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Biomedical subjects

M Daniels

Publications and source records attributed to M Daniels.

At least 55 records · Page 3Linked to original sources
PubMed1994

Effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with and without steroids.

OBJECTIVE: To assess the effect of hormone replacement therapy (HRT) on bone mass in rheumatoid arthritis (RA) patients treated with and those not treated with steroids. METHODS: Two hundred postmenopausal women with RA (ages 45-65 years) were randomly allocated to receive transdermal estradiol (hormone replacement therapy; HRT) (50 micrograms daily) or calcium supplementation (400 mg daily) for 2 years. Forty-two of the patients (21%) were taking corticosteroids. Bone mineral density of the lumbar spine (BMDLS) and of the proximal femur (BMDF) was measured at study entry and at 12 months and 24 months. RESULTS: In the HRT group overall, mean BMDLS had changed by +2.22% (95% confidence interval [95% CI] +0.72, +3.72) and mean BMDF by -0.41% (95% CI -1.89, +1.07) after 24 months. In the calcium group, mean BMDLS changed by -1.19% (95% CI -2.29, -0.09) and mean BMDF by -0.56% (95% CI -2.60, +1.48). Differences between treatment groups were significant for the spine only (P < 0.001). In the 21 HRT-treated patients taking steroids, BMDLS increased by 3.75% (95% CI +0.72, +6.78) and BMDF by 1.62% (95% CI -1.27, +4.51). CONCLUSION: This study shows that HRT increases spinal BMD and maintains femoral BMD in postmenopausal RA. HRT is also an effective agent in preserving bone mass in patients taking low-dose corticosteroids.

Adrenal Cortex Hormones↗
PubMed1994

Preoperative autologous donation: surgery clinic staff knowledge/attitudes. Preoperative Autologous Blood Donation Study Group.

Preoperative autologous blood donation (PABD) is both under- and overused. Although the decision to order PABD lies with the surgeon, it is quite likely that other surgery clinic personnel influence patient acceptance and enrollment into PABD programs. Accordingly, we measured knowledge, attitudes, and the referral practice of clinic personnel pertaining to PABD. We administered a questionnaire to 102 nurses and 33 clerks working in surgery clinics at three university medical centers--one center in an area with a high incidence of AIDS and two centers in areas of low incidence of AIDS. Knowledge of PABD was poor when assessed by six questions. Only 6% each of nurses and clerks answered all questions correctly; 55% of nurses and 54% clerks missed three or more of the six questions. Surprisingly, no differences (P > .05) in knowledge deficits were noted when personnel from high and low AIDS areas were compared--indicating an overall need for education about PABD. In general, attitudes about PABD were positive, as most respondents (63%) gave favorable answers. Clinic personnel from the high AIDS area had even more favorable attitudes (P = .02). Because of these favorable attitudes, it seems likely that educational programs dealing with PABD would be readily accepted by clinic personnel. Greater knowledge should enhance the effectiveness of clinic staff in identifying, counseling, and referring eligible patients for this service.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Chronic oral etoposide in advanced breast cancer.

Chronic oral etoposide has shown activity in some metastatic refractory tumors. To test its activity in previously treated metastatic breast cancer patients, we started a study in 18 consecutive patients given etoposide orally at 50 mg/m2 daily for 21 days. A partial response was observed in 4 of 18 patients (22%); of the responding patients, 3 had visceral metastases and 1 had multiple bone metastases. Leukopenia of grade 3 or 4 was the main hematological toxic effect (23% of patients) and alopecia was the most important nonhematological toxicity. Chronic oral etoposide shows some activity in pretreated patients with metastatic breast cancer, with tolerance being good and toxicity, acceptable. Further studies of this drug given as first-line chemotherapy or in combination with other drugs can establish all its potential activity in this cancer.

Administration, Oral↗
PubMed1994

Expanded distribution of an investigational drug in parallel with ongoing controlled clinical trials: the didanosine model.

The purpose of the didanosine Expanded Access Program was to provide a needed antiretroviral agent to individuals who were unable to tolerate other therapy for human immunodeficiency virus infection or in whom such therapy was failing. The logistics of establishing this program are described, and the results of on-site auditing that confirmed the validity of the data obtained through this program are presented.

Didanosine↗
PubMed1994

Rates and risk factors for adverse events associated with didanosine in the expanded access program.

The didanosine Expanded Access Program was the largest AIDS treatment program to prospectively evaluate the safety of an antiretroviral agent among patients with advanced human immunodeficiency virus (HIV) disease in whom therapy with zidovudine was failing. A total of 21,198 patients who had infections refractory to zidovudine or who were intolerant of the drug received didanosine as a buffered powder for oral solution (sachet), with total daily doses of 6.6-10 mg/kg; the median CD4 lymphocyte count was 0.04 x 10(9)/L for this population. At the currently recommended dose (6.6-8.29 mg/[kg.d]), 6-month estimated rates of pancreatitis ranged from 1.2% for patients with AIDS-related complex (ARC) and CD4 lymphocyte counts of > or = 0.1 x 10(9)/L to 6.7% for patients with AIDS and CD4 lymphocyte counts of < 0.05 x 10(9)/L. Laboratory toxicities of World Health Organization grades 3 and 4 developed in fewer than 4% of patients entering the study with normal baseline values; the sole exception was leukopenia, which was documented in 8% of these patients. The results of this program demonstrated that patients with CD4 lymphocyte counts of < 0.10 x 10(9)/L or with a diagnosis of AIDS (defined by the 1987 classification system of the Centers for Disease Control and Prevention) were less tolerant of didanosine and significantly more likely to develop adverse clinical reactions and myelosuppression than other patients.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Oncoprotein immunoreactivity in human pituitary tumours.

OBJECTIVE AND DESIGN: The immediate early gene locus AP-1, incorporating the cellular oncogenes c-fos and c-jun (and their oncoprotein products Fos and Jun respectively) play a key role in regulating cell growth and differentiation. The myc-gene is also known to promote cell growth. In order to investigate the possible role of these oncogenes in human pituitary adenomas, Fos, Jun and Myc oncoprotein immunoreactivities were assessed in surgically resected pituitary adenomas in relation to in-vivo characteristics (hormone secretion, size and invasiveness) and an in-vitro index of cell proliferation (Ki-67 immunoreactivity). Thirty-three human pituitary adenomas and 16 normal pituitary glands were examined. MEASUREMENTS: Oncoprotein immunoreactivity was recorded as present (+) or absent (-), and Ki-67 labelling indices were scored quantitatively. Tumour size was scored from CT scan appearances and radiographic evidence of bone erosion was noted. RESULTS: Oncoprotein immunoreactivity was present in a total of 32/33 cases. Myc immunoreactivity was restricted to the only ACTH-secreting tumour in the series (1/33). Ki-67 immunoreactivity was present in 24/32 cases and labelling indices varied from 0.1 to 3.2%. CONCLUSIONS: Oncoprotein immunoreactivity did not correlate with hormonal profile, bone erosion or the size of the proliferating compartment estimated by Ki-67 labelling indices. Although oncoprotein expression is common in human pituitary adenomas, its significance remains to be elucidated.

Adenoma↗
PubMed1994

Gs alpha and Gi2 alpha mutations in clinically non-functioning pituitary tumours.

BACKGROUND AND OBJECTIVE: Activating mutations of Gs alpha (gsp) and Gi2 alpha (gip) have been described in various endocrine neoplastic conditions. The objective of this study was to assess the prevalence of gsp and gip mutations in clinically non-functioning pituitary tumours (NFTs) and to compare the clinical phenotypic characteristics of tumours bearing G protein gene mutations with wild-type tumours. DESIGN: Twenty-two NFTs and 20 normal anterior pituitary glands screened for G protein gene mutations. PATIENTS: Twenty-two patients; 14 female (median age 59 years, range 19-76) and 8 males (median age 66.5 years, range 50-77). MEASUREMENTS: Site-directed hybridization or direct sequencing of polymerase chain reaction amplified Gs alpha and Gi2 alpha DNA. RESULTS: G protein gene mutations were identified in 3/22 (13%) of NFTs. Two tumours demonstrated gsp mutations, one at codon 201 arginine to cysteine, and the second at codon 227 glutamine to arginine. Three tumours demonstrated gip mutations at codon 205 glutamine to arginine. Two tumours with gsp mutations also harboured gip mutations. All tumours with G protein gene mutations demonstrated local bone infiltration into the surrounding structures. CONCLUSIONS: G protein gene mutations have been demonstrated in a proportion of non-functioning pituitary tumours. The presence of dual gsp and gip mutations in two tumours suggests the possibility of multiple hits in a stepwise pathogenesis of pituitary neoplasia.

Adenoma↗
PubMed1994

A randomised controlled trial of the effect of hormone replacement therapy on disease activity in postmenopausal rheumatoid arthritis.

OBJECTIVE: To assess the effects of hormone replacement therapy (HRT) on disease activity in postmenopausal rheumatoid arthritis (RA). METHODS: Two hundred postmenopausal outpatients (aged 45-65 years) were admitted into a single blind randomised placebo controlled trial of transdermal oestradiol (50 micrograms daily) over six months. Patients continued with routine antirheumatic medications. Compliance with HRT was monitored using serum oestradiol (E2) levels. Disease activity was monitored at entry, three and six months using erythrocyte sedimentation rate (ESR), articular index (AI), visual analogue pain scale (VPS) and early morning stiffness (EMS). RESULTS: Ninety one and 77 patients completed six months treatment with placebo and HRT respectively. There were no significant differences in baseline characteristics between the groups and no overall effects of treatment. However, 35 patients (41.6%), who completed HRT, failed to achieve serum E2 levels > 100 pmol/l at either three or six months and were considered 'poor-compliers'. In the remaining HRT 'compliers' (58.4%) there were significant improvements after six months in articular index (28.9%; p < 0.01) and pain score (21.7%; p < 0.05) compared with placebo, as well as reductions in ESR (8.9%; NS) and morning stiffness (25.2%; NS). Comparisons between HRT 'compliers' and 'poor-compliers' confirmed significant improvements in articular index (p < 0.001), pain score (p < 0.05) and morning stiffness (p < 0.001) in the 'compliers'. CONCLUSIONS: This study did not show an overall effect of HRT on disease activity when used as an adjunct therapy in postmenopausal patients. A subgroup of patients, who had greater increments in serum E2 whilst taking HRT, demonstrated improvements in some parameters of disease activity, suggesting a potential beneficial effect with good compliance and higher dose HRT. Most importantly, in the treatment of RA associated bone loss, HRT can be prescribed without fear of a disease flare up.

Aged↗
PubMed1994

Use of CA 19-9 in the early detection of recurrences in colorectal cancer: comparison with CEA.

The serum levels of CA 19-9 were determined in the follow-up of 370 patients with colorectal cancer and compared with CEA. An increase in CA 19-9 preceded clinical diagnosis of recurrence in 25% of 72 patients. The mean time between the rise in CA 19-9 and clinical diagnosis of relapse was 3.7 months (median 3). Sensitivity of CA 19-9 in the early diagnosis of recurrence was much lower than that obtained for CEA (75%). Only 1 patient had elevated CA 19-9 levels and normal CEA.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1994

Production of bioactive and immunoreactive interleukin-6 (IL-6) and expression of IL-6 messenger ribonucleic acid by human pituitary adenomas.

Preliminary studies have demonstrated that some pituitary adenomas secrete immunoreactive interleukin-6 (irIL-6) when cultured in vitro. We have extended these studies by investigating 100 pituitary adenomas of different types measuring immunoreactive and bioactive IL-6. Tumors were cultured either as explants without fetal calf serum or as dispersed cells with 10% total calf serum. Fifty-three of the 100 (53%) pituitary cultures were found to release irIL-6 and in 44 adenomas examined, 32 (72.7%) secreted bioactive IL-6. In 61 explant cultures, 30 adenomas released IL-6, indicating autonomous secretion. The amount of IL-6 released by adenomas in cell culture was generally higher, although the incidence was similar to explant cultures. IrIL-6 was released by 7 of 14 prolactinomas, 15 of 27 somatotrophinomas, 5 of 7 corticotrophinomas (including 2 Nelson's adenomas), 1 of 1 thyrotrophinomas, 2 of 2 gonadotrophinomas, and 23 of 49 clinically non-functioning adenomas. Periadenomatous tissue removed from a patient with a corticotrophinoma was found to secrete IL-6 but in much lower concentration than from the adenoma tissue. Tumor necrosis factor-alpha and -gamma-interferon were not detected in the conditioned media. Four IL-6-secreting adenomas were examined by in situ hybridization for IL-6 messenger RNA, and three of these were positive with fluorescence present throughout the tissue examined. We have provided evidence that over half of pituitary adenomas secrete IL-6 which is bioactive and that IL-6 is synthesized within the tumor by the adenoma cells.

Adenoma↗
PubMed1993

[Surgical treatment combined with radiotherapy and chemotherapy in an unselected population of patients with malignant glioma].

BACKGROUND: Malignant gliomas are tumors of bad prognosis with a mean survival of 12 months. In the present report 74 patients diagnosed of malignant glioma were studied with the following aims: 1) evaluate how many could receive combined radiotherapy (RT) and chemotherapy (BCNU) treatment following surgery and 2) analyze whether the patients treated presented a survival similar to that described in the literature. METHODS: The records of 74 patients operated on for malignant glioma between 1987-1990 and consecutively included in a protocol of treatment with RT and BCNU were reviewed. RESULTS: Out of the total of 74 patients, 29 (39%) were considered evaluable. The medians of progression free interval and survival were of 10 and 16 months, respectively in these patients. Forty-five (61%) patients could not fulfill the protocol mainly because of tumoral progression prior to completion of RT and severe post surgical complications. The evaluable patients were significantly younger (p = 0.004) and tumoral exeresis wider (p = 0.0003) than in those who were not evaluable. CONCLUSIONS: Most of the patients operated on for malignant glioma may not receive treatment considered as standard, principally due to tumor progression in the first weeks following surgery and the presence of severe post surgical complications.

Adult↗
PubMed1993

Horizontal spread of an altered penicillin-binding protein 2B gene between Streptococcus pneumoniae and Streptococcus oralis.

The region encoding the transpeptidase domain of the penicillin-binding protein 2B (PBP 2B) gene of two penicillin-resistant clinical isolates of Streptococcus oralis was > 99.6% identical in nucleotide sequence to that of a penicillin-resistant serotype 6 isolate of Streptococcus pneumoniae. The downstream 849 base pairs of these genes were identical. Analysis of the data indicates that the PBP gene has probably been transferred from S. pneumoniae into S. oralis, rather than vice versa, and shows that one region of this resistance gene has been distributed horizontally both within S. pneumoniae and into two different viridans group streptococci.

Amino Acid Sequence↗
PubMed1993

Positive results of adjuvant mitomycin-C in resected gastric cancer: a randomised trial on 134 patients.

In order to evaluate the results on successful adjuvant chemotherapy in resected gastric cancer we performed a randomised trial on 134 patients in two arms: a control one with no further treatment after surgery versus a treatment arm given mitomycin-C (MMC), 20 mg/m2 intravenously one day every 6 weeks for four courses, starting before the sixth week after surgery. The median follow-up was 105 months. In the control arm, 49 out of 66 patients died due to recurrence, versus 40 out of 68 patients in treatment arm. Actuarial survival curve was statistically significant (P < 0.025) in favour of the treatment group. Liver metastases were lower in adjuvant group than in the control group (8/68 versus 19/66). Toxicity was mild. Main toxic effects were thrombocytopenia, leukopenia, nausea and vomiting. A pelvis renal cancer as a second malignancy 8 years after gastric cancer was observed. In that particular case MMC was given after surgery. We conclude that adjuvant chemotherapy based on MMC given in the early period after surgery, improves survival rate in gastric cancer resected patients.

Adult↗
PubMed1993

Carboplatin, methotrexate, vinblastine and epirubicin (Carbo-MVE) for transitional cell bladder carcinoma.

BACKGROUND: MVAC is considered the most effective chemotherapy regimen for transitional cell bladder carcinoma. However, due to its significant toxic effects we substituted carboplatin for cisplatin and epirubicin for adriamycin in an attempt to produce the same response with less toxicity. PATIENTS AND METHODS: Twenty-seven patients with invasive transitional cell bladder carcinoma received Carbo-MVE: carboplatin (300 mgr/m2 d2), methotrexate (30 mgr/m2 d1, 15, 22), vinblastine (3 mgr/m2 d2, 15, 22) and epirubicin (30 mgr/m2 d2) every 4 weeks. RESULTS: There were 2 complete clinical responses (8.4%), 5 partial clinical responses (20.8%), 8 stabilizations (33.3%) and 9 progressions (37.5%). The overall clinical response rate was 29.2% (11%-47.4%, 95% CI), but 2 partial clinical remissions were not pathologically confirmed; were they to be considered as non-responses the response rate would fall even lower (20.8%). Toxicity was moderately severe, with 77.8% developing WHO grade III-IV granulocytopenia, 22.2% grade III-IV thrombocytopenia and 59.3% grade II-III vomiting. There were no toxic deaths nor any renal toxicity. CONCLUSIONS: Our results suggest that Carbo-MVE is less active and at least as hematotoxic as multiagent CDDP-based regimens.

Aged↗
PubMed1993

Molecular epidemiology of penicillin-resistant pneumococci isolated in Nairobi, Kenya.

A total of 26% of the pneumococci isolated from an outpatient clinic in Nairobi, Kenya, during 1991 to 1992 had intermediate levels of penicillin resistance. Gene fingerprinting and DNA sequencing were used to distinguish the penicillin-binding protein (PBP) 1A, 2B, and 2X genes in 23 resistant isolates. Isolates were grouped into those that had identical forms of each of the three PBP genes (fingerprint groups) and those that had identical rRNA gene restriction patterns (ribotypes). Both methods divided the isolates into 11 groups. In a few cases, horizontal gene transfer appeared to have distributed an identical altered PBP gene into different pneumococcal lineages. Eight isolates were indistinguishable by ribotyping or multilocus enzyme electrophoresis and contained identical PBP 1A genes. Although these isolates were therefore members of the same clone, they were divided into two fingerprint groups which contained different PBP 2X and 2B genes. Presumably, members of this clone have acquired different altered PBP 2X and 2B genes on two separate occasions. One of these fingerprint groups contained isolates of serotype 14, whereas the other contained isolates of both serotypes 14 and 7. The identification of isolates in the latter group that are identical by all criteria, except serotype, implies the occurrence of a change in serotype. The predominant serotypes of the penicillin-resistant pneumococci from Nairobi were serotypes 14 and 19. In both cases, isolates of the same serotype which required the same MIC of penicillin were not members of a single clone, indicating that identity of serotype and MIC are not sufficient criteria for defining clones of resistant pneumococci even when the bacteria are isolated from a single clinic.

Amino Acid Sequence↗
PubMed1993

Effects of recombinant human activin A on growth hormone secretion by human somatotrophinomas in vitro.

Activin A is a homodimer of inhibin beta A subunits, and was first isolated from gonadal fluids on the basis of its ability to stimulate FSH secretion by rat pituitary cells in vitro. The beta A subunits of activin and their mRNAs have been found in many cell types, in several species and at different stages of development, suggesting that activin A has a wide range of diverse biological roles. Apart from the modulation of gonadotroph function, in-vitro studies have demonstrated inhibitory effects of activin A on GH synthesis, GH secretion and possibly somatotroph proliferation. We have therefore investigated the potential role of activin A in the pathophysiological regulation of GH secretion by human somatotrophinoma cells using in-vitro techniques. Cell cultures were established by enzyme dispersion of adenoma tissue obtained from six patients with acromegaly, and treated for 72 h with 0.01-10 nmol recombinant human activin A/l followed by a 2-h stimulation test with 10 nmol GH-releasing factor (GRF)/l. Medium was collected at 24, 48 and 72 h, as well as after GRF treatment, and GH concentrations were measured by immunoradiometric assay. Basal GH secretion from the cells of two tumours was significantly stimulated 12-63% above control values during treatment with 0.01-10 nmol activin A/l, whereas the peptide had no effect on GH release from cells of the remainder of the tumours. GRF significantly stimulated GH release from the cells of two different adenomas, and pretreatment with 0.01-1 nmol activin A/1 partially but significantly blocked GRF-stimulated GH release from the cells of one of these.(ABSTRACT TRUNCATED AT 250 WORDS)

Activins↗