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Biomedical subjects

M Daniels

Publications and source records attributed to M Daniels.

At least 19 recordsLinked to original sources
PubMed1992

Chronic oral etoposide in non-small cell lung carcinoma.

25 consecutive inoperable or extended non-small cell lung cancer (NSCLC) patients (19 non-chemotherapy pretreated, 6 non-heavily pretreated) were given oral etoposide, 50 mg/m2/day for 21 successive days, every 4 weeks. 5 partial responses (PR), 9 disease stabilizations were achieved; the overall response rate of 20% (95% confidence interval, 4% to 36%) or 26% in non-pretreated patients. Median survival and PR duration probabilities were 6.7 months and 6.3 months, respectively. Alopecia excepted (96% of patients), non-haematological toxicity was mild. Haematological toxicity WHO grade II+III mainly consisted of leukopenia (28%).

Administration, Oral↗
PubMed1992

Cancer diagnosis disclosure in a Spanish hospital.

At the Clinic Hospital in Barcelona, Spain, 167 cancer patients and 380 hospital health care workers were interviewed about cancer diagnosis disclosure. Only 25 patients (15%) were correctly informed of their diagnoses. Breast cancer patients were significantly more often informed than patients with other malignancies (p less than 0.05). Two hundred seventy-two of 380 hospital health workers interviewed (71%, p = 0.00) would want to know their own diagnoses should they suffer from cancer in the future, but only 19% (p = 0.00) would want such a diagnosis revealed to their similarly afflicted relatives. This information model, based on cancer taboo, is largely preferred by these healthy people and is followed by doctors, patients and family members. To inform our patients better, the mandatory uniform disclosure of the true diagnosis is not likely to be constructive at present. In our opinion a pragmatic approach is more realistic and humane. Nevertheless, we must hope that more modern cancer education will lead to the gradual elimination of this taboo in our society.

Aged↗
PubMed1992

Phase II trial of carboplatin and etoposide activity in pretreated breast cancer patients.

Twenty-seven metastatic breast adenocarcinoma patients, pretreated with standard hormonotherapy or chemotherapy, received carboplatin 100 mg/m2/day x 3 intravenously (i.v.) plus etoposide 100 mg/m2/d x 3 i.v. repeated at 4-week intervals. There were five partial responses (18.5%), two minor responses, and 12 disease stabilizations. The dominant metastatic disease sites were soft tissue in three partially responding patients and visceral metastases in the two remaining responders. The median duration of response and time to progression were, respectively, 10 and 26 weeks. Major toxicity was myelosuppression with 85% of patients developing leukopenia; 48%, anemia; and 30%, thrombocytopenia. Carboplatin plus etoposide has shown antitumor activity in our group of pretreated patients. Based on the same schedule, a first-line carboplatin plus etoposide Phase II trial has been started.

Adenocarcinoma↗
PubMed1992

Gonadotrophin secretion in vitro by cells of a pituitary tumour from a patient with multiple endocrine neoplasia type I.

OBJECTIVE: The aim was to investigate the hormone secretory products of a pituitary tumour from a patient with multiple endocrine neoplasia type I (MEN I) utilizing cell culture and immunoassay techniques. DESIGN: Adenoma tissue was enzymically dispersed and established in cell culture. Medium was collected for hormone measurement after 2 days, and also after 24-hour periods during long-term culture. In addition, tissue fixed at surgery was analysed by immunocytochemistry and electron microscopy. PATIENT: The subject was a 59-year-old male with a clinical history characteristic of familial MEN I syndrome. MEASUREMENTS: Pituitary hormones in serum and culture medium were measured by fully characterized radioimmunoassays. RESULTS: Preoperative serum LH and FSH levels were normal, or slightly elevated, and there was a progressively blunted gonadotrophin response to GnRH throughout the 8 years prior to adenomectomy. TRH induced a small, paradoxical increase in serum gonadotrophin levels 2 weeks preoperatively. Post-operative pituitary hormone responses to standard stimulation tests showed an active normal pituitary. In vitro, the pituitary tumour cells secreted only gonadotrophins and glycoprotein hormone alpha-subunit. The fixed tumour tissue immunostained for alpha-subunit alone, and electron microscopy confirmed the presence of secretory granules with diameters of 100-280 nm. Gonadotrophin secretion continued throughout 77 days in long-term culture, but whilst LH was released at a steady rate, that of FSH transiently increased between days 29 and 48 in vitro. CONCLUSIONS: These data demonstrate that a pituitary tumour associated with the MEN I syndrome secreted gonadotrophins in vitro.

Adenoma, Chromophobe↗
PubMed1992

Genetics of resistance to third-generation cephalosporins in clinical isolates of Streptococcus pneumoniae.

Resistance to third-generation cephalosporins in a clinical isolate of Streptococcus pneumoniae was shown to be due to the production of altered forms of penicillin-binding proteins (PBPs) 2X and 1A. The cloned PBP2X gene from the resistant strain was able to transform a susceptible strain to an intermediate level of resistance. The resulting transformant could be transformed to the full level of resistance of the clinical isolate using the cloned PBP1A gene from the latter strain. Chromosomal DNA from the resistant strain (and from other resistant strains) could readily transform a susceptible strain to the full level of resistance to third-generation cephalosporins (greater than 250-fold for cefotaxime; greater than 100-fold for ceftriaxone) in a single step (transformation frequency of about 10(-5)). The resistant transformants obtained with chromosomal DNA were shown by gene fingerprinting to have gained both the PBP1A and PBP2X genes from the DNA donor.

Bacterial Proteins↗
PubMed1992

Intracavitary oxytetracycline in malignant pericardial tamponade.

We started a treatment trial for malignant pericardial tamponade with intracavitary oxytetracycline, 500-1,000 mg/day, administered via an indwelling pericardial cannula after extraction of as much pericardial fluid as possible. This procedure was repeated every 24 h for 6 consecutive days or until no more fluid could be drained. Eleven consecutive patients were entered in the study. The responses were obtained by clinical examination, chest roentgenogram and echocardiogram, prior to and after treatment. The primary cancer was located in the breast in 7 patients, in the stomach in 2 patients, and in the lung in 2 patients. In all cases, systemic chemotherapy or hormonal therapy was started after the pericardial tamponade was cured. The mean tetracycline dose per patient was 3,000 mg (range 1,500-6,000). All patients responded to the treatment with rapidly improving symptoms. Response persisted during a median of 9 months coinciding roughly with the median survival because all patients died because of progression of the neoplasm at sites other than the pericardium with no evidence of pericardial relapse. The main concomitant effects were mild local pain during tetracycline instillation in 4 patients, and transient fever (less than 39 degrees C) in 3. These data suggest that intracavitary oxytetracycline is perhaps less toxic and similar by successful as tetracycline hydrochloride in malignant pericardial tamponade.

Adult↗
PubMed1991

Actions of L-363,586, a cyclic hexapeptide analogue of somatostatin, on GH secretion by human somatotrophinoma cells in vitro.

L-363,586 is a cyclic, hexapeptide analogue of somatostatin-14 with potent inhibitory actions on rat growth hormone (GH) release in vitro. The studies reported here investigate the direct effects of L-363,586 on basal and growth hormone-releasing factor (GRF)-stimulated GH secretion from 3 human somatotrophinomas in dispersed cell culture. 1nM and 10nM L-363,586 inhibited both basal and GRF-stimulated GH release from cells of all 3 somatotrophinomas during a 2h treatment period, whilst 100nM L-363,586 had a prolonged inhibitory action on basal GH secretion from cells of 2 of the tumours throughout treatment and recovery periods. Rebound release of GH was observed with cells of 1 tumour following treatment with L-363,586 plus GRF. The actions of L-363,586 were similar to those of somatostatin-14. These data suggest that L-363,586 may have a role in the treatment of acromegaly.

Adenoma, Acidophil↗
PubMed1991

Time-resolved fluorescence emission and excitation spectroscopy of d(TA) and d(AT) using synchrotron radiation.

The photophysics of the sequence isomers d(TA) and d(AT) has been investigated at room temperature in 5 x 10(-5) M neutral aqueous solution using pulsed ultraviolet excitation from the ACO synchrotron and detection by time correlation or gated single-photon counting. Decay profiles of the emissions at 350, 400 and 460 have been analyzed both independently and globally by reiterative non-linear least-squares fitting to models of two and three independently emitting species. No evidence has been observed for excited-state reaction. Time-windowed spectra, both emission and excitation, have been collected for three time windows and have been deconvoluted to give time-resolved spectra using the lifetimes resulting from the decay analyses. Spectra are separated into two classes, with picosecond and nanosecond lifetimes, respectively. The picosecond spectra have the emission and excitation spectral characteristics of mixed monomer (A and T) fluorescences and are assigned as originating from the unstacked fractions of d(TA) and d(AT). The nanosecond emission spectra from d(TA) and d(AT) are both two-component, with lambda max approximately 350 and approximately 425 nm and lifetimes of 2.3 and 6.1 ns, respectively. The time-resolved excitation spectra for the nanosecond emissions are quite different from the isotropic absorption spectra of d(TA) and d(AT) but correlate with the anisotropic absorption for out-of-plane transitions between stacked bases of co-crystals of 9-methyladenine and 1-methylthymine reported by Stewart and Davidson. The nanosecond spectra thus represent the direct excitation and emission of stacked pairs of bases. These results provide no evidence for energy transfer and are probably related to sequence-specific photo-adduct formation.

Dinucleoside Phosphates↗
PubMed1991

Intercontinental spread of a multiresistant clone of serotype 23F Streptococcus pneumoniae.

Isolates of serotype 23F Streptococcus pneumoniae with high levels of resistance of penicillin have been commonly recovered in Spain for more than a decade. Recently penicillin-resistant serotype 23F S. pneumoniae strains were also isolated from children attending a day-care center in Cleveland. A number of Spanish and Cleveland isolates were compared by electrophoretic analysis of penicillin-binding protein (PBP) profiles and DNA restriction endonuclease cleavage profiles of the PBP 2X and 2B genes amplified with the polymerase chain reaction and by multilocus enzyme electrophoresis. All strains were identical by these criteria. The findings demonstrate that the Spanish and Cleveland isolates are clonally related and suggest that this antibiotic resistant clone of serotype 23F S. pneumoniae has spread intercontinentally from Spain to the United States.

Bacterial Proteins↗
PubMed1991

Mitomycin C as an adjuvant treatment to resected gastric cancer. A 10-year follow-up.

Seventy consecutive patients were entered in a two-arm randomized trial after surgical resection for locally advanced gastric cancer. In the first arm, 37 patients were included as a control group, receiving no further treatment after surgery. In the second arm, 33 patients were treated with adjuvant chemotherapy consisting of mitomycin C (MMC), 20 mg/m2 administered intravenously once every 6 weeks for four consecutive cycles. All patients in both arms were followed in the same way for 5 years. At 5 years 23 of 37 patients in the control arm and 7 of 33 patients in the treatment arm were dead because of relapse. Actuarial survival curve was statistically significant in favor of patients given adjuvant MMC (p less than 0.001). After 10 years follow-up, 31 of 37 patients in the control arm and 16 out of 33 patients in the treatment arm were dead because of relapse, the statistical differences continuing in the actuarial survival curve in favor of treated patients (p less than 0.01). The best advantages of adjuvant treatment were observed in the T3N0M0 stage. The most frequent relapse site was the peritoneal cavity and the relapse pattern shows special decrease in liver metastases in treated patients. Toxicity was acute and mild. No delayed toxicity or second malignancies were observed. These data suggest that adjuvant MMC after resected surgery of gastric cancer is a successful treatment and its effects are still evident after 10 years of follow-up.

Adult↗
PubMed1991

Horizontal transfer of multiple penicillin-binding protein genes, and capsular biosynthetic genes, in natural populations of Streptococcus pneumoniae.

Multiply antibiotic-resistant serotype 23F isolates of Streptococcus pneumoniae are prevalent in Spain and have also been recovered recently in the United Kingdom and the United States. Analysis of populations of these isolates by multilocus enzyme electrophoresis, and restriction endonuclease cleavage electrophoretic profiling of penicillin-binding protein (PBP) genes, has demonstrated that these isolates are a single clone (Muñoz et al., 1991). Here we report studies of non-serotype 23F penicillin-resistant pneumococci isolated in Spain and the United Kingdom. One of the isolates expressed serotype 19 capsule but was otherwise indistinguishable from the serotype 23F clone on the basis of multilocus enzyme electrophoresis, antibiotic resistance profiling, and restriction endonuclease patterns of genes encoding PBP1A, PBP2B and PBP2X, a result which suggests that horizontal transfer of capsular biosynthesis genes had occurred. These same techniques revealed that six other resistant isolates, all expressing serotype 9 polysaccharide capsule, represent a clone. Interestingly, the chromosomal lineage of this clone is not closely related to the 23F clone; however, the serotype 9 and 23F clones harbour apparently identical PBP1A, -2B and -2X genes. To explain these data, we favour the interpretation that horizontal gene transfer in natural populations has distributed genes encoding altered forms of PBP1A, -2B and -2X to distinct evolutionary lineages of S. pneumoniae.

Alleles↗
PubMed1991

On the evidence from high-intensity two-photon laser photolysis for energy transfer from high-lying quasi-Rydberg states of thymine to iso-energetic states of water.

High intensity two-photon picosecond excitation at 266 nm (effective energy 9.2 eV) has been shown to cause efficient photolysis of thymine in aqueous solution. Experimental results for the quantum yield of solvated electrons, phi (eaq-), and the net consumption of thymine, phi(-Thy) have been interpreted (Oraevsky and Nikogosyan, 1985) as indicating a stoichiometric excess of solvated electrons over thymine radical-cations. To account for this under conditions in which direct two-photon photolysis of water is negligible, it has been concluded that it is necessary to postulate the occurrence of extensive energy transfer from high-lying thymine states to dissociating/ionizing states of water. This Note demonstrates that: (i) the supposed excess of eaq- depends on an implicit assumption concerning the secondary radical reactions (dimerization) such that -delta Thy = delta Thy+; if secondary radicals dismutate then -Thy = 1/2 delta Thy+, leading a stoichiometric deficit of eaq-; and (ii) the experimental results can be accounted for by a mixed dimerization/dismutation mechanism, without invoking energy transfer. Thus there is no evidence unambiguously requiring the postulate of energy transfer. But if it occurs, stoichiometry places restrictions on the extent of transfer and the nature of the secondary radical reactions.

Energy Transfer↗
PubMed1991

Adjuvant treatment in stage I and II malignant melanoma: a randomized trial between chemoimmunotherapy and immunotherapy.

A randomized trial comparing chemoimmunotherapy (bacillus Calmette-Guérin + chemotherapy) and immunotherapy (bacillus Calmette-Guérin alone) was carried out in high-risk stage I and II malignant melanoma patients. Eight-two evaluable patients were included. The follow-up median duration was 11 years. Recurrent melanoma developed in 28 patients (34%). The overall survival rate was 76% at 5 years and 65% at 10 years. There were no statistical differences in survival probability or disease-free survival (DFS) probability between the two treatment groups. Survival and DFS were also analyzed in relation to various prognostic factors. Statistically significant differences were only seen in a subset of 33 patients with lower limb malignant melanoma, the prognosis being better for the chemoimmunotherapy group in this location. Because of the small number of patients in each group, a week positive effect of either of these two treatments cannot be ruled out. Chemoimmunotherapy only seems to improve the prognosis of stage I or II malignant melanoma of the legs.

Adult↗
PubMed1991

Effects of insulin-like growth factor-II on growth hormone release from human somatotrophinoma cells in vitro.

Insulin-like growth factor-I (IGF-I) and IGF-II receptors have previously been demonstrated on membranes prepared from human somatotrophinomas. IGF-I has been shown to have a variable effect on GH secretion by these tumours in vitro. The effects of purified IGF-II on GH secretion have not been described. We have studied the direct actions of human recombinant IGF-II on GH release from eight somatotrophinomas cultured in vitro. Somatotrophinoma cells were cultured as monolayers at a density of 10(5) cells/0.5 ml. Treatment with IGF-II for 4 and 24 h resulted in discrete inhibitory effects on GH release from two tumours (tumour 5: 4 h, IGF-II 0.5 nmol/l; tumour 2; 24 h, IGF-II 1 nmol/l). Treatment with IGF-II for 24 h resulted in significant inhibitory effects on GH release from one tumour over a range of concentrations tested (IGF-II 0.5-10 nmol/l). Addition of human GH-releasing factor (hGRF) (1-44) (20 nmol/l) for 4 and 24 h resulted in stimulation of GH release by five tumours. Two tumours demonstrated significant inhibitory effects of IGF-II on GRF-stimulated GH release (tumour 2: 24 h, IGF-II 1-5 nmol/l; tumour 3; 4 h, IGF-II 5 nmol/l; 24 h, IGF-II 0.5-50 nmol/l). These data emphasize the heterogeneity of somatotrophinomas in terms of their response to modulators of GH secretion. IGF-II does not appear to have a modulatory role on GH release by most somatotrophinomas.

Adult↗
PubMed1991

The use of role-play in teaching medical students obstetrics and gynaecology.

There is a great need to review and critically assess medical education. Role-play has seen increasing use as an educational tool. We investigated its role in a 'conventional speciality', Obstetrics and Gynaecology. This is a part of the medical curriculum where communication skills are particularly important, but difficult to learn in practice. Twenty-one medical students took part in three role-play case studies. An innovation we implemented was the use of 'time outs' which could be called at any time through a session. After the exercise students were required to complete a questionnaire designed to probe their attitudes towards the experience. The results indicate that this technique can be successfully used in teaching a conventional speciality. Unlike some previous studies we also found this to be a satisfactory tool in teaching the factual part of the course. We found the 'time out' innovation to be an important aid. We argue that there is an important niche for role-play in medical education.

Clinical Competence↗
PubMed1990

A structured interview version of the Hamilton Depression Rating Scale: evidence of reliability and versatility of administration.

A structured interview version of the Hamilton Depression Rating Scale (SI-HDRS) is described. Data are presented in support of its inter-rater and internal consistency reliability. SI-HDRS scores were reproducible by trained interviewers who lacked psychiatric backgrounds. Test-retest scores of a subset of patients who were interviewed twice (once in person and once by telephone) were highly correlated. Scores on the SI-HDRS did not differ between face-to-face and telephone administration groups, controlling for demographic factors, depression-specific indicators, and social and physical functioning. Since the SI-HDRS does not require a face-to-face interview by an experienced clinician, this instrument can be used economically in large-scale, community-based research projects.

Adult↗
PubMed1990

Surgeons' knowledge, attitude, and use of preoperative autologous blood donation.

Before a comprehensive educational program on preoperative autologous blood donation was begun, 118 surgeons from three different areas of the country were tested to assess their baseline knowledge and attitude about this practice. Test results were correlated with the percentage of eligible patients that the surgeons actually referred for preoperative donation during a period of observation. The purpose of this preliminary effort was to identify areas in the educational program that required emphasis. Overall, the surgeons' attitude toward preoperative donation was quite favorable, but their depth of knowledge varied. Misunderstandings may have led to diminished use of this service (eg, about 50% didn't realize that many patients with medical conditions or low hematocrits are permitted to donate). However, it is not clear that simply bolstering surgeons' knowledge will increase their appropriate use of preoperative donation. When all 118 surgeons were studied, their knowledge and attitude were unrelated to the percentage of eligible patients referred. However, when 44 surgeons who managed the largest number of eligible patients were analyzed separately, their use of preoperative donation was directly correlated with their knowledge and attitude. The local awareness of AIDS also significantly influenced the use of this service. It is proposed that knowledge of preoperative donation may be important for inducing surgeons to begin referring patients for this service. Once a pattern of successful participation is established, referral seems to increase with the acquisition of working knowledge.

Blood Transfusion, Autologous↗