Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase

The metallochaperone Atox1 directly interacts with the copper-transporting ATPases and plays a critical role in perinatal copper homeostasis. To determine the cell biological mechanisms of Atox1 function, intracellular copper metabolism, and Menkes ATPase abundance, localization and trafficking were examined in immortalized fibroblast cell lines derived from Atox1(+/+) and Atox1(-/-) embryos. Consistent with the proposed role for Atox1 in copper delivery to the secretory pathway, a marked increase in intracellular copper content secondary to impaired copper efflux was observed in Atox1-deficient cells. Although the localization of the Menkes ATPase was identical in Atox1(+/+) and Atox1(-/-) cells under conditions of equivalent intracellular copper content, a significant impairment in copper-mediated Menkes ATPase trafficking was observed in the absence of Atox1. When quantitative confocal immunofluorescence was used, significant differences in the time and dose-dependent trafficking of the Menkes ATPase from the Golgi compartment in response to copper were observed between Atox1(+/+) and Atox1(-/-) cells. These data reveal an essential role for Atox1 in establishing the threshold for copper-dependent movement of the copper-transporting ATPases within the secretory compartment and that, in the absence of Atox1, this movement alone is not sufficient to restore normal copper efflux. Taken together, these findings provide a cell biological model for the role of this metallochaperone under the physiological conditions of copper limitation in mammalian cells.     

Hypertrophic cardiomyopathy: a rare cause of vascular dementia. A case report

Herein, we report a case of a 51 year old man who experienced three ischemic cerebral infarcts in a time of few months. The patient consulted after the third accident. Neurological presentation included pseudobulbar syndrome with a mild cognitive deficit, aphasia, left hemiparesia, hemiasomatognosia and homonymous lateral hemianopsia. Cerebral tomodensitometry and magnetic resonance imaging evidenced large infarcts images involving right middle cerebral artery territory and bilateral borderline zones in the junction of the territories of the middle and posterior cerebral arteries. Ambulatory 24 hours ECG recording (Holter) revealed two hits of non-sustained ventricular tachycardia. Transoesophageal echocardiography conveyed to the diagnosis of hypertrophic cardiomyopathy and displayed the presence of a left auricular thrombus. Anticoagulant therapy and rehabilitation allowed a substantial recovering of the patient's cognitive functions and wasting of the intracardiac thrombus. The clinical features observed in our patient meet the recommended DSM IV diagnosis criteria of vascular dementia, an exceptional complication of HCM. The clinical findings, neuroimagery investigation results, and the chronological link between cerebral attacks and cognitive function deterioration argue for a demential syndrome of vascular origin resulting from multiple embolic infarcts involving medium sized arteries (multi-infarct dementia). The authors emphasize the rarity of such observation. HCM must be considered as a potential cause of embolic stroke and likewise a multi-infarct dementia.     

Preoperative coagulation tests in former preterm infants undergoing spinal anaesthesia

BACKGROUND: Clinical history is insufficient to detect disorders of haemostasis in infants aged less than 1 year and laboratory coagulation testing is recommended in infants before perimedullar anaesthesia. METHODS: We designed a retrospective study to assess the preoperative coagulation tests [activated partial thromboplastin time (aPTT), prothrombin time, platelet count] performed in 141 former preterm infants who underwent spinal anaesthesia for elective inguinal hernia repair. All the infants had recovered from any significant medical event (necrotizing enterocolitis, intracranial haemorrhages, transfusions of blood products, sepsis, etc.) when they were scheduled for surgery. RESULTS: Mean values for aPTT were frequently abnormal (60.4%) in infants with a postconceptional age of less than 45 weeks. No complication related to the puncture or abnormal perioperative bleeding was detected. CONCLUSIONS: Other coagulation tests should be evaluated to assess the coagulation status in infants with a postconceptional age of less than 45 weeks.     

Evaluation of the WHO clinical decision rule for streptococcal pharyngitis.

AIMS: To prospectively assess the WHO clinical decision rule (CDR) for group A beta haemolytic streptococcal (GABHS) pharyngitis in three countries. METHODS: A prospective, observational cohort study in urban outpatient clinics in Rio de Janeiro, Cairo, and Zagreb. There were 2225 children aged 2-12 years with cough, rhinorrhoea, red or sore throat; 1810 of these with sore throat were included in the analysis. RESULTS: The proportion of children presenting with sore throat and found to have GABHS pharyngitis ranged from 24.6% (Brazil) to 42.0% (Croatia). WHO CDR sensitivity was low for all sites in both age groups. In children age 5 or older, sensitivity ranged from 3.8% in Egypt to 10.8% in Brazil. In children under 5, sensitivity was low (0.0-4.6%) Specificity was high in both age groups in all countries (93.8-97.4%). CONCLUSIONS: In these populations, the current WHO CDR has high specificity, but low sensitivity; it did not detect up to 96.0% of children who have laboratory confirmed GABHS pharyngitis. A CDR with higher sensitivity should be developed for use in regions where rheumatic fever and rheumatic heart disease are still major health problems.     

Pelvic ganglioneuroma. Case report

Ganglioneuroma is a neurogenic tumor originating from autonomic ganglia. It most commonly occurs in patients younger than 20 years with a slight predominance of females. The pelvic localization is rare. Imaging can lead to diagnosis but it is not specific. The diagnosis can only be confirmed by the pathologic study. The authors report one case of pelvic ganglioneuroma diagnosed in an 11-year-old child who also had hypertension and renal failure.     

The effect of montage on the analgesic response to percutaneous neuromodulation therapy

The analgesic response to percutaneous neuromodulation therapy (PNT) is influenced by the location, frequency, and duration of electrical stimulation. We evaluated the effect of different patterns of stimulation (montages) on the acute analgesic response to PNT when applied at the same dermatomal levels in 72 consenting patients with low back pain. All of the patients received a standardized montage (I) and three alternative montage (II-IV) patterns according to a randomized, single-blinded, crossover study design. All of the PNT treatments were administered at identical alternating stimulation frequencies of 15 and 30 Hz for a period of 30 min, three times per week for two consecutive weeks, with 1 wk "off" between each modality. Pretreatment assessments included the health status survey short form (SF-36) questionnaire, as well as visual analog scale scores for pain, physical activity, and quality of sleep (with 0 = the best to 10 = the worst). The pain visual analog scale was repeated 5--10 min after each treatment session. The daily oral analgesic usage was recorded in a patient diary. All four montages produced significant improvements in pain (42%--64%), physical activity (35%--51%), and quality of sleep (28%--46%), as well as 23% to 47% reductions in the daily oral analgesic usage. However, Montage II was significantly more effective than the standard (Montage I) and the other two montages studied. These data suggest that the pattern of stimulation (i.e., montage) can influence the acute analgesic response to PNT.     

Mammography screening of breast cancer in Tunisia. Results of first experience]

This article reports the results of a mammography screening program of breast cancer, realized in the department of Radiology, Charles Nicolle hospital. A free screening mammography with two incidences was offered to women aged from 40 to 70 years old. 2200 mammographies were realized from May 1995 till July 1997. Women having a positive test benefited of a diagnostic explorations in the same unity. The positive test rate was 24%. Predictive positive value was 31%. This program allowed to detect 10 subclinical cancers, corresponding to a rate of detection of 4.5 cancers for 1000 women. This program is a first experience which demonstrated the feasibility of the mammography screening to wide scale and allowed the medical and paramedical team to acquire an experience.