Slowly progressing form of type 1 diabetes mellitus in children: genetic analysis compared with other forms of diabetes mellitus in Japanese children

AIMS: Slowly progressing insulin-dependent diabetes mellitus (SPIDDM, hereafter referred to as IDDMS in this article) is a unique subtype of type 1 diabetes in Japanese children. To clarify the genetic background of IDDMS, we analyzed HLA-DRB1, -DQB1 and -DQA1 alleles, phenotypes, and genotypes and compared them with acute-onset type 1 diabetes, non-insulin-dependent diabetes mellitus (NIDDM), and control subjects. METHODS: HLA-DRB1, -DQA1, and -DQB1 types were defined by DNA analysis using polymerase chain reaction (PCR), and typing for human leukocyte antigen (HLA) was performed by the sequencing-based typing (SBT) method using Match Maker and MT Navigator in combination. HLA-A24 was determined by the PCR-sequence-specific oligo-nucleotide probe (PCR-SSOP) method. The 234 patients with type 1 diabetes were divided into three groups: 32 cases of IDDMS, 137 cases of acute-onset form aged more than 5 yr (IDDMA), and 65 cases of acute-onset form less than 5 yr of age at onset (IDDME). In addition, we studied 55 children with type 2 diabetes (NIDDM) and 97 normal controls. RESULTS: The patients with IDDMS were older at diagnosis and had a greater body mass index (BMI) than those with IDDM (A + E). The prevalence of islet autoantbodies was not significantly different from IDDMA. The allele frequencies of DRB1*0405, DQA1*0302, and DQB1*0401 were significantly increased; however, DRB1*0901, DQA1*03, DQB1*0303, and HLA-A24 were low and not significantly different from control subjects. CONCLUSIONS: HLA phenotypes and genotypes in patients with IDDMS were different from those in NIDDM and control subjects and were closer to those of IDDMA. Together with a low prevalence of HLA-A24, the genetic features are similar to those of SPIDDM and latent autoimmune diabetes in adults (LADA) in adults. In our series, the clinical features such as lack of obesity and lack of responsiveness to oral hypoglycemic agents were most different from those of adults' onset.     

Early detection of liver failure after hepatectomy by indocyanine green elimination rate measured by pulse dye-densitometry

BACKGROUND/PURPOSE: Following a major hepatectomy, some degree of clinical and biochemical dysfunction occurs. Surgeons usually check serum total bilirubin levels to diagnose postoperative liver dysfunction. However, we cannot predict liver failure by biochemical data alone within the early postoperative period. Using newly developed pulse dye-densitometry (PDD), we measured serial postoperative indocyanine green elimination rate (ICG-K) values and investigated the possible relation between postoperative ICG-K values and complications. METHODS: Fifty-one patients scheduled for hepatectomy between January 2000 and December 2002 were enrolled. Pulse-dye densitometry was used to evaluate postoperative liver function. We analyzed the relation between postoperative ICG-K and postoperative outcome, assessed in terms of morbidity and mortality. RESULTS: Liver failure was seen in seven patients. The ICG-K value on postoperative day 1 in patients with liver failure was significantly lower than that in patients without liver failure (0.070 +/- 0.018 vs 0.152 +/- 0.056/min respectively; P < 0.001). There were no differences between preoperative ICG-K values in patients with and without liver failure. The sensitivity and specificity of an ICG-K value of less than 0.07 on postoperative day 1 were 71.4% and 95.5%, respectively, for predicting liver failure. CONCLUSIONS: We can measure the ICG-K value by PDD at the bedside without time delay, and we can predict liver failure in the early postoperative period by the ICG-K values on postoperative day 1. ICG-K values measured by PDD can provide important information for perioperative management.     

Delayed L-DOPA-induced hyperalgesia

Previously we reported on L-DOPA's antinociceptive effect on substance P-induced nociceptive behaviors in mice [Shimizu T, Iwata S, Morioka H, Masuyama T, Fukuda T, Nomoto M. Antinociceptive mechanism of L-DOPA. Pain 2004;110;246-9.]. Since significant hyperalgesia was noted following antinociception, our study was designed to investigate the mechanism of this hyperalgesia. Nociceptive behaviors were enhanced 2 h after L-DOPA administration. L-DOPA induced hyperalgesia occurred after conversion to dopamine because co-administration of benserazide, a DOPA decarboxylase inhibitor, completely abolished the L-DOPA-induced hyperalgesia. The D2 receptor agonist, quinpirole, depressed these behaviors entirely, while the D1 antagonist, SCH23390, inhibited the enhancement of these behaviors by L-DOPA. The D2 receptor antagonist, sulpiride, which induced hyperalgesia of the substance P-induced behaviors in naive mice, did not have any effects on L-DOPA-induced hyperalgesia. Spinal cord dopamine content increased rapidly after L-DOPA administration, exhibiting levels 100 times greater than baseline, and then returned to control after 1 h. These results suggested that the dopaminergic inhibitory system for pain sensation was temporarily impaired by excess amounts of exogenous dopamine that were derived from L-DOPA and both D1 and D2 receptors were involved in L-DOPA-induced hyperalgesia.     

Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis

Tumour growth depends on angiogenesis, which is closely associated with vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Extracellular MMP inducer (EMMPRIN) was reported to involve in the progression of malignancies by regulating expression of VEGF and MMPs in stromal cells. To clarify the role of EMMPRIN in progression and angiogenesis of gastric carcinoma, expression of EMMPRIN, ki-67, MMP-2, MMP-9 and VEGF was examined on tissue microarray containing gastric carcinomas (n=234) and non-cancerous mucosa adjacent to carcinoma (n=85) by immunohistochemistry. Additionally, microvessel density (MVD) was assessed after labelling with anti-CD34 antibody. Extracellular MMP inducer expression was compared with clinicopathological parameters of tumours, including levels of ki-67, MMP-2, MMP-9 and vascular endothelial growth factor (VEGF), MVD as well as survival time of carcinoma patients. Gastric carcinoma cell lines (HGC-27, MKN28 and MKN45) were studied for EMMPRIN expression by immunohistochemistry and Western blot. Extracellular MMP inducer expression was gradually increased from normal mucosa to carcinomas through hyperplastic or metaplastic mucosa of the stomach (P<0.05). There was strong EMMPRIN expression in all gastric carcinoma cell lines despite different levels of glycosylation. Extracellular MMP inducer expression was positively correlated with tumour size, depth of invasion, lymphatic invasion, expression of ki-67, MMP-2, MMP-9 and VEGF of tumours (P<0.05), but not with lymph node metastasis, UICC staging or differentiation (P>0.05). Interestingly, there was a significantly positive relationship between EMMPRIN expression and MVD in gastric carcinomas (P<0.05). Survival analysis indicated EMMPRIN expression to be negatively linked to favourable prognosis (P<0.05), but not be independent factor for prognosis (P>0.05). Further analysis showed three independent prognostic factors, depth of invasion, lymphatic and venous invasion, to influence the relationship between EMMPRIN expression and prognosis. Upregulated expression of EMMPRIN possibly contributes to genesis, growth and local invasion of gastric carcinomas. Altered EMMPRIN expression might enhance growth, invasion and angiogenesis of gastric carcinoma via upregulating MMP expression of both stromal fibroblasts and gastric cancer cells and could be considered as an objective and effective marker to predict invasion and prognosis.     

Malignant transformation eight years after removal of a benign epidermoid cyst: a case␣report

Summary Malignant transformation of benign epidermoid cysts is rare and their prognosis remains poor. A 56-year-old woman presented with left facial hypoesthesia and photophobia in the left eye. She had undergone removal of a benign epidermoid cyst in the cerebellopontine angle 8 years previously. Magnetic resonance imaging of the brain revealed a cystic lesion in the left cerebellopontine angle. The cyst wall was enhanced by gadolinium-DTPA. She underwent removal again and the histopathologic diagnosis was squamous cell carcinoma. Gamma knife radiosurgery was performed on the remnant lesion with a marginal dose of 15 Gy. The tumor shrank rapidly for 2 months after radiosurgery, but recurred 9 months later. She underwent radiosurgery again with a marginal dose of 12 Gy. A gradual increase in the size of the enhanced lesion was seen during the 4-month follow-up period subsequent to the second radiosurgery. Careful observation, employing serial magnetic resonance images, is necessary for incompletely resected epidermoid cysts because intervals before malignant transformation reportedly range from 3 months to 33 years. Newly identified contrast enhancement strongly indicates malignant change in epidermoid cysts. Gamma knife radiosurgery may be useful for short-term control of intracranial squamous cell carcinomas, but long-term effects are presently unknown.     

Assessment criteria of lower urinary tract symptom severity for general practitioners

OBJECTIVES: We conducted a preliminary study to examine the validity of assessment criteria of lower urinary tract symptoms (LUTS) severity for general practitioners (GPs). MATERIALS AND METHODS: This study included 194 patients with LUTS, who visited the urology clinics in three hospitals. In 177 who completed International Prostate Symptom Score (I-PSS), International Consultation on Incontinence Questionnaire : Short-Form (ICIQ-SF), frequency-volume chart, uroflowmetry and post-void residual urine measurement, three overall grades (mild, moderate and severe) of LUTS were determined using the newly-developed assessment criteria for GPs. The relationship between diagnoses and treatments by the urologists, and overall LUTS grades were examined. RESULTS: All of the 70 patients with "severe" grade and 68 (94%) of 72 with "moderate" grade were diagnosed as having urination problems. Sixty-eight (97%) with "severe" grade and 64 (89%) with "moderate" grade were treated with fluid restriction, behavioral therapy, and/or drug therapy. Of 35 with "mild" grade, 17 (49%) were diagnosed as having normal urination. In this grade, eight patients (23%) were treated with fluid restriction and 15 (43%) with drug therapy. CONCLUSIONS: This preliminary study revealed that our criteria of LUTS severity for GPs were useful to determine whether the elderly patients should be treated or not. It is necessary to examine the validity of the criteria in a model in which GPs participate.     

A pilot study evaluating the safety and effectiveness of Lactobacillus vaginal suppositories in patients with recurrent urinary tract infection

Changes in the indigenous vaginal microflora with uropathogenic bacteria can predispose women to frequently recurring bacterial cystitis. Lactobacilli used as probiotics have played an important role in preventing the colonization of pathogenic bacteria in the vagina. A prospective clinical pilot study was performed to confirm the safety and effectiveness of Lactobacillus vaginal suppositories against the recurrence of bacterial urinary tract infection (UTI). The patients enrolled in the study were instructed to administer vaginal suppositories containing the strain Lactobacillus crispatus GAI 98322. A significant reduction in the number of recurrences was noted, without any adverse complication (P=0.0007). The administration of vaginal suppositories containing L. crispatus GAI 98332 seemed to be a safe and promising treatment for the prevention of recurrent UTI.