Surgical removal of subfoveal hard exudates in diabetic maculopathy

PURPOSE: To examine the efficacy of surgical removal of subfoveal hard exudates during surgery in diabetic maculopathy. PATIENTS AND METHODS: This study was done on 60 patients (66 eyes) that all underwent surgical removal of subfoveal hard exudates under the same surgeon. Thirty-two men (37 eyes) and 28 women (29 eyes) were included in this study. The average age of the patients was 60 years (range, 30-77 years). The average follow-up period was 21 months (range, 12-48 months). All eyes were classified into 3 groups: 13 postoperative massive type eyes, 31 massive type eyes, and 22 scatter type eyes. We evaluated the visual results of these types. RESULTS: Preoperative and postoperative mean visual acuity was as follows: postoperative massive type 0.11, 0.22, massive type 0.12, 0.29, and scatter type 0.19, 0.33. Postoperatively visual acuity improved significantly in all types. There were no subfoveal hard exudates postoperatively in any eyes. CONCLUSION: Surgical removal of massive subfoveal hard exudates is effective, but its effects on vision are limited. Surgical removal of deposited subfoveal hard exudates may prevent massive subfoveal hard exudates postoperatively and improve visual prognosis.     

Genetic identification of cinnamon (Cinnamomum spp.) based on the trnL-trnF chloroplast DNA

Genetic identification among cinnamon species was studied by analyzing nucleotide sequences of chloroplast DNA from four species (Cinnamomum cassia, C. zeylanicum, C. burmannii and C. sieboldii). The two regions studied were the intergenic spacer region between the trnL 3'exon and trnF exon (trnL -trnF IGS) and the trnL intron region. We found nucleotide variation at one site in the trnL-trnF IGS, and at three sites in the trnL intron. With the sequence data from analysis of these regions, the four Cinnamomum species used in this study were correctly identified. Furthermore, single-strand conformation polymorphism (SSCP) analysis of PCR products from the trnL-trnF IGS and the trnL intron resulted in different SSCP band patterns among C. cassia, C. zeylanicum and C. burmannii.     

Bupivacaine attenuates contractility by decreasing sensitivity of myofilaments to Ca2+ in rat ventricular muscle

BACKGROUND: Bupivacaine exhibits a cardiodepressant effect, the molecular mechanism(s) of which have yet to be fully understood. Bupivacaine may directly act on contractile proteins and thereby decrease myofibrillar Ca2+ sensitivity. METHODS: Rat ventricular muscle was used. First, the effect of bupivacaine was examined on tetanic contractions in isolated intact myocytes. Next, Triton X-100-treated ventricular trabeculae were used to investigate the effect of bupivacaine on the pCa (= -log [Ca2+ ])-tension relation as well as on maximal Ca2+ -activated tension. Furthermore, to test whether bupivacaine inhibits the pathway downstream from Ca2+ binding to troponin C, tension was elicited in the skinned preparations by lowering the Mg-adenosine triphosphate (MgATP) concentration in the absence of Ca2+. The effect of bupivacaine on the pMgATP (= -log [MgATP])-tension relation was examined. RESULTS: In myocytes, 3 microm bupivacaine significantly (P < 0.01) increased intracellular Ca2+ concentration required for 5% cell shortening from the resting cell length. In skinned preparations, bupivacaine shifted the pCa-tension relation to the lower pCa side; the midpoint of the pCa curve (pCa50) was significantly (P < 0.05) changed by 10 and 100 microm bupivacaine. A highly correlated linear relation (R = 0.81; P< 0.0005) was present between pCa50 and maximal Ca2+ -activated tension. Bupivacaine (10 and 100 microm) significantly (P < 0.05) shifted the midpoint of the pMgATP-tension relation to the higher pMgATP side. CONCLUSIONS: Bupivacaine decreases myofibrillar Ca2+ sensitivity in ventricular muscle, and this is coupled with the compound's inhibitory effect on the pathway beyond Ca2+ binding to troponin C, possibly on the actomyosin interaction. The current results may partly explain the overall cardiodepressant effect of bupivacaine in vivo.     

The new TNM classification of lymph node metastasis minimises stage migration problems in gastric cancer patients

The present study aimed at investigating whether in gastric cancer patients stage migration occurs with extension of lymphadenectomy, when node metastases are staged according to the new pN classification (UICC 1997). The investigation involved 921 patients, who underwent R0 gastric resection for gastric cancer between 1988 and 1998 in three different Italian centres: Verona (n=236), Forlì (n=409), Siena (n=276). The relation among lymphadenectomy and pN category was assessed by Kendall's partial rank-order correlation coefficient, controlling for depth of tumour invasion. A direct evaluation of the Will Rogers phenomenon was accomplished in the Verona series, by comparing the number of positive nodes actually observed with the number of positive nodes which would have been retrieved by a less extended lymphadenectomy (D1). The number of positive nodes increased remarkably with the enlargement of lymphadenectomy, especially in pT2 patients (from 2.2+/-3.9 in D1 to 3.9+/-5.0 in D3) and in pT3/pT4 patients (from 5.1+/-5.9 in D1 to 11.3+/-12.6 in D3). Non-parametric statistics highlighted a weak (Kendall's partial T=0.128) but significant (P<0.001) correlation between pN category and extension of lymphadenectomy. In the direct analysis of the Verona series, 22 patients out of 230 (9.6%) migrated to a lower pN tier when ignoring positive nodes retrieved from the second and third level. This percentage increased to 39.1% (90 out of 230) when adopting the TNM 87 classification. In conclusion stage migration is of minor importance in gastric cancer patients, staged according to the new pN classification.     

Polymyositis and dermatomyositis associated with malignancy: a 30-year retrospective study

BACKGROUND: Polymyositis and dermatomyositis in association with malignancy are paraneoplastic syndromes, but the incidence, treatment and factors that predict associated cancer and its prognosis all remain unclear. PATIENTS AND METHOD: During the 30-year period 1969-99, we treated 64 patients who had polymyositis (including two with cancer) and 28 patients who had dermatomyositis (including 10 with cancer). We compared the clinical findings of the patients who had cancer with the findings of those who did not have cancer. RESULTS: The risk of cancer is significantly higher in dermatomyositis and somewhat higher in polymyositis. An increased cancer risk was found in male patients with dermatomyositis who were older than 50 years. Cancer was diagnosed within 4 years before or after the diagnosis of polymyositis or dermatomyositis, and usually within 1 year. An operation was not possible in many of the patients with cancer because of the advanced stage of the disease. CONCLUSION: Our findings suggest that early discovery of malignancy is critical in cases of polymyositis and dermatomyositis.     

Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent, with the cytochromes P450.

The biotransformation of prasugrel to R-138727 (2-[1-2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-mercapto-3-piperidinylidene]acetic acid) involves rapid deesterification to R-95913 (2-[2-oxo-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]-1-cyclopropyl-2-(2-fluorophenyl)ethanone) followed by cytochrome P450 (P450)-mediated formation of R-138727, the metabolite responsible for platelet aggregation. For identification of the P450s responsible for the formation of the active metabolite, the current studies were conducted with R-95913 as the substrate. Incubations required supplementation with reduced glutathione. Hyperbolic kinetics (K(m) 21-30 microM), consistent with a single enzyme predominating, were observed after incubations with human liver microsomes. Correlation analyses revealed a strong relationship between R-138727 formation and CYP3A-mediated midazolam 1'-hydroxylation (r(2) = 0.98; p < 0.001) in a bank of characterized human liver microsomal samples. The human lymphoblast-expressed enzymes capable of forming R-138727, in rank order of rates, were CYP3A4>CYP2B6>CYP2C19 approximately CYP2C9>CYP2D6. A monoclonal antibody to CYP2B6 and the CYP3A inhibitor ketoconazole substantially inhibited R-138727 formation, whereas inhibitors of CYP2C9 (sulfaphenazole) and CYP2C19 (omeprazole) did not. Scaling of in vitro intrinsic clearance values from expressed enzymes to the whole liver using a relative abundance approach indicated that either CYP3A4 alone or CYP3A4 and CYP2B6 are the major contributors to R-138727 formation. R-95913 and R-138727 were also examined for their ability to inhibit metabolism mediated by five P450s. R-138727 did not inhibit the P450s tested. In vitro, R-95913 inhibited CYP2C9, CYP2C19, CYP2D6, and CYP3A, with K(i) values ranging from 7.2 microM to 82 microM, but did not inhibit CYP1A2. These K(i) values exceed circulating concentrations in humans by 3.8- to 43-fold. Therefore, neither R-95913 nor R-138727 is expected to substantially inhibit the P450-mediated metabolism of coadministered drugs.     

An autopsy case of atypical adrenoleukomyeloneuropathy in childhood

Adrenoleukomyeloneuropathy (ALMN) usually occurs in adulthood, it being extremely rare in childhood. We reported a quite atypical clinical case of ALMN as a variant of adrenoleukodystrophy (ALD). The onset was at 5 years 7 months and ataxia was the major symptom. His condition progressed rapidly to a vegetative state within 1 year. At the age of 11 years and 11 months he died of pneumonia and an autopsy was performed. We herein reported the neuropathological findings in this rare case. The autopsy revealed marked atrophy with diffuse demyelination and astrogliosis throughout the cerebrum, cerebellum and brainstem. Massive degeneration of the pyramidal tracts and loss of neurons were also seen in the spinal cord. The adrenal cortex showed marked atrophy with a striated cytoplasm in ballooned cells. These findings include pathological characteristics of both ALD and adrenomyeloneuropathy (AMN), suggesting ALMN. However, diffuse demyelination with gliosis in the cerebrum and cerebellum is quite atypical for ALMN. They might explain his atypical clinical course, especially the early onset of the disease with ataxia and rapid deterioration.     

Intraoperative electro-oculographic Monitoring for Skull Base Surgery

During surgery on the skull base, preservation of the integrity of the ocular motor nerves is vitally important. Intraoperative electrophysiological monitoring methods for protecting such functions have been reported by several investigators. However, these methods so far have not been popularized sufficiently, due to the difficulty and complexity of the procedures involved. The authors have developed an extremely simple but far more reliable method using electro-oculography under total intravenous anesthesia with propofol to preserve the integrity of the ocular motor nerves. The ocular motor nerves were stimulated with a monopolar electrode intracranially, and the polarity of the waves was recorded using surface electrodes placed around the eyeball, yielding precise information concerning the locations of the oculomotor nerve and/or abducent nerve. In addition, by performing continuous monitoring, invasive procedures affecting the ocular motor nerves could be detected as spontaneous ocular movements. In practice at our department, this method has been applied in 12 cases with tumors close to the ocular motor nerves, and has produced excellent results.     

Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D.

Epidemiological evidence suggests a potential role for vitamin D in colon cancer prevention. Vitamin D, absorbed from the intestine or derived from solar ultraviolet light, is metabolized in the liver to 25-hydroxyvitamin D (25-OH D(3)). Previous studies examining effects of vitamin D upon carcinogenesis have focused upon the active metabolite 1,25-dihydroxyvitamin D [1,25-(OH)(2) D(3)], which interacts with nuclear vitamin D receptors in several organs. Until recently, the metabolism of 25-OH D(3) to 1,25-(OH)(2) D(3) was believed to occur only in the kidney, but more recent studies have shown that 25-OH D(3) conversion to 1,25-(OH)(2) D(3) can occur in other tissues. We examined the association between fasting levels of 25-OH D(3), 1,25-(OH)(2) D(3), and BsmI polymorphism of the vitamin D receptor (VDR) gene with indices of colonic epithelial cell proliferation and differentiation in a chemoprevention study, after giving vitamin D or calcium and taking rectal biopsies that were incubated with bromodeoxyuridine. Vitamin D receptor polymorphism was determined by genotyping of the 3' BsmI polymorphism in intron eight of the VDR gene. No significant changes in cell proliferation or in differentiation were found in subjects between study start and end. However, fasting serum levels of 25-OH D(3) showed a highly significant decrease with whole crypt labeling index and the size of the proliferative compartment (phi h). There was no correlation between serum levels of 1,25-(OH)(2) D(3) and the proliferative parameters. Calcium supplementation induced a significant effect upon the relationship between serum 25-OH D(3) and rectal epithelial cell labeling index and phi h when studied by covariance analysis without a relationship with 1,25-(OH)(2) D(3) levels. VDR genotype did not influence the effects of serum 25-OH D(3) or serum 1,25-(OH)(2) D(3) levels upon proliferation. These data suggest that there might be a local effect of 25-OH D(3) on colonic epithelial cells through conversion of 25-OH D(3) to 1,25-(OH)(2) D(3). Subsequent studies have demonstrated the presence of 1alpha-hydroxylase mRNA in normal colorectal epithelium and in colorectal cancer. Thus, vitamin D may have an important role in determining the effects of calcium on colorectal epithelial proliferation and may explain some of the discrepancies found previously in studies that examine the direct role of calcium on the colorectal epithelium.     

Four cases of reversible posterior leukoencephalopathy syndrome

We reported four children cases with reversible posterior leukoencephalopathy syndrome (RPLS). Magnetic resonance imaging (MRI) of the brain demonstrated reversible multiple cortical and subcortical lesions predominant in the occipital region. All patients presented with neurological symptoms associated with hypertension, such as headache, seizures and visual disturbances, which were successfully treated with antihypertensive therapy. Although RPLS is rare in childhood, characteristic lesions on MRI in the hypertensive children should be recognized as manifestations of RPLS. Subsequent clinical management should focus on the treatment of the hypertension and/or its underlying causes.