Maximized combined modality treatment of an unselected population of oral and oropharyngeal cancer patients. Final results of a pilot study compared with a treatment-dependent prognosis index.

BACKGROUND: In an attempt to raise the survival of an unselected and representative population of oral and oropharyngeal squamous cell cancer patients, a pilot study of an integrated four-modality treatment was conceived. Final endpoints were compliance, loco-regional control, survival (after complete 5-year follow-up), and a concept of trial assessment using the treatment-dependent prognostic index TPI. PATIENTS: Eighty-seven consecutive patients with histologically proven untreated stages I-IV disease presented in the period between 1997 and 1999 of whom 14 had to be considered uncurable and 73 were fit to be treated with the intention of achieving a cure. METHODS: All patients received one cycle of neoadjuvant intraarterial chemotherapy with 150 mg/m(2) cisplatin (systemically neutralized with sodium thiosulphate), and, if possible, by consecutive treatment applying both surgery of the primary tumour and the neck lymphatics, as well as by adjuvant radiation over 5 weeks (51.3 Gy) plus concurrent chemotherapy (weekly systemic docetaxel 25 mg/m(2)). RESULTS: Ninety per cent of all cases and 96% of the patients treated with curative intention received more than one modality due to study design. Patient non-compliance in the group treated with curative intention has been 18/73 (=25%), and protocol compliance has been 32/73 (=44%). The locoregional control rate for all cases was 71% (62/87 patients) and for the patients treated with curative intention 83.5% (61/73 patients). Thirteen/fourteen non-curable patients died after a mean period of 4 months. After a median observation time of 5 years, the final absolute survival of the unselected population was 53%, and of the patients treated with curative intention 62% (especially, 70% and 50% for patients with operable stages III and IV, respectively). CONCLUSION: The multimodality regimen as presented proved feasible and showed high objective and relative survival rates in comparison with known data from tumour registries of unselected populations. Intra-arterial chemotherapy should be considered a valuable addition to treatment. The potential of survival benefit from this multimodality regimen in comparison with the prognosis index TPI should be investigated in further studies.     

Notfallversorgung eines seltenen malignen Nervenscheidentumors

BACKGROUND: Malignant peripheral epineurial tumours are a group of tumours that derive histomorphologically from peripheral nerve sheaths. They occur sporadically, with an incidence of approximately 0.001%, and very rarely require emergency operation. PATIENT AND PROCEDURE: An athletic 19-year-old man presented to an orthopaedic outpatient clinic with lumboischialgia and weakness of the third and fourth left toes. A 12 x 10 x 8-cm paravertebral/retroperitoneal tumour was diagnosed by CT, and the patient was referred to our clinic. For classification, CT-assisted puncture of the tumour was carried out. A haemorrhage into the tumour resulted from the puncture, with consequently lower Hb level and progressive peripheral sensomotoric deficits demanding emergency surgery on a weekend. On this occasion, the tumour was resected together with the L5 and S1 nerve roots through cooperation between the general surgical and neurosurgical departments and was classified as a malignant peripheral epineurial tumour in the rapid stage. Due to the spinal R2 resection, after-loading probes were inserted and the tumour bed was clip-marked. Percutaneous radiotherapy and brachytherapy followed postoperatively. Shortly afterwards, relaparotomy had to be performed due to an adhesive ileus, from which the patient recovered quickly. Chemotherapy was carried out due to a G2 tumour classification. The patient is currently undergoing rehabilitation, during which the peripheral neurological deficits are improving gradually. CONCLUSION: This rare case of a malignant peripheral epineurial tumour with acute symptoms demonstrates the ability of hospitals with maximum care facilities to maintain services even in times of financial cuts in health care services.     

PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels

Two-pore (2-P) domain potassium channels are implicated in the control of the resting membrane potential, hormonal secretion, and the amplitude, frequency and duration of the action potential. These channels are strongly regulated by hormones and neurotransmitters. Little is known, however, about the mechanism underlying their regulation. Here we show that phosphatidylinositol 4,5-bisphosphate (PIP₂) gating underlies several aspects of 2-P channel regulation. Our results demonstrate that all four 2-P channels tested, TASK1, TASK3, TREK1 and TRAAK are activated by PIP₂. We show that mechanical stimulation may promote PIP₂ activation of TRAAK channels. For TREK1, TASK1 and TASK3 channels, PIP₂ hydrolysis underlies inhibition by several agonists. The kinetics of inhibition by the PIP₂ scavenger polylysine, and the inhibition by the phosphatidylinositol 4-kinase inhibitor wortmannin correlated with the level of agonist-induced inhibition. This finding suggests that the strength of channel PIP₂ interactions determines the extent of PLC-induced inhibition. Finally, we show that PIP₂ hydrolysis modulates voltage dependence of TREK1 channels and the unrelated voltage-dependent KCNQ1 channels. Our results suggest that PIP₂ is a common gating molecule for K⁺ channel families despite their distinct structures and physiological properties.     

Differential ontogeny of divalent cation effects on rat brain delta-, mu-, and kappa-opioid receptor binding

The effect of the divalent cations, Mn2+, Mg2+ and Ca2+ on rat forebrain delta-, mu- and kappa-receptor binding was examined during postnatal development. It was found that delta-receptor binding, assessed with [3H]D-Ala2-D-Leu5-enkephalin ([3H]DADLE) (+ 10 nM D-Ala2- MePhe4-Gly-ol5-enkephalin (DAMGE)), was stimulated by the 3 cations in a dose- and developmental time-dependent manner. delta-Binding was most sensitive to the cations during the first week postnatal, prior to the appearance of high-affinity delta-binding. In contrast, inhibition of mu-receptor binding ([3H]DAMGE) by divalent cations appeared early in development and remained constant throughout the postnatal period. Divalent cation inhibition of kappa-binding ([3H]ethylketocyclazocine ([3H]EKC) + 100 nM DAMGE and 100 nM DADLE) appeared after the second week postnatal. These results demonstrate that the characteristics and postnatal development of divalent cation modulation of mu-, delta- and kappa-binding is distinctly different. Thus, the neonate may be a good model system to examine the binding properties and functions of delta- and kappa-receptor subtypes.     

Intracarotid histamine administration results in dose-dependent vasogenic brain oedema formation in new-born pigs

Inflammation Research -     

α2-adrenoceptor blockade,pituitary-adrenal hormones,and agonistic interactions in rats

The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. α₂ adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an α₂ adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different α₂ adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the α₂ adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed.     

A new method for the termination of cervical pregnancy]

The authors described a 7 weeks old cervical pregnant case, whome was administered 250 mg methotrexate in infusion to eliminate the throphoblastic tissue. 3 days later the HCG was negative in the urine. After the dilatation of cervix by laminaria, the collapsed amniotic sac came from the cervix with minimal hemorrhage. They suggest the method is suitable to prevent the serious complications of cervical pregnancy.