Biomedical subjects

P Milkiewicz

Publications and source records attributed to P Milkiewicz.

24 records · Page 2Linked to original sources

PubMed1999

Successful treatment of acquired perforating dermatosis with rifampicin in an Asian patient with sclerosing cholangitis.

Acquired perforating dermatosis (APD) is a very rare disorder which has been described in association with systemic diseases such as diabetes mellitus, HIV infection or lymphoma. In this report we describe a patient with APD associated with sclerosing cholangitis and diabetes mellitus who was successfully treated with rifampicin. A 33-year-old Indian woman with a history of extensive pancreatic surgery, sclerosing cholangitis and insulin dependent diabetes mellitus was referred to our unit with intractable pruritus. She was treated with cholestyramine, ursodeoxycholic acid, several analgesics, UVB therapy, topical steroids, sedative antihistamines and plasmapheresis without significant improvement. Increasingly severe itching was associated with papular skin changes limited initially to the lower limbs but which later involved her entire body. Biopsy of a representative lesion showed the changes of APD. She was subsequently treated with rifampicin which produced a dramatic resolution of pruritus within 3 weeks and the skin changes progressively resolved over subsequent months. In this newly described association of APD with sclerosing cholangitis, rifampicin treatment appeared to be efficient in ameliorating pruritus and the papular skin changes typical of APD.

Adult↗

PubMed1997

Synthesis, physical and biological properties of lithocholyl-lysyl-fluorescein: a fluorescent monohydroxy bile salt analogue with cholestatic properties.

We have synthesised and characterised a fluorescent monohydroxy bile salt analogue, lithocholyl-lysyl-fluorescein and compared its physical and biological properties with those of lithocholate, glycolithocholate, sulpholithocholate, lithocholic acid glucuronide and taurocholate. The synthetic method used excess N-epsilon-CBZ-L-lysine methyl ester hydrochloride and lithocholic acid via N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinolone (EEDQ) to give lithocholyl-lysine. Lithocholyl-lysyl-fluorescein (LLF) was then prepared using equimolar amounts of lithocholyl-lysine and fluorescein isothiocyanate (FITC) in bicarbonate buffer. LLF retained an apple green fluorescence, similar to that of fluorescein. Unlike lithocholate, the critical micellar concentrations (CMCs) of LLF, glycolithocholate (GLC), lithocholic acid glucuronide (LG) and sulpholithocholic acid (SLC) were similar. HPLC retention times (tRs) of LLF and GLC were similar with a ratio of LLF/GLC of 1.05. In contrast, the tR of SLC (6.52 min) but not of LG (21.2 min) was more comparable to that of taurocholate (5.73 min). In rats under pentobarbital anaesthesia, the plasma half-life (t(1/2alpha)) (min) was 4.5 +/- 1.3 (n = 6) for LLF, 2.9 +/- 0.4 (n = 5) for [14C]sulpholithocholate (14C-SLC) and 4.3 +/- 0.3 (min) for [14C]lithocholic acid glucuronide (14C-LG). Plasma clearances of 14C-SLC, LLF and 14C-LG were 15.5 +/- 2.2 (n = 6), 18.1 +/- 4.2 (n = 6) and 17.8 +/- 0.5 ml/min/kg (n = 6) (P = 0.15), respectively. Biliary excretion in bile-fistula rats gave cumulative 20 min biliary output as a percentage of injected dose as follows: LLF, 71.6 +/- 0.8% (n = 10); 14C-SLC, 75.5 +/- 2.8% (n = 6) and 14C-LG, 61.7 +/- 0.5% (n = 6) (P = NS). Peak biliary excretion rates, given as % dose/2 min, were 10.2 +/- 0.3 for LLF, 13.5 +/- 0.6 for 14C-SLC and 12.8 +/- 0.4 for 14C-LG. In another group of bile-fistula rats, a 3.0 micromol/500 microl saline i.v. bolus of LLF caused a 15.4 +/- 1.9% decrease in bile flow and, similarly, sodium lithocholate in a solution of albumin caused a 17.9 +/- 1.8% (P = NS) diminution in bile flow. Despite the similar cholestatic properties of LLF and lithocholate, LLF was more soluble than lithocholate, with a relative retention time on HPLC similar to that of GLC. LLF is a divalent 'unipolar' anionic fluorescent monohydroxy bile salt analogue with physical, biological and cholestatic properties that are similar to those of lithocholate, glycolithocholate and their derivatives and thus offers a potentially useful probe for studying mechanisms of monohydroxy bile salt-induced cholestasis at the hepatocellular level.

Animals↗

PubMed1997

Plasma clearance of cholyl-lysyl-fluorescein: a pilot study in humans.

BACKGROUND/AIMS: Cholyl-lysyl-fluorescein is a fluorescent analogue of the natural bile acid, cholyl glycine. In vivo and in vitro studies showed that this analogue has many biological characteristics similar to cholyl glycine. In this study we analysed cholyl-lysyl-fluorescein plasma clearance in six healthy volunteers as a potential quantitative liver function test. METHODS: The compound in water for injection was administered as an i.v. bolus in the dose of 0.02 mg/kg b.w. RESULTS: The plasma elimination curve showed rapid, intermediate and slow phases of clearance. Half-life (T1/2 time) for the first (t1/2 1st phase), second (t1/2 2nd phase) and third (t1/2 3rd phase) phases of elimination was 1.7+/-0.9 min, 6.7+/-1.6 min and 68+/-17 min, respectively. Ninety-minute plasma retention (% dose/l plasma) was 2.2%. Cholyl-lysyl-fluorescein volume of distribution and residual fluorescence after 60 min were similar to the data obtained by others for natural or radiolabelled bile acids. In five out of six healthy volunteers a 25-fold higher dose of cholyl-lysyl-fluorescein (0.5 mg/kg b.w.) was injected to estimate the safety margins of the compound. This dose was eliminated at a disappearance rate similar to that of the dose of 0.02 mg/kg b.w. and did not cause any adverse reactions. Serum liver tests measured before and after injection did not change significantly. CONCLUSIONS: This study showed that cholyl-lysyl-fluorescein clearance is similar to the clearance of endogenous natural bile acids and may potentially offer a new, dynamic test of liver function.

Adult↗

PubMed1997

Obstructive sleep apnoea syndrome (OSAS) as a complication of carcinoid syndrome treated successfully by hepatic artery embolization.

Obstructive sleep apnoea syndrome (OSAS) appears to be an extremely rare complication of carcinoid syndrome and has not yet been reported in the literature. We describe a 75-year-old patient with a history of bronchial carcinoid who besides typical carcinoid syndrome symptoms developed sleep disturbance and day lethargy caused by massive facial and nasal tissue oedema. Sleep apnoea was confirmed by sleep study. Abdominal ultrasound and computed tomography (CT) scan showed the presence of multiple liver metastases. Because the patient did not respond to octreotide therapy, embolization of the hepatic artery was performed. After this procedure we observed dramatic improvement of the patient's life quality, and rapid disappearance of facial swelling and sleep apnoea symptoms. We conclude that hepatic artery embolization appeared to be an effective method of abolishing obstructive sleep apnoea associated with carcinoid syndrome.

Aged↗

PubMedDate not supplied

Recurrent autoimmune LKM hepatitis with multiple relapses.

We describe three females who since childhood and puberty have presented with several relapsing episodes of acute or chronic LKM positive hepatitis. Many episodes resolved spontaneously with recovery of normal liver function, although treatment with steroids, steroids/azathioprine was used at occasions. No clear pattern of precipitating factors has emerged though in some cases possible temporal relationship of episodes to menarche, oral contraceptives use or pregnancy has suggested a role for female sex hormones. We discuss briefly the possible mechanisms of LKM positive hepatitis, particularly in terms of drugs as possible trigger factors.

Adult↗

PubMedDate not supplied

Cholyllysyl fluroscein and related lysyl fluorescein conjugated bile acid analogues.

There have been attempts to couple bile acids to fluorescein to permit their visualization during studies of physiology and pathophysiology. Although conjugation has been achieved by many, the product differed in many respects from the parent bile acid congener. We describe lysylfluorescein conjugated bile acid analogues (LFCBAA) synthesized in our laboratory as model divalent "unipolar" molecules. We have determined LFCBAA properties including their water:octanol partition coefficient, HPLC retention time and critical micellar concentration and compared them with their parent bile acid congeners. Cholyl lysylfluorescein (CLF) and lithocholyl lysylfluoroscein (LLF) have properties similar to cholylglycine (CG) and glycolithocholate (GLC), respectively. In human and rat hepatocytes uptake of CLF follows Michaelis-Menten kinetics with K(m) and Vmax similar to CG. Biliary excretion rates of CLF and LLF closely resemble those of CG and GLC in both normal and mutant TR- rats which lack the multiorganic anion transporter (MOAT), strongly supporting the notion that CLF and LLF are substrates for the canalicular bile salt transporter (cBST). The close similarity of hepatocyte uptake and biliary secretion of these LFCBAA and their parent bile acid congeners makes them potentially useful probes for the intracellular visualization of bile salt movement and deposition in various models of bile formation and secretion.

Animals↗