Neurofibromatosis type 2: Hearing preservation and rehabilitation.

The main manifestation of neurofibromatosis type 2 (NF2) is the development of bilateral vestibular schwannomas (VS). Consequently, one of the most severe functional sequelae is bilateral sensorineural hearing loss, caused by spontaneous tumor progression and/or treatment-related damage (surgery or radiosurgery). Preserving or restoring hearing is still challenging in NF2 no matter the strategy applied to each individual based on the natural history of VS. In this review, the different strategies for hearing preservation or rehabilitation are discussed and illustrated by several cases. A decisional algorithm for NF2 patients with VS is proposed that takes into consideration the tumor size and hearing level.

Calcium Signaling in the Ventricular Myocardium of the Goto-Kakizaki Type 2 Diabetic Rat.

The association between diabetes mellitus (DM) and high mortality linked to cardiovascular disease (CVD) is a major concern worldwide. Clinical and preclinical studies have demonstrated a variety of diastolic and systolic dysfunctions in patients with type 2 diabetes mellitus (T2DM) with the severity of abnormalities depending on the patients' age and duration of diabetes. The cellular basis of hemodynamic dysfunction in a type 2 diabetic heart is still not well understood. The aim of this review is to evaluate our current understanding of contractile dysfunction and disturbances of Ca2+ transport in the Goto-Kakizaki (GK) diabetic rat heart. The GK rat is a widely used nonobese, nonhypertensive genetic model of T2DM which is characterized by insulin resistance, elevated blood glucose, alterations in blood lipid profile, and cardiac dysfunction.

Inefficiency of ulipristal acetate on uterus leiomyomas as an additional sign to suspect leiomyosarcoma.

The unexpected diagnosis of a leiomyosarcoma from a surgical specimen of a presumed leiomyoma is rare, but with deleterious consequences, especially if morcellation techniques are used. There are currently no effective methods for such a preoperative diagnosis. Ulipristal acetate has demonstrated efficacy for the preoperative treatment of leiomyomas, but not for all patients. We report two cases of leiomyosarcomas in patients treated with ulipristal acetate for a presumed leiomyoma. We propose that ineffective ulipristal acetate treatment may indicate a population in which uterine leiomyosarcoma is more prevalent. Attention should be given to any features of clinical and imaging examinations which raise the suspicion of a leiomyosarcomas in this population. Such suspicion should guide appropriate measures to avoid seeding the tumor, postponing the diagnosis, upstaging the patient and delaying the treatment (SPUD).

Impact of sentinel node biopsy on long-term quality of life in breast cancer patients.

BACKGROUND: The aim of this study was to assess long-term quality of life (QoL) over a period of 6 years in women with breast cancer (BC) who underwent sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), or SLNB followed by ALND. METHODS: The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30 and the EORTC-QLQ-BR-23 questionnaires were used to assess QoL before surgery, just after surgery, 6, 12 and 72 months later. The longitudinal effect of surgical modalities on QoL was assessed with a mixed model analysis of variance for repeated measurements. RESULTS: Five hundred and eighteen BC patients were initially included. The median follow-up was 6 years. During the follow-up, 61 patients died. None of the patients of the SLNB group developed lymphedema during follow-up and the relapse rate was similar in the different groups (P=0.62). Before surgery, global health status (P=0.52) and arm symptoms (BRAS) (P=0.99) QoL scores were similar whatever the surgical procedure. The BRAS score (P=0.0001) was better in the SLNB group 72 months after surgery. Moreover, during follow-up, patients treated with SLNB had lower arm symptoms scores than ALND patients and there was no difference for arm symptoms between patients treated with ALND and those treated with SLNB followed by complementary ALND. CONCLUSION: Long-term follow-up showed that SLNB was associated with less morbidity than ALND.

A multicenter cohort study to compare quality of life in breast cancer patients according to sentinel lymph node biopsy or axillary lymph node dissection.

BACKGROUND: This prospective multicenter study assessed and compared the impact of different surgical procedures on quality of life (QoL) in breast cancer patients. PATIENTS AND METHODS: The EORTC QLQ-C30 and the EORTC QLQ-BR-23 questionnaires were used to assess global health status (GHS), arm (BRAS) and breast (BRBS) symptom scales, before surgery, just after surgery and 6 and 12 months later. The Kruskal-Wallis test with the Bonferroni correction was used to compare scores. A mixed model analysis of variance for repeated measurements was then applied to assess the longitudinal effect of surgical modalities on QoL. RESULTS: Before surgery, GHS (P = 0.7807) and BRAS (P = 0.7688) QoL scores were similar whatever the surgical procedure: sentinel node biopsy (SLNB), axillary node dissection (ALND) or SLNB + ALND. As compared with other surgical groups, GHS 75.91 [standard deviation (SD) = 17.44, P = 0.041] and BRAS 11.39 (SD = 15.36, P < 0.0001) were better in the SLNB group 12 months after surgery. Whatever the type of surgery, GHS decreased after surgery (P < 0.0001), but increased 6 months later (P = 0.0016). BRAS symptoms increased just after surgery (P = 0.0329) and until 6 months (P < 0.0001) before decreasing (P < 0.0001). CONCLUSIONS: SLNB improved GHS and BRAS QoL in breast cancer patients. However, surgeons must be cautious, SLNB with ALND results in a poorer QoL.

Bilateral facial nerve schwannomas.

Facial nerve schwannoma is an uncommon tumor and bilateral facial nerve tumors are extremely rare. A case is presented in which neuromas affecting the intra-canalicular and labyrinthine portions of both facial nerves occurred. Radiologic assessment demonstrated the origin of these tumors. Eventual tumor involvement of the sole functioning cochlea resulted in the development of total hearing loss. Management entailed symptomatic care and surgical resection. Auditory rehabilitation was attempted using cochlear implantation, but results have not been satisfactory. Genetic screening identified a mutation in the NF2 gene. It is proposed that this patient's condition should be considered a variant of neurofibromatosis 2 and that bilateral facial neuromas should be included in the clinical criteria for this condition.

Serial precision of metabolite peak area ratios and water referenced metabolite peak areas in proton MR spectroscopy of the human brain.

The precision of cerebral proton magnetic resonance spectroscopy (MRS) measurements is critical both in the clinical setting and for research purposes. Marshall et al. have recently concluded that "disappointing in vivo repeatability...is likely to limit" the ability of MRS to detect modest changes. We present here a comprehensive study of the precision of short- and long-term metabolite peak area ratios and water referenced metabolite peak areas for long echo time point resolved spectroscopy (PRESS) spectra (repetition time (TR) = 2000 ms, echo time (TE) = 136 ms) acquired from the occipital lobes of normal volunteers and a phantom using a conventional whole body 1.5 T MR system and conventional acquisition and analysis protocols. Short-term in vitro precision determined by five repeat scans on five occasions was excellent as measured by a mean coefficient of variation (NAA/Cho = 1.3%, NAA/Cr + PCr = 1.0%, Cho/Cr + PCr = 1.6%, NAA/H2O = 0.5%, Cho/H2O = 1.2%, Cr + PCr/H2O = 0.8%). Long term in vitro precision using 100 spectra acquired over 2 years was also very good (NAA/Cho = 2.7%, NAA/Cr + PCr = 1.4%, Cho/Cr + PCr = 2.2%, NAA/H2O = 1.5%, Cho/H2O = 2.4%, Cr + PCr/H2O = 1.5%). Short-term in vivo precision determined by five repeat scans in a single scanning session on eight subjects was also excellent (NAA/Cho = 5.2%, NAA/Cr + PCr = 3.0%, Cho/Cr + PCr = 6.6%, NAA/H2O = 1.4%, Cho/H2O = 4.9%, Cr + PCr/H2O = 2.7%) and only worsened slightly for long-term in vivo precision determined by five repeat scans on eight subjects over 3 months (NAA/Cho = 5.2%, NAA/Cr + PCr = 4.8%, Cho/Cr + PCr = 7.7%, NAA/H2O = 2.5%, Cho/H2O = 6.4%, Cr + PCr/H2O = 3.8%). We attribute the excellent precision reported here to the use of highly automated techniques for voxel shimming, water suppression and peak area measurements. These results allow us to repudiate Marshall's assertion regarding disappointing repeatability of in vivo MRS.

[Cancers of the corpus uteri on the Côte-d'Or 1982-1990. Incidence, clinical stage and survival]. / Cancers du corps de l'utérus dans le département de la Côte-d'Or 1982-1990. Incidence, stade clinique et survie.

In the French administrative "departement" of Côte-d'Or, between 1982 and 1990, the crude incidence rate and the age-adjusted world standardised incidence rate (ASR) for corpus uteri cancer were respectively 16.0 +/- 0.8 and 10.7 +/- 0.6 per 100,000 women per year. The incidence increased after 50 years of age, reaching a maximum of 66.7 per 100,000 women per year at the age of 70-74 and thereafter declined. Ninety-six percent of the patients were older than 50. The 5- and 10-year crude survival rates (all histologic types) were 66 +/- 3% and 61 +/- 4%. The 5- and 10-year relative survival rates were 76%. Histologic types were specified in 99.7% of cases, categorized as follows: 92.7% carcinomas (333 cases), 6.7% sarcomas (24 cases) and 0.3% lymphoma (one case). Carcinomas were clinically evaluated according to FIGO staging: stage I: 61.4% (205 cases); stage II: 7.7% (59 cases); stage III: 7.8% (26 cases); stage IV: 6.6% (22 cases) and unspecified stage: 6.6% (22 cases). The ASR by stage, were 6.4 +/- 0.5 (stage I); 0.8 +/- 0.2 (stage II); 1.3 +/- 0.2 (stages III and IV); 0.6 +/- 0.2 (unspecified stage). The 5-year relative survival rates related to FIGO stage were 90% (stage I); 85% (stage II); 25% (stage III) and 0% (stage IV). Elderly patients (> 75) had significantly lower survival rates. With respect to localized disease (stages I and II) the relative risk of death associated with age older than 75 was 4.9. The 5-year relative survival rate of patients with sarcoma was 37%.

Improved high-performance liquid chromatographic separation of urinary paracetamol metabolites using radially compressed columns.

Methods have been adapted for the high-performance liquid chromatographic (HPLC) analysis of urinary paracetamol metabolites on radial compression columns. Enhanced resolution and decreased analysis time were two major advances. Various modifications to existing methods were made to counter the effect of the different C18 surface. Thus in ion suppression HPLC the addition of triethylamine at pH 3.0 (phosphate buffer) was necessary to block residual hydroxyl sites, while in ion-pair HPLC a higher tetrabutyl-ammonium hydroxide concentration of 0.01 M at pH 5.0 was used to enhance selectivity. The methods were successfully applied to the study of the metabolism of paracetamol, its glutathione conjugate and 3-thiomethylparacetamol in Sprague-Dawley rats. 3-Thiomethyl-paracetamol sulphoxide and its glucuronide and sulphate conjugates were shown to be metabolites of both 3-thiomethylparacetamol and paracetamol. 3-Thiomethylparacetamol sulphate was unresolved from the sulphates of paracetamol and 3-methoxyparacetamol in ion-pair HPLC. This raises a previously unrecognised problem in which the peak normally attributed to paracetamol sulphate contains metabolites arising from an oxidative metabolic pathway. Elevated levels of 3-methoxyparacetamol conjugates were found in human overdose urine and to some extent in analgesic nephropathy.

3-thiomethylparacetamol sulphate and glucuronide: metabolites of paracetamol and N-hydroxyparacetamol.

1. Two new metabolites of paracetamol, 3-thiomethylparacetamol sulphate and glucuronide, have been isolated and identified. 2. The metabolites occurred in both rat and mouse urine after administration of either paracetamol of N-hydroxyparacetamol. The amount excreted increased proportionally with the dose.

Hepatotoxicity of phenacetin and paracetamol in the Gunn rat.

Both phenacetin and paracetamol produce acute centrilobular liver necrosis in the homozygous Gunn rat. Paracetamol is more hepatotoxic than phenacetin, and both are more hepatotoxic to the homozygous Gunn rat than to the heterozygous Gunn rat or to the albino rat. These findings have relevance to the role of the compounds in the clinical syndromes of paracetamol induced liver necrosis and analgesic nephropathy.

Paracetamol and the isolated perfused kidney: metabolism and functional effects.

1. Renal metabolism of paracetamol has been studied in the isolated perfused rat kidney. 2. The major metabolites of paracetamol normally observed in vivo were present in low concentrations in the urine of the isolated perfused rat kidney. 3. Paracetamol was bound covalently to kidney protein in a linear relationship to dose up to 31.9 mM paracetamol in the perfusate. 4. Using Michaelis-Menten kinetics, the apparent Km of 5.5 mM and Vmax of 139 nmol/h/g wet wt. for renal paracetamol oxidation were observed. 5. Concn. of paracetamol greater than 14.2 mM induced immediate diuresis and diminished sodium reabsorption. Lower concn. were without effect on function.