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Biomedical subjects

S Block

Publications and source records attributed to S Block.

At least 19 recordsLinked to original sources

ent-trachyloban-3beta-ol, a new cytotoxic diterpene from Croton zambesicus.

The dichloromethane extract of leaves of Croton zambesicus (Euphorbiaceae) showing in vitro cytotoxicity against human cervix carcinoma cells was investigated in order to identify its active compounds. A bio-guided fractionation by HSCCC followed by MPLC led us to isolate a trachylobane diterpene, ent-trachyloban-3beta-ol, with cytotoxic properties (IC50 on HeLa cells = 7.3 microg/ml). This is the first report on the cytotoxicity of a trachylobane diterpene.

Antineoplastic Agents↗

Cytotoxic aporphine alkaloids from Cassytha filiformis.

Purification of a cytotoxic crude alkaloid extract of Cassytha filiformis led to the isolation of four known aporphine alkaloids: neolitsine, dicentrine, cassythine (= cassyfiline) and actinodaphnine. Their structures were determined by analysis of spectroscopic data. All isolated alkaloids were tested for their cytotoxic activities on cancer and non-cancer cell lines in vitro. Neolitsine was the most active against HeLa and 3T3 cells (IC 50 :21.6 microM, and 21.4 microM, respectively). Cassythine and actinodaphnine showed the highest activity against Mel-5 (IC 50 : 24.3 microM and 25.7 microM, respectively) and HL-60 (IC 50 : 19.9 microM and 15.4 microM, respectively). This is the first report on the cytotoxic activity of C. filiformis extract and of neolitsine and cassythine. Furthermore, the complete NMR data of cassythine and actinodaphnine are given here for the first time.

3T3 Cells↗

[Characterization of therapy failures in radioiodine therapy of Graves' disease without simultaneous antithyroid agents].

UNLABELLED: Aim of this study was a characterization of radioiodine therapy (RIT) failures in Graves' disease without simultaneous carbimazole. METHOD: 226 patients with a confirmed diagnosis of Graves' disease received 686.8 +/- 376.4 MBq of iodine-131 orally for thyroid ablation. Target dose was 250 Gy. All patients were followed up for 6 months. Therapy failures were compared with successes regarding possible influencing variables initial thyroid volume, thyroid function, immune activity (TRAb), I-131 uptake, effective half-life, absorbed energy dose, age and gender. RESULTS: 212 of 226 patients (93.8%) were treated successfully, 14 (6.2%) showed a hyperthyroidism relapse within 6 months which required a second radioiodine therapy. A success rate of 92.5% (62/67) could also be achieved with 67 patients who were hyperthyroid at the time of RIT. Compared to the therapy successes, the 14 failures achieved significantly lower absorbed doses (223.8 +/- 76.6 Gy vs. 285.2 +/- 82.1 Gy, p < 0.005), but with no significant differences regarding age, thyroid volume, function or TRAb (all p > 0.2). Of the 14 failures, n = 8 reached an absorbed dose < 200 Gy and n = 1 a dose < 250 Gy, although 5 of the failures reached an absorbed dose of > 250 Gy. Stepwise logistic regression revealed only absorbed energy dose as a variable significantly influencing therapy success (p < 0.005), but no influence of initial thyroid volume, function, TRAb value, age (all p > 0.2) or gender (p = 0.13). Two-tailed Fisher's exact test showed no significant influence of gender on success rates (failures/successes: male 1/36, female 13/176, p = 0.48). CONCLUSIONS: Except for the absorbed energy dose, no other significant variable influencing the outcome of radioiodine therapy in Graves' disease without simultaneous carbimazole could be found. It should be noted, though, that 5 therapy failures (2.2%) reached an absorbed energy dose of > 250 Gy.

Adult↗

[An approach for comparative quantification of myocardial blood flow (O-15-H2O-PET), perfusion (Tc-99m-tetrofosmin-SPECT) and metabolism (F-18-FDG-PET)].

AIM: In the present study a new approach has been developed for comparative quantification of absolute myocardial blood flow (MBF), myocardial perfusion, and myocardial metabolism in short-axis slices. METHODS: 42 patients with severe CAD, referred for myocardial viability diagnostics, were studied consecutively with 0-15-H2O PET (H2O-PET) (twice), Tc-99m-Tetrofosmin SPECT (TT-SPECT) and F-18-FDG PET (FDG-PET). All data sets were reconstructed using attenuation correction and reoriented into short axis slices. Each heart was divided into three representative slices (base, midventricular, apex) and 18 ROIs were defined on the FDG PET images and transferred to the corresponding H2O-PET and TT-SPECT slices. TT-SPECT and FDG-PET data were normalized to the ROI showing maximum perfusion. MBF was calculated for all left-ventricular ROIs using a single-compartment-model fitting the dynamic H2O-PET studies. Microsphere equivalent MBF (MBF_micr) was calculated by multiplying MBF and tissue-fraction, a parameter which was obtained by fitting the dynamic H2O-PET studies. To reduce influence of viability only well perfused areas (> 70% TT-SPECT) were used for comparative quantification. RESULTS: First and second mean global MBF values were 0.85 ml x min-1 x g-1 and 0.84 ml x min-1 x g-1, respectively, with a repeatability coefficient of 0.30 ml x min-1 x g-1. After sectorization mean MBF_micr was between 0.58 ml x min-1 x ml-1 and 0.68 ml x min-1 x ml-1 in well perfused areas. Corresponding TT-SPECT values ranged from 83% to 91%, and FDG-PET values from 91% to 103%. All procedures yielded higher values for the lateral than the septal regions. CONCLUSION: Comparative quantification of MBF, MBF_micr, TT-SPECT perfusion and FDG-PET metabolism can be done with the introduced method in short axis slices. The obtained values agree well with experimentally validated values of MBF and MBF_micr.

Coronary Circulation↗

[Angiomyolipoma of the liver].

HISTORY AND ADMISSION FINDINGS: A 66-year-old woman, known for 4 years to have a space-occupying lesion in the liver thought to be a lipoma, was admitted because the increasing size of the mass. She was hypertensive and had recurrent supraventricular tachycardia, but was otherwise asymptomatic and physical examination was unremarkable. INVESTIGATIONS: Laboratory tests were within normal limits. Abdominal ultrasound demonstrated a well-circumscribed, echodense space-occupying lesion. Magnetic resonance imaging revealed a hyperintense encapsulated tumour with contrast-medium enhancement. DIAGNOSIS AND TREATMENT: Because the imaging tests were equivocal, a segmental liver resection was performed to exclude malignancy. Histological examination revealed an angiomyolipoma of the liver. CONCLUSION: Angiolipoma is a benign mixed-cell tumour that very rarely affects the liver but must be included in the differential diagnosis of hepatic space-occupying lesions. Its manifestations may be highly variable and histological examination is required if there is any uncertainty about possible malignancy. If the biopsy is diagnostic of a benign lesion, expectant observation with regular monitoring is indicated.

Aged↗

Implantable spinal fusion stimulator: assessment of MR safety and artifacts.

The objective of this investigation was to perform magnetic resonance (MR) imaging safety and artifact testing of an implantable spinal fusion stimulator. Magnetic field interactions, artifacts, and operational aspects of an implantable spinal fusion stimulator were evaluated in association with a 1.5 T MR system. Magnetic field-related translational attraction was measured using the deflection angle test. A special test apparatus was used to determine torque at 4.7 T. Artifacts were characterized using fast multiplanar spoiled gradient-echo, T1-weighted spin-echo, and T1-weighted fast spin-echo sequences. Operational aspects of the implantable spinal fusion stimulator before and after exposure to MR imaging at 1.5 T were assessed. In addition, nine patients (six lumbar spine and three cervical spine) with implantable spinal fusion stimulators underwent MR imaging. The findings indicated that magnetic field interactions were relatively minor, artifacts were well characterized and should not create diagnostic problems, and there were no changes in the operation of the spinal fusion stimulator. The nine patients underwent MR procedures without substantial adverse events or complaints. Based on the results of this investigation and in consideration of the findings from previous studies of MR imaging safety for the implantable spinal fusion stimulator, MR imaging may be performed safely in patients using MR systems operating at 1.5 T or less following specific recommendations and precautions.

Artifacts↗

Renal handling of drugs in the healthy elderly. Creatinine clearance underestimates renal function and pharmacokinetics remain virtually unchanged.

OBJECTIVE: It is commonly assumed that renal function, and in parallel the excretion of drugs, is considerably reduced in the elderly. Endogenous creatinine clearance or indirect estimates of this parameter are generally recommended for adapting drug dosage. The present study evaluates the validity of both assumptions. METHODS: We compared pharmacokinetics (and pharmacodynamics) of 50 mg atenolol, 800 mg piracetam and 25 mg hydrochlorothiazide plus 50 mg triamterene in ten healthy young [25 (2) years] and 11 healthy elderly subjects [68 (5) years]. Inulin (Cin) and para-aminohippurate [PAH (CPAH)] clearance (infusion clearance technique), endogenous (C(Cr)) and calculated (Cockroft-Gault) creatinine clearance, analysis of drugs and their metabolites (HPLC), were performed. Renal haemodynamics and the pharmacokinetics of beta-adrenergic blocking agent, diuretics and the nootropic agent piracetam, respectively, were measured on separate days. RESULTS: Cin was significantly (P < 0.01) lower in the healthy elderly subjects [104 (12) vs 120 (14) ml x min(-2) x 1.73 m(-2) in the young], but remained within the normal range (> 90 ml x min(-2) x 1.73 m(-2)). In contrast, C(Cr) was even lower in healthy elderly subjects [95 (24) vs 121 (20) ml x min(-1) in the young], and the Cockroft-Gault clearance underestimated true glomerular filtration rate (GFR) even more seriously [74 (17) vs 122 (16) ml min(-1)]. For atenolol the mean area under the curve (AUC) was similar in both groups [3.16 (0.48) microg x h(-1) x ml(-1) in the elderly vs 3.01 (0.30) in the young], as was the mean maximal plasma concentration [0.42 (0.07) vs 0.44 (0.06) microg x ml(-1)], but the proportion of the drug excreted in urine was marginally (P < 0.025) lower in the elderly. Similar results were obtained for hydrochlorothiazide, whereas no marked differences between the groups were found for triamterene and its metabolite. Furthermore, the pharmacodynamic action of diuretics was not significantly altered in the elderly. CONCLUSIONS: The true GFR of the healthy elderly remains within the normal range and is underestimated by creatinine clearance and more so by its surrogate (Cockroft-Gault clearance). In parallel, pharmacokinetics of renally excreted drugs are not affected in the healthy elderly to a clinically significant extent. For drugs with a narrow therapeutic window, indirect estimates of GFR appear to be an unreliable means for calculating correct dosage in the elderly.

Adrenergic beta-Antagonists↗

Nurturing humanism through teaching palliative care.

After many years of neglect by the medical establishment, the discipline of palliative medicine is finally moving into academic health centers (AHCs). While hospice programs have cared for dying patients in the community for years with little input from mainstream medicine, palliative care is gaining a foothold in AHCs, challenging these centers to integrate the hospice approach with biomedicine. The discipline of palliative care promises to be a rich source of learning and growth for physicians-in-training. Teaching about palliative care affirms two essential but vulnerable dimensions of the practice of medicine--the importance of relationship-centered care and the value of doctoring as a source of meaning and growth for physicians. In addition to fostering fundamental humanistic learning, palliative medicine is an excellent vehicle for teaching basic but often neglected clinical competencies, including pain and symptom control, communication, and working as part of a health care team. Because palliative care settings offer extraordinary learning opportunities, the authors recommend that clinical experiences in palliative care be integrated into the core curricula of all medical schools as well as appropriate residency programs.

Academic Medical Centers↗

[Granisetron (per os) compared with ondansetron (per os) in the prevention of nausea and vomiting induced by mildly emetogenic chemotherapies. Groupe de Recherches en Cancerologie du Nord].

It is a randomised cross-over multicenter study comparing the efficacy and the tolerance of granisetron (Gra) 1 mg and ondansetron (Ond) 8 mg, oral, given during two consecutive cycles to 188 naive patients scheduled to receive a moderately emetogenic chemotherapy. The antiemetic treatment is given one day per course, 1 hour before chemotherapy and the second administration from 8 to 12 hours after the beginning, during each of the two cycles; alternatively according to the randomisation. Five criteria are assessed; nausea (ordinal and visual analogic scales), emeric episodes (vomiting orland retching), complete response (minor or no nausea, no emetic episode and no rescue treatment), patient preference and tolerance. The intent to treat analysis showed no significant difference at cycle 1 between Gra and Ond; at cycle 2, there is no significant difference in the number of emetic episodes; for the prevention of nausea, the ordinal scale shows a significant difference (p = 0.028 in favour of Gra at day 1 (D1) but not from D2 to D5. Gra induced more complete response than Ond at D1 (p = 0.028), but not from D2 to D5. The cross-over study did not show any period or order effect, whereas a treatment effect on Ond was significant in favour of Gra (p = 0.01). There is no significant patients preference in favour of Gra or Ond. In conclusion, Gra was more efficient in preventing nausea and obtaining complete response on the first day of treatment, significantly at the second cycle. Both Gra and Ond had a good antiemetic activity for moderately emetogenic chemotherapy with complete response rates always over 50% on day 1; delayed emesis remain less weli controlled.

Adult↗

Palliative care in undergraduate medical education. Status report and future directions.

OBJECTIVE: To describe the status of palliative care education in the undergraduate medical curriculum and to offer recommendations for improvement. DATA SOURCES: Review of literature on palliative care and of recently submitted grants on medical education for end-of-life care. STUDY SELECTION: English-language reports of educational programs targeted toward medical students were examined, as well as surveys of medical schools. DATA EXTRACTION: Studies were reviewed by the authors to assess the quality of the educational program, evaluation methodology, and conclusions. From over 9000 citations on palliative care and related topics that were retrieved from MEDLINE searches from 1980 through 1995, and from reviewing 14 palliative care journals published from 1985 through 1996, 310 articles were identified that addressed medical education for end-of-life care, and 180 were carefully examined. DATA SYNTHESIS: While nearly all medical schools offer some formal teaching about end-of-life care, there is considerable evidence that current training is inadequate, most strikingly in the clinical years. Teaching about palliative care is received favorably by students, positively influences student attitudes, and enhances communication skills. However, curricular offerings are not well integrated; the major teaching format is the lecture; formal teaching is predominantly preclinical; clinical experiences are mostly elective; there is little attention to home care, hospice, and nursing home care; role models are few; and students are not encouraged to examine their personal reactions to these clinical experiences. CONCLUSIONS: The increasing attention to palliative care education has created major opportunities for improving education about care at the end of life. Educational programs should be rigorously evaluated to identify best educational practices.

Cultural Diversity↗

Renal function in the elderly: impact of hypertension and cardiac function.

In senescence renal function is thought to decline markedly even in the absence of renal disease. It has also been proposed that the changes in renal function with age are not uniform and that confounding factors such as hypertension or atherosclerosis may play a role. We performed a comprehensive study to compare several aspects of renal function in four groups: (i) young healthy normotensive subjects (N = 24; 13 males; mean age 26 +/- 3 years); (ii) elderly healthy normotensive subjects (elderly NT; N = 29; 13 males; 68 +/- 7 years); (iii) elderly treated and untreated hypertensive patients (elderly HT; N = 25; 13 males; 70 +/- 6 years); and (iv) elderly patients with compensated mild to moderate heart failure (elderly HF; N = 14; 6 males; 69 +/- 6 years). Compared to young subjects mean GFR (C(In)) and ERPF (C(PAH)) were significantly lower in the elderly, despite similar mean plasma creatinine levels (young, 121 +/- 11, 650 +/- 85 ml/min/1.73 m2; elderly NT, 103 +/- 11, 486 +/- 102; elderly HT, 103 +/- 13, 427 +/- 55; elderly HF, 92 +/- 14, 377 +/- 103). Nevertheless, GFR was within the normal range in the majority of elderly NT and HT, but not in elderly HF. ERPF was significantly lower in elderly HT as compared with elderly NT, and still lower in elderly HF. Mean renovascular resistance and filtration fraction were significantly higher in the elderly, particularly in elderly HT and HF as compared with the young. Mean fractional excretion of Na+ was similar in all groups studied, but the lithium clearance was significantly lower in the elderly, suggesting a greater proximal and less distal sodium reabsorption in senescence. In the elderly, mean PTH concentration and urinary excretion of pyridoline cross-links were significantly higher and mean 25-(OH)D3, calcitriol and phosphate concentrations significantly lower; the correlation between PTH and GFR was significant (r = -0.432, P < 0.001). The results document that the decrease in renal hemodynamics with senescence is less marked than suggested by some studies using less stringent methodology and inclusion criteria. Comorbid conditions confound renal function in the elderly. Age-associated changes in renal hemodynamics are accompanied by significant alterations of renal hormones and of renal sodium handling.

Adult↗

Infant immunization with pneumococcal CRM197 vaccines: effect of saccharide size on immunogenicity and interactions with simultaneously administered vaccines.

Six pentavalent pneumococcal conjugate vaccines (Pn-CRM197) were evaluated among 400 infants. The vaccines differed in saccharide chain length (oligosaccharide [OS] or polysaccharide [PS]) and saccharide quantity (0.5, 2, or 5 microg). Subjects were randomized into groups 1-6 (Pn-CRM197 recipients) or 7 (controls) for immunization at 2, 4, and 6 months of age. Pn-CRM197 were well tolerated and elicited mean antibody concentrations that exceeded those in controls for all 5 capsular serotypes. PS formulations were generally more immunogenic than their OS counterparts. For PS vaccines, a dose-response was documented (5 microg > 2 microg > 0.5 microg), but the differences between the 5- and 2-microg formulations were insignificant. The mean anti-PRP antibody concentration was significantly higher among Pn-CRM197 recipients. It is concluded that PS vaccines are more immunogenic than OS vaccines. The improved immunogenicity from Haemophilus type b oligosaccharide conjugate (HbOC) vaccine when given with Pn-CRM197 suggests that a decreased dose of HbOC vaccine may be sufficient to elicit protection.

Antibodies, Bacterial↗

Mycoplasma pneumoniae and Chlamydia pneumoniae in pediatric community-acquired pneumonia: comparative efficacy and safety of clarithromycin vs. erythromycin ethylsuccinate.

We evaluated 260 previously healthy children ages 3 through 12 years who had clinical signs and symptoms of pneumonia, radiographically confirmed. Patients were randomized 1:1 to a 10-day course of either clarithromycin suspension 15 mg/kg/day divided twice a day or erythromycin suspension 40 mg/kg/day divided twice a day or three times a day. Evidence of infection with Chlamydia pneumoniae was detected in 28% (74) of patients: 13% (34) by nasopharyngeal culture and 18% (48) by serology with the microimmunofluorescence assay. Evidence of infection with Mycoplasma pneumoniae was detected in 27% (69) of patients: 20% (53) by nasopharyngeal culture or polymerase chain reaction and 17% (44) by serology with the use of enzyme-linked immunosorbent assay. Serologic confirmation of infection was observed in 23% (8) and 53% (28) of patients with bacteriologically detected C. pneumoniae and M. pneumoniae, respectively. Treatment with clarithromycin vs. erythromycin, respectively, yielded the following outcomes: clinical success 98% (121 of 124) vs. 95% (105 of 110); radiologic success 98% (109 of 111) vs. 94% (92 of 110); and eradication by pathogen, C. pneumoniae 79% (15 of 19) vs. 86% (12 of 14) and M. pneumoniae 100% (9 of 9) vs. 100% (4 of 4). Adverse events were primarily gastrointestinal occurring in almost one-fourth of patients in both groups, and were mild to moderate in severity. Clarithromycin and erythromycin were similarly effective and safe for the treatment of radiographically proved, community-acquired pneumonia in children older than 2 years old.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗