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J R Green

Publications and source records attributed to J R Green.

At least 73 records · Page 4Linked to original sources
PubMed1993

Identification of two subunit A isoforms of the vacuolar H(+)-ATPase in human osteoclastoma.

Subunit A is thought to be the main component of the catalytic site of the vacuolar-type H(+)-ATPase. Screening of a cDNA library made from human osteoclastoma tumor tissue revealed the presence of two isoforms of subunit A. HO68 is a cDNA of 3.1 kilobase pairs, corresponding to a mRNA of approximately 3.4 kilobases in osteoclastoma only, encoding a protein of 615 amino acids with a predicted molecular mass of 68177 Da. A second subtype, VA68, corresponding to a mRNA of approximately 4.8 kilobases was present in all tissues analyzed, and codes for a predicted protein of 617 residues and theoretical molecular mass of 68264 Da. These clones share homology with previously published subunit A sequences, and this, together with the tissue distribution of the mRNA, suggests there are ubiquitous (VA68-type) and tissue-specific (HO68-type) isoforms. HO68 shows the closest sequence homology (95% at the amino acid level) to subunit A of a proton-secreting vacuolar-type H(+)-ATPase located in the apical membrane of midgut goblet cells of tobacco hornworm larva (Manduca sexta). We propose that HO68 could correspond to an isoform of subunit A specific for a vacuolar-type H(+)-ATPase located in the osteoclast plasma membrane.

Adenosine Triphosphatases↗
PubMed1993

Temporal variations in iliac trabecular bone formation in vertebral osteoporosis.

The histologic heterogeneity of osteoporosis relative to normal controls has attracted great interest. There has been controversy as to whether patients with high turnover osteoporosis may convert to a normal or low turnover form, and vice versa. We have studied 44 patients over 12 years by dynamic histomorphometry and 85Sr kinetics+calcium balance performed within 60 days in 20 patients (Group 1) and 75-808 days apart in the remainder (Group 2). In the first group, the histologic tissue level bone formation rate (BFR/BV or BFR/BS) was predictive of the 85Sr measurements of bone formation (r = 0.66 P < 0.01). There was no statistically significant correlation in Group 2 and the regression coefficients were significantly different (P = 0.01). Periodic regression was used to determine if seasonal changes were responsible for this loss of correlation; none was found that was of statistical significance. No systematic changes with time in bone formation were found in Group 2 during the period of observation; nor were consistent secular changes detected when the data for both groups were examined according to procedure date. In conclusion, bone formation may change with time in postmenopausal osteoporosis. Evidence that these changes are systematic was not found and this has implications for the design of treatment studies.

Aged↗
PubMed1993

HLA-DQ, DR and complement C4 variants in systemic lupus erythematosus.

We have defined HLA-DQA, DQB, DR and complement C4 variants in 92 subjects with SLE and 73 controls. Subjects with SLE showed an increased frequency of HLA-DQA*0501 (P < 0.01 corrected, odds ratio (OR) = 4.97; 95% C.I. = 2.52-9.81), DR3 (P < 0.001, OR = 3.18; 95% C.I. = 1.67-6.04) and C4A*Q0 (P < 0.05, OR = 1.91; 95% C.I. = 0.999-3.65) vs controls. These increases were particularly marked in those subjects positive for antibodies to both Ro and La. HLA-DQB*0501 (P < 0.01 corrected, OR = 0.03), DQA*0101 (P = 0.0012 uncorrected, OR = 0.23) and DR7 (P = 0.0018 uncorrected, OR = 0.28) were decreased in frequency in SLE. SLE patients with disease onset prior to age 30 yr were more likely to possess a DR3-bearing haplotype (P < 0.05 corrected) than those with onset after age 30 yr. No significant associations were found in patients with circulating antibodies to double-stranded DNA, Ro alone, U1 RNP, Sm or in those SLE patients with renal disease or vasculitis. The different associations found in different clinical and immunological subsets of SLE support the concept that SLE contains a variety of immunogenetic subgroups. Analysis of the associations between SLE and DR3, DQA*0501 and C4A*Q0 using the empirical logistic test suggests that the association of SLE with HLA-DQA*0501 is likely to be primary to the associations with both DR3 and C4A*Q0 (P < 0.001). Our results therefore raise the possibility that genes within the HLA-DQ region may have a direct effect upon susceptibility to SLE.

Adolescent↗
PubMed1993

Power comparison of various sibship tests of association.

There are several tests available for use with family studies to test if there is significant evidence of association with a particular disease gene locus, especially of HLA. We have used large simulations to compare the powers of tests using criteria N, R, T, PR, WP and some new tests involving both affecteds and unaffecteds in a sibship. It was found that tests using both affected and unaffected siblings were often more powerful.

Genetic Diseases, Inborn↗
PubMed1993

Pelvic inflammatory disease in human immunodeficiency virus-infected women.

OBJECTIVE: To determine whether the clinical course of pelvic inflammatory disease differs between women with human immunodeficiency virus (HIV) infection and seronegative controls. METHODS: All admissions for acute pelvic inflammatory disease from January 1, 1986 to December 31, 1992 at San Francisco General Hospital were reviewed, identifying 23 HIV-seropositive women. Their clinical course was compared with a control group of 108 seronegative women admitted for acute pelvic inflammatory disease. RESULTS: Human immunodeficiency virus-seropositive women with acute pelvic inflammatory disease had significantly lower abdominal tenderness scores (P < .05), lower admission and discharge white blood cell counts (WBC) (P < .01, P < .05), and fewer gonococcal infections (odds ratio 0.3, 95% confidence interval [CI] 0.1-0.9; P < .05) than the seronegative controls. There were no significant differences in duration of treatment, length of hospitalization, or incidence of tubo-ovarian abscess. Significantly more HIV-positive women with acute pelvic inflammatory disease required surgical intervention than seronegative women (odds ratio 5.5, 95% CI 1.0-29.3; P < .05). CONCLUSION: Human immunodeficiency virus-seropositive women with acute pelvic inflammatory disease may have an altered immune response, resulting in inadequate response to antimicrobial agents and the need for more surgical intervention. Future studies must include larger numbers of HIV-infected women, and the results must be stratified for CD4 counts, clinical HIV stage, and other measures of immunocompromise.

Adult↗
PubMed1992

Bone remodelling does not decline after menopause in vertebral fracture osteoporosis.

There is considerable current interest in whether activators of bone remodelling, such as IL-1 and other cytokines, are involved in the pathogenesis of osteoporosis. We have therefore studied indices relating to remodelling activation in 50 patients with postmenopausal vertebral osteoporosis and 12 with hip fracture osteoporosis in comparison with 25 age- and sex-matched controls. Because of uncertainty regarding the accuracy of current biochemical markers of bone formation with respect to the estimation of whole body rates of bone formation, a 85Sr-based radioisotopic method was used. This method was previously validated by comparison with data obtained after double in vivo labelling of transiliac biopsies taken nearly simultaneously. Bone resorption was estimated from urinary hydroxyproline data. Controls selected for their continued good health showed a progressive and statistically highly significant decline in indices of bone formation with time after menopause. No such decline was seen in the vertebral fracture patients (P less than 0.005). There were no hip fracture patients within 10 years of menopause so this statistical test could not be applied appropriately to them. The hydroxyproline data were consistent with the suggestion arising from the bone formation data that remodelling declines progressively after menopause in the controls but not in the vertebral fracture patients. The data also suggested that these two fracture groups were in more negative calcium balance than the controls, this being particularly marked in the hip fracture cases. Plasma osteocalcin data correlated moderately well with the kinetic measurements of bone formation. It is concluded that vertebral fracture osteoporosis is associated with prolongation of menopausal levels of bone remodelling which is inappropriate by comparison with healthy controls.

Age Factors↗
PubMed1992

Whole-body and site-specific bone remodelling in patients with previous femoral fractures: relationships between reduced physical activity, reduced bone mass and increased bone resorption.

1. A new tracer method is described for the non-invasive measurement of bone formation in the proximal femur. The method is based on our previously described whole-body method using 85Sr as the tracer (Reeve, J., Hesp, R. & Wootton, R. Calcif. Tissue Res. 1976; 22, 191-206). It allows correction to be made for long-term exchange processes within the skeleton. 2. The method has been applied in a study of regional and whole-body bone formation in 12 rehabilitated patients who had previously suffered a fracture of the proximal femur. Twelve healthy control subjects were studied, who were selected for their good health and continued physical activity. The aim was to explore the relationship between bone formation and physical activity. 3. Bone formation was similar in the two groups, both regionally and in the whole body. Based on analyses of four cadaver specimens, bone formation in the proximal femur was about one and two-thirds times that in the whole skeleton when related to mass of calcium in the region of interest. 4. Whole-body bone resorption, estimated from five measurements per subject of hydroxyproline excretion in relation to creatinine excretion, was significantly higher in the fracture patients (P < 0.01, Wilcoxon's test). 5. Estimates of current physical activity (and immediate pre-fracture physical activity) were made with a newly devised questionnaire. Historical levels of physical activity (at ages 15-45 years) were determined with Astrom's questionnaire. No bone formation index correlated with any index of physical activity. Urinary hydroxyproline excretion correlated inversely both with current physical activity and historical physical activity (for both regression coefficients P < 0.01). 6. The results are discussed in the light of our current understanding of the control of bone remodelling by the discrete basic multicellular units of bone. The opportunity to study regional bone resorption by the additional use of serial dual X-ray absorptiometry of the same region will in future allow the direct monitoring of the effects of therapeutic interventions which have been designed to prevent contralateral hip fracture.

Aged↗
PubMed1992

Short report: comparison of two doses of balsalazide in maintaining ulcerative colitis in remission over 12 months.

In a four-centre prospective double-blind trial, 108 patients with ulcerative colitis in remission were randomized to receive balsalazide in doses of 3 g or 6 g/day for 12 months. The patients were assessed at 3-monthly intervals clinically, sigmoidoscopically and with routine haematology and biochemistry. Remission rates of 77% (3 g/day) and 68% (6 g/day) at 12 months were not significantly different. Intolerance reactions leading to withdrawal from the study occurred in only 9 patients (8%), all occurring in the first 7 weeks of the study. Balsalazide is therefore both highly effective in maintaining remission in ulcerative colitis and well tolerated in both conventional and high dosage (the latter equivalent to 5.5 g/day of sulphasalazine). In this study no distinct advantage in maintenance of remission has been found for the higher dose of balsalazide.

Adult↗
PubMed1992

The effects of flumazenil on alertness and hypoxia in elderly patients after ERCP.

It is not known whether hypoxia, associated with upper gastrointestinal endoscopic procedures when midazolam sedation is used without narcotics, persists into the post-procedure recovery period. Thirty consecutive patients aged over 60 years, undergoing ERCP using midazolam sedation alone, were monitored clinically and by pulse oximetry before, during and for 2 hours after the procedure. They were randomized prospectively to receive either 0.5 mg flumazenil or normal saline on extubation. Results show that patients were most hypoxic in the first 30 minutes after the procedure and that mean oxygen saturation had not returned to pre-sedation values by 2 hours. Treatment with flumazenil increased alertness 2 minutes after the procedure, and was associated with a significantly higher arterial oxygen saturation at 15 minutes.

Aged↗
PubMed1992

Hoarseness after tracheal intubation.

The reported incidence of hoarseness following short-term tracheal intubation varies widely. It has been reported as being permanent in 3%. This suggests that an enormous problem exists considering the numbers of patients intubated daily in the United Kingdom. A prospective study of 235 adult patients undergoing general anaesthesia in a district general hospital included 167 patients whose tracheas were intubated. Of these 167, 54 (32%) complained of hoarseness postoperatively. All but five returned to normal within 7 days. The others were hoarse for 9, 10, 12, 54 and 99 days. Those who were hoarse for 54 and 99 days had vocal cord granulomata. Regression analyses showed that certain patient and anaesthetic factors had a significant effect on the hoarseness. This study confirms a low incidence of prolonged or permanent hoarseness following short-term tracheal intubation.

Adolescent↗
PubMed1992

The power of the N-test of haplotype concordance.

The N-test of haplotype concordance among siblings affected by some disease under investigation is used to decide whether there is a disease susceptibility gene linked to a marker locus or chromosomal region. The use of this test and appropriate modifications of it is briefly reviewed. The power of the ordinary N-test is then derived as a function of several parameters. The sample size needed to attain a given power is then derived. Some of the parameters are specified and the required sample sizes are given in tables for different values of the main unknown parameters.

Algorithms↗
PubMed1992

Dependence of ocular protrusion, asymmetry of protrusion and lateral interobital width on age.

Ocular protrusion and lateral interorbital width were measured in 462 patients; 187 females and 275 males ranging in age from 9 to 92 years. The object of this study was to determine if ocular protrusion, asymmetry of protrusion and lateral interorbital width was dependent upon age. There was a significant reduction in ocular protrusion and lateral interorbital width with increasing age in both females and males. There was a strong correlation between ocular protrusion and lateral interorbital width. Asymmetry of ocular protrusion did not develop with age. These findings may help in the longitudinal assessment of patients.

Adolescent↗
PubMed1992

Does nasal oxygen reduce the cardiorespiratory problems experienced by elderly patients undergoing endoscopic retrograde cholangiopancreatography?

Elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) have an increased risk of sedation related complications during the procedure. To determine whether nasal oxygen supplementation (2 l/min) reduces these risks, half of 66 patients aged over 60 undergoing ERCP using minimal midazolam sedation alone were randomised to receive nasal oxygen. The arterial oxygen saturation and pulse rate of all patients were monitored by pulse oximetry before and during the procedure. Only three patients in the oxygen supplemented group (n = 33) required any form of intervention for hypoxia compared with six in the control group (n = 33). Comparison of mean arterial oxygen saturation between the groups showed significantly higher levels in the nasal oxygen group throughout the procedure. Pulse rate comparisons showed no significant difference from control group values, both groups had short periods of significant tachycardia. We conclude that minimal sedation with midazolam alone still produces hypoxia during ERCP in a substantial number of elderly patients. Nasal oxygen supplementation increases the level of patient oxygenation and reduces the need for intervention, but does not reduce tachycardia in the elderly patient. Because hyoscine may be a significant factor contributing to the tachycardia, sparing rather than routine use of this agent is advisable.

Administration, Intranasal↗
PubMed1991

hPTH 1-34 treatment of osteoporosis with added hormone replacement therapy: biochemical, kinetic and histological responses.

Twelve patients with vertebral fracture osteoporosis were recruited into a trial of treatment with hPTH 1-34 by daily injection for 1 year combined (from the 5th month) with an anti-resorptive agent (oestrogen, n = 9; nandrolone, n = 3). Treatment outcomes were monitored by biochemical and radiotracer measurements together with histomorphometry of transiliac biopsies before and at the end of treatment following double in vivo pre-labelling with demethylchlortetracycline. Indices of whole body bone formation, obtained from the analysis of 85Sr data, showed substantial increases (P less than 0.005) for all three indices measured) while biochemical (hydroxyproline) and kinetic measurements of bone resorption showed modest and equivocal changes only. As a result calcium balance improved. Gastrointestinal calcium absorption showed a tendency to improve, while urine calcium decreased; but these changes were statistically not significant except for radiocalcium absorption in the oestrogen treated subgroup. Histomorphometry revealed substantial increases in cancellous bone volume as reported previously with hPTH 1-34 given alone. However, iliac (as distinct from whole body) indices related to bone formation and resorption appeared to have returned towards pre-treatment values by the time of the second biopsy under the influence of the anti-resorptive agent given with the hPTH 1-34. It is confirmed that hPTH 1-34 therapy can increase iliac cancellous bone mass (as well as spinal cancellous bone mass as reported earlier) without a long-term increment in whole body bone resorption, providing the hPTH is combined with an anti-resorptive agent.

Aged↗
PubMed1991

The relationship between serum vitamin D concentrations and in vivo tetracycline labeling of osteoid in crush fracture osteoporosis.

Twenty of 22 consecutive British patients with crush fracture osteoporosis had transiliac bone biopsies following double in vivo tetracycline labeling synchronized with the collection of serum for the measurement of vitamin D metabolites. A significant but direct (rather than inverse) relationship was found between 25-hydroxyvitamin D (calcidiol) levels and the fraction of cancellous surfaces covered with osteoid not taking either tetracycline label (r = 0.53, P less than 0.02). There was no correlation with 1,25-dihydroxyvitamin D levels. No patient had frankly thickened osteoid seams although 3 had reduced but measurable calcidiol levels. These results make it unlikely that the majority of patients with osteoporosis who have osteoid of normal thickness but reduced uptake of tetracycline have a mineralization defect secondary to vitamin D deficiency. The pathophysiological significance of unlabeled osteoid in osteoporosis requires further investigation.

Aged↗
PubMed1991

Combination antimicrobial therapy in the treatment of acute pelvic inflammatory disease.

We compared the clinical and microbiologic efficacy of two broad-spectrum combination antimicrobial regimens in the treatment of 148 patients with acute pelvic inflammatory disease. Patients were randomized to inpatient treatment with either cefoxitin and doxycycline (n = 75) or clindamycin and tobramycin (n = 73). These antibiotics were administered intravenously for at least 4 days, and up to 48 hours beyond defervescence. Patients were discharged on a regimen of oral doxycycline or clindamycin in accordance with the intravenous regimen to complete a total duration of therapy of 2 weeks. Neisseria gonorrhoeae (53%) and Chlamydia trachomatis (31%) were the microorganisms that were isolated most frequently from the genital tract of enrolled patients. At follow-up, N. gonorrhoeae was isolated in two patients, and C. trachomatis was isolated in none. The overall initial favorable response rate to combination antimicrobial therapy was 98.5% (130/132) in patients with uncomplicated pelvic inflammatory disease and 81% (13/16) in patients with pelvic inflammatory disease that was complicated by tuboovarian abscess. A greater than 70% decrease in abdominal tenderness score occurred in 89% of 111 patients within 6 weeks of hospital discharge. There were no significant differences between antibiotic treatment groups in any response categories or in toxicity. During the initial hospitalization, five patients (three with tuboovarian abscess; one with a pyosalpinx, and one with intractable acute and chronic pelvic inflammatory disease) required surgical intervention. These results support the recommendation to use broad-spectrum combination antimicrobial therapy for the treatment of acute pelvic inflammatory disease.

Acute Disease↗