Rhabdomyolysis Due to Severe Hypophosphatemia in Diabetic Ketoacidosis.

Rhabdomyolysis is a syndrome characterized by injury to skeletal muscle fibers with disruption and release of toxic metabolites into circulation. It is characterized by triad of muscle weakness, myalgia and dark urine and is associated with increased creatine kinase and lactate dehydrogenase. A severely malnourished 10 year old girl with severe diabetic ketoacidosis as hemr initial presentation of type 1 diabetes mellitus developed rhabdomyolysis (CK- 12,000 U/L) with non-oliguric renal failure during her initial course of hospital stay. The possible cause of her RM was attributed to severe hypophosphatemia (minimum serum phosphate, 0.8 mg/dL). Management of diabetic ketoacidosis phosphate supplementation and urinary alkalinization with diuresis improved her clinical course. She was discharged on Day 9 with Insulin. We recommend frequent monitoring of serum phosphate during early period of DKA, particularly in malnourished children, and its normalization in case of severe hypophosphatemia.

Conformal radiotherapy plus local hyperthermia in patients affected by locally advanced high risk prostate cancer: preliminary results of a prospective phase II study.

PURPOSE: Hyperthermia has been used in several trials to treat pelvic cancers without excessive toxicity and with positive results. The aim of this study was to evaluate feasibility and results in terms of biochemical recurrence-free, disease-free survival, overall survival, and treatment toxicity profile of hyperthermia combined with radiotherapy in locally advanced high risk prostate cancer. PATIENTS AND METHODS: From November 1998 to December 2004, 144 patients with locally advanced prostate cancer (LAPC) were enrolled in a phase II study. They were treated using conformal radiotherapy (CRT) plus local hyperthermia (LHT) and androgen suppression therapy (AST). Treatment modalities consisted of: 1) CRT with a mean dose of 74 Gy (2 Gy/fraction/5 fractions per week); 2) LHT: one session per week during the first, second, third, and fourth week of the radiotherapy course; 3) AST was administered as neo-adjuvant and adjuvant therapy in more than 60% of patients. RESULTS: The median follow-up time was 51.7 months. Four patients were lost at follow-up. Of 140 evaluated patients, four died because of intercurrent diseases and 12 because of progression of disease. Patients were evaluated in terms of five-year overall survival (87%), and five-year biochemical progression-free survival (49%). No significant side effects, except symptoms related to AST have been reported. No late grade 3 toxicity occurred. CONCLUSIONS: In advanced high risk prostatic cancer, hyperthermia is feasible and well tolerated. It may be useful to enhance the radiotherapy efficacy at intermediate dose in order to avoid higher doses of irradiation which increases acute and late sequelae. The advantage of LHT combined with CRT should be confirmed by a randomized phase III trial, comparing irradiation plus AST with or without hyperthermia.

A method for the quantitative evaluation of SAR distribution in deep regional hyperthermia.

The Specific Absorption Rate (SAR) distribution pattern visualization by a matrix of E-field light-emitting sensors has demonstrated to be a useful tool to evaluate the characteristics of the applicators used in deep regional hyperthermia and to perform a quality assurance programme. A method to quantify the SAR from photographs of the sensor array--the so-called 'Power Stepping Technique'--has already been proposed. This paper presents a new approach to the quantitative determination of the SAR profiles in a liquid phantom exposed to electromagnetic fields from the Sigma-60 applicator (BSD-2000 system for deep regional hyperthermia). The method is based on the construction of a 'calibration curve' modelling the light-output of an E-field sensor as a function of the supplied voltage and on the use of a reference light source to 'normalize' the light-output readings from the photos of the sensor array, in order to minimize the errors introduced by the non-uniformity of the photographic process. Once the calibration curve is obtained, it is possible, with only one photo, to obtain the quantitative SAR distribution in the operating conditions. For this reason, this method is suitable for equipment characterization and also for the control of the repeatability of power deposition in time.

Guinea-pig gonadotropin-releasing hormone: immunoreactivity and biological activity.

The DNA sequence of the encoding gene predicts a unique structure for guinea-pig gonadotropin-releasing hormone (GnRH). We assessed the immunoreactivity of synthetic mammalian GnRH, of a synthetic peptide with predicted guinea-pig GnRH structure, and of extracts from rat and guinea-pig hypothalami, using two different RIA systems. Whereas immunoreactivity of mammalian and guinea-pig GnRH was rather similar when using an antiserum with conformational specificity for mammalian GnRH (Root RR-5 antiserum), binding of both peptides to an antiserum with sequential specificity (Kelch R-13 antiserum) was markedly different. The findings for GnRH extracted from rat and guinea-pig hypothalami were similar to those for the corresponding synthetic peptides. Assessment of in-vivo biological activity of synthetic mammalian and guinea-pig GnRH in the intact male guinea-pig showed that both peptides stimulate LH secretion dose-dependently, the response to mammalian GnRH being slightly greater at low dose. This study confirms that the GnRH expressed in the brain of the adult guinea-pig differs from mammalian GnRH and indicates that mammalian and guinea-pig GnRH display conformational similarity and that both can stimulate guinea-pig luteinizing hormone secretion.

The N-methyl-D-aspartate-mediated inhibitory control of gonadotropin-releasing hormone release in the hypothalamus of the adult male guinea pig is expressed through opioidergic systems.

Previously, we reported on a dual role of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission in the control of GnRH secretion from the medial basal hypothalamus (MBH) of the adult male guinea pig, with a predominantly inhibitory action in the intact animal, which is reversed to a facilitatory role by orchidectomy. In the present study we examined the hypothesis that endogenous opioids are involved in the NMDA receptor-mediated inhibition of GnRH release. A static incubation system was used to test the effects of excitatory amino acid agonists and an excitatory amino acid antagonist, alone or in the presence of either the opiate agonist morphine or the mu-receptor antagonist naloxone, on in vitro GnRH release from the isolated MBH of intact, orchidectomized, or sham-operated guinea pigs. GnRH output from the MBH of intact guinea pigs was markedly suppressed in the presence of the NMDA-specific receptor agonist, N-methyl-D,L-aspartic acid (NMA; 50 mM), whereas NMDA-specific receptor blockade with D,L-amino-5-phosphonovaleric acid (AP-5; 1 mM) resulted in a pronounced facilitation of GnRH release, as did exposure to the non-NMDA-specific receptor agonist, kainic acid (50 mM). Opioidergic blockade with naloxone (1 mM) caused a reversal of the responses to NMA and AP-5, with exposure to these compounds this time resulting in clear facilitation and inhibition, respectively. The stimulatory action of kainic acid, on the other hand, remained unaffected by the presence of naloxone. Morphine inhibited basal GnRH output and also annulled the stimulatory effect of AP-5 on GnRH secretion. The results obtained from MBHs of sham-operated guinea pigs were identical to those seen for the intact animals, with naloxone effectively increasing baseline GnRH release and reversing the inhibitory effect of NMA and stimulatory action of AP-5 on GnRH secretion to a facilitation and inhibition, respectively. On the other hand, NMA caused a marked stimulation, whereas AP-5 produced a significant inhibition of GnRH release from the MBHs of orchidectomized guinea pigs; neither of these effects was altered by the presence of naloxone, which, moreover, had only a marginal effect on basal GnRH output in this group of animals. In conclusion, our present data provide evidence to support the view that the primary inhibitory action of NMDA receptor-mediated neurotransmission on GnRH release in the MBH of the intact male guinea pig is the result of activation of opioidergic systems and that a marked reduction of opioid tone after orchidectomy brings a facilitatory NMDA receptor-mediated system to the fore. On the other hand, non-NMDA-specific kainate receptor-mediated facilitation of GnRH, previously shown to be unaffected by gonadal status, appears to be also independent from opioidergic modulation.

Involvement of neuroexcitatory amino acids in the control of gonadotropin-releasing hormone release from the hypothalamus of the adult male guinea pig: predominantly inhibitory action of N-methyl-D-aspartate-mediated neurotransmission and its reversal after orchidectomy.

Excitatory amino acids (EAA) have been implicated in the control of LH secretion through facilitation of GnRH release, although disparate findings of an inhibitory effect of EAA on LH secretion in several species after gonadectomy have been reported. Using a static incubation system, we studied the effects of EAA receptor agonists and antagonists on in vitro GnRH release from the isolated medial basal hypothalamus (MBH) of the male guinea pig. In the presence of 0.4 mM glycine, the N-methyl-D-aspartate (NMDA)-specific receptor agonist N-methyl-D,L-aspartic acid (NMA) exerted a dose-dependent inhibition of GnRH output from the MBH of intact guinea pigs, which was significant (P < or = 0.01) at concentrations of 1 and 50 mM. The NMDA-specific receptor antagonist D,L-2-amino-5-phosphonovaleric acid (AP-5) significantly stimulated GnRH release at 10(-3) and 1 mM (P < or = 0.001) and was ineffective at 10(-6) mM. NMA (50 mM) and AP-5 (1 mM) produced similar effects when tested at a lower glycine concentration of 10 nM. The presence of the two compounds together resulted in overall unchanged GnRH output. The inhibitory effect of 50 mM NMA was also effectively blocked in the presence of 2 mM Mg2+ at both high and low glycine concentrations. When, for comparative purposes, isolated MBHs of 50-day-old intact male rats were exposed to 50 mM NMA, a response opposite to that seen in the intact guinea pig was observed, with a marked increase in GnRH output (P < or = 0.001). When tested at 10 nM glycine, 50 mM kainic acid, a non-NMDA-specific receptor agonist, on the other hand, had a marked stimulatory effect on GnRH output (P < or = 0.01) from intact guinea pig MBHs, an action that was prevented in the presence of the kainate/quisqualate receptor antagonist 6,7-dinitro-quinoxaline-2,3-dione (0.1 mM); 6,7-dinitro-quinoxaline-2,3-dione alone inhibited GnRH release (P < or = 0.01). In a separate series of experiments, the effects of EAA (in the presence of 10 nM glycine) on GnRH release from the MBHs of long term orchidectomized and sham-operated guinea pigs were compared. Orchidectomy led to a dramatic reversal of the NMDA-mediated inhibition of GnRH secretion observed in MBHs of sham-operated animals, with 50 mM NMA producing a marked increase (P < or = 0.0001) and 1 mM AP-5 resulting in a clear inhibition (P < or = 0.0001) of GnRH release. Kainic acid (50 mM), on the other hand, had a similar stimulatory action on GnRH release from the MBHs of both orchidectomized (P < or = 0.0001) and sham-castrated (P < or = 0.001) guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)