebo-controlled trial. PATIENTS: Infants (N = 1278), aged 6 to 22 weeks, enrolled during the summer and fall of 1991 and followed up until July 1, 1992. INTERVENTION: Immunization schedule of three doses of orally administered tetravalent or serotype 1 rhesus rotavirus vaccine, or placebo. MAIN OUTCOME MEASURES: Incidence of rotavirus gastroenteritis, total direct medical costs, direct nonmedical costs, and indirect costs of rotavirus and nonrotavirus gastroenteritis for the duration of the study and of any illness during 5 days after each dose. The cost of the vaccine was not included. RESULTS: Median total cost per infant among the 1187 infants who completed the immunization schedule was $9 in the tetravalent vaccine group, $9 in the serotype 1 vaccine group, and $49 in the placebo group (P = .01). Rotavirus gastroenteritis occurred in 195 infants (16%): 13% (51/398) in the tetravalent group, 12% (47/404) in the serotype 1 group, and 25% (97/385) in the placebo group (P < .0001). Of infants with an episode of rotavirus gastroenteritis, the proportion who incurred cost during the episode and the median cost during the episode did not differ by treatment group. The baseline net cost savings for treatment of rotavirus gastroenteritis and break-even cost of immunization were $11 per infant for the tetravalent vaccine and $12 for the serotype 1 vaccine. In sensitivity analysis, savings ranged from $40 to -$6, because of a large variance in the costs of rotavirus gastroenteritis. CONCLUSION: The results of the baseline analysis suggest that society should be willing to pay between $11 and $12 for immunization against rotavirus. It might be willing to pay an additional amount for the intangible benefits of reduced parental inconvenience or anxiety associated with this illness in infants.

Cost Savings↗
PubMed1995

Role of a potential endoplasmic reticulum retention sequence (RDEL) and the Golgi complex in the cytotonic activity of Escherichia coli heat-labile enterotoxin.

Recent experimental evidence indicates that Escherichia coli heat-labile enterotoxin and the closely related cholera toxin gain access to intracellular target substrates through a brefeldin A-sensitive pathway that may involve retrograde transport through the Golgi-endoplasmic reticulum network. The A subunits of both toxins possess a carboxy-terminal tetrapeptide sequence (KDEL in cholera toxin and RDEL in the heat-labile enterotoxins) that is known to mediate the retention of eukaryotic proteins in the endoplasmic reticulum. To investigate the potential role of the RDEL sequence in the toxic activity of the heat-labile enterotoxin we constructed mutant analogues of the toxin containing single substitutions (RDGL and RDEV) or a reversed sequence (LEDR). The single substitutions had little effect on Chinese hamster ovary cell elongation or the ability to stimulate cAMP accumulation in Caco-2 cells. Reversal of the sequence reduced the ability of the toxin to increase cAMP levels in Caco-2 cells by approximately 60% and decreased the ability to elicit elongation of Chinese hamster ovary cells. The effects of the heat-labile enterotoxin were not diminished in a mutant Chinese hamster ovary cell line (V.24.1) that belongs to the End4 complementation group and possesses a temperature-sensitive block in secretion that correlates directly with the disappearance of the Golgi stacks. Collectively, these findings suggest that the brefeldin A-sensitive process involved in intoxication by the heat-labile enterotoxin does not involve RDEL-dependent retrograde transport of the A subunit through the Golgi-endoplasmic reticulum complex. The results are more consistent with a model of internalization involving translocation of the A subunit from an endosomal or a trans-Golgi network compartment.

Amino Acid Sequence↗
PubMed1995

Independent parental administration of prednisone in acute asthma: a double-blind, placebo-controlled, crossover study.

OBJECTIVE: To determine the effectiveness of a single dose of prednisone administered by a parent to a child early in an asthma attack. DESIGN: A randomized, double-blind, placebo-controlled, crossover study with children enrolled for 12 months (6 months prednisone, 6 months placebo). SETTING: A primary-care clinic and emergency department of an inner-city teaching hospital from March 1992 through May 1993. CHILDREN: Children 2 to 14 years of age enrolled in this clinic who had made two or more outpatient (emergency department or primary-care clinic) visits for acute asthma in the preceding year. SELECTION: There were 204 eligible children, of whom 86 were contacted and enrolled; of these, 78 (91%) completed the study. INTERVENTION: Capsules containing prednisone (2 mg/kg up to 60 mg) or placebo. Parents were instructed to give their child one capsule for an asthma attack that had not improved after a dose of the child's regular acute asthma medicine. MEASUREMENTS: Parents were interviewed every 3 months. Computerized patient records and chart reviews were used to verify parent reports. Outcome measures were the numbers of outpatient visits and hospitalizations for treatment of acute asthma. RESULTS: Neither the total number of attacks nor the number for which medicine was used differed significantly by arm of study. There was a larger number of attacks resulting in outpatient visits when children were in the group that received prednisone (1.1 +/- 0.59 versus 0.59 +/- 0.86). This trend was less pronounced but persisted when limited to attacks for which the medicine was given (0.58 +/- 0.99 versus 0.35 +/- 0.55). Neither the number of attacks resulting in admission nor the number of hospital days differed significantly by arm of study. CONCLUSIONS: A single dose of prednisone available for use at home early in an asthma attack was associated with an increase in outpatient visits made for acute asthma. When prednisone was given for an attack, there was no reduction in outpatient visits. This intervention can not be recommended for children with asthma. These results should be confirmed in other pediatric populations.

Acute Disease↗
PubMed1994

Role of trypsin-like cleavage at arginine 192 in the enzymatic and cytotonic activities of Escherichia coli heat-labile enterotoxin.

Previous studies of cholera toxin and Escherichia coli heat-labile enterotoxin have suggested that proteolytic cleavage plays an important role in the expression of ADP-ribosyltransferase activity and toxicity. Specifically, several studies have implicated a trypsin-like cleavage at arginine 192, which lies within an exposed region subtended by a disulfide bond in the intact A subunit, in toxicity. To investigate the role of this modification in the enzymatic and cytotonic properties of heat-labile enterotoxin, the response of purified, recombinant A subunit to tryptic activation and the effect of substituting arginine 192 with glycine on the activities of the holotoxin were examined. The recombinant A subunit of heat-labile enterotoxin exhibited significant levels of ADP-ribosyltransferase activity that were only nominally increased (approximately twofold) by prior limited trypsinolysis. The enzymatic activity also did not appear to be affected by auto-ADP-ribosylation that occurs during the high-level synthesis of the recombinant A subunit in E. coli. A mutant form of the holotoxin containing the arginine 192-to-glycine substitution exhibited levels of cytotonic activity for CHO cells that were similar to that of the untreated, wild-type holotoxin but exhibited a marked delay in the ability to increase intracellular levels of cyclic AMP in Caco-2 cells. The results indicate that trypsin-like cleavage of the A subunit of E. coli heat-labile enterotoxin at arginine 192 is not requisite to the expression of enzymatic activity by the A subunit and further reveal that this modification, although it enhances the biological and enzymatic activities of the toxin, is not absolutely required for the enterotoxin to elicit cytotonic effects.

ADP Ribose Transferases↗
PubMed1993

Role of flagella in adherence, internalization, and translocation of Campylobacter jejuni in nonpolarized and polarized epithelial cell cultures.

Previous studies of Campylobacter jejuni have suggested that flagellin is an adhesin for epithelial cells and that motility is a virulence factor of this bacterium. The role of flagella in the interactions of C. jejuni with nonpolarized and polarized epithelial cells was examined with flagellar mutants. Flagellated, nonmotile (flaA flaB+ Mot-) and nonflagellated, nonmotile (flaA flaB Mot-) mutants of C. jejuni were constructed by in vivo homologous recombination and gene replacement techniques. Both classes of mutants were found to adhere to cells of human epithelial origin (INT 407) equally well; however, on the basis of the percentage of the inoculum internalized, internalization of the flaA flaB Mot- mutants was decreased by factors ranging from approximately 30 to 40 compared with the parent. The flaA flaB+ Mot- mutant was internalized by the INT 407 cells at levels six- to sevenfold higher than the flaA flaB Mot- mutants. Both classes of mutants, unlike the parent, were unable to translocate across polarized Caco-2 monolayers. These results indicate that flagella are not involved in C. jejuni adherence to epithelial cells but that they do play a role in internalization. Furthermore, the results suggest that either the motility of C. jejuni or the product of flaA is essential for the bacterium to cross polarized epithelial cell monolayers.

Bacterial Adhesion↗
PubMed1992

Functional outcome in children with traumatic brain injury. Agreement between clinical judgment and the functional independence measure.

As improvements in the delivery of trauma care have increased survival from injury, it has become essential to assess the resulting morbidity to plan for medical and psychosocial services, particularly for children whose needs may be wide and long term. This paper focuses on the assessment of disability of 598 children, age 8 to 19 yr, hospitalized for traumatic brain injury with or without injury to other body regions, exclusive of spinal cord injury. The disability was measured at discharge from acute care in nine areas of functional activities and a recovery time assigned by a clinician. For the study, children were divided into three groups: those whose recovery was expected in less than 7 months (Group A: n = 463), in 7 to 24 months (Group B: n = 66) and in greater than 2 yr (Group C: n = 69). The clinician's expectation of recovery time significantly (P less than 0.01) reflected the injury severity as measured by the Glasgow Coma Scale and the Injury Severity Score. By the Glasgow Coma Scale, 16.4% were comatose on admission in Group A, 51.5% in Group B and 58% in Group C. The Injury Severity Score was significantly different with 25.5% severely injured in Group A, 68.2% in Group B and 84% in Group C. At discharge, 15% in Group A had four or more areas of impairments, 61% in Group B and 84% in Group C. The Functional Independence Measure confirmed the clinician's assessment of compromise with significantly (P less than 0.01) different average values of 110, 80 and 58 for Groups A, B and C, respectively.

Accidents, Traffic↗
PubMed1991

Children with traumatic head injury: morbidity and postacute treatment.

The purpose of this paper was to describe pediatric head trauma and the factors that affect the extent, characteristics, and postacute service needs of functional limitations resulting from head trauma. Data are presented on 4,870 children who survived head injuries and who were enrolled in the National Pediatric Trauma Registry during 1985 to 1988. The sample excluded 349 children who died and 151 children who had impairments before injury. More than 50% of the surviving children sustained extracranial injury in addition to head injury, and this occurrence was related to age and mechanism of injury. Although 78% of the children were discharged from acute care without obvious impairments, 787 had one to three impairments, and 286 had four or more impairments. Discharge to rehabilitation or extended care facilities depended on the number and type of resulting impairments.

Activities of Daily Living↗
PubMed1989

Regulation of exotoxin A synthesis in Pseudomonas aeruginosa: characterization of toxA-lacZ fusions in wild-type and mutant strains.

A mobilizable plasmid which carries the promoter for the exotoxin A (ETA) structural gene fused to lacZ was integrated into the chromosome of wild-type and mutant strains of Pseudomonas aeruginosa at the toxA locus by homologous recombination. beta-galactosidase synthesis in the strains (cointegrates) carrying the toxA-lacZ fusions was regulated like ETA synthesis is in P. aeruginosa. Two multicopy plasmids carrying a positive regulatory gene designated toxR were constructed which are identical except with respect to the orientation of toxR to the lacZ promoter on the plasmid. These plasmids were then introduced into P. aeruginosa cointegrate strains. When toxR was using its own promoter, synthesis of beta-galactosidase in the cointegrate strains was increased but the pattern of iron regulation was not altered. In contrast, when the lacZ promoter was directing synthesis of the toxR product in the cointegrate strains, iron regulation of beta-galactosidase and ETA synthesis were abolished.

ADP Ribose Transferases↗
PubMed1988

Characterization by monoclonal antibodies of a target cell antigen complex recognized by nonspecific cytotoxic cells.

Fish nonspecific cytotoxic cells (NCC)3 recognize and lyse a large variety of human and mouse transformed cells. In an effort to determine the Ag recognized by NCC on these targets, mAb were raised against NC-37 target cells. Four anti-NC-37 mAb were chosen for further characterization based on their effects on NCC lysis of target cells. Purified mAb 18C2 and 1E7 (IgM isotype) inhibited NCC killing of the following targets: U937, MOLT-4, K562, HL-60, DAUDI, NC-37, P815, and YAC-1. The dose-dependent inhibitory activity occurred at the target cell level and ranged from 50 to 70% at a concentration of 50 micrograms/well when compared to noninhibitory mAb 7C6 and 1D4 (IgG isotype). Similarly, mAb 18C2 protected the fish parasite Tetrahymena pyriformis from lysis by NCC when compared to mAb 7C6. Adsorption experiments demonstrated that the inhibitory effect on NC-37 lysis by NCC could be removed in a titratable fashion by incubation of mAb 1E7 with any one of the other target cell lines, but it could not be removed by incubation with effector cells. The inhibitory activity of mAb 1E7 and 18C2 was shown to be caused by the inhibition of conjugate formation between effector and NC-37 target cells. The relative membrane concentration of the antigenic determinants recognized by these mAb on the target cells was studied by flow cytometry using FITC-labeled mAb. These experiments showed that all four mAb bound to the surface of the cells tested. Biochemical analysis with Western blots and immunoprecipitation showed that mAb 18C2 and 1E7 recognize two Ag in NC-37 lysates: a larger protein of around 80 kDa and a smaller one of 42 kDa.

Animals↗