[Localization diagnostics and operative strategy for the first intervention in sporadic primary hyperparathyroidism]. / Lokalisationsdiagnostik und Operationsstrategie beim Ersteingriff bei sporadischem primärem Hyperparathyreoidismus.

Primary hyperparathyroidism (pHPT) is a frequent endocrine disease, the incidence of which is clearly increasing. In addition to the classical symptoms of bone pain, osteoporosis and renal calculi, nonspecific complaints, such as listlessness and exhaustion, anxiety states and depressive symptoms also often occur. The diagnosis is simple and is carried out by determination of calcium and parathormone (PTH) serum levels. The majority of parathyroid adenomas can be localized by ultrasound and Tc-99m-MIBI scintigraphy. The indications for surgery can normally already be identified by the laboratory biochemical detection. Surgery is the only curative treatment of pHPT and is normally successful. In addition to bilateral exploration, a focused parathyroidectomy can be planned. The success of surgery can be intraoperatively documented by the determination of intraoperative Quick PTH (IOPTH).

[Hereditary medullary thyroid cancer]. / Hereditäres medulläres Schilddrüsenkarzinom.

Parafollicular C cells progress via C cell hyperplasia to medullary thyroid cancer (MTC), which can be present even in the first years of life in multiple endocrine neoplasia (MEN) type 2A and 2B patients. Basal calcitonin and carcinoembryonic antigen (CEA) are useful tumor markers for the diagnosis and monitoring. The prognosis depends on the stage when the disease is diagnosed and there is a good genotype-phenotype correlation with the RET proto-oncogene, which can be used for estimation of the risk. The risk-stratified prophylactic thyroidectomy plays a decisive role in the prognosis of known gene mutation carriers.

The South Asian monsoon-pollution pump and purifier.

Air pollution is growing fastest in monsoon-affected South Asia. During the dry winter monsoon, the fumes disperse toward the Indian Ocean, creating a vast pollution haze, but their fate during the wet summer monsoon has been unclear. We performed atmospheric chemistry measurements by aircraft in the Oxidation Mechanism Observations campaign, sampling the summer monsoon outflow in the upper troposphere between the Mediterranean and the Indian Ocean. The measurements, supported by model calculations, show that the monsoon sustains a remarkably efficient cleansing mechanism by which contaminants are rapidly oxidized and deposited to Earth's surface. However, some pollutants are lofted above the monsoon clouds and chemically processed in a reactive reservoir before being redistributed globally, including to the stratosphere.

Reduced residual gene expression of nuclear factor of activated T cells-regulated genes correlates with the risk of cytomegalovirus infection after liver transplantation.

BACKGROUND: Pharmacokinetic monitoring of calcineurin inhibitors (CNIs) is unsatisfactory because, at comparable blood concentrations, side effects vary considerably. We recently confirmed the applicability of a pharmacodynamic (PD) assay that measures the suppression of CNI target genes, specifically the suppression of nuclear factor of activated T cells (NFAT)-regulated genes in liver transplant (LT) recipients. The aim of this prospective study was to prove the clinical reliability of this assay. Therefore, we quantified the residual gene expression (RGE) of NFAT-regulated genes and evaluated the association between the RGE of NFAT-regulated genes and the incidence of cytomegalovirus (CMV) infection. PATIENTS AND METHODS: In 20 LT recipients, 10 patients on cyclosporine (CsA) and 10 patients on tacrolimus (Tac) therapy, who presented with CMV infection, the RGEs of interleukin-2, interferon-γ (IFNγ), and granulocyte-monocyte colony-stimulating factor were measured and compared with the RGEs of these cytokines in 40 healthy dose-matched LT controls. RESULTS: CsA-treated CMV patients demonstrated a lower RGE of all NFAT-regulated genes compared with controls (30 ± 17 vs. 44 ± 20, P = 0.067). For IFNγ, the level of significance was reached (26 ± 17 vs. 43 ± 17, P = 0.0125). Daily CsA dosage, CsA baseline (C0 ) and 2 h (C2 ) concentrations were comparable (CsA dosage 169 mg/day vs. 165 mg/day; CsA C0 94 µg/L vs. 85 µg/L; CsA C2 389 µg/L vs. 381 µg/L). In addition, Tac-treated CMV patients demonstrated a lower RGE of all NFAT-regulated genes compared with controls (68 ± 25 vs. 84 ± 22, P = 0.0769). Analogous to CsA-treated CMV patients, the level of significance was reached for IFNγ (61 ± 24 vs. 88 ± 29, P = 0.0154). Daily Tac dosage and Tac 1.5 h concentrations (C1.5 ) were comparable in both groups (Tac dosage 4 mg/day vs. 4 mg/day; Tac C1.5 8 µg/L vs. 10 µg/L), whereas Tac C0 concentrations were significantly higher in controls (Tac C0 4 µg/L vs. 6 µg/L, P = 0.0276). CONCLUSION: Measuring the RGE of NFAT-regulated genes is appropriate to assess the risk of infections in LT recipients. Measuring the RGE of IFNγ is particularly suitable to assess the risk of CMV infection. PD monitoring of CNIs in LT recipients is an approach to individualize immunosuppression, which may help to reduce infectious complications.

Increased dissolution and physical stability of micronized nifedipine particles encapsulated with a biocompatible polymer and surfactants in a wet ball milling process.

Suspensions of nifedipine, a practically water-insoluble drug, were prepared in the presence of a biocompatible polymer, polyvinylpyrrolidone (PVP, K value 17), and three surfactants, sodium lauryl sulfate (SLS, anionic), cetyltrimethylammonium bromide (CETAB, cationic), polysorbate 80 (Tween 80, nonionic), by wet milling in ceramic ball mills. Nifedipine powders encapsulated with PVP and the surfactants were recovered from the suspensions after milling and evaluated for changes in particle size, morphology, sedimentation rate in aqueous suspensions, crystal form, and dissolution. Particle size analysis indicated that milling of suspensions in solutions of PVP and surfactants is an efficient method for reducing the particle size of nifedipine to below 10 microm. Furthermore, DSC and XPS analysis indicated that during milling the nifedipine crystals were coated with the PVP or surfactants and that milling with PVP stabilized the nifedipine crystal form during milling while nifedipine was gradually amorphisized when milled in a quaternary nifedipine/PVP/SLS/CETAB system. The decrease in particle size caused a significant decrease in sedimentation rate and increased the dissolution rate of nifedipine in simulated gastric fluid when compared to milled nifedipine and powder mixtures of the drug and the excipients.

Retarded release phosphatidylcholine benefits patients with chronic active ulcerative colitis.

BACKGROUND AND AIMS: We examined the hypothesis of an anti-inflammatory effect of phosphatidylcholine in ulcerative colitis. METHODS: A phase IIA, double blind, randomised, placebo controlled study was performed in 60 patients with chronic active, non steroid dependent, ulcerative colitis, with a clinical activity index (CAI) of > or = 4. Retarded release phosphatidylcholine rich phospholipids and placebo were administered at a dose of 6 g daily over three months. The primary end point was a change in CAI towards clinical remission (CAI < or = 3) or CAI improvement by > or = 50%. Secondary end points included > or = 50% changes in endoscopic activity index (EAI), histology, and quality of life scores. RESULTS: Induction of clinical remission (CAI < or = 3) as the primary outcome variable was attained by 16 (53%) patients in the phosphatidylcholine treated group compared with three (10%) in the placebo group (p<0.00001). The rate of clinical remission and CAI improvement was 90% in the phosphatidylcholine group and only 10% in the placebo group. A median drop of seven points in the CAI score (70% improvement) was recorded in the phosphatidylcholine group compared with no change in the placebo group. Secondary end point analysis revealed concomitant drops in EAI and histology scores (p = 0.00016 and p = 0.0067 compared with placebo, respectively). Improvement in quality of life was reported by 16 of 29 evaluated patients in the phosphatidylcholine group compared with two of 30 in the placebo group (p = 0.00005). CONCLUSION: Retarded release oral phosphatidylcholine is effective in alleviating inflammatory activity caused by ulcerative colitis.

Measurement of gastric emptying by 13C-octanoic acid breath test versus scintigraphy in diabetics.

In this prospective study, we compared the assessment of gastric emptying by the 13C-octanoic acid breath test to gastric emptying scintigraphy in diabetics. We also examined the relationship between gastric emptying parameters and gastric symptoms and cardiovascular autonomic function. The 13C-octanoic acid breath test and scintigraphy were performed simultaneously in 24 diabetics with a solid test meal (1 egg, doubly labelled with 91 mg 13C-octanoic acid and 50 MBq 99mTechnetium-Nanocoll, 60 g white bread, 5 g margarine and 150 ml water). At fifteen-minute intervals, breath samples were taken over 4 hours and examined by mass spectrometry. In parallel, scintigraphy was performed for 2 hours at one minute intervals. Using breath test data, gastric emptying half time (t (1/2) ), lag-phase (t lag ) and gastric emptying coefficient (GEC) were calculated. Subsequently, the correlation of these results with the equivalent data from scintigraphy were determined employing a regression method. To detect a cardiovascular autonomic neuropathy, a 24-h ECG recording was performed. The prevalence of gastrointestinal symptoms in our collective was assessed by a standardized questionnaire. There was a highly significant positive correlation of both 13C-octanoic acid breath test t (1/2) and scintigraphic t (1/2) (r = 0.8257; p < 0.0001) and 13C-octanoic acid breath test t lag and scintigraphic t lag (r = 0.6302; p < 0.001). The sensitivity of the 13C-octanoic acid breath test was 1 and the specificity was 0.73. In our study, there was no significant association of cardiovascular and gastrointestinal autonomic neuropathy. Furthermore, there was no significant relationship between the prevalence of gastrointestinal symptoms and gastric emptying disorders. We conclude that the 13C-octanoic acid breath test represents a suitable method to measure disordered gastric emptying in diabetics due to its highly significant positive correlation to scintigraphy and due to its validity. It is not possible to predict diabetic gastroparesis on the basis of other autonomic function disorders or because of dyspeptic symptoms.

Vegetative endocarditis in six cats.

Between 1990 and 1997 vegetative endocarditis was diagnosed in six neutered cats (three males, three females) aged between 3 and 9 years. Two cats were purebred (one Persian and one Tonkinese), the remaining four being domestic short haired cats. The diagnosis was made using echocardiography (five cases) or at necropsy (one case). Concurrent involvement of the aortic and mitral valve was noted in four cats, the aortic valve alone was affected in one case, and the tricuspid valve in another. A likely microbiological diagnosis was obtained in three cats: a Bartonella species in two cats based on positive blood culture and a Streptococcus species in one cat based on Gram stain of valve lesions at necropsy. In another cat, Gram-positive cocci were demonstrated histologically in tricuspid vegetations. Invariably, cats had signs of congestive heart failure (left-sided in five cats, right-sided in one), and this was the major factor contributing to mortality in four cases. Signs referable to sepsis were prominent in only two patients. Appropriate medical therapy, consisting of antimicrobials and drugs to treat congestive heart failure, resulted in survival for 5 and 11 months, respectively, in two cases. The other cats died within 2 weeks of diagnosis, including two which received aggressive treatment in hospital.

Comparison of a colorimetric end-tidal CO2 detector and an esophageal aspiration device for verifying endotracheal tube placement in the prehospital setting: a six-month experience.

INTRODUCTION: Hand held, colorimetric, end-tidal CO2 detector devices are being used to verify correct endotracheal tube (ETT) placement. The accuracy of these devices has been questioned in situations of cardiac arrest. The use of the esophageal detector device (EDD) is an easy alternative for detection of ETT placement, and may be more accurate in situations of cardiac arrest. HYPOTHESIS: The use of the esophageal aspiration device in comparison with a colorimetric end-tidal CO2 detector is more accurate in detecting proper ETT placement and easier to use in the prehospital setting than is the colorimetric end-tidal CO2 detection device. METHODS: This was prospective alternating weeks, 6-month study in a prehospital setting. Participants included all patients older than 18 years who were intubated by the Portsmouth, Virginia Emergency Medical Services (EMS) personnel from 01 July 1993 through 31 December 1993. The aspiration device used, also known as an esophageal detector device (EDD), was a 60 ml, luer-lock syringe attached to a 15 mm ETT adapter. Its efficacy was compared with an already accepted method of ETT position detection, the colorimetric end-tidal CO2 detector. Each device was used on alternating weeks, and correct ETT placement was determined by the receiving emergency department physician using standard techniques. Chi-square analysis and Fisher's Exact test were used to compare parameters, time of device use, and ease of use. Sensitivity and specificity were calculated, and provider preference was assessed using a survey instrument administered following completion of the study. RESULTS: There were 49 patients who met the inclusion criteria, but six were excluded because of situational circumstances rendering use of the device a possible compromise of patient care. Twenty-five patients were in the EDD group, and 18 were in the end-tidal CO2 detector group. There was no statistically significant difference detected between groups for the gender ratio, underlying condition, CPR in progress, perceived difficulty of intubation, or percentage of nasotracheal intubation. The EDD was significantly easier to use (p < 0.005). There was no statistically significant difference in time required for use of end-tidal CO2 detector device versus the EDD. The sensitivity and specificity for correct tracheal placement using the EDD was 100%, and the sensitivity for correct tracheal placement using the end-tidal CO2 detector device was 78%. Use of the EDD was preferred over use of the end-tidal CO2 detector device by 75% of participating EMS providers. One case of nasotracheal intubation with an ETT placement above the cords raised the question of accuracy of this device in situations where direct visualization is not utilized. CONCLUSION: The EDD was accurate in all cases of orotracheal intubation, and was easier to use than was end-tidal CO2 detector device. It was preferred by 75% of participating EMS providers. In cases in which the ETT may be above the vocal cords, caution must be used with interpreting the results obtained by use of the EDD.