Regional effects of nafamostat, a novel potent protease and complement inhibitor, on severe necrotizing pancreatitis.

BACKGROUND: We evaluated the effect of the novel protease inhibitor nafamostat on rat necrotizing pancreatitis through different routes of administration. METHODS: Three hours after the induction of severe pancreatitis, the rats received intravenous gabexate or intravenous or local mesenteric intra-arterial nafamostat. At 9 hours, ascites and bronchoalveolar lavage fluid were collected for the evaluation of capillary leakage (Evans blue extravasation). Pancreas and lung were excised for histologic features, myeloperoxidase, and trypsinogen activation peptide. Twenty-four hour survival was evaluated. RESULTS: Only the intravenous infusion of nafamostat significantly reduced myeloperoxidase (11.7 +/- 2.3 vs 18.3 +/- 1.8 mU/mg; P <.05) and capillary leakage in lungs (Evans blue dye, 1.6 +/- 0.3 vs 2.6 +/- 0.3; P <.05). Only intra-arterial infusion of nafamostat significantly diminished capillary peritoneal leakage (Evans blue dye, 3.6 +/- 0.9 vs 9.4 +/- 0.4; P <.01). Typsinogen activation peptide levels were significantly reduced in all groups, but only intra-arterial infusion did so to baseline. Histologic inflammation in the pancreas was most significantly reduced after intra-arterial infusion (0.92 +/- 0.08 vs 2.91 +/- 0.06; P <.05). No form of protease inhibition reduced mortality rates. CONCLUSIONS: The effects of protease inhibition depend on the route of administration. Nafamostat has maximal effects on the pancreas and peritoneal capillary leakage when delivered by way of local intra-arterial infusion, and shows a greater reduction of lung leukocyte infiltration and capillary leakage by the intravenous route. Nafamostat is more effective than gabexate.

Leukocyturia in women with diabetes and its clinical implications.

BACKGROUND: Urinalysis is one of the most common studies performed on the diabetic patient at every visit. The presence of leukocyturia is relatively common but it is not clear what the attitude of the physician toward this particular finding should be. The main objective of the present study was to investigate the clinical significance of leukocyturia in diabetic women. METHODS: Ninety-eight diabetic women (84.7% type 2) aged 57 +/- 13 years who were being seen at the diabetic out-patient clinic were randomly selected. All patients underwent a clinical and gynecologic examination and a urinalysis. A Papanicolaou smear and a urine culture were also obtained. RESULTS: The overall prevalence of leukocyturia (>5 cells/high power field (hpf)) was 46.5%. Patients with urinary tract infections (UTI) were 7.5 times more likely to have leukocyturia, while a leukocyte count <5cells/hpf predicted the absence of UTI in 96% of the women. In the comparison of patients with and without leukocyturia, we found that proteinuria (p = 0.06) and bacteriuria (p <0.002) were more common in the women with leukocyturia. A significant association with leukorrhea was not demonstrated. The empirical use of antibiotics was 12 times more frequent in the patients with leukocyturia. CONCLUSIONS: A urinary culture should be requested in all diabetic patients with leukocyturia. The possibility of a UTI is remote when leukocyturia is absent.

Comparison of in-phase and out-of-phase gradient recalled echo T1-weighted pulse sequence for MR imaging of malignant liver masses following administration of paramagnetic gadolinium-chelate.

BACKGROUND: The purpose of this study was to compare the performance of in-phase and out-of-phase gradient recalled echo (GRE) pulse sequences on paramagnetic contrast-enhanced magnetic resonance (MR) imaging of malignant liver lesions. METHODS: Fifty patients (27 women, 23 men; mean age = 50 +/- 27 years) with known or suspected focal liver lesions, nine of whom had a fatty liver, were examined at 1.5 T before and 60 min after injection of gadobenate dimeglumine at a dose of 0.05 or 0.1 mmol/kg using two GRE techniques: echo time of 2.3 ms (out-of-phase) or 4.6 ms (in-phase). Liver signal-to-noise ratio (SNR) and lesion-liver contrast-to-noise ratio (CNR) were calculated. RESULTS: In patients with a nonfatty liver, liver SNR increased from 26 +/- 9 to 41 +/- 17 on in-phase images and from 28 +/- 8 to 45 +/- 14 on out-of-phase images. In patients with a fatty liver, in-phase images provided significantly higher (p < 0.01) liver SNR than did out-of-phase images predose (34 +/- 8 on in-phase vs. 21 +/- 8 on out-of-phase) and postdose (44 +/- 13 on in-phase vs. 33 +/- 14 on out-of-phase). In patients with a nonfatty liver, lesion-liver CNR was similar on in-phase and out-of-phase images, predose and postdose. In patients with fatty liver, lesion-liver CNR was significantly (p < 0.01) lower on out-of-phase images on predose and postdose images. CONCLUSION: In-phase GRE imaging is recommended for imaging focal liver lesions on paramagnetic contrast-enhanced MR imaging in patients with fatty infiltration of the liver.

Endoscopic treatment of Zenker's diverticulum.

BACKGROUND: The most important aspect of the surgical management of Zenker's diverticulum is probably the cricopharyngeal myotomy. Endoscopic diverticulotomy can be performed with a needle-knife papillotome, which allows simultaneous myotomy of the upper esophageal sphincter. METHODS: Since 1978, 47 patients (28 men and 19 women 51 to 81 years of age) underwent endoscopic diverticulotomy. Most patients underwent more than one treatment session (mean value 2.2). The procedure was performed with sedation. Tubes were not used, and oral intake of food was begun the first day after the operation. RESULTS: Forty-five (95.74%) patients had no dysphagia or only occasional, mild dysphagia during the postoperative course. No fistula, no recurrent laryngeal paralysis, and no deaths occurred. CONCLUSION: Endoscopic diverticulotomy seems to be a good choice of therapy at least for patients with associated diseases that increase surgical risk.

Peritoneal metastases in pancreatic carcinoma.

Peritoneal metastases are present in about 50% of patients with pancreatic cancer at the time of death, and are the second most common site of involvement, following the liver. The small size of peritoneal metastases precludes their identification by CT scan, and thus they have to be identified by direct visualization, either at laparotomy or through laparoscopy. Adding laparoscopy to the staging protocol permits pre-operative identification of patients who will not benefit from surgery. Malignant cells are also found within the peritoneal cavity in 20 to 30% of patients with pancreatic cancer who otherwise have no peritoneal or liver metastases. Their presence, documented by peritoneal washings during laparoscopy or at the time of surgery, seems to be associated with an adverse prognosis.

Variable, voltage-dependent, blocking effects of nitrendipine, verapamil, diltiazem, cinnarizine and cadmium on adrenomedullary secretion.

1. Catecholamine release from cat adrenal glands perfused at a high rate (4 ml min-1) at 37 degrees C with modified Krebs solutions lacking Ca and containing 1.2 mM K (hyperpolarizing solution) or 118 mM K (depolarizing solution) was triggered by 10-s pulses of Ca (0.5 mM) in the presence of 118 mM K. Hyperpolarized glands released 1280 +/- 135 ng per pulse and depolarized glands 831 +/- 98 ng per pulse (n = 29). 2. While the dihydropyridine Ca channel blocker nitrendipine inhibited secretion in hyperpolarized glands with an IC50 of 214 nM, in depolarizing conditions the drug was much more potent (IC50 = 0.99 nM). In contrast, the inorganic Ca channel blocker cadmium inhibited secretion with the same potency both in hyperpolarized or depolarized glands. 3. Cinnarizine, diltiazem and verapamil exhibited intermediate degrees of voltage-dependence in blocking secretion. The IC50 ratios between hyperpolarized and depolarized glands were 215, 36, 19, 8 and 0.76 respectively for nitrendipine, cinnarizine, diltiazem, verapamil and cadmium. Because the experimental design (strong depolarization in the absence of Ca) favours the highest opening probability of Ca channels, it seems that these drugs bind preferentially to their receptors when these channels are in their open state. 4. Variable voltage-dependent effects of the five Ca channel blockers on adrenomedullary catecholamine release suggests different sites and mechanisms of action on, or near L-type Ca channels in chromaffin cells. In addition, these findings might help to explain why these drugs exhibit tissue selectivity and why they act differently in normal polarized as compared to ischaemic depolarized cells.

Voltage-dependence of nitrendipine provides direct evidence for dihydropyridine receptor coupling to calcium channels in intact cat adrenals.

Nitrendipine behaves as a powerful inhibitor of catecholamine release in perfused cat adrenal glands stimulated with pulses of Ca (0.5 mM) in high K (118 mM). Its blocking ability is considerably enhanced if, before Ca stimulation, the adrenomedullary tissue is impregnated with nitrendipine in depolarizing (IC50 = 0.99 nM) as opposed to hyperpolarizing (IC50 = 214 nM) conditions. 3H-nitrendipine binding to adrenomedullary tissue was considerably enhanced in depolarization; blockade of 45Ca uptake into and catecholamine secretion from the same glands was also enhanced in depolarized tissues. This study shows for the first time the a good correlation between these three parameters in the same intact preparation, providing direct evidence for a functional coupling between dihydropyridine receptors, Ca channels and secretion.