Classification and treatment of plantar fibromatosis

A retrospective study of 18 patients (23 feet) with plantar fibromatosis who required surgical excision between January, 1991, and June, 1998, was performed. Subtotal plantar fasciectomy was performed to remove the tumor with a wide disease-free margin. 16 patients (21 feet) were interviewed and 14 patients (19 feet) were examined with an average followup of 36 months. Two patients (2 feet) with less than 12 months followup were excluded. Both subjective and objective evaluations and pre- and postoperative x-rays were reviewed to assess the alignment of the bony arch. There were nine males and nine females, age 49 years, average, at the time of diagnosis. Sixty-seven percent of patients had bilateral disease, and 28% had associated Dupuytren's contracture. There were 18 primary and five recurrent tumors. An operative staging system, I to IV, for plantar fibromatosis is presented which incorporates the extent of plantar fascia involvement, the presence of skin adherence, and the depth of tumor extension. The stage of the tumor correlated well with postoperative wound healing, skin necrosis, and recurrence. In fifteen of 21 feet, the patients were satisfied without reservations, and in three of 21 feet, they were satisfied with reservations. In 18/21 (86%) feet, the patient reported he/she would have surgery done again. There were two recurrent tumors. One was reoperated and the patient was disease free twelve months postoperatively. The other recurrence was asymptomatic 40 months postoperatively and required no treatment. One patient required an excision of a postoperative cutaneous neuroma. Eleven of 21 feet (52%) experienced delayed healing and of which four required a split thickness skin graft. Ten of the eleven feet with delayed wound healing and all four cases requiring a skin graft had a stage ill or IV tumor. Pre- and postoperative weightbearing radiographs revealed a slight decrease in the calcaneal pitch angle, navicular height, and medial cuneiform height indicating a decrease in the height of the medial longitudinal arch.     

Leiomyosarcoma of the submandibular gland. Report of a case and review of the literature

This report describes the first case of primary leiomyosarcoma of the submandibular salivary glands and emphasizes the role of immunohistochemical study for a correct diagnosis of this tumour. In line with results of international literature, we associated surgery with radiotherapy and 2 years postoperatively there was no sign of recurrence.     

No clinically relevant CYP3A induction with the dual angiotensin-converting enzyme/neutral endopeptidase inhibitor, M100240

M100240, an acetate thioester of MDL 100,173, is a dual angiotensin-converting enzyme/neutral endopeptidase inhibitor currently in Phase II development. M100240 and MDL 100,173 were evaluated in an in vitro cytochrome P450 human hepatocyte model for enzyme induction. Although a dose-dependent CYP3A induction was observed between 10 and 100 microM, at 1 microM-which approaches clinically relevant plasma concentrations in humans-there was no evidence of CYP3A induction. An in vitro reporter gene assay also demonstrated the CYP3A isozyme induction potential of M100240 and MDL 100,173 with an EC(50) approximately 1.5 microM. The present study evaluated the potential for CYP3A enzyme induction in healthy volunteers. In an open-label, single-sequence, replicate-design study using midazolam as a CYP3A probe in 13 healthy volunteers, we found no evidence of clinically relevant CYP3A induction after multiple-dose administration of 50 mg M100240 orally once daily for 15 days. Single and multiple doses of M100240 increased the midazolam AUC(0-24 h) about 1.6-fold compared to baseline, suggesting weak CYP3A inhibition. Concomitant administration of midazolam and M100240 was generally safe and well tolerated. Although in vitro CYP3A induction at exposures in excess of clinically relevant human plasma concentrations has been demonstrated, there is no clinical evidence of CYP3A induction with M100240 administration at proposed therapeutic doses.     

FLT3 mutations do not influence MDR-1 gene expression in acute myeloid leukemia

BACKGROUND: A worse outcome for patients carrying FLT3 mutations or expressing MDR1 gene has been reported. This study was designed to verify the possible co-expression of mutated-FLT3 and MDR1 genes and to evaluate their independent prognostic role. PATIENTS AND METHODS: Sixty-one AML patients were tested for MDR1-mRNA levels by real-time PCR and for FLT3 mutations by PCR and Genescan analysis. RESULTS: FLT3 mutations were detected in 31% of patients, more frequently in patients < 60 years and at standard cytogenetic risk. Among 92% of patients MDR1-positive, 50% expressed high levels of mRNA. No significant correlation was found between FLT3 mutations and high levels of MDR1. FLT3 or MDR1 mutations failed to show any role concerning the CR achievement and OS. On the contrary, a significant disadvantage for DFS was found in the group of patients carrying FLT3/ITD. CONCLUSION: The results reported above show that FLT3 mutations and MDR1 expression represent two independent clinical prognostic factors for AML patients.     

Identification of families with hereditary breast and ovarian cancer for clinical and mammographic surveillance: the Modena Study Group proposal

Hereditary factors play a fundamental role in the pathogenesis of breast cancer (BC). Approximately 15–20% of all BCs have been reported to show familial clustering. In spite of the recent demonstration and chromosomal localization of BC predisposing genes, clinical clues and careful inspection of pedigree still remain major instruments in HBC diagnosis. The aim of the present study was to develop minimum operational criteria for the selection of family groups at high risk of developing BC. Following a stepwise procedure, families were stratified into four clusters with increasing probability of genetic involvement. So far, 317 BCprone families have been identified and distributed in the four groups, and 151 high risk women underwent our clinical and mammographic surveillance program. Among these, after a mean followup of 24 months, six BCs and one OC were diagnosed (one BC and one OC occurred in the same woman) and one interval BC was observed. Since the prevalence rate so far detected is dramatically higher than that seen at the first round of Italian populationscreening programs, our preliminary data support the usefulness of the proposed procedure in selecting high risk individuals.     

Quantitative measurement of delta activity in Alzheimer's disease

Quantitative measurements of delta activity were made in 10 healthy elderly controls and 31 subjects with Alzheimer's disease. Delta activity did not discriminate between the healthy elderly controls and the early mild Alzheimer's disease subjects. However, delta activity was a significantly greater percentage of total EEG power in the moderate-to-advanced Alzheimer's subjects when compared to either the healthy controls or mild Alzheimer subjects. In the T3 and T4 electrodes, delta activity in the moderate-to-advanced Alzheimer subjects was 78.3% and 47.6% higher, respectively, than in control subjects. Furthermore, delta activity was an excellent predictor of dementia severity within the 31 subjects with Alzheimer's disease.     

Effects of stress and neuropeptides on airway responses in ovalbumin-sensitized rats

OBJECTIVE: The aim of this study was to investigate the influence of stress and neuropeptides on airway responses in ovalbumin (OVA)-sensitized rats. METHODS: Three experimental conditions were employed: neonatal capsaicin treatment, foot shock stress and OVA sensitization. For neuropeptide depletion, male Wistar rats were neonatally treated with capsaicin (50 mg/kg) or with control solution 2 days after birth. Ninety days later, they were injected with OVA and aluminum hydroxide (ED0) or no injection. Thereafter, rats of the stressed groups were individually placed in a shuttle box where they received 50 mild escapable foot shocks/day; the stressful stimuli were repeated until ED14, when the animals received OVA aerosol. Pulmonary mechanic function was measured before and after OVA challenge in anesthetized and mechanically ventilated rats. RESULTS: Data on ultrasonic vocalizations and corticosterone showed high levels of anxiety in stressed animals. As expected, a significant increment in airway elastance and resistance after the OVA challenge was found in sensitized rats compared to non-sensitized ones. Capsaicin treatment decreased the values of elastance in sensitized and non-stressed rats; however, after the OVA challenge, elastance was increased in stressed animals. No differences were found in the levels of resistance among sensitized and non-stressed rats; however, a reduced increment in resistance was verified in capsaicin-treated, stressed animals. CONCLUSIONS: Our results suggest that neurokinin depletion and stress may affect smooth muscle tonus around the airways during an anaphylactic reaction. These data suggest that stress and neuropeptides play a significant role in pulmonary function in OVA-sensitized rats.