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Biomedical subjects

H Matthews

Publications and source records attributed to H Matthews.

At least 19 recordsLinked to original sources

Hip fracture-dislocation in football: a report of two cases and review of the literature.

Soccer is the world's most popular sport, with over 200 million participants world wide. Fractures account for only 4-9% of acute injuries, and hip fracture-dislocation is extremely uncommon. The potentially serious long term sequelae require that team physicians have an awareness of this injury. Two cases of traumatic hip fracture-dislocation are here reported in recreational soccer players sustained by low energy mechanisms. Prompt reduction and fixation are important to produce a stable and congruent joint.

Adult↗

Expression ratios of the Bcl-2 family proteins and disease activity in multiple sclerosis.

There is emerging evidence that failure of apoptosis (programmed cell death) of potentially pathogenic T lymphocytes may be involved in the pathogenesis of multiple sclerosis (MS). The commitment of T lymphocytes to die is partly regulated by the Bcl-2 family proteins, which act as a checkpoint upstream of mitochondrial dysfunction. These proteins include the death antagonists Bcl-2 and Bcl-X(L), and death agonists Bax and Bad. Recent studies suggest that altered expression of Bcl-2 family proteins in T lymphocytes is involved in promoting cellular resistance to apoptosis in patients with MS. However, the relationship between these alterations in Bcl-2 proteins expression and clinical disease activity has not yet been evaluated. In this study, we analyzed the expression ratios of pro- to anti-apoptosis Bcl-2 family proteins in patients with clinically active MS and compared results to corresponding ratios in patients with stable MS and relevant control groups. We observed a significant reduction in the expression ratios of pro- to anti-apoptosis Bcl-2 members in peripheral lymphocytes from patients with active MS when compared to corresponding ratios in patients with stable MS or other controls. This imbalance in the expression ratios of pro- and anti-apoptosis proteins was functionally active in reducing cellular susceptibility to apoptosis in active MS. It also correlated with clinical features of disease activity, such as the number of gadolinium-enhancing MRI lesions and clinical relapses. Our findings indicate that dysregulated expression of Bcl-2 family proteins in peripheral lymphocytes is a feature of clinically active multiple sclerosis.

Apoptosis↗

Prospective study of local cutaneous reactions in patients receiving IV phenytoin.

The authors prospectively examined the occurrence of subacute local cutaneous reactions (LCR) in patients receiving IV phenytoin over a 12-month period at a general hospital. LCR were detected in 29 of 115 patients (25.2%; 22 mild and seven moderate). All resolved within 3 weeks. Patients with LCR were older (median 68 versus 54.5 years, p = 0.004), were more likely to be in a general ward (86% versus 66%, p = 0.04), and had larger catheters (median 16 G versus 18 G, p = 0.05). The authors conclude that LCR are common in routine hospital practice, but are generally mild and benign.

Adult↗

Outgassing behavior and composition of comet C/1999 S4 (LINEAR) during its disruption.

The gas activity of comet C/1999 S4 (LINEAR) was monitored at radio wavelengths during its disruption. A runaway fragmentation of the nucleus may have begun around 18 July 2000 and proceeded until 23 July. The mass in small icy debris (</=30-centimeter radius) was comparable to the mass in the large fragments seen in optical images. The mass budget after breakup suggests a small nucleus ( approximately 100- to 300-meter radius) that had been losing debris for weeks. The HNC, H2CO, H2S, and CS abundances relative to H2O measured during breakup are consistent with those obtained in other comets. However, a deficiency in CH3OH and CO is observed.

Journal Article↗

Childhood vaccination against varicella: persistence of antibody, duration of protection, and vaccine efficacy.

OBJECTIVE: To document the duration of protection afforded by Oka/Merck varicella vaccine over a 7-year period. STUDY DESIGN: The subjects were healthy children 1 to 12 years of age originally enrolled in clinical studies to evaluate the primary immune response to varicella vaccine 6 weeks after vaccination. Each was monitored for antibody persistence, breakthrough infection, and household exposure to varicella to produce estimates of vaccine efficacy. RESULTS: The 6-year cumulative varicella antibody persistence rate was 99.5% (95% CI: 98.9%, 100.0%). The annual breakthrough rate through 7 years ranged from 0.2% to 2.3% per year; the estimated cumulative event rate was 6.5%. Comparison of the observed average annual breakthrough rate with the age-adjusted expected annual incidence rate of varicella in unvaccinated children corresponded to an estimated vaccine efficacy of 93.8% to 94.6%. Eighty vaccinated children were exposed to varicella in the household, resulting in 8 (10%) cases of infection. When compared with the historical attack rate of 86.8% in unvaccinated susceptible persons exposed to varicella in the household, this yields an estimated vaccine efficacy of 88.5% (95% CI: 80.9%, 96.1%). Varicella cases in vaccinated children generally were mild. CONCLUSION: The live attenuated varicella vaccine is highly effective in inducing persistent immunity and long-term protection against breakthrough varicella infection.

Age Distribution↗

Antibody responses of healthy infants to concurrent administration of a bivalent haemophilus influenzae type b-hepatitis B vaccine with diphtheria-tetanus-pertussis, polio and measles-mumps-rubella vaccines.

OBJECTIVE: To confirm that children given a bivalent Haemophilus influenzae type b-hepatitis B vaccine (bivalent Hib-HB vaccine; COMVAX) concurrently with priming doses of diphtheria-tetanus-pertussis vaccine (DTP), a booster dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP), inactivated or oral polio vaccine (IPV or OPV) and measles-mumps-rubella vaccine (M-M-R(II)) have satisfactory antibody responses to all antigens. DESIGN: 126 healthy 2-month-old infants were scheduled to receive bivalent Hib-HB vaccine concurrently with DTP (2 and 4 months of age), OPV or IPV (random allocation to OPV or IPV at 2 months of age; OPV at 4 and 14 to 15 months of age), DTaP and M-M-R(II) (14 to 15 months of age). A response was judged "adequate" if the lower bound of the 95% confidence interval on the proportion of vaccinees having a critical antibody level was <10 percentage points below prediction. RESULTS: Antibodies to hepatitis B virus surface antigen, H. influenzae polysaccharide, diphtheria toxin, tetanus toxin, pertussis agglutinogens, pertussis toxin (as measured by enzyme immunoassay but not by Chinese hamster ovary cell assay), pertussis filamentous haemagglutinin after a booster dose of DTaP, poliovirus type 2, measles virus, and mumps virus all equalled or exceeded expected levels. Antibodies to rubella virus and pertussis filamentous haemagglutinin (after priming doses of DTP) fell slightly, and in the case of rubella significantly, below predicted levels. Antibodies to poliovirus types 1 and 3 were also below expectation after 2 doses of polio vaccine but were adequate following a third dose of vaccine. CONCLUSION: Concurrent administration of bivalent Hib-HB vaccine with priming doses of DTP, a booster dose of DTaP, OPV, IPV, or M-M-R(II) was well tolerated and, with the possible exception of rubella, did not substantially impair the antibody response to any antigen.

Antibodies, Bacterial↗

NHS National Plan.

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Clinical Competence↗

Histidine phosphorylation of annexin I in airway epithelia.

Although [Cl(-)](i) regulates many cellular functions including cell secretion, the mechanisms governing these actions are not known. We have previously shown that the apical membrane of airway epithelium contains a 37-kDa phosphoprotein (p37) whose phosphorylation is regulated by chloride concentration. Using metal affinity (chelating Fe(3+)-Sepharose) and anion exchange (POROS HQ 20) chromatography, we have purified p37 from ovine tracheal epithelia to electrophoretic homogeneity. Sequence analysis and immunoprecipitation using monoclonal and specific polyclonal antibodies identified p37 as annexin I, a member of a family of Ca(2+)-dependent phospholipid-binding proteins. Phosphate on [(32)P]annexin I, phosphorylated using both [gamma-(32)P]ATP and [gamma-(32)P]GTP, was labile under acidic but not alkaline conditions. Phosphoamino acid analysis showed the presence of phosphohistidine. The site of phosphorylation was localized to a carboxyl-terminal fragment of annexin I. Our data suggest that cAMP and AMP (but not cGMP) may regulate annexin I histidine phosphorylation. We propose a role for annexin I in an intracellular signaling system involving histidine phosphorylation.

Adenosine Triphosphate↗

Safety, tolerability and immunogenicity of concomitant injections in separate locations of M-M-R II, VARIVAX and TETRAMUNE in healthy children vs. concomitant injections of M-M-R II and TETRAMUNE followed six weeks later by VARIVAX.

OBJECTIVES AND STUDY DESIGN: The primary objectives of this study were to compare immunologic responses, antibody persistence, safety and varicella breakthrough rates when VARIVAX (varicella vaccine) is given at the same time as M-M-R II (measles, mumps, rubella vaccine) and TETRAMUNE (conjugate Haemophilus influenzae type b, diphtheria, tetanus and whole cell pertussis vaccine) at separate injection sites (Group A) vs. VARIVAX given 6 weeks after M-M-R II and TETRAMUNE (Group B). Six hundred nine healthy children, 12 to 23 months of age, were randomized to one of two treatment (immunization) groups (Group A and Group B). Blood for antibody titers was drawn on the day of immunization, 6 weeks after each injection and 1 year later. Local and systemic adverse reactions were recorded. Exposure and cases of varicella were documented through a 1-year follow-up period. RESULTS: Measles, mumps and rubella seroconversion rates and geometric mean titers (GMTs) were similar for both treatment groups. Varicella seroconversion rates were also similar between groups. However, varicella GMTs and percent with a varicella-protective level [> or =5.0 glycoprotein (gp) enzyme-linked immunosorbent assay (ELISA) units] did not meet the prespecified criteria for similarity were lower for Group A (GMT 10.5; 82.8% > or =5.0 gp ELISA units) than for Group B (GMT 14.5; 91.2% > or =5.0 gp ELISA units). The GMTs between groups for other antibodies were similar. At the 1-year follow-up antibody titers were comparable in both groups and breakthrough varicella cases appeared generally similar. There were fewer local adverse events (AEs) at the VARIVAX injection sites (9.8% and 2.9%, Group A and B, respectively) than at the TETRAMUNE sites (27.9% and 24.0%). Systemic AEs were not statistically different when M-M-R II was administered alone (8.6%) or concomitantly with VARIVAX (8.9%). When VARIVAX was given alone AEs were 1.8%. The rate of fever > or =102 degrees F after M-M-R II and TETRAMUNE administered together was 10.7% on Days 0 to 3 and 23.7% on Days 7 to 21. When VARIVAX was administered alone, the rate of fever was 5.4% on Days 0 to 3 (P = 0.018) and 10.8% on Days 7 to 21 (P<0.001). CONCLUSION: Because the varicella titers were comparable and varicella breakthrough rates generally similar at 1 year in both groups, we expect that the concomitant administration of VARIVAX with M-M-R II and TETRAMUNE has clinical effectiveness similar to that with VARIVAX 6 weeks after the administration of these other two vaccines. VARIVAX appears to be less reactogenic than M-M-R II and TETRAMUNE.

Antibodies, Bacterial↗

Vertebral column and spinal cord malformation in children with exstrophy of the cloaca, with emphasis on their functional correlates.

Exstrophy of the cloaca is a dramatic malformation whose embryology is poorly understood. While the management of this disorder has received significant attention in the urology and general surgery literature, the neurologic status of these children has been poorly addressed. In order to better characterize the spinal cord and vertebral column malformations found in children with exstrophy of the cloaca, we undertook a clinical review of 26 consecutive children with exstrophy of the cloaca who had been seen at a single institution over 28 years. The prevalence of vertebral malformations in the 25 children who could be evaluated was 25/25 (100%). Twenty (80%) of the children had at least one vertebral fusion, most frequently at T-7. Twenty-two (88%) of the children had at least one vertebra with deficient posterior elements, and the spinal levels most frequently involved were S-2, S-3, S-4 and S-5. Nine (36%) of the children had at least one vertebra with a narrowed interpedicular distance, most frequently at T-7. Nine (36%) of the children had at least one vertebra with atrophic facet anatomy, most frequently at L-3. The prevalence of myelodysplasia in the 19 children for whom spinal magnetic resonance imaging or intraoperative findings were available was 100%. Of these 19 children, 15 (79%) had myelocystocele, 2 (11%) had a lipomeningocele, 2 (11%) had a meningocele, 2 (11%) had hydromyelia, and 4 (21%) had a tethered cord. These data suggest that spinal cord and vertebral column malformations are very common in children with exstrophy of the cloaca.

Abnormalities, Multiple↗

Measles, mumps, rubella, and varicella combination vaccine: safety and immunogenicity alone and in combination with other vaccines given to children. Measles, Mumps, Rubella, Varicella Vaccine Study Group.

Eight hundred and twelve children, 12 months to 3.5 years of age, were enrolled in two clinical studies to evaluate the safety and immunogenicity of a live, attenuated combination vaccine for measles, mumps, rubella, and varicella (MMRV). Children were enrolled in one of two randomized, multicenter studies, involving administration of (1) MMRV and placebo vs. measles, mumps, and rubella vaccine (M-M-R(II)) and varicella-zoster virus vaccine (VARIVAX), given at separate anatomic sites at the same office visit; or (2) MMRV, DTaP (diphtheria, tetanus, and acellular pertussis vaccine) and OPV (oral polio vaccine) vs. M-M-R(II), DTaP, and OPV, with VARIVAX given 6 weeks later. All vaccine regimens were generally well tolerated. More than 95% of vaccinees seroconverted for measles, mumps, rubella, and varicella, regardless of the vaccine or regimen used. In each study, the level of antibody titer to varicella virus was significantly lower in vaccinees receiving MMRV than in those who received VARIVAX in a separate syringe.

Chickenpox Vaccine↗

Safety and immunogenicity of concurrent administration of measles-mumps-rubella-varicella vaccine and PedvaxHIB vaccines in healthy children twelve to eighteen months old. The MMRV Study Group.

OBJECTIVE: To determine the safety and immunogenicity of concurrent administration of measles-mumps-rubella-varicella vaccine (MMRV) and PedvaxHIB (Haemophilus influenzae type b conjugate vaccine) vs. M-M-R II and PedvaxHIB followed by an optional dose of VARIVAX 6 weeks later. DESIGN: Healthy children, 12 to 18 months of age, were randomly assigned to two groups to receive (1) MMRV and PedvaxHIB given concurrently or (2) M-M-R II and PedvaxHIB followed by an optional dose of VARIVAX 6 weeks later. SUBJECTS: The study group included 294 healthy children, ages 12 to 18 months, with a negative history of measles, mumps, rubella and varicella. MAIN OUTCOME MEASURES: The seroconversion rate and magnitude of antibody responses when MMRV was given concurrently with PedvaxHIB compared with the antibody responses when VARIVAX was given 6 weeks after M-M-R II and PedvaxHIB. RESULTS: Healthy children, 12 to 18 months of age, who received MMRV and PedvaxHIB concurrently showed immune responses similar to those in the control group who received M-M-RII vaccine with PedvaxHIB followed by VARIVAX 6 weeks later. Antibody titers for varicella were significantly lower when MMRV was administered than when varicella vaccine was given separately (0.712-fold difference, P = 0.028). No vaccine-related serious adverse reactions were reported, and no clinically significant differences were seen in the safety profiles of the two treatment groups. CONCLUSIONS: There were no statistically significant differences in the seroconversion rates between the two treatment groups for any of the antigens tested at 6 weeks and 1 year. Significantly lower geometric mean titers for varicella were noted in the group who received MMRV compared to VARIVAX given alone. Six-week seroconversion rates, persistence of immune responses at 1 year and the frequency of local and systemic reactions were comparable when MMRV was administered with PedvaxHIB compared with M-M-R II and PedvaxHIB followed by VARIVAX 6 weeks later.

Antibodies, Viral↗

Observations of carbon monoxide in comet Hale-Bopp.

The recently discovered comet Hale-Bopp (C/1995 01) sports a bright dust coma even though it is still far from the sun (presently 6 astronomical units). This feature has attracted considerable interest in the public and scientific arenas. The comet is headed toward perihelion at 0.92 astronomical unit in April 1997 and is widely expected to then become a spectacular naked-eye comet. With millimeter-wave observations, carbon monoxide (CO) has been identified as the driver for the early activity observed in Hale-Bopp.

Carbon Monoxide↗

Safety and immunogenicity of one vs. two injections of Oka/Merck varicella vaccine in healthy children.

OBJECTIVE: To compare the safety and immunogenicity of a one- vs. two-dose regimen of Oka/Merck varicella vaccine in approximately 2000 healthy children 12 months to 12 years of age. METHODOLOGY: Subjects with a negative history of varicella were randomized to receive either one or two injections of the vaccine given 3 months apart and were followed for clinical reactions and serologic response (glycoprotein-based enzyme-linked immunosorbent assay). RESULTS: Both one- and two-dose vaccine regimens were generally well-tolerated. The incidences of varicelliform rash and fever were less frequent after the second injection. However, a slight increase in the incidence of injection site reactions was noted after the second injection; these were generally mild. Seroconversion rates by glycoprotein-based enzyme-linked immunosorbent assay were 98.2% (1700 of 1731) after one injection and 99.9% (717 of 718) after two injections. A significant (P < 0.001) boost in geometric mean titers was observed in children who received a second injection of vaccine 3 months after the first injection. Of the children who seroconverted at 6 weeks postregimen (one or two doses as assigned), 99.8% (528 of 529) of the one-dose group and 99.8% (473 of 474) of the two-dose group maintained antibody to varicella at 1 year with geometric mean titers of 19.5 and 31.2, respectively. CONCLUSIONS: Administration of a one- or two-dose regimen of the live Oka/Merck varicella vaccine (VARIVAX) is immunogenic and is generally well-tolerated in healthy children 1 to 12 years old. Antibody to varicella persists in > 99% of vaccinees 1 year after vaccination regardless of a one- or two-dose regimen. Long-term follow-up studies of this cohort of children may determine whether a two-dose regimen offers superior protection against chickenpox.

Antibodies, Viral↗

Safety, tolerability, and immunogenicity of two regimens of Oka/Merck varicella vaccine (Varivax) in healthy adolescents and adults. Oka/Merck Varicella Vaccine Study Group.

A multicenter clinical trial was conducted among 757 healthy adolescents and adults, 13-54 years, to compare two regimens of Oka/Merck varicella vaccine with respect to safety, tolerability, and immunogenicity. Participants were randomized to receive two injections of vaccine either four or eight weeks apart and were followed for clinical reactions and serologic response. The two vaccine regimens were equally well tolerated. The seroconversion rates (gpELISA) four weeks after injection 1 and 2 were 72 and 99%, respectively, for those who received vaccine four weeks apart and 78 and 99%, respectively, for those who received vaccine eight weeks apart. The differences in seroconversion rates were not statistically significant. However, delaying the second dose to eight weeks resulted in a higher antibody titer one month after the second injection. Administration of a two-dose regimen of varicella vaccine to susceptible adolescents and adults is well tolerated and highly immunogenic.

Adolescent↗