Hyperfractionated-accelerated or conventionally fractionated radiotherapy for early glottic cancer.

PURPOSE: To evaluate the effect of shortening overall treatment time by hyperfractionated-accelerated radiotherapy for T2N(0)M(0) glottic carcinomas. Results for local control and survival were calculated and compared to those for T1N(0)M(0) tumors treated with a once-a-day fractionated schedule. METHODS AND MATERIALS: Between 1990 and 1998, 92 patients with T1N(0)M(0) and 45 patients with T2N(0)M(0) glottic cancers were treated with radical radiotherapy. The T1N(0)M(0) tumors were treated with a once-a-day fractionated schedule lasting 6.5 weeks to a total dose of 62.4 Gy. The T2N(0)M(0) tumors received a split-course hyperfractionated-accelerated treatment over a total of 4.5 weeks to a total dose of 64.6 Gy.Results: The 5-year local control was 85% for T1N(0)M(0) and 88% for T2N(0)M(0), whereas the 5-year locoregional control was 85% for both groups. The 5-year overall survival was 70% and 53% for T1N(0)M(0) and T2N(0)M(0), respectively. No significant statistical difference was found between the two groups for the parameters analyzed. The number of serious late complications was few and comparable for the two groups. CONCLUSIONS: Hyperfractionated-accelerated radiotherapy proved beneficial for T2N(0)M(0) glottic cancer, giving local control rates comparable to those for T1N(0)M(0) tumors.     

Tamoxifen Impairs Both Longitudinal and Cortical Bone Growth in Young Male Rats

Tamoxifen (Tam) has been used experimentally to treat boys with gynecomastia and girls with McCune‐Albright syndrome. This drug was recently shown to inhibit the growth of cultured fetal rat metatarsal bones and thus might also affect bone growth in vivo. Four‐week‐old Sprague‐Dawley rats were gavaged daily with vehicle alone (peanut oil), Tam (40 mg/kg/d; 1 or 4 wk), or estradiol (40 μg/kg/d; 4 wk). Five of the 10 rats in each group were killed after 4 wk and the other five after 14 wk of recovery. Bone growth was followed by repeat DXA scans, whereas other bone parameters and spine length were evaluated by pQCT and X‐ray at the time of death. Four‐week Tam treatment significantly decreased body weight, nose‐anus distance, spinal and tibial bone lengths, trabecular BMD, cortical periosteal circumference, and bone strength and also reduced serum IGF‐I levels (424 ± 54 versus 606 ± 53 ng/ml in control; p < 0.05). Analysis of the tibial growth plate of treated rats showed elevated chondrocyte proliferation (BrdU) and apoptosis (TUNEL), as well as decreases in the number of hypertrophic chondrocytes and in the size of terminal hypertrophic chondrocytes. Despite a complete catch‐up of body weight after 14 wk of recovery, the tibia was still shorter (p < 0.001) and its cortical region was smaller. We conclude that, when administered at a clinically relevant dose, Tam causes persistent retardation of longitudinal and cortical radial bone growth in young male rats. Our findings suggest that this inhibition results from local effects on the growth plate cartilage and systemic suppression of IGF‐I production. Based on these rat data, we believe that Tam, if given to growing individuals, might compromise cortical bone growth, bone strength, and adult height.     

Treatment of myelodysplastic syndromes with recombinant human erythropoietin.

12 patients with myelodysplastic syndromes were treated with recombinant human erythropoietin (r-epo). 5 patients had stable anemia, 78-92 g/l, and 7 were transfusion-dependent. In 11 patients, r-epo was given intravenously three times a week, with dose escalation after 4 and 8 wk if hemoglobin did not increase more than 15 g/l. The doses were 600, 1500 and 3000 U/kg bodyweight/wk. The 12th patient was treated subcutaneously with a dose of 560 U/kg/wk. 3 patients showed a significant response with an increase in hemoglobin of greater than or equal to 15 g/l. 2 of these had stable anemia before treatment and increased in hemoglobin from 87 to 116 g/l and from 80 to 99 g/l, respectively. The 3rd patient was transfusion-dependent and rose to a stable hemoglobin level between 76 and 80 g/l without transfusions. 2 patients showed a reduction of their transfusion need. Mean initial serum erythropoietin in the responding group was 366 U/l compared to 1049 among the non-responders (p = 0.367). Response was observed in 5/7 patients without bone marrow sideroblasts and in 0/5 patients with sideroblasts (p = 0.027). Erythropoietin seems to be an effective and well-tolerated treatment for a certain proportion of patients with MDS. A larger patient material might provide a model for predicting responses.     

Synthesis and antiviral activity of 3'-heterocyclic substituted 3'-deoxythymidines

Various 3'-deoxythymidine analogues with an heterocyclic five-membered ring in the 3'-erythro position have been synthesized. The pyrrol-1-yl (3) and the 1,2,4-triazol-4-yl (5) compounds were synthesized from 1-(3-amino-2,3-dideoxy-beta-D-erythro-pentofuranosyl)thymine. The pyrazol-1-yl (16a), imidazol-1-yl (16b), and 1,2,4-triazol-1-yl (16c) derivatives were obtained by epoxide opening of the corresponding 1-(2,3-anhydro-beta-D-lyxofuranosyl)thymines followed by 2'-deoxygenation. Only the 3'-pyrrol-1-yl derivative showed marginal antiviral activity against human immunodeficiency virus.     

Chronic Hemofiltration

The experiences which have been compiled in more than 2400 hemofiltrations confirm that this method represents an alternative way of treating uremic patients. The main advantages of chronic hemofiltration are the comfort of the patient and the ease in handling excess overhydration without extending treatment time, which is less than 3 × 3 hours/week if adequate hemofilters are used. With regard to the improvement of such typical uremic complications as severe hypertension, hypertriglyceridemia or neuropathy, hemofiltration does not seem to be superior to hemodialysis. However, since most hemofiltration patients do not require phosphate binders and, additionally, remarkable amounts of parathyroid hormone are removed during one hemofiltration, it appears possible that hemofiltration might be an important therapeutic alternative for those renal patients who suffer from severe hyperphosphatemia and secondary hyperparathyroidism.     

Painful and non-painful neuropathy in HIV-infected patients: an analysis of somatosensory nerve function.

Fifteen to 50% of AIDS-patients suffer from distal predominantly sensory neuropathy (DSP), which is commonly associated with painful symptoms. In the present study, we have focused on the function of fine calibre nerve channels, in 36 consecutive HIV-1-infected patients with painful (PPN) (n=20; 54%) and non-painful (PN) (n=16) sensory neuropathy, assessed by clinical, quantitative thermal testing (QTT) (31/36), and peripheral nerve conduction examination (32/36). Control QTT data were obtained from 49 healthy subjects with a corresponding age- and sex distribution. Demographics, antiviral treatment, immunological status, and nerve conduction examination did not differ between patients with and without painful symptoms. Hypoaesthesia to warmth, cold, and heat pain was observed in both neuropathy groups when compared to healthy controls. However, the perception threshold to warmth was more often impaired (p<0.01) and the level of impairment was more pronounced (p<0.001) in patients with painful neuropathy. Furthermore, increased pain sensitivity to cold was found only in patients with painful symptoms (p<0.05). An abnormal outcome of any QTT parameter was found in all patients with pain, but only among 62% of patients without pain, p<0.01, and the cumulative frequency of abnormalities in any of the four thermal percepts (warmth, cold, heat pain, and cold pain) was higher in patients with painful symptoms, p<0.0001. This study demonstrates a more pronounced impairment of C-fibre-mediated innocuous warm perception in patients with painful neuropathy, which in the setting of impaired or absent heat pain perception suggests a more generalised loss of function in somatosensory C-fibre channels.