Concomitant radiotherapy with mitomycin C and bleomycin compared with radiotherapy alone in inoperable head and neck cancer: final report

Purpose: To compare the efficacy of concomitant irradiation with mitomycin C and bleomycin in patients with inoperable head and neck carcinoma with radiotherapy alone.

Methods and materials: Between March 1991 and December 1993, 64 patients with inoperable head and neck carcinoma (41 with oropharyngeal site) were randomized to radiotherapy alone (group A) or radiotherapy combined with simultaneous application of mitomycin C and bleomycin (group B). In both groups patients were irradiated five times weekly with 2 Gy to a total dose of 66–70 Gy. The planned concomitant treatment in group B was: bleomycin 5 units twice a week IM, total dose 70 units, mitomycin C 15 mg/m² IV after delivery of 10 Gy, and 10 mg/m² IV on the last day of radiotherapy. To enhance the effect of these two drugs, patients received also nicotinamide, chlorpromazine, and dicoumarol.

Because significantly better results were achieved in arm B for patients with inoperable oropharyngeal carcinoma, the study was closed and such patients were after December 1993 routinely treated with the combined therapy (as in arm B). Until October 1996, we treated and followed up 48 such consecutive patients.

Results: Median follow-up of our study patients is 42 months. Complete remission (CR) rate in group A was 31% and in group B 59% (p = 0.04); disease-free survival (DFS) in group A was 8% and in group B 37% (P = 0.01); and overall survival (OS) was 7% in group A and 26% in group B (p = 0.08). CR rate for patients with oropharyngeal carcinoma was 29% in group A (N = 21) and 75% in group B (N = 20) (p = 0.007); DFS in group A was 10% and in group B 48% (p = 0.001); and the OS was 10% in group A and 38% in group B (p = 0.019). In patients with inoperable oropharyngeal carcinoma treated after December 1993, complete remission was achieved in 32/48 (67%, 95% CI: 52%–80%). DFS at the median follow-up of 14 months was 60% (95% CI 43–77%) and OS 58% (95% CI 42–74%).

Conclusion: From the results of our study it seems that the concomitant treatment significantly improves CR rate, DFS, and OS in patients with inoperable oropharyngeal carcinoma in comparison with radiotherapy alone.     

Kinetics of lactose fermentation in milk with kombucha starter

The aim of this research was to investigate the effect of new, non-conventional starter culture on the kinetics of the lactose transformation during milk fermentation by kombucha, at pH 5.8; 5.4; 5.1; 4.8; and 4.6, at two different temperatures 37 °C and 42 °C. Milk fermentation at 42 °C lasted significantly shorter (about 5 h, 30 min) compared to the fermentation at 37 °C. Changes of lactose concentration at the both temperatures are consisting of two retaining stages and very steep decline in–between. The analysis of the rate curves showed that the reaction rate passes through the maximum after 9 h, 30 min at 37 °C and after 4 h at 42 °C. The sigmoidal saturation curve indicates a complex kinetics of lactose fermentation by kombucha starter.     

The Evolution of Transcranial Laser Therapy for Acute Ischemic Stroke, Including a Pooled Analysis of NEST-1 and NEST-2

Intravenous tissue plasminogen activator is the only proven therapy for acute ischemic stroke. Not enough patients are eligible for treatment and additional new therapies are needed. Recently, laser technology has been applied to acute ischemic stroke. This noninvasive technique uses near-infrared wavelengths applied to the scalp within 24 h of symptom onset. The mechanism is incompletely understood but may involve increased mitochondrial adenosine triphosphate production. Animal models demonstrated safety and efficacy warranting randomized controlled trials in humans. NEST-1 (phase 2) and NEST-2 (phase 3) confirmed the safety of transcranial laser therapy, although efficacy was not found in NEST-2. Pooled analysis of NEST-1 and NEST-2 revealed a significantly improved success rate in patients treated with laser therapy. Further phase 3 testing is planned and may create a new paradigm for the treatment of acute ischemic stroke.     

Beneficial effect of a novel pentadecapeptide BPC 157 on gastric lesions induced by restraint stress,ethanol, indomethacin,and capsaicin neurotoxicity

Very recently, the integrity of capsaicin somatosensory neurons and their protection were suggested to be related to the activity in nociception of a newly discovered 15-amino acid peptide, BPC 157, shown to have strong beneficial effect on intestinal and liver lesions. Therefore, from this viewpoint, we have studied the gastroprotective effect of the pentadecapeptide BPC 157, on gastric lesions produced in rats by 96% ethanol, restraint stress, and indomethacin. The possible involvement of sensory neurons in the salutary actions of BPC 157 (10µg/kg, 10 ng/kg intraperitoneally) was studied with capsaicin, which has differential effects on sensory neurons: a high dose in adult (125 mg/kg subcutaneously, 3 months old) or administration (50 mg/kg subcutaneously) to neonatal animals (age of the 7 days) destroys sensory fibers, whereas a low dose (500µg/kg intraperitoneally) activates neurotransmitter release and protective effects on the mucosa. In the absence of capsaicin, BPC 157 protected gastric mucosa against ethanol, restraint, and indomethacin application. In the presence of neurotoxic doses of capsaicin, the negative influence of capsaicin on restraint, ethanol, or indomethacin lesions consistently affected salutary activity of BPC 157. However, BPC 157 protection was still evident in the capsaicin-treated rats (either treated as adults or as newborns) in all of these assays. Interestingly, after neonatal capsaicin treatment, a complete abolition of BPC gastroprotection was noted if BPC 157 was applied as a single nanogram-regimen, but the mucosal protection was fully reversed when the same dose was used daily. In line with the excitatory dose of capsaicin the beneficial effectiveness of BPC 157 appears to be increased as well. Taken together, these data provide evidence for complex synergistic interaction between the beneficial effectiveness of BPC 157 and peptidergic sensory afferent neuron activity.     

The effects of sex steroids on thyroid C cells and trabecular bone structure in the rat model of male osteoporosis

Androgen deficiency is one of the major factors leading to the development of osteoporosis in men. Since calcitonin (CT) is a potent antiresorptive agent, in the present study we investigated the effects of androgen deficiency and subsequent testosterone and estradiol treatment on CT-producing thyroid C cells, skeletal and hormonal changes in middle-aged orchidectomized (Orx) rats. Fifteen-month-old male Wistar rats were either Orx or sham-operated (SO). One group of Orx rats received 5 mg kg⁻¹ b.w. testosterone propionate (TP) subcutaneously, while another group was injected with 0.06 mg kg⁻¹ b.w. estradiol dipropionate (EDP) once a day for 3 weeks. A peroxidase–antiperoxidase method was applied for localization of CT in the C cells. The studies included ultrastructural microscopic observation of these cells. The metaphyseal region of the proximal tibia was measured histomorphometrically using an imagej public domain image processing program. TP or EDP treatment significantly increased C cell volume (Vc), volume densities (Vv) and serum CT concentration compared with the Orx animals. Administration of both TP and EDP significantly enhanced cancellous bone area (B.Ar), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and reduced trabecular separation (Tb.Sp). Serum osteocalcin (OC) and urinary Ca concentrations were significantly lower after these treatments in comparison with Orx rats. These data suggest that testosterone and estradiol treatment in Orx middle-aged rats affect calcitonin-producing thyroid C cells, which may contribute to the bone protective effects of sex hormones in the rat model of male osteoporosis.