Acid Secretory Changes in Streptozotocin-Diabetic Rats

We examined gastric acid secretion in response to various stimuli in streptozotocin (STZ) induced diabetic rats and characterized the alteration of acid secretory responses in diabetic conditions. Animals were injected STZ (70 mg/kg, intraperitoneally) and used after five weeks of diabetes with blood glucose >350 mg/dl. Under urethane anesthesia, the experiment was performed in a chambered stomach or a whole stomach preparation, and the acid secretion was measured at pH 7.0 using a pH-stat method and by adding 100 mM NaOH. The acid secretion was stimulated by intravenous infusion of either histamine (4 mg/kg/hr), pentagastrin (60 g/kg/hr), or carbachol (20 g/kg/hr) or by intraluminal application of peptone solution (4%), or vagal electrical stimulation (2 msec, 3 Hz, 0.5 mA). In normal rats, acid secretion was increased in response to either histamine, pentagastrin, carbachol, peptone, or electrical vagal stimulation. In STZ diabetic rats, however, changes in acid secretion varied depending on the stimuli; the acid response to histamine remained unchanged, but the responses to vagal electrical stimulation or pentagastrin and carbachol were significantly decreased or enhanced, respectively, as compared to normal rats. Likewise, the acid response to peptone was also markedly enhanced in STZ-diabetic rats, and this response was significantly blocked by atropine and YM022 (a CCK_B/gastrin antagonist) as well as famotidine in both normal and diabetic rats. Both pentagastrin and carbachol increased the luminal release of histamine in normal rats, and these responses were significantly augmented in STZ-diabetic rats. The altered acid response and histamine release induced by pentagastrin in STZ diabetic rats were partially reversed by daily injection of insulin. These results suggest that STZ-diabetic rats showed different changes in gastric acid secretion in response to various stimuli. The increased acid secretory response may be associated with an enhanced release of mucosal histamine, while the decreased response may be due to vagal neuropathy.     

Polaprezinc Exerts a Salutary Effect on Impaired Healing of Acute Gastric Lesions in Diabetic Rats

We examined the influence of diabetes mellitus (DM) on the healing of HCl-induced gastric lesions and the healing promoting effect of polaprezinc [N-(3-aminopropionyl)-l-histidinato zinc] on these lesions. Studies were performed on rats injected intraperitoneally with streptozotocin (STZ, 70 mg/kg) five weeks prior to experiments. Diabetic rats had blood glucose levels (BGLs) higher than 350 mg/100 ml. Randomly chosen animals were treated subcutaneously with insulin (4 IU/day/rat) starting 1 week after STZ. Animals were given 1 ml of 0.6 N HCl by oral gavage (per os) following 18 hr of fasting; they were fed normally from 1 hr later and killed at various time points after HCl administration. Polaprezinc (3–30 mg/kg) or its components ZnSO₄/7H₂O and l-carnosine were given orally, twice daily for four days following HCl treatment. Gastric lesions induced by HCl healed macroscopically to quiescence within 10 days. DM and insulin did not affect the development of HCl-invoked gastric lesions, but the healing of such lesions was markedly impaired in animals with DM. Daily administration of insulin returned high BGLs to significantly lower ranges (190–208 mg/100 ml) and markedly antagonized the healing impairment. Polaprezinc (>10 mg/kg) significantly reversed the delay observed in diabetic rats without any notable effects on BGLs or acid secretion. Similar trends were observed with ZnSO₄/7H₂O or a mixture of ZnSO₄/7H₂O and l-carnosine, but not by l-carnosine alone. The mucosal expression of insulin-like growth factor-1 (IGF-I) mRNA was significantly lower in diabetic rats, a dysregulation partially corrected by insulin and polaprezinc. In addition, the delayed healing in diabetic rats was also significantly promoted by the repeated subcutaneous administration of rhIGF-I (>10 g/kg, twice daily) without any notable effect on BGLs or acid secretion. These results suggest that DM exerted a deleterious influence on the healing of acute gastric lesions in both insulin- and zinc-sensitive manner. The salutary effects of polaprezinc on the impaired healing of gastric lesion in STZ-diabetic animals may at least be partly explained by enhancement of mucosal IGF-I mRNA expression in the stomach.     

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

Clinical, light- and electron microscopic, and immunohistochemical findings of a 44-year-old woman with progressive multifocal leukoencephalopathy were presented. Autopsy revealed a wide distribution of the demyelinating lesion in the cerebrum, cerebellum, brain stem and spinal cord, and intranuclear inclusion bodies and papova-like virions in transmission electron microscopy in the nuclei of oligodendrocytes. SV40 antigen was immunohistochemically detected in these inclusion bodies. The widespread extension of the lesions seemed to correlate with the duration of the patient's illness. The prolongation of the clinical course in this case may be dependent upon the lack of serious underlying diseases except for a small nodule of thyroid carcinoma, SV40 infection rather than JC virus infection and/or improved care of that kind of patient.     

Presence of a mutation in ponA1 of Neisseria gonorrhoeae in numerous clinical samples resistant to various β-lactams and other, structurally unrelated, antimicrobials

The number of resistant strains in patients with Neisseria gonorrhoeae urethritis has been increasing, making effective treatment difficult. Chromosomally mediated penicillin-resistant N. gonorrhoeae arise through alterations in penicillin-binding proteins (PBPs) and a decrease in outer membrane permeability. To understand the occurrence of penicillin resistance in patients with N. gonorrhoeae infection, we performed this study. In addition, we studied minimum inhibitory concentrations (MICs) of antimicrobials against N. gonorrhoeae strains. We measured the MICs of penicillin G, other β-lactams, and other kinds of antimicrobials against 53 clinical N. gonorrhoeae isolates from male patients with urethritis in Hyogo and Osaka, Japan. The ponA genes, encoding PBP 1 of these isolates, were sequenced. Of the 53 isolates tested, 41 strains showed some resistance to penicillin G. A mutation in the ponA (ponA1) gene was identified in 46 isolates. There was a tendency that ponA mutant (ponA1) in N. gonorrhoeae led to higher antimicrobial MICs of β-lactam antimicrobial agents (including penicillin) than those of non-ponA mutants. However, we found lower than expected MICs of penicillin and β-lactams even in ponA mutants. Therefore, we consider that detailed investigations for the further understanding of the effect of other genes, such as penC (which is reported to be related to ponA1 in achieving high-level penicillin resistance) should be our next step.     

Low incidence of vascular complications in patients with diabetes mellitus associated with liver cirrhosis as compared with type 2 diabetes mellitus

We compared clinical features and vascular complications of patients with diabetes mellitus associated with liver cirrhosis versus patients with type 2 diabetes mellitus. Subjects were 19 patients (LC-DM group) in whom diabetes was diagnosed after development of liver cirrhosis. Control consisted of 38 patients with type 2 diabetes (T2DM group) matched for sex, age, duration of diabetes, body mass index, treatment, and degree of glycemic control, which was determined by glycoalbumin. The LC-DM group had significantly more smokers, higher serum insulin levels, more insulin resistance calculated by homeostasis model assessment, lower blood counts (white and red blood cells, hemoglobin, and platelets), and lower serum levels of total cholesterol, triglyceride, low density lipoprotein cholesterol and lipoprotein (Lp)(a) than the T2DM group. The incidence of diabetic retinopathy and cerebrovascular disease was significantly lower in the LC-DM group compared to the T2DM group. Logistic regression analysis indicated that Lp(a) and the diabetes duration were significant predictors for the retinopathy, while Lp(a) was a significant predictor for the cerebrovascular complication. In diabetes associated with liver cirrhosis, the incidence of diabetic retinopathy and cerebrovascular disease is lower than in type 2 diabetes mellitus in this study, probably because of lower levels of serum Lp(a).     

Selective hepatic vascular exclusion for the hepatic resection of HCC

BACKGROUND/AIMS: Selective hepatic vascular exclusion (SHVE) is an effective technique for the control of bleeding in major hepatic resections. Outcomes of the procedures of the SHVE group were compared with the non-SHVE group. METHODOLOGY: A retrospective study was carried out of 312 hepatic resections performed over a period of 10 years. The cases in this study were limited to Child's classification A, because of the rate of Child A in the SHVE group (n=82) was significantly higher than that within the non-SHVE group (n=158) (93% vs. 71%; p < 0.001). Preoperative factors, like age, gender, tumor size, intraoperative blood loss, operation time, and the postoperative course of the two groups were compared for both groups. RESULTS: The SHVE group showed significantly less blood loss, necessary blood transfusion, and a significant rate of severe postoperative complications. The rate of segmentectomy and subsegmentectomy in the SHVE group was higher than in the non-SHVE group, and the rate of partial hepatectomy and lobectomy in the non-SHVE group was higher than that in the SHVE group. Although the more difficult operations were performed in the SHVE group than in the non-SHVE group, there was no significant difference in the postoperative hospital stays in both groups. CONCLUSIONS: The SHVE technique is effective for bleeding control in major liver resections.     

Pathogen occurrence and antimicrobial susceptibility of urinary tract infection cases during a 20-year period (1983-2002) at a single institution in Japan

Urinary tract infections are one of the most common infectious diseases diagnosed in outpatients as well as in hospitalized patients. Recently, urinary tract infections have become more complicated and difficult to treat. Therefore, the present study analyzed the occurrence and antimicrobial susceptibility of uropathogens isolated at Kobe University Hospital between 1983 and 2002. This study was performed with three patient groups: urology inpatients, urology outpatients, and inpatients of other departments. During the 20-year study period, we studied 15,925 urine isolates obtained from those patients who were diagnosed with urinary tract infection. Overall, Enterococcus faecalis was the most frequently isolated pathogen, followed by Pseudomonas aeruginosa and Escherichia coli. The frequency of Staphylococcus aureus increased over time, corresponding to an increase in the occurrence of methicillin-resistant S. aureus (MRSA). In addition, the rate of isolation of Serratia marcescens also increased over time, especially among patients with urinary tract catheters. Our results demonstrate that the uropathogens isolated at a single institution have shown a trend of increasing resistance to various classes of antimicrobial agents. In addition, serious problems should be anticipated in the treatment of multidrug-resistant P. aeruginosa, fluoroquinolone-resistant E. coli, and arbekacin-resistant MRSA.     

A case of Wilson’s disease with characteristic laparoscopic findings

A 44-year-old male was pointed out liver function abnormality by medical check-up. Blood examination and computed tomography showed liver cirrhosis. Then, he was referred to our hospital for further examination. After blood test, viral markers revealed previous infection of hepatitis B virus (HBV). We estimated the etiology of his liver disease as previous HBV infection. On laparoscopic examination, his liver surface was nodular with mixed yellowish nodules and ash gray to copper-colored nodules in the diameter of 3–10 mm. There were large regenerative nodules in segments 3 and 4. Large regenerative nodules and irregular steatosis were contradictory to HBV-related liver cirrhosis, so then we supposed Wilson’s disease. The amount of copper excretion in the urine was 326.6 μg (>100 μg/24 h). After D-penicillamine administration, urinary copper excretion increased to 2151.5 μg/24 h. Though hepatic copper concentration was 174.5 μg/g wet tissue (>200 μg/g wet tissue), his laboratory data fulfilled the Leipzig diagnostic criteria proposed by EASL. Laparoscopic examination with liver biopsy has advantages to survey many disease-specific findings on liver surface and to obtain adequate liver sample. Laparoscopic examination is one of the effective procedures for diagnosing relatively rare liver disease like Wilson’s disease.     

Efficacy of Granulocyte and Monocyte Adsorption Apheresis for Treatment of Palmoplantar Pustulosis

Palmoplantar pustulosis (PPP) is characterized by neutrophilic pustules with erythema, which are limited to the hands and feet. Although granulocyte and monocyte adsorption apheresis (GMA) has shown remarkable effects on generalized pustular psoriasis, there are few reports of PPP treated with GMA. We treated three refractory PPP patients using GMA weekly for 5 weeks. The skin eruptions were assessed by a 5‐grade score for scales, pustules, and erythema. GMA decreased the total grade from 9 to 2 in patients 1 and 2, and from 7 to 3 in patient 3. The GMA effects were estimated to be excellent in all three patients. Pustule formation and pain disappeared in all cases. The treatment effect lasted for at least 5 months after GMA. GMA was also effective for relieving the arthralgia in one patient, but it recurred at 6 weeks. Based on these findings, GMA could be an effective therapy for refractory PPP.