Fourteen novel OPA1 mutations in autosomal dominant optic atrophy including two de novo mutations in sporadic optic atrophy

The OPA1 gene, encoding a dynamin-related GTPase that plays a role in mitochondrial biogenesis, is implicated in most cases of autosomal dominant optic atrophy (ADOA). Sixty-nine pathogenic OPA1 mutations have been reported so far. Most of these are truncating mutations located in the GTPase domain coding region (exons 8-16) and at the 3'-end (exons 27-28). We screened 44 patients with typical ADOA using PCR-sequencing. We also tested 20 sporadic cases of bilateral optic atrophy compatible with ADOA. Of the 18 OPA1 mutations found, 14 have never been previously reported. The novel mutations include one nonsense mutation, 3 missense mutations, 6 deletions, one insertion and 3 exon-skipping mutations. Two of these are de novo mutations, which were found in 2 patients with sporadic optic atrophy. The recurrent c.2708_2711delTTAG mutation was found in 2 patients with a severe congenital presentation of the disease. These results suggest that screening for OPA1 gene mutations may be useful for patients with optic atrophy who have no affected relatives, or when the presentation of the disease is atypical as in the case of early onset optic atrophy.     

Effect of a rhodium complex on alterations of hepatic function in thioacetamide-induced hyperplastic noduligenesis in rats

An in vivo model of liver hyperplastic noduligenesis was inducedin rats by long-term administration of thioacetamide (TAM) (50mg/kg/day i.p.). Three doses of 50 mg/kg of an antitumoral Rh(III)complex were administered at 14, 9 and 5 days before the endof TAM treatment. Plasma and urine were obtained from eitherTAM or Rh(III) complex or TAM plus Rh(III) complex treated ratsto determine the interactions of both substances with the biochemicalparameters related to liver function. The rise in alkaline phosphatase(ALP), teucine aminopeptidase (LAP), -gtutamyl transferase (GGT)and the unchanged activities in the aspartate and alanine aminotransferases(AST, ALT) in plasma of TAM-treated rats indicated that thedisease induced by this substance can be considered as a chronicobstructive biliary disease with indices of cell proliferationand tumors. The increased concentration of bilirubin both inthe plasma and urine of TAM-treated rats suggested liver cholestasisand hepatobiliary obstruction. The very low values of creatinineclearance indicated that there was some degree of kidney failuredue to the effect of TAM. The increased concentration of ammoniaboth in plasma and urine were probably a consequence of thedecreased flux in the urea cycle in the liver. The Rh(III) complexalone did not produce significant changes in the plasma enzymeactivities. The only significant changes were found in the concentrationsof uric acid and ammonia in the urine. When the Rh(III) complexwas administered to TAM-treated rats, significant restorationof the following parameters were observed: plasma enzymaticactivities, blood bilirubin and ammonia, uric acid and creatininein the urine and the creatinine clearance. These results suggestthat the altered liver function induced by TAM can be restoredby Rh(III) complex. The mechanisms by which this complex actsto counteract the TAM-induced changes are not yet established.     

Zinc Nutritional Status in a Series of Children with Chronic Diseases: A Cross-Sectional Study

Background: Zinc is an essential trace element for the normal growth and development of human beings. The main objective was to evaluate the nutritional status of zinc and its association with nutritional indicators in a series of children with chronic diseases. Methods: The prevalence of patients with dietary zinc deficiency or deficit zinc intake (<80% DRI: dietary reference intake) was analyzed through prospective 72 h dietary surveys, and serum zinc deficiency or hypozincemia (≤70 µg/dL in children under 10 years of age in both sexes and in females older than 10 years and <74 μg/dL in males older than 10 years) was measured through atomic absorption spectrophotometry. The participants were classified according to their nutritional status by body mass index (BMI). Results: Mean serum zinc level in obese (87 µg/dL), undernourished (85 µg/dL), and eutrophic children (88 µg/dL) were normal, but in the undernutrition (60% DRI) and eutrophic (67% DRI) groups the mean dietary zinc intake was low compared to that in the obesity group (81% DRI). There were different associations between nutritional parameters, dietary zinc intake, and serum zinc. All patients with hypozincemia had dietary zinc deficiency. Conclusions: In the whole series, 69% of participants showed a zinc intake lower than recommended and might be at high risk of zinc deficiency.     

Nasotracheal enterococcal carriage and resistomes: detection of optrA-, poxtA- and cfrD-carrying strains in migratory birds,livestock, pets,and in-contact humans in Spain

European Journal of Clinical Microbiology & Infectious Diseases - This study determined the carriage rates and antimicrobial resistance (AMR) genes of enterococci from...     

Prevalence and control of arterial hypertension in the south-east of Spain: A radical but still insufficient improvement

Stroke mortality rates in Spain are one of the highest in all of Europe. At the same time, the Murcia region (south-east Spain) shows, for both genders, the highest age-adjusted stroke mortality rates in all of Spain. The earliest available hypertension figure estimations for this area go back to 1981, when a high prevalence combined with an almost nonexistent control was detected. One decade later, updated prevalence estimations of hypertension are presented jointly with their degree of control and their association with other risk factors based on the results of a prevalence survey in a random population sample (n = 3,091). Arterial blood pressure was measured following the MONICA protocol, maintaining a tight quality control on between and within-observer variability. As hypertensive was considered as any person with systolic blood pressure (SBP) 140 mmHg or with diastolic blood pressure (DBP) 90 mmHg or with antihypertensive pharmacological treatment. Detected prevalence rises to 32.3% (CI 95%: 29.1%–35.5%) among males and to 23.7% (CI 95%: 21.4%– 26%) among females, maintaining its level regarding figures observed back in 1981. However, its control has been increased, especially among hypertensive women [from less than 5% in 1981 to 35% (95% CI: 32%–37.8%) at present]. Hypertension is strongly associated to hipercholesterolemia, overweight, obesity and diabetes (p < 0.01). On the contrary, it shows an opposite association with current smoking, higher educational level and leisure time physical activity (p < 0.01). The highest educational level was associated with better hypertension treatment and control. In summary, while hypertension prevalence is stabilized in our population, its control has improved in a measurable but still insufficient way. These results are in accordance with a decreasing trend in stroke mortality registered in the Murcia Region along the last decade.     

Interventional Radiology for Treating Soft Tissue Sarcomas

The role of interventional radiology for soft tissue sarcomas is only occasionally addressed in the literature. However, different techniques such as embolization, selective chemotherapy, chemoembolization, and acrylic cement osteoplasty can be helpful with the primary tumor, recurrences, and metastases. This article discusses these techniques and their complications in treatment of soft tissue sarcomas.     

Spatial and Temporal Patterns of Neurogenesis in the Chick Retina

Chick embryo retinas were labelled in ovo by single injections of [3H]thymidine at selected times between days 2 and 12 of incubation. Embryos were later removed, at different stages of development, and the retinas processed for autoradiography of either serial sections or dissociated cell preparations. Analysis of unlabelled cells shows that neurogenesis starts, on day 2 of incubation, in a dorsotemporal area of the central retina, close to the posterior pole and to the optic nerve head. A gradient of neurogenesis spreads from this central area to the periphery, where neurogenesis ends, shortly after day 12, when the last few bipolar cells withdraw from the cell cycle. Additional dorsal-to-ventral and temporal-to-nasal gradients can be discerned in our autoradiographs. In all retinal sectors, ganglion cells start first to withdraw from the cell cycle, followed, with substantial overlapping, by amacrine, horizontal, photoreceptor plus Müller, and bipolar neuroblasts. Ganglion cells are also the first to reach the 50% level of unlabelled cells, followed this time by horizontal, photoreceptor, amacrine, Müller and bipolar cells. Finally, 100% levels of unlabelled cell populations are attained simultaneously by ganglion, horizontal and photoreceptor cells, followed by amacrine, then by Müller, and last by bipolar cells. Although all classes of neurons, in varying proportions, are being produced most of the time, our results also demonstrate that, in any given retinal area, the first cells leaving the cycle are determined to become ganglion cells, and the last ones bipolar cells, and not other types.     

Nerve growth factor and striatal glutathione metabolism in a rat model of Huntington's disease

Purpose: To test the influence of nerve growth factor (NGF) on striatal glutathione (GSH) content and the activities of GSH-related enzymes from quinolinic acid-lesioned rats. Methods: Rats were intrastriatally injected with QA and NGF. Enzymatic and GSH assays were performed one week later. Results: NGF prevented the QA-induced decline in glutathione reductase activity and GSH content. Conclusions: NGF is able to prevent some of the disturbances induced by the excitotoxic insult in the striatal GSH metabolism.     

Phase II trial of fortnightly irinotecan (CPT-11) in the treatment of colorectal cancer patients resistant to previous fluoropyrimidine-based chemotherapy

Introduction This phase II study investigated the anti-tumour activity and toxicity of CPT-11 (250 mg/m2 i.v. infusion over 60 minutes) administered every 2 weeks as second-line chemotherapy in patients with advanced colorectal cancer (CRC). Material and methods Patients (n=63) with histology diagnosis of advanced CRC and proven resistance to previous fluoropyrimidine therapy were enrolled. Results A total of 510 CPT-11 cycles were administered, with a mean of 8 cycles per patient (range: 1–32). The median relative dose intensity was 93%. Partial response (PR) was obtained in 11 patients (17.5%; 95%CI: 8.1%–26.7%) and 29 patients (46.0%) showed stable disease (clinical benefit of 63.5%). The median duration of response was 6.8 months (95%CI: 6.1–7.5 months), median survival was 8.8 months (95%CI: 6.3–11.5 months) and median time to disease progression was 4.5 months (95%CI: 3.9–5.0 months). Overall, this schedule of CPT-11 chemotherapy was well tolerated by the patient. Neutropenia was the most frequent grade 3/4 haematological toxicity (20.6% of patients and 4.1% of cycles). Neutropenia with concurrent fever or infection occurred in 7 patients (11.1%). Late onset diarrhoea was the most frequent grade 3/4 non-haematological toxicity (19.0% of patients and 2.3% of cycles). Other, lower-incidence, toxicities were anaemia, fever, infection, mucositis, nausea and vomiting. There were no toxic deaths. Conclusions We found that CPT-11, administered as 250 mg/m² i.v. infusion over 60 minutes every 2 weeks, was active and well tolerated schedule in the second-line chemotherapy of advanced CRC patients. This bi-weekly scheme could be used as an alternative to the weekly or the every-three-week schedule as well as in combined therapies with other chemotherapeutic agents for the treatment of advanced, metastatic, CRC.     

Oftalmoplejía completa izquierda por metástasis ósea de cáncer de próstata

Prognosis in prostate cancer is determined, in greater part, by the presence of metastases. Bone metastases can occur in any part of the skeleton even, for example, at the base of the skull. We present a case of a 78 year old male who, in December 2001, presented with paralysis of the third cranial nerve. The NMR and CAT scans were normal and circulating levels of PSA were elevated. He was referred to the Urology Service where the treatment guidelines included complete androgen block. Subsequently, he developed retro-orbital pain, divergent strabismus and palpebral ptosis. CAT and NMR indicated a soft tissue mass at the sphenoid level. Treatment was Gamma Knife Radio-surgery. Since August 2004, in conjunction with the latest rise in PSA, the patient's general status deteriorated considerably and he was referred to the Oncology Service. there was an increase in the paralysis of the third, fourth and sixth cranial nerve (complete left ophthalmoplegia) and left-central facial paralysis. Metastases from prostate cancer can be disseminated via the lymphatic or the blood system. Currently, there are more metastases from large-size tumours. Metastases are critical in prostate cancer because of their adverse effect on the patient's survival. Measurements of circulating levels of prostate specific antigen and prostate acid phosphatase are very useful in the clinical diagnosis of the primary tumour, or its metastases.