The use of a new hydrophilic polymer, Kollicoat IR, in the formulation of solid dispersions of Itraconazole.

Kollicoat IR, a new pharmaceutical excipient developed as a coating polymer for instant release tablets, was evaluated as a carrier in solid dispersions of Itraconazole. The solid dispersions were prepared by hot stage extrusion. Modulated temperature differential scanning calorimetry and X-ray powder diffraction were used to evaluate the miscibility of the drug and the carrier. The pharmaceutical performance was evaluated by dissolution experiments, performed in simulated gastric fluid without pepsin (SGF(sp)). In the X-ray diffractograms no Itraconazole peaks were visible; the polymer on the other hand appeared to be semi-crystalline. Moreover, its crystallinity increased during the extrusion process due to exposure to heat and shear forces. Modulated temperature differential scanning calorimetry analysis showed that the drug and the polymer formed a two phase system. Separate clusters of glassy Itraconazole were present for drug loads of 40% or higher, indicating further phase separation. Dissolution measurements demonstrated a significantly increased dissolution rate for the solid dispersions compared to physical mixtures. Interestingly the physical mixture made up of glassy Itraconazole and Kollicoat IR (20/80, w/w) showed a dissolution rate and maximum that was much higher than that of the physical mixture made up of crystalline Itraconazole and that of pure glassy Itraconazole. The results of this study show that Kollicoat IR is a promising excipient for the formulation of solid dispersions of Itraconazole prepared by hot stage extrusion.     

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Infarktbedingter kardiogener Schock

Cardiogenic shock remains the major cause of death among patients with acute myocardial infarction. Besides supportive therapy there is clear evidence that revascularization of the infarct related artery should be performed as soon as possible with percutaneous transluminal coronary angioplasty. Placement of coronary stents and administration of platelet glycoprotein IIb/IIIa antagonists may further improve outcome. Intra-aortic balloon pumping should be integral part of this treatment strategy but is unfortunately underused in clinical practice. Routine bypass surgery for cardiogenic shock patients is deferred and restricted to selected patients.     

Plasma metallothionein concentration in patients with liver disorders: special emphasis on the relation with primary biliary cirrhosis

The plasma metallothionein concentration was evaluated in healthy subjects and in patients with several types of liver disorders. Plasma metallothionein concentrations in controls varied between 2.4 and 4.8 ng/ml. Patients with disorders associated with increased liver copper concentrations (i.e., primary biliary cirrhosis and primary sclerosing cholangitis) had significantly (both p less than 0.002) elevated plasma metallothionein concentrations (range = 1.8 to 52.2 ng/ml), and a considerable number of these were above the maximum control level (21 of 41 patients). In contrast, patients with liver disorders not associated with increased liver copper concentrations (alcoholic and cryptogenic cirrhosis, and acute viral and chronic active hepatitis) generally had normal plasma metallothionein concentrations and only a few were above the maximum control level (11 of 64 patients, maximum = 8.8 ng/ml). The metallothionein concentrations in plasma samples from patients in stage I or II primary biliary cirrhosis were within or slightly above the control range, whereas most patients in stage III had elevated levels (p less than 0.002), and almost all patients in stage IV had clearly elevated (p less than 0.0001) concentrations. In primary biliary cirrhosis the plasma metallothionein concentration tended to increase during the evolution of the disorder, and the concentration correlated significantly with the serum total bilirubin concentration. In conclusion, the plasma metallothionein concentration is significantly elevated in patients with primary biliary cirrhosis and in patients with primary sclerosing cholangitis. Although related to the histological stage of primary biliary cirrhosis, the measurement of plasma metallothionein concentrations contributes little to the diagnosis or the evaluation of the severity of these disorders.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distinction between renal and nonrenal hematuria using immunoperoxidase staining of erythrocytes in urine for Tamm-Horsfall protein]

A recently described immunocytochemical staining method to distinguish renal from non-renal haematuria was adapted for use in the standard clinical chemical laboratory. The method is based on the observation that only in case of renal haematuria are erythrocytes in urine coated with so-called Tamm-Horsfall protein, originating from the renal tubuli. Erythrocytes in urine were stained using an indirect immunoperoxidase method, resulting in cells with dark-brown stained surfaces. The staining methods were validated with material from clinically diagnosed cases of haematuria of renal or non-renal origin and compared with scores of the number of dysmorphic erythrocytes, another method to distinguish renal from non-renal haematuria. In specimens of presumed strictly renal haematuria 86% (SD 8.7; n = 26) of the erythrocytes stained immunocytochemically. However, in specimens of haematuria originating from bleeding in the renal pelvis few cells stained (6%; SD 5.8; n = 4). In specimens of purely non-renal haematuria only 13% (SD 13.5; n = 21) stained. Immunocytochemical staining of erythrocytes permitted a much better distinction between renal and non-renal haematuria, with better sensitivity and specificity, than the inspection of erythrocyte morphology. We conclude that immunochemical staining of erythrocytes in urine is a valuable method for distinguishing renal and non-renal haematuria.     

Mn Concentration in Organs of Rats After Implantation of Battery Cathode Material

The distribution of Mn, originating from MnO₂ in miniaturized batteries, was studied in rats. Forty young male Wistar rats were included in a randomized block experiment with body weight, weight gain, relative organ weight, and the concentration of Mn as dependent variables. Mn containing cathode material was implanted subcutaneously and after 1 month, animals were sacrificed and organs collected. Mn levels were determined by ICPES after destruction of the organic matter using microwave energy. Body weight, weight gain, and relative weight of heart, brain, liver, and kidneys were not significantly altered after implantation of cathode material. However, Mn levels were largely increased in the four organs under study. These high levels did not provoke any of the well-known clinical signs associated with Mn intoxication. Effects of Mn in larger farm animals can be considered as insignificant.     

Tibial fractures following Maquet's tuberosity advancement. Apropos of 2 clinical case reports

Although accustomed to using the Maquet tibial tuberosity advancement, the authors had two similar and rare complications in which a fracture of the tibial shaft occurred at the end of the vertical osteotomy. Both incidents arose from a mechanical incision effect. This can be prevented by making a larger circular hole in the distal portion of the osteotomy.     

Evidence for intact V1-vasopressin receptors in congenital nephrogenic diabetes insipidus

The binding of tritium-labelled arginine vasopressin to human platelet vasopressin receptors was investigated in patients with congenital nephrogenic diabetes insipidus. Binding characteristics, that is receptor affinity and the maximum number of binding sites, were not significantly different from those found in normal control individuals. The findings confirm the concept of intact V₁ receptors in congenital nephrogenic diabetes insipidus. The defect in nephrogenic diabetes insipidus apparently only affects the cyclic adenosine monophosphate dependent V₂ receptors.     

Pentachlorophenol concentrations in human cerebrospinal fluid

Pentachlorophenol (PCP) is a widely applied insecticide and fungicide, particularly in wood preservation. Significant amounts of this compound have been reported in human serum, adipose tissue and urine. PCP is even found in people not occupationally exposed to this toxin or not living in PCP-treated log-houses. Substantial concentrations of this possible neurotoxic agent were detected in the cerebrospinal fluid (CSF) of 16 neurologic patients as measured by a high resolution gas chromatographic method using electron capture detection. This is the first report on PCP levels in (human) CSF. The observed level in CSF ranged from 0.24 up to 2.03 micrograms/L (ppb), with an average value of 0.75 +/- 0.49. The cerebrospinal fluid level did not correlate with the serum PCP concentration nor with the protein level of the cerebrospinal fluid.