Zinc sulfate inhibits the enterohepatic cycling of unconjugated bilirubin in subjects with Gilbert's syndrome

We have previously observed that UCB binds to ZnSO4 in vitro, and suppressed the biliary bilirubin secretion in the hamster. The aim of this study was designed to investigate whether Zn salts might inhibit the enterohepatic cycling of UCB in subjects with Gilbert s syndrome. Fifteen patients with Gilbert s syndrome and 5 normal healthy volunteers were included in this study according to the following criteria: fasting hyperbilirubinemia, no hemolysis, and free of any medication. Patients were randomly assigned to receive acute o chronic treatment. Subjects treated in acute form and normal healthy volunteers were treated with 40 mg of ZnSO4 in a single dose, where as patients treated in chronic form received 100 mg ZnSO4 in a single dose daily for 7 days. The serum UCB levels (mg/dL) decreased from 2.64 +/- 1.04 to 2.02 +/- 0.87 (p < 0.001) and 1.8 +/- 0.36 to 1.48 +/- 0.32 (p < 0.005) in subjects treated in acute an chronic form respectively, but not in the control group. Whereas, the serum Zn levels (mg/dL) increased from 96.3 +/- 16.8 to 118.8 +/- 19. 5, (p < 0.01) and from 117.6 +/- 8.5 to 130.7 +/- 6.6 (p < 0.03) in subjects treated in acute an chronic form and also in subjects in the control group (98.0 +/- 7.3 to 128.0 +/- 21.9) p < 0.03. This study showed that acute and chronic oral administration of ZnSO4 decreased serum UCB levels significantly in subjects with Gilbert s syndrome. Most likely by the inhibition of the "normal" enterohepatic cycling of UCB.     

Symptomatic diabetic and non-diabetic neuropathies in a series of 100 diabetic patients

We have reviewed the clinical and pathological data of a series of 100 consecutive diabetic patients with symptomatic neuropathy in order to learn more about the causes of neuropathy in this population and on the signs and symptoms that could suggest another cause than diabetes in this setting. After diagnostic procedures, patients were assigned one (at most two) of a final total of 18 different causes of neuropathy. Diabetes accounted for 74 % of the neuropathies in the whole group of patients and for 79 % of those with a fiber length dependent pattern of neuropathy. One third of patients had a neuropathy unrelated to diabetes. As a group, 71 % of the patients presented either a length dependent diabetic polyneuropathy (LDDP) or a proximal diabetic neuropathy (PDN). The LDDP group was biased towards more severely affected patients owing to our specialization. Conversely, most patients with proximal diabetic neuropathy had usual features. Chronic inflammatory demyelinating neuropathy that was diagnosed in 9 % of the patients was the most common non-diabetic cause of neuropathy in this population. We conclude that a short interval between diagnosis of diabetes and the onset of the neuropathy, early motor deficit, markedly asymmetrical deficit and generalized areflexia, which are all uncommon in the LDDP, argue in favor of a non diabetic origin of the neuropathy and should lead to further investigation. Received: 19 June 2001, Received in revised form: 21 September 2001, Accepted: 8 October 2001     

Percutaneous tumor ablation: increased necrosis with combined radio-frequency ablation and intravenous liposomal doxorubicin in a rat breast tumor model

PURPOSE: To determine whether a combination of intravenous liposomal doxorubicin and radio-frequency (RF) ablation increases tumor destruction compared with RF alone in an animal tumor model. MATERIALS AND METHODS: R3230 mammary adenocarcinoma 1.4-1.8-cm- diameter nodules were implanted subcutaneously in 132 female Fischer rats. Initially, tumors were treated with (a) conventional, monopolar RF (mean, 250 mA +/- 25 [SD] at 70 degrees C +/- 1 for 5 minutes) ablation alone, (b) RF ablation followed by intravenous administration of 1 mg of liposomal doxorubicin, (c) RF ablation followed by intravenous administration of 1 mg of empty liposomes, (d) RF ablation and direct intratumoral administration of liposomal doxorubicin, or (e) no treatment. Subsequently, the dose (0.06-2.00 mg) of liposomal doxorubicin, the timing of administration (3 days before to 3 days after RF ablation), and the time of pathologic examination (0-72 hours after treatment) were varied. RESULTS: Mean coagulation diameter for treated tumors follows: 6.7 mm +/- 0.6, RF ablation alone; 11.1 mm +/- 1.5, RF ablation and intravenous administration of empty liposomes (P <.05, compared with RF ablation alone); and 8.4 mm +/- 1.1, RF ablation with intratumoral administration of liposomal doxorubicin (P <.05, compared with RF ablation alone). Maximal increased mean coagulation diameter (13.1 mm +/- 1.5) was observed with a combination of liposomal doxorubicin and RF ablation (P <.001, for all comparisons). The increased coagulation for combination therapy developed over 48 hours after therapy. Coagulation diameter did not vary with the doxorubicin concentration range and was not dependent on the timing of administration of liposomal doxorubicin from 3 days before to 24 hours after RF ablation. CONCLUSION: Intravenous administration of liposomal doxorubicin can improve RF ablation, since it increases coagulation diameter in solid tumors compared with RF ablation alone or a combination of RF ablation with administration of empty liposomes.     

Characterization of the RF ablation-induced 'oven effect': the importance of background tissue thermal conductivity on tissue heating.

PURPOSE: To determine the effect of background tissue thermal conductivity on RF ablation heating using ex vivo agar phantoms and computer modelling. METHOD: Two-compartment cylindrical agar phantom models (5% agar, 5% NaCl, 3% sucrose) were constructed. These included a standardized inner compartment (2 cm diameter, 4 cm length, 0.25% agar) representing a tumour, surrounded by an outer compartment representing background tissue. The thermal conductivity of the outer compartment was varied from 0.48 W m-1 degrees Celsius (normal liver) to 0.23 W m-1 degrees Celsius (fat) by adding a fat-saturated oil-based solute (10-90%) to the agar. RF ablation was applied at 2000 mA current for 2 min. Temperatures were recorded up to 4 cm from the electrode tip at 1 cm intervals. Subsequently, a 2-D finite element computer model was used to simulate RF ablation of 2-24 min duration for tumours measuring 2-4 cm in diameter surrounded by tissues of different thermal conductivity with the presence or absence of perfusion (0-5 kg m-3 s-1) (n = 44). A comparison of results was performed. RESULTS: In agar phantoms, the amount of fat in the background tissue correlated with thermal conductivity as a negative exponential function (r2 = 0.98). Significantly increased temperatures were observed at the edge of the inner compartment (1 cm from the electrode tip) as the fat content of the outer compartment increased (p < 0.01). Thus, temperatures at 2 min measured 31.5 +/- 2.2 degrees Celsius vs 45.1 +/- 3.1 degrees Celsius for thermal conductivities of 0.46 W m-1 degrees Celsius (10% fat) and 0.23 W m-1 degrees Celsius (90% fat), respectively. On the other hand, higher levels of fat led to lower temperature increases in the background compartment (0.2 +/- 0.3 degrees Celsius for 90% fat vs. 1.1 +/- 0.05 degrees Celsius for 10% fat, p < 0.05). Phantom thermal heating patterns correlated extremely well with computer modelling (r2 = 0.93), demonstrating that background tissues with low thermal conductivity increase heating within the central tumour, particularly for longer durations of RF ablation and in smaller tumours. Furthermore, computer modelling demonstrated that increases in temperature at the tumour margin for background tissues of lower thermal conductivity persisted in the presence of perfusion, with a clinically relevant 4.5 degrees Celsius difference between background thermal conductivities of fat and soft tissue for a 3 cm tumour with perfusion of 2 kg m-3 s-1, treated for 12 min. CONCLUSION: Lower thermal conductivity of background tissues significantly increases temperatures within a defined ablation target. These findings provide insight into the 'oven effect' (i.e. increased heating efficacy for tumours surrounded by cirrhotic liver or fat) and highlight the importance of both the tumour and the surrounding tissue characteristics when contemplating RF ablation efficacy.     

Ranitidine-induced bradycardia in a neonate — a first report

Bradycardia, an extremely rare side-effect of ranitidine therapy is described in a 4-day-old full-term male neonate, who was admitted because of massive gastro-intestinal bleeding. Two hours after the intravenous injection of 1 mg/kg body weight per day, ECG showed sinus bradycardia of 60 beats/min with normal axis and QRS complex.The bradycardia gradually resolved in the next 24 h.     

Diagnostic significance of air in the head and neck

Air in the head and neck is normally found in the sinuses and air and food passages. The presence of air in an abnormal location indicates a pathologic change which may require observation, further diagnostic tests, or immediate therapeutic action. The various causes are listed and possible treatment modalities are considered.     

Magnetic resonance imaging in the exploration of hepatic masses

Exploration was conducted by magnetic resonance imaging (MRI) at 0.15 T in 33 patients with hepatic masses, including 18 with malignant tumors, 11 with benign tumors and 4 with non-tumoral masses. All tumors appeared hyperintensive in relation to liver on images acquired by long TR spin echos (SE) and all, except for one fatty tumor, appeared hypointense in relation to liver on images acquired in inversion-recuperation (IR). The study seemed to provide data demonstrating that MRI at 0.15 T enables visualization of hepatic masses with a degree of precision that approaches that of other imaging methods. Tumors of the small size of the order of a centimetre can be detected. Tumor outlines and vascular relations are clearly demonstrated without use of contrast. Characterization of masses is still insufficient since the simple play of contrasts between tumor, parenchyma and vessels does not allow differentiation of malignant from benign tumors, nor the identification of a given histologic type.