Riscos da suplementação com doses excessivas de vitamina D / Risks of Supplementation with Excessive Doses of Vitamin D

A intoxicação por vitamina D era pouco frequente no Brasil até seu crescente uso na última década. Neste artigo relatamos um caso de intoxicação por vitamina D em que houve a prescrição intencional de dose muito superior ao recomendado pela literatura, com a finalidade de prevenir doenças via "modulação hormonal". A paciente em questão, idosa, previamente hígida, foi submetida a um tratamento não regulamentado e sem respaldo científico, que culminou em sintomas como náuseas e vômitos, além de perda de peso, inapetência, poliúria e astenia ao longo dos meses. Através da história e exames laboratoriais foi diagnosticada intoxicação por vitamina D e lesão renal aguda. Após o tratamento houve remissão completa dos sintomas. A "modulação hormonal" é uma prática condenada pelos Conselhos Federais de Medicina e Odontologia e pela Sociedade Brasileira de Endocrinologia e Metabologia. O ato de prescrever é de grande responsabilidade ética e técnica e deve ser embasado em evidências científicas, oferecendo o melhor tratamento possível aos pacientes, seja ele preventivo ou curativo, minimizando riscos e danos, respeitando as recomendações das autoridades competentes. (AU)

Vitamin D poisoning was not frequent in Brazil until its increasing use in the last decade. In this article, we report a case of intoxication by intentional prescription of vitamin D in a much higher dose than the literature recommends, in order to prevent diseases via "hormonal modulation". The case described in this report was an elderly woman, previously healthy patient that was submitted to an unregulated treatment without scientific support, leading to symptoms such as nausea and vomiting, in addition to weight loss, lack of appetite, polyuria and asthenia over the months. Through the history and laboratory testing, vitamin D intoxication and acute kidney injury were diagnosed. After treatment, there was a complete remission of the symptoms. "Hormonal modulation" is a practice condemned by the Federal Councils of Medicine and Dentistry and by the Brazilian Society of Endocrinology and Metabology. The act of prescribing is of great ethical and technical responsibility and it must be based on scientific evidence. Thus, the patient can receive the best possible treatment, for either preventive or curative nature, by respecting the recommendations of the competent authorities and, therefore, minimizing risks and damages to patients. (AU)

The current practice of cytoreductive surgery and HIPEC for colorectal peritoneal metastases: Results of a worldwide web-based survey of the Peritoneal Surface Oncology Group International (PSOGI).

BACKGROUND: At present, selected patients with resectable colorectal peritoneal metastases (CRC-PM) are increasingly treated with a combination therapy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to investigate the current worldwide practice. METHODS: HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning their personal expertise and current hospital and countrywide practice. RESULTS: It is estimated that currently more than 3800 patients with CRC-PM (synchronous and metachronous) are annually treated with CRS and HIPEC in 430 centers. Integration of CRS and HIPEC in national guidelines varies, resulting in large treatment disparities between countries. Amongst the experts, there was general agreement on issues related to indication, surgical technique and follow up but less on systemic chemotherapy or proactive strategies. CONCLUSION: This international survey demonstrates that CRS and HIPEC is now performed on a large scale for CRC-PM patients. Variation in treatment may result in heterogeneity in surgical and oncological outcomes, emphasising the necessity to reach consensus on several issues of this comprehensive procedure. Future initiatives directed at achieving an international consensus statement are needed.

Nutrient and light limitation of periphyton in the River Thames: implications for catchment management.

Soluble reactive phosphorus (SRP) concentrations in the River Thames, south east England, have significantly decreased from an annual maximum of 2100 µg l(-1) in 1997 to 344 in 2010, primarily due to the introduction of phosphorus (P) removal at sewage treatment works within the catchment. However, despite this improvement in water quality, phytoplankton biomass in the River Thames has greatly increased in recent years, with peak chlorophyll concentrations increasing from 87 µg l(-1) in the period 1997 to 2002, to 328 µg l(-1) in 2009. A series of within-river flume mesocosm experiments were performed to determine the effect of changing nutrient concentrations and light levels on periphyton biomass accrual. Nutrient enrichment experiments showed that phosphorus, nitrogen and silicon were not limiting or co-limiting periphyton growth in the Thames at the time of the experiment (August-September 2010). Decreasing ambient SRP concentration from 225 µg l(-1) to 173 µg l(-1) had no effect on periphyton biomass accrual rate or diatom assemblage. Phosphorus limitation became apparent at 83 µg SRP l(-1), at which point a 25% reduction in periphyton biomass was observed. Diatom assemblage significantly changed when the SRP concentration was reduced to 30 µg l(-1). Such stringent phosphorus targets are costly and difficult to achieve for the River Thames, due to the high population density and intensive agriculture within the Thames basin. Reducing light levels by shading reduced the periphyton accrual rate by 50%. Providing shading along the River Thames by planting riparian tree cover could be an effective measure to reduce the risk of excessive algal growth. If the ecology of the Thames is to reach the WFD's "good ecological status", then both SRP concentration reductions (probably to below 100 µg l(-1)) and increased shading will be required.

Application of a fuzzy logic control system for continuous anaerobic digestion of low buffered, acidic energy crops as mono-substrate.

A fuzzy logic control (FLC) system was developed at the Hamburg University of Applied Sciences (HAW Hamburg) for operation of biogas reactors running on energy crops. Three commercially available measuring parameters, namely pH, the methane (CH4) content, and the specific gas production rate (spec. GPR = m(3)/kg VS/day) were included. The objective was to avoid stabilization of pH with use of buffering supplements, like lime or manure. The developed FLC system can cover most of all applications, such as a careful start-up process and a gentle recovery strategy after a severe reactor failure, also enabling a process with a high organic loading rate (OLR) and a low hydraulic retention time (HRT), that is, a high throughput anaerobic digestion process with a stable pH and CH4 content. A precondition for a high load process was the concept of interval feeding, for example, with 8 h of interval. The FLC system was proved to be reliable during the long term fermentation studies over 3 years in one-stage, completely stirred tank reactors (CSTR) with acidic beet silage as mono-input (pH 3.3-3.4). During fermentation of the fodder beet silage (FBS), a stable HRT of 6.0 days with an OLR of up to 15 kg VS/m(3)/day and a volumetric GPR of 9 m(3)/m(3)/day could be reached. The FLC enabled an automatic recovery of the digester after two induced severe reactor failures. In another attempt to prove the feasibility of the FLC, substrate FBS was changed to sugar beet silage (SBS), which had a substantially lower buffering capacity than that of the FBS. With SBS, the FLC accomplished a stable fermentation at a pH level between 6.5 and 6.6, and a volatile fatty acid level (VFA) below 500 mg/L, but the FLC had to interact and to change the substrate dosage permanently. In a further experiment, the reactor temperature was increased from 41 to 50 degrees C. Concomitantly, the specific GPR, pH and CH4 dropped down. Finally, the FLC automatically enabled a complete recovery in 16 days.

Improving laser-induced thermotherapy of liver metastases--effects of arterial microembolization and complete blood flow occlusion.

INTRODUCTION: A prerequisite for an oncologically curative application of laser-induced thermotherapy (LITT) of liver metastases is complete tumor destruction. This increased effectiveness was achieved experimentally by combining LITT with interrupted hepatic perfusion. The aim of this study was to evaluate whether an interventional selective arterial microembolization might be as effective as complete blood flow occlusion using an open Pringle's maneuver. PATIENTS AND METHODS: We included patients with unresectable colorectal liver metastases. LITT was performed without interrupted hepatic perfusion (control group) compared to LITT in combination with interrupted perfusion either by embolization of intraarterial degradable starch microspheres (DSM) (percutaneous access) or by complete hepatic inflow occlusion (Pringle's maneuver; open access). Online monitoring was performed using intraoperative ultrasound or MRI. Volumetric techniques were used to assess metastases and postinterventional lesions. RESULTS: Fifty-six patients with 104 metastases (control group (25), DSM (37), and Pringle (42)) were treated. The preinterventional tumor volumes were significantly smaller than the postinterventional lesion volumes (control group: 9.8 vs. 25.3 cm3; DSM: 9.5 vs. 65.4 cm3; Pringle: 12.9 vs. 76.5 cm3). The morbidity rate was 21.4% without treatment-related mortalities. After 6 months follow-up, tumor recurrence was diagnosed in 6 patients (control group (4), LITT with DSM (1), and Pringle (1)). CONCLUSIONS: Combining LITT with blood flow occlusion leads to a significant increase in lesion size. The application of DSM offers a safe and effective alternative to the open access with Pringle's maneuver. Compared to LITT-monotherapy, this modality achieves significantly larger thermal lesions with the need of fewer applications.

Isolation rearing or methamphetamine traumatisation induce a "dysconnection" of prefrontal efferents in gerbils: implications for schizophrenia.

A miswiring of prefrontal efferents is generally discussed by the name of "dysconnection" as the anatomical substrate of schizophrenia. Since direct histological confirmation of this hypothesis can hardly be obtained in humans, we used an animal model of schizophrenia to trace prefrontal efferents to distal cortical fields. Mongolian gerbils were intoxicated with a single high dose of methamphetamine on postnatal day 14 and reared in isolation after weaning (day 30). Controls received a saline injection and/or were reared under enriched conditions. Upon reaching adulthood (day 90), biocytin was injected into the medial prefrontal cortex into either deep or superficial laminae. The density of passing fibres and terminal fields in the frontal, parietal and insular cortices was assessed by digital image analysis. Isolation rearing or methamphetamine treatment alone reduced the projections from lamina V/VI to the frontal and from lamina III to the insular cortex, and from both laminae to the parietal cortex. In contrast, isolation rearing of methamphetamine-intoxicated gerbils significantly increased the projections from the deep laminae to the frontal and parietal cortices, compared to isolation-reared controls, with no difference in the efferents from superficial laminae. These results are the first to demonstrate a miswiring of prefrontal efferents in response to adverse systemic influences. They might give a hint at the anatomical basis of "dysconnection" in schizophrenia.

Laser-induced thermotherapy: intra- and extralesionary recurrence after incomplete destruction of experimental liver metastasis.

PURPOSE: The aim of this study was to determine the energy (J/mm3 tumor volume) and temperature required for a complete laser-induced thermotherapy (LITT) of experimental liver tumors, and to find out causes and areas of local recurrence followed by incomplete treatment. METHODS: In VX-2 tumor-bearing rabbits LITT was performed using neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (1064 nm) with a diffuser-tip applicator and a temperature feedback system. The animals were randomized into four groups (n = 20) that differed in the target temperature at the tumor border as follows: 45 degrees C, 50 degrees C, 55 degrees C and 60 degrees C. The target temperature was held for 10 min constant. Histologic examination (hematoxylin and eosin [H and E], nicotinamide adenine dinucleotide phosphate [NADPH]-dehydrogenase) was performed at 0 h, 24 h, 96 h, and 14 days after LITT. RESULTS: The pretreatment tumor volume of 2191 +/- 61 mm3 was the same for all groups (p > 0.05). Energy up to target temperature and total energy required, lesion size, and the rate of incomplete tumor ablation (recurrences) are listed below (ap < 0.05, Kruskal-Wallis test). Histologically, two forms of local recurrences could be differentiated intralesionary and extralesionary. CONCLUSIONS: To achieve complete in situ ablation under the given conditions, it is necessary to apply laser energy of 3 J/mm3 tumor volume. A minimum temperature of 60 degrees C on the tumor border presumed an application of 10 min. Recurrence was found outside the coagulation zone (extralesionary) and in high vascularized areas within the coagulation zone (intralesionary).

The contrast-detail behaviour of a photostimulable phosphor based computed radiography system.

Contrast-detail measurements were performed on a computed radiography imaging system as a function of detector entrance air kerma over the dose range from 0.743 microGy (0.085 mR) to 277 microGy (31.8 mR). A theoretical model of contrast-detail behaviour for a photostimulable phosphor computed radiography system has been derived, which is based on a modified version of the Rose theory of threshold detection. Included in the model are both system and x-ray quantum noise terms, as well as the response of the eye. The zero-frequency noise power of the computed film images was measured with a double-beam scanning microdensitometer. For a given detector dose, good agreement was found between the predicted and measured data when this measurement of system noise was included in the model. The contrast-detail results obtained for the computed radiography system were also compared with contrast-detail results for an image intensifier-TV based digital imaging system and a conventional film-screen system.

[Circulatory changes with urapidil (Ebrantil) in general and regional anesthesia. Studies with normo- and hypertensive patients]. / Kreislaufveränderungen unter Urapidil (Ebrantil) in Allgemein- und Regionalanaesthesie. Untersuchungen mit normo- und hypertensiven Patienten.

Urapidil (Ebrantil) is a new antihypertensive agent exerting central and peripheral action which is recognized for the treatment of both chronic and acute hypertension. The purpose of the present study was to investigate the extent of the antihypertensive effect of urapidil in various forms of general or regional anaesthesia. To this end, a retrospective analysis was first carried out on the typical reactions of the circulatory system in 200 patients during either neuroleptanalgesia with diazepam and droperidol, or halothane, enflurane or intrathecal local anaesthesia. In a prospective study, each of 5 normo- or hypertensive patients undergoing elective surgery with one of the aforementioned anaesthetic procedures received 50 mg urapidil intravenously 25-30 min after start of anaesthesia. Blood pressure and heart rate measurements were performed for up to 24 h after the injection. Whereas anaesthesia alone caused a moderate drop in systolic and diastolic blood pressure of 3.1 and 2.1%, respectively (in normotensive patients), and of 12.0 and 6.7%, respectively (in hypertensive patients), urapidil caused a further significant fall in blood pressure in the hypertensive patients within a few minutes, but not in the normotensive groups. This effect was particularly pronounced under spinal anaesthesia and usually persisted until the end of the operation. Heart rate was (not significantly) increased for a few minutes after administration of urapidil. Temporary blood pressure reduction to hypotensive values was observed in 2 of the 50 patients only. From the results it is concluded that urapidil is an effective and relatively safe drug for the treatment of elevated blood pressure during routine surgery. Even if it has been administered on the basis of wrong indication (e.g. hypertensive phases as a result of insufficient anaesthesia), it rarely will cause blood pressure to fall to undesired low levels after anaesthesia has been normalized.

[The kinetics of lithium in the rat serum, brain and liver]. / Die Kinetik von Lithium in Serum, Leber und Gehirn der Ratte

The kinetics of lithium in the serum, liver and brain of rats is described. The serum levels resembled those of man, whereas considerable quantitative differences were observed when comparing specific kinetic parameters. The brain level increased with the increasing doses, approaching the corresponding serum level. Concentration differences between different brain areas could be observed only after repeated administrations. Striatum, cortex and hippocampus showed significantly higher levels than the thalamus. The liver content remained low with increasing doses, and was below the brain level.