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Biomedical subjects

I Reid

Publications and source records attributed to I Reid.

At least 37 records · Page 2Linked to original sources
PubMed1996

Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis.

To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, 19 centers enrolled 516 postmenopausal women aged 45-80 years with spine bone mineral density (BMD) at least 2.5 SD below the mean for young premenopausal women in a 3-year, double-blind, placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate, 5 or 10 mg/day for 3 years; or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mg/day of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites. Nonsignificant mean decreases in BMD of the spine, femoral neck, and trochanter of 0.6, 0.7, and 0.4%, respectively, occurred in the placebo group at 3 years. Relative to placebo-treated patients, spine BMD increased by 5.4%, 7.4%, and 8.4% in the 5, 10, and 20/5 mg ALN groups, respectively. Increases at the femoral neck were 3.5%, 5.5%, and 4.3%, and those at the trochanter were 5.1%, 7.2%, and 7.2%, respectively. Thus, efficacy of 10 and 20/5 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continued to increase over the entire 3-year study duration in the ALN-treated groups and, compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confirmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary, 10 mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women.

Administration, Oral↗
PubMed1996

Tumour marker detection in oesophageal carcinoma.

Levels of the tumour markers CEA, CA 19-9, CA 125 and SCC were measured in 58 patients presenting with oesophageal carcinoma and compared with levels in patients with benign oesophageal disease and levels in normal volunteers. CEA and CA 19-9 were significantly increased in the patients with oesophageal cancer, however, individual sensitivity for CEA, CA 19-9, CA 125 and SCC was only 28, 34, 10, and 32%, respectively. The combined sensitivity of all markers was 64% and specificity was 80%. There was no difference in combined tumour marker sensitivity between squamous or adenocarcinomas of the oesophagus. No consistent change in marker levels occurred with treatment, and tumour marker levels could not be significantly correlated with stage of disease or short-term survival. These results indicate that tumour marker sensitivity is too low for oesophageal cancer screening and has poor prognostic significance in those undergoing treatment.

Adult↗
PubMed1996

Medroxyprogesterone acetate enhances the spinal bone mineral density response to oestrogen in late post-menopausal women.

OBJECTIVES: The relative contributions of administered oestrogen and progestin to protection of the post-menopausal skeleton remain unclear. We have compared the effect on spinal bone mineral density of continuous combined oestrogen/medroxyprogesterone therapy with that of unopposed oestrogen in late post-menopausal women. DESIGN: Observational study. SUBJECTS: Seventy-three osteoporotic post-menopausal women attending the Auckland Hospital Bone Clinic. Twenty-three hysterectomized women were treated with unopposed oestrogen (0.625 mg oral conjugated oestrogens daily), and 50 non-hysterectomized women were treated with continuous combined oestrogen/medroxyprogesterone therapy (5 mg medroxyprogesterone acetate and 0.625 mg oral conjugated oestrogens daily). MEASUREMENTS: Baseline and one-year measurements of lumbar spine bone mineral density were performed using dual-energy X-ray absorptiometry. RESULTS: After one year of therapy, spinal bone mineral density increased by 6.6% (95% confidence interval 5.6-7.6, P < 0.001 vs baseline) in the combined oestrogen/medroxyprogesterone therapy group, compared to 4.0% (CI 2.4-5.7, P < 0.001 vs baseline) in the unopposed oestrogen group (difference between means 2.6% (CI 0.8-4.4, P < 0.01). CONCLUSION: In osteoporotic post-menopausal women, one year of continuous combined oestrogen/medroxyprogesterone therapy is associated with a 65% greater increment in spinal bone mineral density than is observed in response to unopposed oestrogen. The prescription of combined oestrogen/progestin therapy should be considered in osteoporotic post-menopausal women who have undergone hysterectomy, in order to maximize the skeletal protection provided by hormone replacement therapy.

Absorptiometry, Photon↗
PubMed1996

Bone mass and metabolism in women aged 45-55.

OBJECTIVE: Changes in calcium homeostasis and bone mass around the climacteric are poorly understood. We examined relations between endocrine factors and indices of bone mass and metabolism in healthy women approaching the menopause. DESIGN: Cross-section study. PATIENTS: Sixty-eight spontaneously menstruating women aged 45-55. MEASUREMENTS: Bone density measured at lumbar spine (LS) and femoral neck (FN) using dual energy X-ray absorptiometry and distal non-dominant forearm using peripheral quantitative computed tomography. We recorded menstrual history, physical activity and dietary calcium, and measured serum calcium, phosphate, alkaline phosphatase, osteocalcin, vitamin D, fT3, T4, TSH, PTH, FSH and oestradiol (E2), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excretion. RESULTS: Using serum FSH level as a marker of ovarian function, 63 subjects could be classified into one of three groups: group A (serum FSH < 10 U/l, n = 29), group B (10-35 U/l, n = 27) and group C (> 35 U/l, n = 7). Bone density fell with declining ovarian function at the LS, FN and forearm trabecular (but not cortical) sites. Serum PTH was lower in group A vs B (mean (SD) 2.68 (0.97) vs 3.52 (1.17) pmol/l, P < 0.05), but similar to group C (2.90 (1.09) pmol/l, P = NS). Serum phosphate was elevated in group C compared to groups A and B (1.17 (0.15) vs 1.04 (0.11) and 1.05 (0.13) mmol/l, P < 0.05), and urinary PYD (61.1 (8.0) vs 50.4 (11.6) and 43.9 (8.1) mumol/mol creatinine) and DPD (15.9 (3.9) vs 12.0 (3.6) and 11.4 (3.6) mumol/mol creatinine) excretion were also increased. There were no significant differences in vitamin D metabolites or osteocalcin. Multivariate analysis suggested serum osteocalcin was positively related to physical activity and serum 1,25-dihydroxycholecalciferol levels. Serum free T3 was positively correlated with urinary DPD excretion, and inversely related to serum PTH. In all subjects, serum PTH was related to body weight (r = 0.38, P = 0.002). CONCLUSIONS: Declining ovarian function before menopause is accompanied by reductions in bone mass and altered calcium metabolism. Free T3 may regulate bone resorption and indirectly modulate PTH release.

Amino Acids↗
PubMed1994

LTP-like synaptic efficacy changes following electroconvulsive stimulation.

Synaptic plasticity is thought to represent a mechanism for memory formation. Memory disturbances commonly follow electroconvulsive therapy (ECT) for depression. Accordingly, we examined the development and duration of the effects of electroconvulsive stimulation (ECS) on hippocampal synaptic plasticity in rats. Daily recording of field potentials during 10 spaced ECS revealed an increase in the dentate gyrus evoked response, reaching a maximum after the fifth seizure. In a second experiment, an identical ECS series substantially reduced the degree to which electrically induced synaptic changes (long-term potentiation--LTP) could be elicited under anaesthesia for up to 40 days. These findings suggest that ECS induces LTP-like long-lasting synaptic changes which may underlie the neuropsychological sequelae of ECT treatment in humans.

Animals↗
PubMed1994

Testicular atrophy as a consequence of inguinal hernia repair.

Testicular atrophy is an uncommon but well recognized complication of inguinal hernia repair and one that frequently results in litigation. A series of ten cases of testicular atrophy occurring after hernia repair in nine patients is presented. Identifiable risk factors were present in eight instances. Surgeons should make careful enquiries as to previous groin or scrotal surgery and, when indicated, warn the patient before surgery of the increased risk of testicular atrophy. Overzealous dissection of a distal hernia sac, dislocation of the testis from the scrotum into the wound and concomitant scrotal surgery should all be avoided.

Adult↗
PubMed1994

Bone mineral density and metabolism in premenopausal women taking L-thyroxine replacement therapy.

BACKGROUND AND OBJECTIVE: Excess endogenous thyroxine causes bone loss, but the effects of exogenous thyroxine are disputed. We report on bone mass and metabolism in women taking L-thyroxine therapy. DESIGN: Cross-sectional and longitudinal studies. PATIENTS: Cross-sectional study: 40 healthy premenopausal women with autoimmune thyroiditis taking either physiological (serum TSH usually normal, 0.35-3.3 mU/l) or suppressive (serum TSH usually < 0.35 mU/l) doses of L-thyroxine; patients were also compared with previously acquired age and weight matched premenopausal volunteers with no history of thyroid dysfunction. Longitudinal study: 28 patients were followed-up > or = 1 year later. MEASUREMENTS: In all subjects bone mineral density (BMD) was measured at the anteroposterior lumbar spine and left hip (femoral neck, greater trochanter and Ward's area) using dual-energy X-ray absorptiometry, and physical activity assessed using the Framingham physical activity index. Serum osteocalcin (OC), PTH and vitamin D, and urinary pyridinoline and deoxypyridinoline excretion were measured in patients. RESULTS: Cross-sectional study: The patient groups were well matched for disease duration and physical activity although the suppressed group were slightly younger (mean 38.1 (SD 7.5) vs 43.3 (3.9) years, P < 0.05). BMD, serum OC, PTH and vitamin D, and urinary cross-link excretion did not differ significantly between the two groups. Multivariate analysis of the whole group suggested that BMD at the femoral neck and greater trochanter was related positively to weight and physical activity and negatively to thyroxine dose (microgram/kg/day) and patient age. At the lumbar spine BMD was reduced non-specifically in the presence of thyroid disease and treatment, but this effect appeared to decline with increasing duration of therapy. A similar analysis of the patient group suggested that urinary cross-link excretion correlated positively with thyroxine dose, and negatively with duration of treatment. Longitudinal study: Annualized changes in BMD were inversely related to thyroxine dose (microgram/kg/day) at all sites but achieved statistical significance only at the femoral neck and Ward's area. CONCLUSION: We did not find any effect of persistent historical TSH suppression on current bone mass, and this might relate to the relative insensitivity of older TSH assays. However, the cross-sectional and longitudinal data suggest that high daily doses of thyroxine in relation to patient body weight might adversely affect bone mass, particularly at the hip. These findings support the contention that excess exogenous thyroxine might predominantly deplete skeletal sites, such as the femoral neck, rich in cortical bone.

Absorptiometry, Photon↗
PubMed1993

Electroconvulsive stimulation and synaptic plasticity in the rat.

The effects of repeated, spaced, electroconvulsive stimulation (ECS) on rodent hippocampal synaptic plasticity was investigated in vivo. Long-term potentiation (LTP) was induced in intact rats using high-frequency perforant path stimulation, and measured by recording extracellular excitatory field potentials and population spikes evoked in the dentate gyrus by low-frequency stimulation before and after LTP induction. LTP induction appeared to be inhibited in animals which had received ECS. However, inspection and analysis of absolute excitatory postsynaptic potential and population spike size before LTP induction in ECS treated animals suggested that LTP may have already been induced as a consequence of seizure activity, reducing the degree to which further potentiation could be elicited experimentally.

Analysis of Variance↗
PubMed1993

Face-processing impairments and the Capgras delusion.

Investigations of two cases of the Capgras delusion found that both patients showed face-processing impairments encompassing identification of familiar faces, recognition of emotional facial expressions, and matching of unfamiliar faces. In neither case was there any impairment of recognition memory for words. These findings are consistent with the idea that the basis of the Capgras delusion lies in damage to neuro-anatomical pathways responsible for appropriate emotional reactions to familiar visual stimuli. The delusion would then represent the patient's attempt to make sense of the fact that these visual stimuli no longer have appropriate affective significance.

Aged↗
PubMed1993

[Mycoplasma hominis and Ureaplasma urealyticum in pregnant and infertile women. Differences in tubal pathology].

We studied the frequency of cervicovaginal bacteria in 47 pregnant women (16-41 weeks of gestational age), in 47 infertile patients and in 4 with gynecological diseases (not infections). When we compared the frequency of bacteria between pregnant and infertile women, we found that the biggest difference was with U. urealyticum. In fact the frequency of this germ was 61% in the total population studied, in pregnant women was of 72% which is statistically higher than the frequency in infertile women which was of 47% (p < 0.025). We think that the reason for the higher frequency of this germ is a consequence of the effect of estrogens that favors the proliferation of this of germ. In the case of M. hominis the frequency in pregnant women was of 13% and in infertile women was of 21% which was not statistically different. Within the group of infertile patients, those that had tubal damage had a higher frequency of germs that the patients that did not have damage, moreover M. Hominis was not detected in the infertile patients without tubal damage and in patients with tubal damage its frequency was of 25%.

Carrier State↗
PubMed1993

Changes in immunological parameters during interleukin 2 and interferon 2 alpha treatment of recurrent renal cell carcinoma and malignant melanoma.

Immunological parameters were studied in patients with either advanced renal cell cancer (n = 7) or advanced malignant melanoma (n = 6) during treatment with a low-dose continuous intravenous treatment with human recombinant interleukin-2 (hr IL-2) and recombinant interferon alpha-2a. Before treatment, natural killer (NK) cell activity was found to be significantly lower in these patients than in 10 normal controls. However, the numbers of NK cells in circulation were equivalent; following incubation of the patients' peripheral blood mononuclear cells (PBMC) with IL-2 for three days normal lymphokine activated killer (LAK) cell activities were induced. Thus, in-vitro incubation with IL-2 appeared to overcome a defect in NK activity. We next examined the effect of IL-2/IFN alpha therapy on in-vitro LAK induction. Treatment significantly increased in-vitro LAK activity in eight of nine patients tested, although in-vivo LAK cell activity was not altered during treatment. The numbers of NK cells (CD16+ CD56+) in peripheral blood showed a significant increase in seven of ten patients as a result of treatment. The three patients who showed the best clinical response also showed the highest increase in expression of these phenotypic markers. T cells were found to be activated in 8/10 patients as indicated by increased co-expression of CD3 with CD25 after completion of 4-day continuous intravenous infusion of IL2. Four days before the start of treatment, cancer patient PBMC stimulated with concanavalin A (con A) produced significantly greater amounts of TNF compared to normal controls. In-vitro inducible TNF was found to decrease following treatment. Since IL-2 production and lymphocyte proliferation in response to Con A were normal in the patient group and were not altered by treatment, the reduction in TNF levels seemed not to be a general inhibitory effect. Further study of these and other changes in the immune system during IL-2/IFN alpha treatment may help to understand how these immunoregulators cause tumour destruction and to predict their usefulness in individual patients.

Adult↗
PubMed1992

Enhancement of in vitro tumor-infiltrating lymphocyte cytotoxicity by heteroconjugated antibodies.

Tumor-infiltrating lymphocytes (TIL) were obtained from a mouse melanoma cell line (CL 62) transfected with the gene for the human melanoma Ag p97. TIL were cultured with anti-CD3 antibody and IL-2 for up to 38 days. Flow cytometry identified these TIL as Thy-1.2 + ve/CD4-ve/CD8 + ve cells. A heteroconjugated antibody 500A2 x 96.5, specific for both the CD3 Ag on TIL and the p97 Ag on CL 62 melanoma cells, was prepared using N-succinimidyl-3-(2-pyridyldithio)-propionate as a linking agent. TIL alone demonstrated low levels of cytotoxicity against autologous CL 62 tumor and also against the parental K1735 tumor and an allogeneic murine melanoma (B16). The addition of 500A2 x 96.5 heteroconjugated antibody enhanced TIL-mediated lysis of CL 62 tumor, but not of the K1735 or B16 tumors. This enhanced cytotoxicity was elicited at E:T ratios as low as 0.4:1, and in TIL cultured for 7 to 38 days. These results suggest that hetero-conjugated antibody may enhance the anti-tumor effect of TIL in vivo.

Animals↗
PubMed1992

Heteroconjugated antibodies enhance lymphocyte-mediated tumour cell lysis in vitro and in vivo.

Covalent linkage of an antitumour antibody specific for a tumour cell surface antigen to an antilymphocyte antibody specific for the T lymphocyte receptor complex produces a heteroconjugated antibody that can activate and redirect cytotoxic T lymphocytes to lyse tumour cells. The ability of an antilymphocyte-antitumour heteroconjugate (500A2 x 96.5) to direct the lysis of murine melanoma cells by cultured murine lymphocytes was tested in vitro using a 4-h chromium release assay and in vivo with a tumour neutralization assay. In vitro, the addition of heteroconjugated antibody significantly increased tumour lysis by murine C3H/HeN lymphocytes (median specific lysis 82.7 per cent with lymphocytes plus heteroconjugate versus 9.5 per cent for lymphocytes alone, P less than 0.001). In vivo, treatment with heteroconjugated antibody plus lymphocytes significantly reduced the development of pulmonary metastases after intravenous tumour administration (median number of pulmonary metastases 28.5 for combined treatment versus 250 for heteroconjugate or lymphocytes alone, P less than 0.001).

Animals↗
PubMed1992

A phase 2 trial of recombinant interleukin-2 and 5-fluorouracil in patients with metastatic colorectal carcinoma.

The toxicity and efficacy of sequential 5-fluorouracil (5-FU) and recombinant interleukin-2 (IL-2) were evaluated in 12 patients with metastatic colorectal carcinoma. This combination of 5-FU and IL-2 produced a 10% partial response rate with 40% of patients remaining in stable disease while on therapy. No clear improvement in survival was demonstrable. In contrast to the disappointing response rates the overall level of toxicity was very low with no treatment related deaths. It is concluded that modifications in treatment schedules are required before further similar studies are commenced.

Adult↗