Biomedical subjects
Publications and source records attributed to A M Jones.
Children presenting with disseminated viral infections should be carefully investigated because they almost invariably have an underlying immunodeficiency. A child is reported who had disseminated cytomegalovirus and a novel form of severe combined immunodeficiency with abnormal expression of the common leucocyte antigen, CD45.
As hospitals redesign into integrated delivery systems, new services and linkages to support patients across the care continuum become necessary. The implementation and outcomes of a transitional care program are discussed and evaluated.
BACKGROUND: Missed opportunities for immunizations are associated with underimmunization of preschool-age children. Practice policies limiting immunizations to scheduled preventive visits and guidelines requiring legal guardians to sign consent forms for vaccinations are 2 factors contributing to missed opportunities. However, methods to change these policies have not been sufficiently evaluated. OBJECTIVE: To measure the effectiveness of (1) changing practice policies to incorporate the new national standard to screen and vaccinate eligible children at all office visits and (2) eliminating legal guardian signature requirements. DESIGN: A randomized controlled trial of 2 interventions: (1) changing practice policy and routine to have office nurses screen for immunization status at all visits, attach immunization reminder cards to medical charts for eligible patients, and have providers vaccinate eligible children ("no missed opportunities" intervention) and (2) changing practice guidelines to allow vaccinations without a legal guardian's signature. The first intervention was performed at both sites; the second only at the neighborhood health center (NHC). SETTING: A Pediatric Continuity Clinic in a teaching hospital (hereafter referred to as Clinic), and an NHC. PATIENTS: Enrolled in the trial were 1005 Clinic patients and 983 NHC patients, 0 to 2 years of age. MAIN OUTCOME MEASURES: Missed opportunity rates, immunization rates, and rates of preventive services. RESULTS: Eliminating the requirement for a legal guardian's signature had no effect on any of the outcome measures. The no missed opportunities intervention was partially effective. Study patients had slightly fewer missed opportunities than control patients at each site: (0.60 vs 0.90 per patient per year at the Clinic, P = .01; 1.1 vs 1.3 per patient per year at the NHC, P = .02). For study group patients, immunization reminder cards were attached to medical charts in only one third of vaccine-eligible visits; when attached, they markedly increased vaccination by providers (odds ratio for vaccinating at a visit was 6.9 comparing visits when immunization reminder cards were attached vs not attached). However, at the end of the study, immunization rates were similar for study and control groups at each site. The number of undervaccinated days was slightly lower for the no missed opportunities study group at the Clinic than for the control group (56 days vs 77 days, P < .001), but they were similar for both groups at the NHC. There were no differences in rates of preventive visits or screening tests between study and control groups. CONCLUSIONS: The interventions evaluated to reduce missed opportunities did not increase immunization rates. The key problem was failure to screen for immunization status at all visits. More effective interventions will be needed to overcome barriers within busy primary care practices to substantially reduce missed opportunities.
When running indoors on a treadmill, the lack of air resistance results in a lower energy cost compared with running outdoors at the same velocity. A slight incline of the treadmill gradient can be used to increase the energy cost in compensation. The aim of this study was to determine the treadmill gradient that most accurately reflects the energy cost of outdoor running. Nine trained male runners, thoroughly habituated to treadmill running, ran for 6 min at six different velocities (2.92, 3.33, 3.75, 4.17, 4.58 and 5.0 m s-1) with 6 min recovery between runs. This routine was repeated six times, five times on a treadmill set at different grades (0%, 0%, 1%, 2%, 3%) and once outdoors along a level road. Duplicate collections of expired air were taken during the final 2 min of each run to determine oxygen consumption. The repeatability of the methodology was confirmed by high correlations (r = 0.99) and non-significant differences between the duplicate expired air collections and between the repeated runs at 0% grade. The relationship between oxygen uptake (VO2) and velocity for each grade was highly linear (r > 0.99). At the two lowest velocities, VO2 during road running was not significantly different from treadmill running at 0% or 1% grade, but was significantly less than 2% and 3% grade. For 3.75 m s-1, the VO2 during road running was significantly different from treadmill running at 0%, 2% and 3% grades but not from 1% grade. For 4.17 and 4.58 m s-1, the VO2 during road running was not significantly different from that at 1% or 2% grade but was significantly greater than 0% grade and significantly less than 3% grade. At 5.0 m s-1, the VO2 for road running fell between the VO2 value for 1% and 2% grade treadmill running but was not significantly different from any of the treadmill grade conditions. This study demonstrates equality of the energetic cost of treadmill and outdoor running with the use of a 1% treadmill grade over a duration of approximately 5 min and at velocities between 2.92 and 5.0 m s-1.
We tested the hypothesis that the amplitude of the additional slow component of O2 uptake (VO2) during heavy exercise is correlated with the percentage of type II (fast-twitch) fibers in the contracting muscles. Ten subjects performed transitions to a work rate calculated to require a VO2 equal to 50% between the estimated lactate (Lac) threshold and maximal VO2 (50% delta). Nine subjects consented to a muscle biopsy of the vastus lateralis. To enhance the influence of differences in fiber type among subjects, transitions were made while subjects were pedaling at 45, 60, 75, and 90 rpm in different trials. Baseline VO2 was designed to be similar at the different pedal rates by adjusting baseline work rate while the absolute increase in work rate above the baseline was the same. The VO2 response after the onset of exercise was described by a three-exponential model. The relative magnitude of the slow component at the end of 8-min exercise was significantly negatively correlated with % type I fibers at every pedal rate (r = 0.64 to 0.83, P < 0.05-0.01). Furthermore, the gain of the fast component for VO2 (as ml.min-1.W-1) was positively correlated with the % type I fibers across pedal rates (r = 0.69-0.83). Increase in pedal rate was associated with decreased relative stress of the exercise but did not affect the relationships between % fiber type and VO2 parameters. The relative contribution of the slow component was also significantly negatively correlated with maximal VO2 (r = -0.65), whereas the gain for the fast component was positively associated (r = 0.68-0.71 across rpm). The amplitude of the slow component was significantly correlated with net end-exercise Lac at all four pedal rates (r = 0.64-0.84), but Lac was not correlated with % type I (P > 0.05). We conclude that fiber type distribution significantly affects both the fast and slow components of VO2 during heavy exercise and that fiber type and fitness may have both codependent and independent influences on the metabolic and gas-exchange responses to heavy exercise.
BACKGROUND AND PURPOSE: The Asymptomatic Carotid Atherosclerosis Study (ACAS) Doppler validation study assessed the performance of individual Doppler machines across a spectrum of laboratories. We attempted to establish a threshold specific to individual machines to predict angiographically defined hemodynamic stenosis. The reliability of these Doppler ultrasound criteria was prospectively and independently evaluated among patients screened with ultrasound in the ACAS trial. METHODS: Regression techniques were used to establish the relationship between Doppler velocity and percent stenosis by angiography for 63 specific Doppler machines. This relationship was used to establish a Doppler threshold to provide a 90% positive predictive value (PPV) of a 60% stenosis by angiography. The sensitivity of each Doppler machine to detect a 60% stenosis (at the 90% PPV threshold) was estimated. The efficacy of these Doppler thresholds was then prospectively evaluated by calculating the PPV among ACAS participants eligible by ultrasound. RESULTS: Of the 63 machines, 13 (21%) had an excellent sensitivity (80%+) at 90% PPV. In 32 devices (51%) only a marginal sensitivity (50% to 80%) could be achieved. In 9 devices (14%) the sensitivity was poor (0% to 50%), and in 9 (14%) no threshold could be established. Despite the heterogeneity of Doppler performance, the standardization program worked as designed in the ACAS trial. Of 825 surgical patients, 399 were eligible by Doppler and 395 subsequently underwent angiography. Of these, 32 (8.1%; 95% confidence interval, 5.4% to 10.8%) did not have hemodynamically significant stenosis by arteriography, a proportion nonsignificantly lower than the planned 10% by the PPV. CONCLUSIONS: The performance of Doppler ultrasound was highly variable. This suggests that Doppler performance is likely overstated in the literature, but specific devices may perform satisfactorily to detect individuals with hemodynamically significant stenosis. Because performance differs substantially among devices, local investigators are strongly urged to maintain local standardization series. With such standardization, ultrasound performance is sufficient for admission to clinical trials and as the is sufficient for admission to clinical trials and as the basis for carotid surgery. However, without quality control many ultrasound machines are not adequate to accurately predict the degree of carotid stenosis and should not be the only test to decide whether surgery is warranted.
Carbamazepine is regularly used in the treatment of trigeminal neuralgia. Although exacerbation of psychosis has been described following abrupt discontinuation of carbamazepine in chronic schizophrenics, a withdrawal syndrome has not been reported previously in patients treated for trigeminal neuralgia. The case presented here suggests that abrupt withdrawal of toxic concentrations of carbamazepine may precipitate a withdrawal reaction, which is manifest some days after discontinuation of the drug. Therefore it may be advisable to withdraw therapy slowly in these situations.
Auxin-binding protein 1 (ABP1) is a unique hormone receptor because it resides primarily in the lumen of the endoplasmic reticulum (ER); however, two lines of evidence presented here suggest that ABP1 does not bind auxin within the endoplasmic reticulum, despite its predominant location there. First, ABP1 cannot be photolabeled in intact cells that have accumulated the auxin and photolabeling reagent 5-[7-3H]azidoindole-3-acetic acid, indicating either that auxin is excluded from the ER and is not available for photolabeling to ABP1 or that binding conditions within the ER lumen are insufficient for photolabeling. Second, at the pH of the ER lumen, auxin binding to ABP1 is not detectable. The pH estimate of the ER lumen is based on an indirect assay, which indicates that the pH is closer to pH 7 than to the binding optimum of pH 5.5. These results indicate that ABP1 does not bind auxin within the ER and point to a site of action that is post-ER. The effect of auxin on its trafficking from the ER was tested in an animal expression system. ABP1 expressed at high levels in COS7 cells is efficiently retained in the ER lumen and is not secreted even in the presence of 190 microM indole-3-acetic acid, an auxin concentration that is 40 times above the Kd for indole-3-acetic acid binding to ABP1.
The allotypes of the C7 M/N polymorphism are determined by comparing the ELISA reaction pattern of the allospecific mAb WU 4-15 with polyclonal anti-C7 IgG. To characterize the molecular basis of this polymorphism, the WU 4-15 epitope was mapped by expression of cDNA fragments. It was found to be located within the boundary region of the two short consensus repeats of C7 (amino acid residues 595-612). Coincidentally an A or C substitution was found in the course of investigation of the gene structure at nucleotide 1759. This leads to an electrically neutral Pro/Thr substitution at residue 565 and alternative Sau961 or RsaI restriction sites, respectively. Enzymatic digestion or sequencing of PCR-amplified genomic DNA from C7 M/N-typed individuals showed a perfect correspondence of the genotype with the phenotype of the C7 M/N polymorphism. In contrast, no association was found with the genotypes of a second polymorphic site at residue 367. Thus, a threonine at amino acid residue 565 allows access of WU 4-15 to its epitope but its substitution with proline almost completely inhibits access in the native molecule, although the epitope is about 40 amino acid residues distant from the polymorphic site in the primary structure. Furthermore, the different conformational structure is probably responsible for the hypomorphic appearance of C7*N.
Mutations in the common gamma chain (gamma c or IL2RG) of the interleukin-2, -4, -7, -9 and -15 receptors have been found to cause X-linked severe combined immunodeficiency (SCIDX1). We report here on the mutations identified in a further ten families. Two of the mutations identified have occurred twice in unrelated families, indicating two possible mutational hotspots. Seven of the mutations, which were identified by single-strand conformational polymorphism (SSCP) analysis, are point mutations, and the eighth is a small deletion. We also report on the first use of assays based on these mutations within IL2RG for unambiguous carrier determination. The consequences for the gamma c proteins produced as a result of these mutations are discussed.
Conconi et al. (1982) reported the development of noninvasive field test for anaerobic threshold (AT) based upon an observed deviation from the linear heart rate (HR)--running velocity (RV) relationship at high RV (HRdev). While the validity of the Conconi test has been debated (Heck and Hollmann 1992; Tokmakidis and Leger 1992), the reliability of the Conconi test has never been independently assessed in athletes performing the protocol outlined by Conconi. This study evaluated the reliability of the Conconi test in 15 well-trained male distance runners (22.5 +/- 3.3 yrs, 67.7 +/- 4.8 kg, VO2 peak 66.4 +/- 4.8 ml.kg-1.min-1) who performed a treadmill simulation of the Conconi test protocol twice within a 4-8 day period. The results were as follows: 6 subjects demonstrated HRdev in both Conconi tests, 5 subjects demonstrated HRdev in only one test, and in 4 subjects HRdev could not be discerned in either test. It was concluded that failure to determine a reproducible HRdev by subjective assessment in 9 of 15 subjects makes the Conconi test unsuitable for reliable evaluation of AT.
We questioned whether a dietary fibre supplement known to lower fasting plasma cholesterol concentrations can also lower the postprandial plasma cholesterol, glucose and insulin concentrations when it is administered just before a meal. Two studies were conducted in healthy middle-aged volunteers of both sexes in whom the fasting plasma total cholesterol concentrations were above normal. In the first study the dietary fibre treatments (2.2 g) were psyllium and a psyllium-citrus pectin mixture to which the subjects (four males, eight females) had no prior exposure. Controls received no supplement. The meals were high-fat breakfasts and lunches. In the second study the dietary fibre (6 g) was from sugar-beet root and the reference control was alpha-cellulose (2 g); the meal was of glucose. The volunteers (eight males, eight females) had prior exposure to the fibre supplements three times daily for 3 weeks. After adjustments for fasting values and changes in haemodilution, the psyllium and psyllium-citrus pectin mixture in the first experiment had no significant effects on the postprandial measurements of plasma glucose, insulin:glucose ratio, total-, LDL- and HDL-cholesterol, and triacylglycerol. By contrast, the sugar-beet fibre in the second study significantly decreased the area under the glucose response curve by 6.9%, the area under the insulin response curve was lower by 9.6%, although not significantly, and the post-glucose meal HDL-cholesterol concentration was significantly (12%) higher. Additionally, the 3-week treatment with sugar-beet fibre significantly lowered the fasting total- and LDL-cholesterol concentrations, by 8.5% and 9.6% respectively. We conclude that low doses of psyllium and citrus pectin at breakfast and lunch have no effects on the postprandial plasma measurements, but that sugar-beet fibre taken daily for 3 weeks affects both fasting and postprandial plasma metabolites favourably in these individuals with mildly increased risk of ischaemic heart disease. Further, we observed that small changes in haemodilution occur after meals, as indicated by plasma albumin concentration and packed cell volume. Underemphasis of the dietary fibre effects may occur when postprandial haemodilution is not taken into account.
Both complete C6-deficiency (C6*Q0) and subtotal C6-deficiency (C6*SD) have been described as simple recessive traits and C6*SD has been described in combination with subtotal deficiency of the C7 coded at an adjacent locus. The trace of C6 protein found in both C6*SD traits is phenotypically indistinguishable, being smaller than normal C6 and having different isoelectric properties. A defect has been found in the C6 gene which plausibly explains the C6*SD phenotype, and this defect is also common to both C6*SD traits. We present data from seven DNA markers of the C6 and C7 genes which show that although at least four haplotypes are associated with C6*Q0, most South African C6*Q0 patients carry a common defective haplotype. The most common haplotype associated with C6*Q0 has been observed only once among unaffected haplotypes of relatives. In one family, the cases of C6*SD share a complete haplotype with both cases of combined deficiency and are probably heterozygous for this condition and complete deficiency of C6. In another family, the C6*SD is on a slightly different haplotype and C7 is normally expressed. Thus, the C6 defect is not sufficient on its own to explain the C7 deficiency in the combined deficient haplotype. The haplotype associated with the combined deficiency is found not only in normal control subjects, but also in one case of complete C6 deficiency. In this case the molecular defect seen in combined or C6*SD cases is absent.
To determine whether the use of hydrophilic guidewires has influenced the success of peripheral percutaneous transluminal angioplasty (PTA), the results of PTA performed before and after the introduction of such guidewires (end of 1989) were analyzed. Before hydrophilic guidewires became generally available, the technical success rates for iliac stenosis PTA were 96%, for femoral stenosis PTA 84%, and for femoral occlusion 78%. After the introduction of hydrophilic guidewires, technical success rates were 100% (NS), 97% (P = 0.018), and 97% (P = 0.011), respectively. A prospective study of 33 patients randomly selected for PTA of femoropopliteal occlusion using either conventional or hydrophilic guidewires was performed. In this group, the technical success rate was 14/15 in the hydrophilic group, and 18/18 in the conventional group (NS). Since the introduction of hydrophilic guidewires, the technical success rates of PTA have improved and are now approaching 100%.
100 consecutive magnetic resonance imaging (MRI) examinations were reviewed independently by two radiologists. Patients were selected so that the anatomical areas of clinical interest coincided with the special interests of the reviewers. The reviewers were both consultant radiologists, one with 3 years' and the other with 6 years' experience of MRI. Hard copy images from the MRI examinations were reported independently by both reviewers. Of the 100 MRI examinations, there was full concordance of opinion in 61/100. Of the remaining 39 cases, four (10%) were considered "minor unrelated" differences, 12 (31%) "minor related" differences and 23 (59%) "major related" differences resulting in a significant change in patient management.
Air has been traditionally used as the negative contrast agent in double contrast barium enema (DCBE) examinations, but causes abdominal pain in the 24 h following the procedure. The frequency of post-procedural pain is less when carbon dioxide (CO2) is used as the negative contrast agent. We evaluated patients following DCBE examinations (using either air or CO2) by means of a questionnaire, to determine whether active drainage of gas altered the post-procedural pain. There was no difference in the pain experienced in the groups receiving CO2 with either active or passive drainage, or in the group receiving air with active drainage. Compared with the other groups there was a significantly higher incidence and severity of pain in the group receiving air and passive drainage. We conclude that active drainage of air following a DCBE examination is as effective as using CO2 in reducing post-procedural pain and swelling.
OBJECTIVE: To test the hypothesis that subfertility in men is familial and to examine the distribution of subfertility within families for consistency with a genetic cause. DESIGN: Case-control study and segregation analysis. SETTING: Two teaching hospitals in Leeds. SUBJECTS: Cases (probands) were men with an abnormal sperm count who attended a subfertility clinic and whose partners had no major factor contravening fertility. Controls were fathers of two or more children recruited through vasectomy clinics or a maternity department. MAIN OUTCOME MEASURES: The incidence of involuntary childlessness among brothers with partners and among sisters and second and third degree male relatives. When possible clinical and laboratory details were obtained from involuntarily childless brothers. RESULTS: Seventeen of the 148 (11.5%) brothers of probands but none of the 169 brothers of controls had sought medical advice for childlessness (P < 0.0005). Four probands had more than one involuntarily childless brother. There were six further brothers whose childlessness was thought to be involuntary bringing the total prevalence of subfertility among brothers of probands to 16%. Segregation analysis was consistent with an autosomal recessive mode of inheritance accounting for 60% of subfertility in men. Seventeen of the 346 (4.9%) uncles of probands and 10 of 420 (2.8%) uncles of controls were reported to be involuntarily childless (P = 0.09), but there was no difference in childlessness among sisters. In three families sperm counts from "affected" brothers confirmed the diagnosis and showed considerable similarities within but not between families. CONCLUSION: Subfertility in men has a familial component, and the observations are consistent with an autosomal recessive mode of inheritance in over half the cases. Several different genes are probably involved.
Auxin-binding protein 1 (ABP1) is a putative receptor for the class of plant growth hormones designated auxins of which indole-3-acetic acid (IAA) is the predominant endogenous member. ABP1 is a homodimeric glycoprotein consisting of subunits of 163 amino acid residues. We have performed a structural study of ABP1 that has localized a region along its primary sequence that is involved in hormone binding. We have used the photoaffinity labeling agent, 5-[7-3H]azidoindole-3-acetic acid (5-[3H]N3IAA), an active auxin analog, to covalently label residues that are within, or near, the auxin-binding site. Photolabeled ABP1 was digested to completion with trypsin, and the resulting peptides were purified by reverse phase high performance liquid chromatography. When 5-[3H]N3IAA was used at a concentration of 0.5 microM (one order of magnitude below the Kd for 5-N3IAA) only one peptide was labeled at a high specific activity. Labeling was blocked by the presence of 50 microM IAA, indicating that the interaction is specific. Sequence analysis determined that this tryptic fragment was derived from Ile130 to Leu145 of ABP1. We suggest that residue Asp134 is the specific target of the photolabeling and is within 1.48 A of the postulated hydrophobic platform of the auxin-binding site. We propose that Trp136 may serve as this hydrophobic platform in the binding site for the aromatic rings of auxins.