A Chromosome 13 locus is associated with male-specific mortality in mice.

BACKGROUND AND AIM: Mortality is a highly complex trait influenced by a wide array of genetic factors. METHODS: We examined a population of 1200 mice that were F2 generation offspring of a 4-way reciprocal cross between C57BL6/J and DBA2/J strains. Animals were sacrificed at age 200, 500, or 800 days and genotyped at 96 markers. The 800 days old cohort, which were the survivors of a much larger breeding group, were examined for enriched frequency of alleles that benefit survival and depletion of alleles that reduce survival. RESULTS: Loci on Chr 13 in males and on Chr X in females were significantly distorted from Mendelian expectations, even after conservative correction for multiple testing. DBA2/J alleles between 35 and 80 Mb on Chr 13 were underrepresented in the age 800 male animals. D2 genotypes in this region were also associated with premature death during behavioral testing. Furthermore, confirmatory analysis showed BXD recombinant inbred strains carrying the D2 alleles in this region had shorter median survival. Exploration of available pathology data indicated that a syndrome involving dental malocclusions, pancreatic islet hypertrophy, and kidney lipidosis may have mediated the effects of DBA alleles on mortality specifically in male mice. The heterozygote advantage locus on the X Chr was not found to be associated with any pathology. CONCLUSIONS: These results suggest a novel locus influencing survival in the B6/D2 genetic background, perhaps via a metabolic disorder that emerges by 200 days of age in male animals.

CHD7 gene polymorphisms and familial idiopathic scoliosis.

STUDY DESIGN: Model-independent linkage analysis and tests of association were performed for 22 single nucleotide polymorphisms in the CHD7 gene in 244 families of European descent with familial idiopathic scoliosis (FIS). OBJECTIVE: To replicate an association between FIS and the CHD7 gene on 8q12.2 in an independent sample of families of European descent. SUMMARY OF BACKGROUND DATA: The CHD7 gene on chromosome 8, responsible for the CHARGE syndrome, was previously associated with FIS in an independent study that included 52 families of European descent. METHODS: Model-independent linkage analysis and intrafamilial tests of association were performed on the degree of lateral curvature considered as a qualitative trait (with thresholds of ≥10°, ≥15°, ≥20°, and ≥30°) and as a quantitative trait (degree of lateral curvature). Results from the tests of associations from this study and the previous study were combined in a weighted meta-analysis. RESULTS: No significant results (P < 0.01) were found for linkage analysis or tests of association between genetic variants of the CHD7 and FIS in this study, failing to replicate the findings from the previous study. Furthermore, no significant results (P < 0.01) were found from meta-analysis of the results from the tests of association from this sample and from the previous sample. CONCLUSION: No association between the 22 genotyped single nucleotide polymorphisms in the CHD7 gene and FIS within this study sample was found, failing to replicate the earlier findings. Further investigation of the CHD7 gene and its potential association to FIS may be required. LEVEL OF EVIDENCE: N/A.

Midazolam for continuous sedation in Japanese critical care patients: phase II study.

This prospective study was undertaken to evaluate the efficacy and safety of midazolam as a sedative agent in 14 critically ill patients without coma admitted to the intensive care unit at Nihon University Itabashi Hospital, Japan. Adequate sedation (sedation score [SS] 4-6) was induced with 0.058- 0.372 mg/ kg midazolam and maintained with a dose range of 0.03-0.4 mg/kg per h. Most burn or trauma patients required higher midazolam doses than patients with cardiovascular disease. The most frequent adverse events observed were hypotension, heart-rate fluctuation and electrocardiogram abnormalities. Pharmacokinetic analysis of the population suggested that lower drug clearance rates correlated with presence of complications. Plasma concentrations (EC50) of SS 5, estimated by logistic regression analysis, varied among patients (mean 194 ng/ml). Midazolam infusion achieved successful sedation in this critical care setting, but the optimum dose differed by patient and was influenced by the presence of complications.

A new endoscopic tattooing technique for identifying the location of colonic lesions during laparoscopic surgery: a comparison with the conventional technique.

BACKGROUND AND STUDY AIMS: Knowledge of the exact location of colorectal lesions is necessary but difficult to establish during surgery. Thus, endoscopic tattooing has been used as an important preoperative marker for identification. Using the conventional technique, we injected tattooing agents directly into the colonic wall. However, to make sure that the tattooing agents were adequately injected into the submucosal layer, and to prevent spillage into the peritoneal cavity, we modified the conventional method and developed a new tattooing technique: using India ink with prior and subsequent injection of saline into the submucosa. The aim of this study was to retrospectively assess the clinical utility and potential complications of the above two techniques of endoscopic tattooing using India ink. PATIENTS AND METHODS: A total of 153 patients underwent laparoscopically assisted colectomy at the National Cancer Center Hospital East, Kashiwa, Chiba, Japan, between June 1994 and December 1999, and 91 patients underwent preoperative endoscopic tattooing by either the conventional or the new technique. The conventional and new techniques were used from June 1994 to December 1997 (n = 36) and from January 1998 to December 1999 (n = 55), respectively. Informed consent was obtained from all the patients. RESULTS: Using the conventional technique, the exact location of the lesion was identified in 31 of 36 cases (86.1 %) during surgery. The complications of this procedure were silent local peritonitis in two patients and reactive lymph node swelling in one patient (3/36, 8.3 %). Using the new technique, in 54 of 55 cases lesions (98 %) were easily identified (p = 0.034),and in only one there was a small leakage of India ink into the peritoneal cavity (1/55; 1.8 %), no other serious complications were observed. CONCLUSIONS: The results demonstrate that our new technique for endoscopic tattooing is probably better than the conventional technique for clinical use, in terms of diagnostic accuracy and safety, but this would have to be proven in a randomized comparison.

Hepatic arterial infusion of 5-fluorouracil for liver metastases from pancreatic carcinoma: results from a pilot study.

BACKGROUND/AIMS: Liver metastasis is a common progression of pancreatic carcinoma, but an effective chemotherapy has not been established. The purpose of this study was to examine the efficacy and safety of a hepatic arterial infusion of 5-FU in patients with liver metastasis from pancreatic carcinoma. METHODOLOGY: Thirteen patients were enrolled in a pilot study of a hepatic arterial infusion of 5-FU therapy. They received 5-FU for 5 days at a dose of 500 mg/m2/day by continuous hepatic arterial infusion every 4 weeks. RESULTS: One patient showed a partial response, while 6 showed no change. Of these 6 patients, 2 showed a minor response. The overall response rate was 8% (95% confidence interval: 0-22%). Nausea and vomiting were the most common types of toxicity. Three patients (23%) had hepatic arterial occlusion. There were no life-threatening toxicities or complications. The overall median survival time was 15.9 weeks. CONCLUSIONS: Hepatic arterial infusion of 5-FU in patients with liver metastasis from pancreatic carcinoma is tolerable but is minimally effective at this dose and schedule. The schedule of administration should be modified.

Visualization of blood flow in hepatic vessels and hepatocellular carcinoma using B-flow sonography.

PURPOSE: A B-flow sonographic technique was recently developed to provide direct visualization of blood flow with gray-scale sonography. Compared with color Doppler sonography, B-flow imaging has wideband resolution and a high frame rate. The purpose of this study was to evaluate the usefulness of B-flow sonography for visualizing blood flow in hepatic vessels and tumor vascularity in patients with liver cirrhosis or hepatocellular carcinoma (HCC). METHODS: Twenty-five patients with liver cirrhosis, including 15 with HCC, were studied by B-flow and color Doppler sonography. Blood-flow detection rates in portal veins and hepatic arteries and tumor vascularity in HCC were analyzed, and the 2 methods were compared. RESULTS: Using B-flow, blood flow was visualized in the portal vein in 23 (92%) of 25 patients and was visualized in the hepatic artery separately from the portal vein in 9 (36%) of 25 patients. The blood-flow signals were visualized only within vessels, never "bleeding" outside the vessel's lumen. Blood flow in the portal vein was observed with color Doppler sonography in all 25 patients, but the hepatic artery was never clearly separated from the portal vein. Vascularity within the HCC tumor was detected in 9 (60%) of 15 nodules with B-flow imaging, and fine arteries flowing into the tumor were observed in 6 nodules. Color Doppler sonography detected blood flow in 13 (87%) of the 15 HCC nodules. CONCLUSIONS: Blood flow in hepatic vessels and tumor vessels of HCC were visualized with B-flow sonography. B-flow sonography is a potentially useful technique for the evaluation of liver vascularity and intratumoral vessels.

Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with peritoneal dissemination: a retrospective study.

BACKGROUND: Most gastric cancer patients with peritoneal dissemination have been excluded from clinical studies because they usually have no measurable lesions. They also have a high risk of toxicity because of complications such as intestinal obstruction and ascites. We conducted a retrospective analysis to evaluate the efficacy and feasibility of sequential methotrexate (MTX) and 5-flurorouracil (5FU) therapy for this population. METHODS: This analysis was based on 56 consecutive chemotherapy-naive patients with confirmed peritoneal dissemination of gastric cancer who were being treated with sequential MTX/5FU. The therapy comprised a weekly schedule of MTX 100 mg/m2, given as a bolus infusion 3 h prior to a bolus infusion of 5FU 600 mg/m2. Leucovorin 10mg/m2 was administered six times, every 6h, starting 24h after MTX administration. RESULTS: Evidence of peritoneal dissemination was confirmed by laparotomy in 16 patients, by cytologic examination of ascites in 11 patients, and by clinical imaging in 29 patients (15 with ascites, 13 with intestinal obstruction; in 10 of the 29 patients, detection was by barium enema or computed tomography [CT] scan). Neutropenia of grade 3 or worse and anemia were observed in 8 (14%) and 10 (18%) of the 56 patients, respectively. There was one treatment-related death due to neutropenic sepsis. Of the 26 patients with measurable lesions, 9 showed a response (36%). The median survival time and median time to treatment failure were 259 days and 167 days, respectively. Objective improvement of ascites was seen in 13 of 26 patients (50%), including 5 with showed complete disappearance of ascites. Seven of the 15 patients (47%) with intestinal obstruction showed resolution, and 8 of the 21 patients (38%) who needed nutritional support before the treatment were free of that support for a median duration of 220 days after the completion of the treatment. Forty-seven of the 56 patients (84%) could be treated at outpatient clinics. CONCLUSIONS: This regimen may be of clinical benefit for patients with peritoneal dissemination of gastric cancer.

Assessment of arterial tumor vascularity in small hepatocellular carcinoma. Comparison between color doppler ultrasonography and radiographic imagings with contrast medium: dynamic CT, angiography, and CT hepatic arteriography.

Hepatocellular carcinoma (HCC) is characterized by tumor vascularization from the hepatic artery. The objective of our work was to compare color Doppler ultrasonography (CDU), including power Doppler ultrasonography (PDU) with radiographic imagings with contrast medium in regard to the detection of the arterial tumor vascularity of small hepatocellular carcinomas (HCC). We examined 42 small HCC lesions 2 cm or less in diameter in 37 patients for arterial tumor vascularity by conventional CDU, PDU, dynamic computed tomography (dCT), digital subtraction angiography (DSA), and CT hepatic arteriography (CTA). Color images were detected in 25 (59.5%) and 28 (66.7%) of the 42 lesions with conventional CDU and PDU, respectively, and tumor vascularity was detected in 26 (61.9%) by dCT, 23 (54.8%) by DSA, and 29 (69.0%) by CTA. Tumor vascularity could be detected in 51.9% by PDU and CTA, more than by conventional CDU, dCT, and DSA (44.4, 44.4, and 33.3%, respectively) in well-differentiated HCC, whereas the detection rates by these techniques were almost equal (86.7% by CDU, 93.3% by PDU, dCT, and DSA, 100% by CTA, respectively) in moderately and poorly differentiated HCC. PDU is superior to CDU, dCT and DSA and equal to CTA for the detection of tumor vascularity in small HCC, particularly in well-differentiated HCC.

Continuous microinstillation of phenol red on liver surface for liver site-selective delivery.

We report a very promising approach for liver site-selective drug delivery through drug instillation on liver surface. Phenol red, which was selected as a model drug, was accumulated in the instillation site after instillation on the rat liver surface. The site-selective localization was enhanced by gradually and continuously instilling a small amount of drug solution on the liver surface.

Clinical significance of magnetic resonance cholangiopancreatography for the diagnosis of cystic tumor of the pancreas compared with endoscopic retrograde cholangiopancreatography and computed tomography.

BACKGROUND: Cystic tumor of the pancreas has been investigated by a variety of imaging techniques. Magnetic resonance cholangiopancreatography (MRCP) is being widely used as a non-invasive diagnostic modality for investigation of the biliary tree and pancreatic duct system. The purpose of this study was to compare MRCP images with those of endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) in order to clarify the diagnostic efficacy of MRCP for cystic tumor of the pancreas. METHODS: We retrospectively studied 15 patients with cystic tumor of the pancreas that had been surgically resected and histopathologically confirmed. There were five cases of intraductal papillary adenocarcinoma, five of intraductal papillary adenoma, two of serous cyst adenoma, two of retention cyst associated with invasive ductal adenocarcinoma and one of solid cystic tumor. RESULTS: In all cases MRCP correctly identified the main pancreatic duct (MPD) and showed the entire cystic tumor and the communication between the tumor and the MPD. On the other hand, the detection rate by ERCP of the cystic tumor and the communication between the cystic tumor and the MPD was only 60%. Although the detection rates by CT for the septum and solid components inside the cystic tumor were 100 and 90.0%, respectively, those of MRCP for each were 58.3 and 20.0%. CONCLUSION: MRCP is capable of providing diagnostic information superior to ERCP for the diagnosis of cystic tumor of the pancreas. Although MRCP may provide complementary information about the whole lesion of interest, the characteristic internal features of cystic tumor of the pancrease should be carefully diagnosed in combination with CT.

Citología por punción aspirativa con aguja fina en tumores de mama: experiencia del hospital de Valdivia / Cytology by aspirative punction with fine needle in breast neoplasms: experience of the Valdivia hospital

Se presenta la experiencia del equipo de cirugía mamaria y de los anatomopatólogos del Hospital de Valdivida en el estudio diagnóstico de nódulos mamarios palpables, mediante citología por punción aspirativa con aguja fina. Se revisa la correlación citológica histológica de 100 casos consecutivos a los cuales se les realizó ambos exámenes. Los resultados obtenidos mostraron que cuando la citología fue concluyente,se logró una sensibilidad del 100 por ciento,una especificidad de 94,9 por ciento,un valor predictivo positivo de 95,7 por ciento, un valor predictivo negativo de 100 por ciento y una exactitud diagnóstica de 97.5 por ciento. No encontramos diferencias significativas entre los operadores ni entre los informantes de las muestras citológicas. Estos resultados nos permitirían realizar un manejo terapéutico de nódulos mamarios palpables, cuya clínica e imagenología sugieren un determinado patrón biológico, con sólo el estudio citológico, sin exigir, como hasta ahora lo hemos hecho, el estudio histopatológico intraoperaorio del nódulo

A study of the bone morphogenetic protein derived from bovine demineralized dentin matrix.

We tried to extract and purify bone morphogenetic protein (BMP) from bovine demineralized dentin matrix (DDM). Crude dentin BMP (d-BMP) was extracted from DDM in 3 sequential steps. Purification of crude d-BMP was carried out by liquid chromatography. The molecular weight and the isoelectric point of the purified d-BMP were determined by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and electrofocusing. All fractioned samples were bioassayed in the thigh muscle pouches of AKR strain mice to test their ability to induce new bone formation. A sequence of 3 extraction steps worked effectively to obtain crude d-BMP. The purified d-BMP was shown to be homogeneous on high performance liquid chromatography (HPLC) and SDS-PAGE. The molecular weight and the pI were 25 kDa and 6.5, respectively. The amino acid composition was different from that of known bone-derived BMP. The purified d-BMP induced new bone formation in the thigh muscle pouches. The molecular weight, pI and amino acid composition were different from those of bone-derived BMP.

Incidental detection of breast cancer during T1-201 myocardial SPECT study.

A case of left breast cancer which was detected incidentally by T1-201 SPECT performed to evaluate the status of myocardial perfusion, is reported. Both stress and redistribution T1-201 SPECT clearly delineated the tumor. It was confirmed later as scirrhous carcinoma of the breast.

Parameters of dynamic and static iodine-123-MIBG cardiac imaging.

UNLABELLED: Dynamic and static 123I-MIBG studies were used to investigate various parameters with regard to their usefulness in evaluating cardiac disorders. METHODS: Four patient groups and one control group were included in this study. Dynamic study was acquired immediately after injection at 1 frame/sec for 2 min and at 1 frame/6 sec for the next 30 min using a 64 x 64 matrix format. Static study consisted of planar images at the anterior and left anterior oblique 45 degrees views in a 512 x 512 matrix format for 1 min. The early and delayed planar images were acquired soon after dynamic acquisition and approximately 4 hr after injection, respectively. Net injection dose was calculated as the difference in syringe counts before and after injection. From the dynamic and static studies, the heart uptake ratios at 3 min and 30 min, early uptake ratio and delayed uptake ratio were calculated at various intervals. Early and delayed clearance rates, Ke and Kd, respectively were also determined. These parameters were compared and correlated with each other. RESULTS: Three-minute heart uptake ratios were significantly higher than early or delayed uptake ratios or uptake ratios at 30 min in all groups. All uptake ratios in hemodialysis patients were significantly higher than those in other groups. The Kd values in dilated cardiomyopathy, doxorubicin therapy and vasospastic angina patients were significantly higher than those in hemodialysis patients and normal controls. At least bi-exponential clearance patterns of MIBG from the heart were observed in all groups. CONCLUSION: Three-minute and delayed heart uptake ratios calculated from dynamic and static studies are helpful in elucidating the uptake at nonvesicular sites, which reflect the severity of sympathetic nervous system abnormalities in the heart.

[Clinical evaluation of endoscopic ultrasonography (EUS) in the diagnosis of superficial esophageal carcinoma].

Pre-operative diagnosis of the depth of invasion is important to decide the treatment of superficial esophageal carcinoma. The ability of EUS to diagnose the depth of invasion was examined in 40 lesions with superficial esophageal carcinoma between January 1993 and April 1994. The depth of invasion was classified as m1 or m2, m3 or sm1, and sm2 or more. Mucosal carcinoma could be detected clearly by using the 20MHz miniature probe. The diagnostic accuracy was 82.5% in all 40 lesions, and 77.8% in mucosal carcinoma (included with sm1). The reasons for incorrect diagnosis were broadness of the lesion, microinvasion, and artifact of endoscopic biopsy. EUS is considered to be useful even for superficial esophageal carcinoma as one of the preoperative diagnostic imagings.

Citología mamaria por punción aspirativa con aguja fina: su rol como herramienta diagnóstica / Breast citology by aspirative punction with fine needle: it role as diagnostic tool

Tradicionalmente, la biopsia quirúrgica ha sido considerada como el procedimiento diagnóstico óptimo en el manejo de los nódulos mamarios. Actualmente la punción aspirativa con aguja fina ha sido propuesta como un procedimiento alternativo. La precisión diagnóstica de este método es variable reportándose falsos positivos que varían entre un 0 a 1.6 por ciento y falsos negativos entre un 0 y 35 por ciento. Se revisa la literatura analizando el rol de la punción aspirativa con aguja fina como herramienta diagnóstica, concluyendo que su uso en conjunto con los métodos diagnósticos rutinarios y efectuado por manos experimentadas aporta una ayuda indiscutible para el diagnóstico, planificación de tratamiento y seguimiento de lesiones mamarias

Citología por punción aspirativa en el bocio uninodular eutiroideo / Needle aspiration cytology in euthyroid uninodular goiter

Fine needloe aspiration cytology (FNAC) has been shown to be second only to surgical biopsy for demonstration of malignancy in thyroid nodules. A prospective study of FNAC for euthyroid uninodular goiter (EUG) was conducted between January 1987 and June 1990, totalizing 87 patients of which 61 were submitted to surgical biopsy. FNAC in the latter were interpreted as benign in 41 cases, suspected malignancy in 8, and definitely malignant in 7. The remaining 5 smears were considered technically inadecuate for diagnosis. In 39 of the 41 patients with a benign (negative- cytology result, the histopathological diagnosis confirmed the absenece of a neoplastic process (2 false negatives). In 12 of the 15 patients with a suspected amloignant (positive) cytology result, a subsequent histopathological report confirmed a neoplastic process (3 false positives). Thus FNAC had a sensitivity of 86% and a specificity of 93%. We conclude that FNAC is a valuable tool for the diagnosis of enthyroid goiter and could help reduce significantly the number of patients who need to be surgically intervened