A novel <Emphasis Type="Italic">KCNA1</Emphasis> mutation in a family with episodic ataxia and malignant hyperthermia

Episodic ataxia type 1 (EA1) is an autosomal dominant channelopathy caused by mutations in KCNA1, which encodes the voltage-gated potassium channel, Kv1.1. Eleven members of an EA family were evaluated with molecular and functional studies. A novel c.746T>G (p.Phe249Cys) missense mutation of KCNA1 segregated in the family members with episodic ataxia, myokymia, and malignant hyperthermia susceptibility. No mutations were found in the known malignant hyperthermia genes RYR1 or CACNA1S. The Phe249Cys-Kv1.1 channels did not show any currents upon functional expression, confirming a pathogenic role of the mutation. Malignant hyperthermia may be a presentation of KCNA1 mutations, which has significant implications for the clinical care of these patients and illustrates the phenotypic heterogeneity of KCNA1 mutations.     

Congenital orbital vascular malformation complicated by massive retrobulbar hemorrhage

A 2-year-old female infant with a presumed diagnosis of infantile hemangioma of the left eyebrow developed acute proptosis of the left eye several days after a mild orbital trauma. Computerized axial tomography (CAT) and carotid angiography confirmed the presence of a vascularized mass in the retrobulbar space, spreading anteriorly to the orbital rim and the frontal area. Due to progression of the proptosis and the development of exposure keratitis, surgical intervention was necessary. A large vascular tumor and a massive hemorrhage occupying the orbit were removed. The pathological examination confirmed the diagnosis of a vascular malformation of the orbit, most probably orbital varices. A relatively good visual acuity was achieved after surgery by occlusion therapy.     

Botulinum toxin improves lid opening delays in blepharospasm-associated apraxia of lid opening

Lid movement and EMG of the orbicularis oculi (OOc) were analyzed in 10 patients with apraxia of lid opening associated with blepharospasm before and after botulinum toxin treatment. The latencies to onset and to complete the eye opening and the time during which eye opening was sustained were studied in relation to OOc activity and compared with control values obtained in 12 healthy subjects. Following treatment there was an improvement of all lid opening measurements, a decrease of the abnormally prolonged OOc activity, and a reduction of the functional disability.     

Serial spot hydroxyproline/creatinine ratios in metastatic prostatic cancer

Analysis of urinary hydroxyproline levels offers a marker to monitor osseous involvement in patients with metastatic malignancies. Such a marker is needed in patients with prostatic cancer when bone metastases predominate. Thirty-two men with stage D2 prostatic cancer were monitored by bone scan, acid and alkaline phosphatase values, and urinary hydroxyproline, beginning from 4 to 36 months after initiation of hormonal manipulation and/or systemic chemotherapy. In patients with disease progression determined by bone scan serial urinary hydroxyproline values progressively increased and were significantly elevated compared to urinary values obtained from patients with a stable or improving scan (p less than 0.001). Simultaneous alkaline phosphatase determinations showed less significant differences between patient groups. Acid phosphatase did not reliably indicate osseous response to therapy. These data suggest that urinary hydroxyproline values are predictive as an early objective sign of osseous response in patients receiving therapy for stage D2 prostatic cancer.     

Meropenem activity against staphylococci

Meropenem is a new carbapenem with excellent activity against different Gram-negative and Gram-positive bacteria. Its good antibacterial activity is closely related to high hydrolysis resistance by bacterial beta-lactamases. The aim of this study was to evaluate antimicrobial activity of meropenem by comparison that of oxacillin, gentamicin, clarithromycin and ciprofloxacin against 458 staphylococci collected during 2004 period from healthy individuals. Minimum inhibitory concentrations were determined by agar dilution technique. Meropenem has an activity clearly superior to the other tested agents. Resistance rate is zero for all investigated strains.     

A novel surgical technique for implanting a new electrostimulation system for treating female overactive bladder: a preliminary report

OBJECTIVE: To assess the results of peripheral electrostimulation of pelvic floor muscles in patients with overactive bladder (OAB) symptoms, and to describe a novel surgical technique for inserting a specially designed implantable electrostimulator which can deliver different forms of muscle stimulation through a para-urethral electrode. PATIENTS AND METHODS: The study included seven women with OAB (mean age 59 years) who had frequency (including nocturia), urgency and urge incontinence for > or = 1 year, and in whom conventional treatment failed. The antepubic technique was used to implant the electrostimulator and a para-urethral electrode. The patients' urinary symptoms and quality of life (King's College Hospital incontinence questionnaire) were compared before and after surgery, and possible complications monitored. RESULTS: The mean (range) follow-up was 14.5 (13-17) months in six and 10 months in the seventh patient (stimulator removed because of infection). The mean (range) frequency of 15 (13-23) voids/24 h before surgery decreased to 9 voids/24 h (i.e. by 40%) afterward. All patients had leakage episodes because of urgency (4-15 times/day) before surgery, which ceased in five afterward; these patients used no further pads. In the remaining two patients urgency incontinence continued after surgery, but with significantly fewer leakage episodes, from 15 and 12 per day before to 6.7 and 4 afterward, respectively. The mean degree of urgency (graded 0-3) decreased from 2 to 1.4 after surgery, and quality of life improved significantly. Urodynamic studies showed a greater mean maximum detrusor capacity, from 135 mL before to 189 mL after implanting the stimulator. CONCLUSIONS: The good results (over a follow-up of 1 year) in patients with OAB symptoms treated by the present electrostimulator should encourage further clinical studies in such patients. A trial to evaluate the efficacy of pelvic floor muscle electrostimulation in a broad spectrum of diseases of the lower urinary tract causing symptoms similar to OAB has been started.     

Muscle glycogen depletion and increased oxidative phosphorylation following status epilepticus

We describe complete glycogen depletion and increased respiratory chain enzyme activity in a muscle biopsy obtained prior to the demise of a patient in multiorgan failure following status epilepticus. These findings validate the theoretical basis of muscle energy turnover during status epilepticus: the increased demand for energy leads to complete depletion of glycogen reserves. The attempt to preserve adenosine triphosphate requirements results in increased activity of respiratory chain enzymes.