Results of irradiation in the squamous cell carcinomas of the anterior faucial pillar-retromolar trigone

Between January 1966 and August 1981, 159 patients with previously untreated squamous cell carcinomas of the anterior faucial pillar or retromolar trigone received definitive radiation therapy at The University of Texas M. D. Anderson Hospital and Tumor Institute. All except 11 patients were treated by external radiation including combination of electron beams with high-energy photons or 60Co to doses ranging from 60 Gy to 75 Gy. In the N0 patients, as a rule, only the ipsilateral subdigastric nodes were treated electively to a dose of 50 Gy. The 5-year determinate survival rate for the overall group was 83%. The cumulative recurrence rate showed that 92% of the patients had recurrence by 2 years. Therefore, all patients except those who died with no evidence of local disease less than 2 years after treatment were evaluated for local control. The failure rate for the evaluable patients was 29% for T1 lesions, 30% for T2 lesions, 24% for T3 lesions, and 40% for T4 lesions. After salvage surgery, which consisted of intraoral resection in one-third of the patients and of a composite operation in the other two-thirds, the ultimate failure rate was 0% for T1 lesions, 6% for T2 lesions, 8% for T3 lesions, and 20% for T4 lesions. Whereas stage was a poor indicator for treatment outcome, there was a significantly higher failure rate for infiltrative and/or ulcerated lesions (35%) than for exophytic or superficial lesions (15%). Histologic grade was of no prognostic significance, nor was there any significant difference in the failure rate for lesions originating on the anterior faucial pillar versus that for lesions on the retromolar trigone. Following radiotherapy, 30% of the patients developed some degree of bone exposure but only 5.6% (9 patients) required a segmental mandibular resection. The probability of bone exposure was not dose related and more likely reflected tumor location on the mucoperiosteum. Of the whole group, 16 patients (10%) experienced a neck failure with 8 ultimate failures after salvage surgery. Among the 16 patients who had neck failures, 13 were originally staged N0; 6 of these patients had failures that occurred in the electively treated ipsilateral subdigastric area, but the field was too small to cover the nodes adequately. Aspects of the radiotherapy techniques with combined electron and photon beams that may influence the treatment outcome are discussed.     

Prospective multicenter clinical trial of Uretex Sup for surgical treatment of stress urinary incontinence

AIM: To evaluate in a prospective multicenter study the efficacy and safety of the suburethral support Uretex (Sofradim, Trevoux, France) delivered by a suprapubic approach in the treatment of female stress urinary incontinence. METHODS: Between March 2002 and March 2003, 57 patients were treated for stress urinary incontinence with Uretex. Preoperative evaluation included urodynamic examination and questionnaires (symptoms and quality of life, Contilife). Forty patients had pure stress urinary incontinence and 17 mixed urinary incontinence. No associated procedure was performed. The objective cure rate was evaluated by clinical examination and pad-test, and the subjective cure rate was assessed through questionnaires at 1, 3 and 12 months. RESULTS: The mean follow-up was 13 months (range 11-24 months). During follow up, chronic urinary retention requiring a tape section occurred in one patient, and in another patient a delay of vaginal healing was followed by a sling exposure and resection at 4 months. No infection or urethral erosion was reported. The objective cure rate was 96.2%, and the subjective cure rate was 79.2%; four patients reported low leakage on stress and nine patients complained of urge incontinence (four de novo and five persistent). CONCLUSION: The suprapubic Uretex Sup procedure is a safe and effective treatment for women with stress urinary incontinence.     

Disease variations in Asians in Leicester

The epidemiological study of ethnic groups provides valuableinformation for physicians in a number of ways. First, it assistsin the diagnostic approach in individual patients, especiallyfor doctors unfamiliar with patients of a particular ethnicbackground. Second, it provides population data to assist inhealth care planning and provision for the present and futurein districts where ethnic minorities are resident in significantnumbers. Third, it may provide pointers for the study of pathogenicmechanisms. Fourth, changing epidemiology in migrant ethnicminorities may help to distinguish the degree of influence ofgenetic and environmental pathogenic factors. These studiesare particularly valuable when minority populations are of asize which allows meaningful data to be collected on uncommonconditions. Furthermore the contrasts between migrant and indigenouspopulations are most clearly seen if migration has occurredover a restricted period. For these and other reasons the studyof the migrant population from the Indian subcontinent (definedas India, Pakistan and Bangladesh) which has settled in Leicestersince the mid-1960s has proved particularly rewarding. Thisreport summarizes the distinctive epidemiological features ofthese people now living in Leicester.     

Tau protein induces bundling of microtubules in vitro: comparison of different tau isoforms and a tau protein fragment.

Expression of tau protein in non-neuronal cells can result in a redistribution of the microtubule cytoskeleton into thick bundles of tau-containing microtubules (Lewis et al.: Nature 342:498-505, 1989; Kanai et al.: J Cell Biol 109:1173-1184, 1989). We reconstituted microtubule bundles using purified tubulin and tau in order to study the assembly of these structures. Taxol-stabilized tubulin polymers were incubated with various concentrations of recombinant human tau and examined by electron microscopy. With increasing concentrations of tau 3 (tau isoform containing three microtubule binding domains) or tau 4 (isoform containing four microtubule binding domains) the microtubules changed orientation from a random distribution to loosely and tightly packed parallel arrays and then to thick cables. In contrast, tau 4L, the tau isoform containing four microtubule binding domains plus a 58-amino acid insert near the N-terminus, showed minimal bundling activity. tau 4-induced bundling could be inhibited by the addition of 0.5 M NaCl or 0.4 mM estramustine phosphate, conditions which are known to inhibit tau binding to microtubules. A tau construct that contained only the microtubule binding domains plus 19 amino acids to the C-terminus was fully capable of bundling microtubules. Phosphorylation of tau 3 with cAMP-dependent protein kinase had no effect on its ability to induce microtubule bundling. These results indicate that tau protein is directly capable of bundling microtubules in vitro, and suggests that different tau isoforms differ in their ability to bundle microtubule filaments.     

Deletion of aldose reductase leads to protection against cerebral ischemic injury.

Previously, we reported that transgenic mice overexpressing endothelin-1 in astrocytes showed more severe neurological deficits and increased infarct after transient focal ischemia. In those studies, we also observed increased level of aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, which has been implicated in osmotic and oxidative stress. To further understand the involvement of the polyol pathway, the mice with deletion of enzymes in the polyol pathway, AR, and sorbitol dehydrogenase (SD), which is the second enzyme in this pathway, were challenged with similar cerebral ischemic injury. Deletion of AR-protected animals from severe neurological deficits and large infarct, whereas similar protection was not observed in mice with SD deficiency. Most interestingly, AR(-/-) brains showed lowered expression of transferrin and transferrin receptor with less iron deposition and nitrotyrosine accumulation. The protection against oxidative stress in AR(-/-) brain was also associated with less poly(adenosine diphosphate-ribose) polymerase (PARP) and caspase-3 activation. Pharmacological inhibition of AR by Fidarestat also protected animals against cerebral ischemic injury. These findings are the first to show that AR contributes to iron- and transferrin-related oxidative stress associated with cerebral ischemic injury, suggesting that inhibition of AR but not SD may have therapeutic potential against cerebral ischemic injury.     

Geste antagonistes in idiopathic lower cranial dystonia.

Geste antagonistes, or sensory tricks, are well described in focal dystonia affecting the neck, hand, and face. Improvement in dystonic movements is typically maintained while the trick is performed, but disappears when the geste ends. We investigated the phenomenological features of geste antagoniste maneuvers in 19 patients with idiopathic lower cranial dystonia who were prospectively evaluated over a period of 6 years. Of the 19, 10 were men, mean age of onset was 49.8 years, and the most commonly involved lower cranial area was the jaw (10 patients). In most patients, dystonia was task-specific. Taking advantage of the improvement with a sensory geste, we manufactured oral appliances that mimicked the geste in 8 patients, and 3 continue to use it.     

Highly resolved in vivo 1H NMR spectroscopy of the mouse brain at 9.4 T.

An efficient shim system and an optimized localization sequence were used to measure in vivo 1H NMR spectra from cerebral cortex, hippocampus, striatum, and cerebellum of C57BL/6 mice at 9.4 T. The combination of automatic first- and second-order shimming (FASTMAP) with strong custom-designed second-order shim coils (shim strength up to 0.04 mT/cm2) was crucial to achieve high spectral resolution (water line width of 11-14 Hz). Requirements for second-order shim strengths to compensate field inhomogeneities in the mouse brain at 9.4 T were assessed. The achieved spectral quality (resolution, S/N, water suppression, localization performance) allowed reliable quantification of 16 brain metabolites (LCModel analysis) from 5-10-microL brain volumes. Significant regional differences (up to 2-fold, P < 0.05) were found for all quantified metabolites but Asp, Glc, and Gln. In contrast, 1H NMR spectra measured from the striatum of C57BL/6, CBA, and CBA/BL6 mice revealed only small (<13%, P < 0.05) interstrain differences in Gln, Glu, Ins, Lac, NAAG, and PE. It is concluded that 1H NMR spectroscopy at 9.4 T can provide precise biochemical information from distinct regions of the mouse brain noninvasively that can be used for monitoring of disease progression and treatment as well as phenotyping in transgenic mice models.     

Treatment of Paget's disease of bone with intravenous 4-amino-1-hydroxybutylidene-1,1-bisphosphonate

Summary 4-amino-1-hydroxybutylidene-1,1-bis-phosphonate (AHButBP) was given intravenously (2.5–25 mg/day for 4 days) to 14 patients with Paget's disease of bone, five of whom had been treated with dichloromethylidene bisphosphonate (Cl₂MBP) 32 months earlier. In the nine patients who had not been treated previously with bisphosphonates, the short course of AHButBP induced a suppression of serum alkaline phosphatase and urinary hydroxyproline values down to 30% of initial values. The biochemical suppression of the disease was sustained for 2–18 months and the time to relapse did correlate to the logarithm of the dose (P<0.001). In the five patients previously treated for Paget's disease, an apparent resistence to treatment with AHButBP was observed. However, in these patients both serum alkaline phosphatase and urinary hydroxyproline fell to or even below the nadir values which had previously been achieved with Cl₂MBP, irrespective of the degree of relapse. Thus the degree of suppression of Paget's disease of bone, achievable after treatment with bisphosphonates, seems to be constant for each patient, such that normal levels of serum alkaline phosphatase and urinary hydroxyproline cannot usually be attained in patients with extremely active disease.