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To examine the association between treatment-achieved HbAAssociations of treatment-achieved HbAA significant linear trend was associated with HbAThese findings suggest that the relationship between treatment-achieved HbA

Background Respondent driven sampling (RDS) is a relatively new network sampling technique typically employed for hard-to-reach populations. Like snowball sampling, initial respondents or “seeds” recruit additional respondents from their network of friends. Under certain assumptions, the method promises to produce a sample independent from the biases that may have been introduced by the non-random choice of “seeds.” We conducted a survey on health communication in Guam’s general population using the RDS method, the first survey that has utilized this methodology in Guam. It was conducted in hopes of identifying a cost-efficient non-probability sampling strategy that could generate reasonable population estimates for both minority and general populations. Methods RDS data was collected in Guam in 2013 (n = 511) and population estimates were compared with 2012 BRFSS data (n = 2031) and the 2010 census data. The estimates were calculated using the unweighted RDS sample and the weighted sample using RDS inference methods and compared with known population characteristics. Results The sample size was reached in 23 days, providing evidence that the RDS method is a viable, cost-effective data collection method, which can provide reasonable population estimates. However, the results also suggest that the RDS inference methods used to reduce bias, based on self-reported estimates of network sizes, may not always work. Caution is needed when interpreting RDS study findings. Conclusions For a more diverse sample, data collection should not be conducted in just one location. Fewer questions about network estimates should be asked, and more careful consideration should be given to the kind of incentives offered to participants.

Acute otitis media (AOM) is a common infectious disease in children. Some children experience recurrent episodes of AOM. Recent investigations demonstrate antigen-specific immunological deficiencies in children prone to AOM. In the present study, the immune responses to non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (S. pneumoniae) were further investigated in otitis-prone children and normal children. Forty-eight percent of otitis-prone children exhibited reduced IgG2 levels to S. pneumoniae and 55% exhibited reduced IgG levels to NTHi. These data suggest that otitis proneness appears to be related to numerous immunological derangements. Pathogen-specific antibodies are a reliable measure of otitis proneness.

Neoadjuvant therapy-induced immunological deterioration may be a key factor in postoperative morbidity in patients with esophageal cancer. This study aimed to determine the effects of perioperative feeding with an immuno-enhanced diet on immune competence in patients treated with neoadjuvant therapy followed by surgery. Because an immuno-enhanced diet that contained several antioxidants was used, perioperative oxidative stress and the effects of the immuno-enhanced diet on this stress were also investigated. Of 39 patients with esophageal cancer who underwent similar surgical procedures, 26 patients who received chemotherapy or chemoradiation therapy before surgery were randomly divided into two groups: group 1 (n= 14) was given an immuno-enhanced diet for 5 days before surgery, and group 2 (n= 12) received no enteral feeding products before surgery. Group 3 (n= 13) consisted of patients that did not receive neoadjuvant therapy and received no enteral feeding products before surgery. Several markers for coagulation and fibrinolysis were determined and immunological assessments were performed for each patient. To measure reactive oxygen metabolites and the total antioxidant capacity, diacron-reactive oxygen metabolites (d-ROMs) and OXY-adsorbent tests were performed using a free radical elective evaluator. Significant depression in lymphocyte numbers was observed in groups 1 and 2 before and early after surgery as compared to group 3. Numbers of B cells, CD4/CD8 ratio, and phytohemagglutinin-induced lymphocyte transformation tests were also significantly decreased in groups 1 and 2 on postoperative day 1. Fibrin and fibrinogen degradation products were significantly elevated in group 2 compared to group 1. d-ROMs and OXY-adsorbent test values were elevated before surgery and were decreased transiently early after surgery. Compared to groups 2 and 3, d-ROMs values were significantly lower in group 1 patients throughout the postoperative period, while OXY-adsorbent test values were significantly higher in group 2 patients. Oxidative index was significantly suppressed in group 1 compared to group 3. No significant intergroup differences were observed with regard to morbidity after surgery. Although the baseline levels of immunological function might have been different because of less-advanced cancer stages in group 3, neoadjuvant therapy significantly affected several immunological parameters. Preoperative administration of an immuno-enhanced diet did not significantly prevent neoadjuvant therapy-induced immunological deterioration prior to esophageal cancer surgery. Patients with esophageal cancer had elevated levels of oxidant and antioxidant activities before surgery, which were transiently decreased early after surgery. Although the underlying mechanisms for these perioperative changes are unclear, this study showed that an immuno-enhanced diet containing several antioxidants may reduce oxidative stress following esophageal cancer surgery. After these mechanisms are studied further, oxidative stress control may become another tool for perioperative management to reduce morbidity after esophageal cancer surgery.

Docetaxel was effective as a second line neoadjuvant chemotherapy after failure of cyclophosphamide, epirubicin and 5-FU (CEF) in 2 cases of breast cancer. In Case 1, 4 cycles of trans-arterial neoadjuvant chemotherapy of docetaxel showed a PR effect after failure of 2 cycles of trans-arterial neoadjuvant chemotherapy with CEF. This patient died of pleuritis carcinomatosa 18 months after surgery for breast cancer (latissimus dorsi muscle myocutaneous flap after radical mastectomy). In Case 2, 6 cycles of neoadjuvant venous drip infusion of docetaxel resulted in a CR effect after failure of 2 cycles of transarterial neoadjuvant chemotherapy with CEF. This patient is alive and disease-free 27 months after the operation for breast cancer (same operation as for Case 1). Docetaxel was effective as neoadjuvant chemotherapy for patients after failure of trans-arterial neoadjuvant chemotherapy with CEF.

The aim of this study was to examine the enhancement of antitumor immunity of irradiated granulocyte macrophage-colony-stimulating factor (GM-CSF) gene-transduced mouse breast cancer cells.BALBMC mouse were vaccinated subcutaneously with saline or irradiated mouse breast cancer cells, BALBMC (1 x 10(6)/mouse), infected or not infected with recombinant adenovirus harboring GM-CSF gene on day-7. Mice were injected with parental cells (1 x 10(5)/mouse) on day 0.No mice vaccinated with irradiated GM-CSF producing BALBMC cells developed a tumor during the observation period of up to 16 weeks, whereas 100% of mice injected with saline developed a tumor.Our study demonstrates the feasibility of this immunotherapeutic approach as a novel adjuvant cancer therapy after surgery for breast cancer.

We conducted a case-control study to elucidate factors contributing to the development of hepatocellular carcinoma (HCC) in Hyogo Prefecture, Japan where its incidence is high. In this study, the incidence of hepatitis virus infection in HCC patients and lifestyle factors including dietary and drinking habits were investigated. One hundred and eight patients with HCC (89 males and 19 females) and 93 controls (63 males and 30 females) were enrolled. Hepatitis C virus (HCV) antibody was identified in 87% of cases of which HCV-RNA was further detected in more than 95%. Genotype distribution of HCV was similar to that reported for the Japanese infected with HCV. There was a positive correlation between HCC and history of blood transfusion (both male and female) and surgery (male). Alcohol consumption over a period of 30 years was higher in the HCC patients than in controls; but not significant. These data indicated that HCV infection is a primary contributing factor to the development of HCC in Hyogo Prefecture.

To compare, in a dog model, the properties of a reconstructed bladder (peristalsis, histological changes and absorption) using an autotransplanted ileal segment with standard enterocystoplasty.Female beagle dogs were divided into two groups. In group 1 (autotransplantation, six dogs), a Heineke-Mikulicz-type pouch was constructed using autotransplanted terminal ileum. The artery and vein of the terminal ileum were anastomosed to the iliac artery and vein, respectively. The pouch was anastomosed to the bladder remnant immediately above the vesical triangle. In group 2 (control, five dogs) the same type of bladder reconstruction using terminal ileum was undertaken but with no vessel anastomosis. Bladder function in these two groups was then compared for peristalsis (by monitoring intravesical pressure), histological changes (by microscopy) and glucose reabsorption (by measuring the amount of glucose remaining in the reconstructed bladder). The mean (range) follow-up was 11 (7-18) months for group 1 and 9.2 (7-12) months for group 2; the recovery time before examination was 4.6 (2-7) months for group 1 and 4.0 (2-6) months for group 2.In group 1, there were no major complications in five dogs after the procedure and they survived for7 months; the autotransplant became necrotic in one dog where the arterial diameter was1 mm. In the control group, all five dogs survived foror = 7 months after surgery. Intestinal peristalsis was inhibited in group 1 but not in group 2. The bladder was oval/spherical in group 1 and elongated in group 2, with a thinner epithelium and fewer goblet cells in the latter. Glucose reabsorption was greater in group 2 than in group 1.Bladder reconstruction using autotransplanted terminal ileum in dogs is technically feasible. For bowel peristalsis and reabsorption of glucose, autotransplanted ileum may have functional advantages over a standard enterocystoplasty.

The p16INK4 gene, which is a tumor suppressor gene, is frequently altered in lung cancers. Hypermethylation of the promoter region of the p16INK4 gene seems to be the major mechanism through which p16INK4 become inactivated. Hypermethylation of the p16INK4 gene was reported to occur at an early stage in lung cancer. To determine whether the change in p16INK4 methylation status occurs at the late stage in the progression of primary lung cancers, we analyzed the primary and metastatic tumor tissues and normal lung samples from 29 cases of advanced lung cancer with distant metastasis. In each tissue sample, we analyzed the p16INK4 and p15INK4b genes for mutations and the methylation status of both genes using PCR-single strand conformation polymorphism, direct sequencing, and methylation-specific PCR analysis. We also analyzed a subset of the samples for p16INK4 protein expression. Genetic mutations in the coding region of the p16INK4 and p15INK4b genes were not found in any of the examined specimens. The promoter region of the p16INK4 gene was hypermethylated in the tumor samples of the primary or metastatic site of 37.0% (10 of 27) of the subjects. The promoter region of the p16INK4 gene was hypermethylated at both the primary and metastatic sites in two of the 10 cases and at only the metastatic site in 8 cases. By immunohistochemical analysis, we confirmed the presence of p16INK4 protein at the primary site of all cases in which the promoter region of the p16INK4 gene was hypermethylated at only the metastatic site. Interestingly, all 8 cases with a hypermethylated p16INK4 promoter region, at only the metastatic site, did not have p53 mutation. The results of this study indicate that tumor cells in which the p16INK4 gene has been inactivated by hypermethylation of the promoter region could have an advantage in progression and metastasis in non-small cell lung cancers, especially in the tumors with normal p53, and that the frequency of p16INK4 gene inactivation by hypermethylation could vary in clinical course.

We report two patients with spiny keratoderma of the palms and soles characterized by multiple tiny keratotic plugs on the palms and soles. This disease was reported to be possibly associated with internal malignancies. We found a tumor from the esophagus to cardia in one patient. Another had no tumor but the lesion occurred soon after a severe bronchial asthma attack. Causal relation between spiny keratoderma of the palms and soles and bronchial asthma is obscure. Since this disease has been under-diagnosed and under-reported, it is important for dermatologists to keep spiny keratoderma of the palms and soles in mind in daily clinical examinations.

When constructing an orthotopic neobladder, a short colonic mesentery may make the operation difficult. We have developed a new technique to autotransplant a free segment of intestine into the pelvis to augment the bladder.In this animal feasibility study, we used eight female dogs to perform orthotopic bladder replacement using a transplanted bowel segment. A segment of bowel was transected and revascularized between the ileal artery of the reservoir and the internal iliac artery in the end-to-end fashion.Follow-up studies revealed that the bladder autoaugmentation using the transplanted bowel segment was functional and free of leakage.Our work in dogs demonstrates that the use of an autotransplanted segment of intestine appears to be feasible for augmenting the bladder in those cases where mechanical difficulty arises in anastomosing the urinary reservoir to the urethra. This procedure merits clinical evaluation in cases that present difficulty for completing orthotopic neobladder.

Unlike other tissues, bone marrow (BM) seldom displays fibrosis after injury, suggesting a possible suppressive mechanism against secondary myelofibrosis in BM tissues. We investigated if fibrosis-related factors, such as matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP), were expressed in BM tissues in vivo. We attempted immunohistochemical studies on specimens of 16 BM aspiration materials with normal hematological findings and 21 BM tissues from autopsy cases who had succumbed to acute heart failure or cerebrovascular diseases without any BM injuries. Identification of immunohistochemically reactive MMP-2, MMP-9 and TIMP-2 in BM tissue samples revealed for the first time that MMP-2 was localized in the myeloid cells, erythroblasts and megakaryocytes, MMP-9 in the myeloid cells and megakaryocytes. In addition, expression of TIMP-2 in the megakaryocytes as well as in the histiocytes within the stroma was verified. In the non-pathological condition, MMP/TIMP expressions were not encountered in BM stromal cells, such as fibroblasts, vascular endothelial cells, reticulum cells on adipocytes, except for TIMP-2 identification in stromal histiocytes. It is highly possible that these MMP and TIMP expressions in the BM hematopoietic cells and stromal histiocytes are significantly associated with suppression or induction of myelofibrosis.

BACKGROUND—Prostaglandin endoperoxide synthase/cyclooxygenase (COX) is the key enzyme in gastric mucosal protection and repair but its cellular localisation in the human stomach is still unclear. AIMS—To investigate immunohistochemically the cellular distribution of COX-1 and COX-2 proteins in the human stomach with or without gastritis or ulceration. PATIENTS AND METHODS—Tissues were obtained by surgical resection of gastric ulcers associated with perforation (n=9) or by biopsy from Helicobacter pylori positive patients with gastric ulcers (n=45) and H pylori negative healthy subjects (n=15). COX expression was detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and light and electron microscopic immunohistochemistry. RESULTS—COX-2 mRNA and protein were detected in gastric ulcer tissues but not in intact gastric mucosa. COX-1 mRNA and protein were detected in the intact mucosa. COX-2 immunostaining was exclusively localised in macrophages and fibroblasts between necrotic and granulation tissues of the ulcer bed. The percentage of COX-2 expressing cells was significantly higher in open than in closed ulcers, and in gastritis than in gastric mucosa without H pylori infection. COX-1 immunoreactivity localised in lamina propria mesenchymal cells was similar in various stages of ulcer disease and in intact gastric mucosa. Electron microscopic immunohistochemistry revealed both COX-1 and COX-2 on the luminal surfaces of the endoplasmic reticulum and nuclear envelope of macrophages and fibroblasts. CONCLUSIONS—Our results showed that COX-2 protein was induced in macrophages and fibroblasts in gastric ulcers and H pylori related gastritis, suggesting its involvement in the tissue repair process. Keywords: cyclooxygenase; macrophage; fibroblast; gastric ulcer; gastritis

Increasing evidence suggests that mesothelial cells contribute to the control of inflammation in the peritoneal cavity by secreting prostaglandins. A study has shown that cyclooxygenase (COX)-2 knockout mice die partly as a result of peritonitis.To investigate the expression and location of COX in peritonitis associated with peptic ulcer perforation.Gastric and duodenal tissues were collected intraoperatively from nine and four patients, respectively, and immunohistochemical staining for COX-1 and COX-2 was performed.Histologically, all patients had severe peritonitis around the perforation sites, into which many inflammatory cells and fibroblasts had infiltrated, and reactive mesothelial cells exhibited hyperplastic change. The COX-1 protein was not detected, whereas COX-2 was abundant in reactive mesothelial cells near the perforation site and disappeared away from the site. Macrophages and fibroblasts around the perforation site also revealed immunostaining for COX-2.Our results showed that COX-2 protein is induced in mesothelial cells, as well as in macrophages and fibroblasts, in inflamed peritoneal tissues associated with peptic ulcer perforation, suggesting involvement of COX-2 in tissue repair.

We examined the usefulness of preoperative chemotherapy using 5-FU and low-dose CDDP in patients with stage IVb gastric cancer. Between 1996 and 1998, seven patients with stage IVb gastric cancer who received preoperative chemotherapy achieved complete or partial response. One course of the chemotherapy was as follows: arterial or venous infusion of 5-FU (500 or 250 mg/day on day 1-5) and low-dose CDDP (5-10 mg/day on day 1-5) for three weeks. In addition to preoperative chemotherapy, biological response modifiers such as OK-432 and lentinan were used. We evaluated the response with abdominal or chest CT and tumor markers. Although preoperative chemotherapy did not improve the survival rate significantly, the prognosis of these patients seemed to be relatively good. Only slight side effects were found. These results suggest that preoperative chemotherapy using 5-FU and low-dose CDDP may be useful for patients with stage IVb gastric cancer.

Polymorphism of the gene that codes for angiotensin I-converting enzyme (ACE) is associated with increased severity of immunoglobulin A (IgA) nephropathy in adult patients. We evaluated the relationship between the polymorphism of ACE genotypes and the pathological and clinical findings in Japanese children with IgA nephropathy. Patients with moderate/diffuse mesangial proliferation, glomerular sclerosis and tubulointerstitial damage showed a significant increase of the D/D type compared to those who had mild/focal mesangial proliferation, without glomerular sclerosis or tubulointerstitial damage (p0.05). Proteinuria at the first renal biopsy was significantly higher in the former group compared with the latter group except glomerular sclerosis (p0.01). IgA nephropathy patients with tubulointerstitial damage also showed an increased serum creatinine level compared to patients without the damage (p0.03). We conclude that ACE gene polymorphism may be correlated with the prognosis of IgA nephropathy in Japanese children.

The crucial points of hepatic segmentectomy include an accurate mapping of proposed segment(s) to be resected and minimization of intra-operative blood loss. This study reports a surgical technique of hepatic resection for segment 7 and 8, and a benefit of supplemental use of topical cooling during consecutive right hepatic inflow occlusion.From January 1993 to December 1996, ten hepatocellular carcinoma patients with pathologic livers underwent hepatic segmentectomy for segment 7 and 8. The mapping of the target segments was guided by en-bloc test occlusion of the relevant portal pedicles and subsequent discoloration, often after the opening hilum method. Of these, five tumors were resected with topical cooling by ice slush seeding during consecutive right inflow occlusion (cooling group) and the remainder without cooling (Normothermic group). In the normothermic group, inflow occlusion was carried out by cyclic clamping and unclamping method.The inflow occlusion time was 54 +/- 9.4 min in the cooling group, much longer than in the normothermic group. Although the post-operative peak transaminase values were twice as high as those in the normothermic group, the blood loss was significantly less, and there was no detrimental effect of prolonged, consecutive ischemia on the other intra- and post-operative data.En-bloc taping of the target portal pedicles with or without the opening hilum method is useful in the mapping of segments, and the use of topical cooling is beneficial in prolonged inflow occlusion during complicated right-sided segmentectomy.

We report a case of uretero-external iliac artery fistula. A 60-year-old female was referred to our hospital complaining of intermittent gross macrohematuria. She had undergone radical hysterectomy, radiation therapy and chemotherapy for advanced cervical cancer 2 years ago. The patient had a 7 Fr ureteral double-J stent for left hydronephrosis. Retrograde urography showed a filling defect (8 mm in diameter) of the left ureter. A contrast-enhanced computed tomographic scan showed left hydronephrosis and hydroureter but no evidence of fistula formation or extravasation. A pelvic arteriography revealed a pseudoaneurysm of the left external iliac artery at the crosspoint between the left ureter and the iliac artery. Surgical repair of the left uretero-external arterial fistula was successfully performed as well as left nephroureterectomy. The possibility of fistula formation between ureter and artery should be kept in mind in patients with long-term indwelling ureteral stents and history of radiation therapy.

In interstitial lung diseases, deposition of extracellular matrix (ECM) in alveoli and degradation of ECM lead to pulmonary structural remodeling. The changes in ECM and the localization of matrix metalloproteinases (MMPs) and a tissue inhibitor of metalloproteinases (TIMP) in the lung tissues of patients with bronchiolitis obliterans organizing pneumonia (BOOP) and idiopathic pulmonary fibrosis (IPF) were investigated. Immunohistochemical analysis for the detection of fibronectin, collagen-I, -III, and -IV, smooth muscle actin, MMP-1 (interstitial collagenase), -2 (gelatinase A), and -9 (gelatinase B), and TIMP-2, and in situ hybridization for the detection of MMP-9 mRNA were performed. Western blotting of lung tissue homogenates was performed for MMP-2 and MMP-9. The gelatinolytic activities of the homogenates were also determined using gelatin zymography. Fibronectin and collagen-I, -III, and -IV were detected in the intra-alveolar fibrosis in addition to the interstitium of these diseases. MMP-1, MMP-2, MMP-9, and TIMP-2 were detected in the regenerated epithelial cells covering intra-alveolar fibrosis. Myofibroblasts in intra-alveolar fibrosis in BOOP showed predominant reaction for MMPs, and they ultrastructurally appeared to be phagocytosing collagen fibrils, and those of IPF showed a predominant reaction for TIMP-2. New vascularization in intra-alveolar fibrosis was exclusively observed in cases of BOOP, and the endothelial cells were positive for MMP-2. Western blotting showed the existence of a latent form of MMP-9 and latent and active forms of MMP-2, and gelatin zymography revealed that the ratio of active/latent forms of MMP-2 in BOOP is significantly larger than that in the control lungs. Predominant MMPs in BOOP may constitute the mechanism of reversibility of fibrotic changes in this disease. TIMP-2 in myofibroblasts in IPF may contribute to the stable ECM deposition and the irreversible pulmonary structural remodeling.

Inorganic mercury has a high affinity for the kidneys and causes acute renal failure. The present investigation was designed to determine the cause of the strain difference in sensitivity of mice to the renal toxicity of inorganic mercury. Renal damage caused by HgCl2 was estimated by histopathological and biochemical assessment, such as increase in blood urea nitrogen and plasma creatinine levels, and was found to be more remarkable in C3H/He than in C57BL/6 mice. Increase in renal lipid peroxidation in C3H/He was greater than that in C57BL/6 mice. However, no strain difference was observed in renal activities of glutathione (GSH) peroxidase, superoxide dismutase and GSH S-transferase in HgCl2-untreated mice. The GSH content and activities of catalase and GSSG reductase in kidney of HgCl2-untreated mice were higher in C3H/He than in C57BL/6. Background level of renal metallothionein content and the extent of metallothionein induction by HgCl2 showed no strain difference. On the other hand, renal mercury accumulation was higher and urinary mercury excretion was lower in C3H/He than in C57BL/6. The activity of renal gamma-glutamyltranspeptidase (gamma-GTP), which plays a key role in renal mercury accumulation, was higher in C3H/He than in C57BL/6. Furthermore, the increase in blood urea nitrogen by HgCl2, renal mercury accumulation and renal gamma-GTP activity in B6C3F1 mice were intermediate between those of the parent strains. These results suggest that the strain difference in renal toxicity of inorganic mercury seems to be caused by the discrepancy in renal mercury accumulation, and therefore, renal gamma-GTP may be an important factor determining the susceptibility of mice to the toxic action of inorganic mercury.

Experimental and clinical studies have found a relationship between blood transfusion and altered immune function. We estimated the risk of transfusions for shorter survival on patients with hepatocellular carcinoma who underwent hepatic resection.The impact of perioperative blood transfusions on 235 patients with hepatocellular carcinoma who had resections from January 1981 to December 1988 was retrospectively examined. All patients underwent hepatic resection and received no additional chemotherapy.Using the Cox proportional hazard model, the number of perioperative blood transfusions was found to be a significant prognostic factor for patient outcome (p = 0.03). Overall, patients who received less than 12 transfused units had a significantly better 5-year survival rate than those who received more than 13 transfused units (46.3% vs. 24.5%, p0.001). This result was also seen when the patients were subdivided by stage: 5-year survival in the early stage group (57.2% vs. 35.5%, p0.01) and in the advanced stage group (30.0% vs. 18.2%, p0.05). The number of perioperative blood transfusions also influenced the survival of patients who underwent a curative resection (66.2% vs. 38.5%, p0.01), but did not affect the survival of those who received a non-curative resection (7.9% vs. 7.4%).This study suggests that the number of perioperative blood transfusions is a significant prognostic factor in patients with hepatocellular carcinoma who undergo hepatic resection.

We evaluated the clinical efficacy of imipenem/cilastatin sodium (IPM/CS--a carbapenem antibiotic) against orthopedic infections, and the drug levels of the bone tissues were determined. The clinical efficacies for 6 patients in the infection group were good in 3 cases, and fair in the other 3; giving an efficacy rate of 50%. Bacteriologically, 8 strains were isolated from patients with the infection and an eradication rate of 87.5% was obtained upon the treatment. In 39 patients that were given the drug prophylactically, no postoperative infections occurred. Mean IPM levels in the bone and the bone marrow at 1 hour after administration in 5 patients of the prophylactic group were 17.3 micrograms/ml and 5.9 micrograms/g, respectively. The ratio of concentrations the bone to those in the bone marrow was 34.6%. The results of this study suggest that IMP/CS reaches to the bone tissue providing sufficient concentrations and that the drug is efficacious for the prophylaxis and the treatment of orthopedic infections.

A safe limit for normothermic consecutive portal triad occlusion in hepatectomy for the cirrhotic liver was believed to be around 30 minutes. Possibly, the occlusion time can be prolonged by cooling the ischemic liver in vivo. We describe the technique of segmentectomy assisted by topical cooling and its usefulness in prolonging the hepatic inflow occlusion time for cirrhotic livers without causing further ischemic injury.Fifty patients with hepatocellular carcinoma and chronic hepatic disease who underwent right-sided segmentectomy under hemihepatic inflow occlusion were divided into two groups: normothermic (n = 27), and hypothermic with hemihepatic topical cooling using ice slush (n = 23). Segmentectomies were carried out in the same way in both groups, guided by initial enbloc ligation of the corresponding portal pedicles.The mean right hepatic inflow occlusion time was significantly longer in the hypothermic group than in the normothermic group (53 +/- 22 minutes compared with 17 +/- 9.3 minutes). Despite the significant difference in occlusion time, no differences were found in the recovery of hepatic functions and the incidence of postoperative complications between the groups. Intraoperative blood loss was significantly less in the hypothermic group.The hepatic right-sided partial inflow occlusion time can safely be prolonged to 60 to 90 minutes in the presence of cirrhosis without causing another injury from ischemia and intermittent reperfusion.

We have provided home treatment mainly for cancer patients since June 1995 and had 7 such patients until March 1996. Among them two patients died not at home but in the hospital, although the patients and their family understood that the patients were in the terminal stage of illness. It home was thought to be difficult that they accept death at their homes. From the standpoint of physical and mental conditions, social status and actual medical care, the factors to promote death at home were examined. The two cases mentioned above and their families wished to have treatment at home. The reasons why we decided to discontinue medical care at their homes were twofold: 1) the difficulty of palliating patients' symptoms and anxiety; and 2) the uneasiness of the family in caring for patients at home. Therefore sufficient palliation of symptoms and "death education" for patients and families are required to encourage death at home.

The extracellular matrices and vascularization of the developing corpus luteum of adult female rats were studied with immunohistochemistry for laminin, type I, III and IV collagen and with electron microscopy. Ovaries were removed from Wistar-Imamichi rats that had a regular 4-day estrous cycle, 6 and 2 h before ovulation, immediately after ovulation, 6, 16 and 24 h after ovulation and at maturity of the corpus luteum and examined. The basement membrane of the follicles and capillaries of the theca interna started to break down around the entire circumference of the Graafian follicle 2 h before ovulation. More than 6 h after ovulation, dot-pattern positive reactions for type IV collagen and laminin were detected in the granulosa layer, and thin basement membrane structures appeared in association with the luteinizing granulosa cells. More than 16 h after ovulation, vascularization with the formation of capillary basement membrane was observed in the granulosa layer, and luteal mesenchymal cells with adjacent interstitial collagen components always appeared in close association with the newly formed capillaries. Our chronological observations revealed that both luteinizing cells and luteal mesenchymal cells are involved in the destruction and reconstruction of the follicular ECM, and that the luteal mesenchymal cells play an essential role in the neovascularization of the developing corpus luteum.

Infection of adenoids has been considered a causative factor of otitis media with effusion (OME). We believe that the deterioration in the mucosal barrier of adenoids makes the adenoids vulnerable to bacterial infections, resulting OME. In this study, we evaluated secretory IgA, secretory component (SC) and reticular and squamous changes of ciliated epithelium in adenoids. Fourteen children with OME (OME(+)) and 6 children without any history of OME (OME(+)) were enrolled in the study. Immunohistological study on the adenoids using anti-IgA and anti-SC revealed no significant difference between two groups in the number of IgA positive cells in the subepithelial layer. However, the proportion of the secretory component-positive area in the epithelium was significantly lower in the OME(+) group (11.4 +/- 13.0%) than in the OME(+) group (20.7 +/- 9.6%) (Mann Whitney U test, p0.05). Histological study using hematoxylin and eosin staining revealed that the area of squamous epithelization was bigger in the OME(+) group (32%) than in the OME(+) group (16%) (p0.05). The number of ciliated cells was decreased in the OME(+) group (13%) compared with the OME(+) group (31%). The epithelium was thicker in the OME(+) group (101 mu m) than in the OME(+) than in the OME(+) group (79 mu mm) (p0.05). These results suggest that the production of the secretory component is lower in the epithelium of adenoids in children with OME. Hyperplasia, squamous epithelization and decreased number of ciliated cells may also hamper mucosal clearance of the adenoids of children with OME. These findings suggest that the adenoids of children with OME are more susceptible to infections than adenoids of children without OME.

Gamma delta-T cells in the tonsil were evaluated by flow cytometric analysis and immunohistological study using monoclonal antibodies to the gamma delta-T cell receptor. Flow cytometric analysis using TCR-gamma/delta-1 showed that 2.2%, of T cells in the tonsil obtained from patients with recurrent or chronic tonsillitis expressed the gamma delta-T cell receptor. Immunohistologically, gamma delta-T cells were found mainly in the extrafollicular area, i.e., the T-cell zone, and showed strong migration to the crypt epithelium in tonsils with infections. The comparison on number of gamma delta-T cells in cases with simple hypertrophic tonsil and in cases with recurrent or chronic tonsillitis showed that tonsils with repeated or chronic infections had a significantly greater number of gamma delta-T cells than tonsils without infection. To address the functional aspects of gamma delta-T cells in the tonsil, the production of IL-2 of separated gamma delta-T cells was measured by solid phase ELISA. Increased IL-2 production was observed with staphylococcal enterotoxin A and B stimulation, and this increase was blocked by antibody to the gamma delta-T cell receptor, indicating that the production of IL-2 may be triggered by the interaction between the gamma delta-T cell receptor and staphylococcal enterotoxin. Our results show that gamma delta-T cells in the tonsil, especially in the crypt epithelium, may be activated by various bacterial antigens or heat shock protein released from damaged epithelial cells. The activated gamma delta-T cells will produce cytokines including IL-2 and function as so-called 'first-layer' immunity.

To evaluate dynamic morphologic changes of the respiratory tract in patients with obstructive sleep apnea syndrome (OSAS), the cross section and the midline sagittal section of the upper respiratory tract of OSAS were examined using ultrafast MR imaging technique. In 10 men and 2 women diagnosed with OSAS, 30 images obtained in 30-90 s at each location of sagittal and multilevel transverse sections were observed with cineloop display in awake and sleeping status. No patients had complete pharyngeal obstruction while awake. On the other hand, 9 patients had at least one occluded site, and 3 patients had wider obstructed sites during sleep. We are convinced that ultrafast MR imaging is very useful in determining the indication and the method for surgical treatment for OSAS.

The present study reports on the usefulness of laparoscopic microwave coagulonecrotic therapy as a new option in the treatment of hepatocellular carcinoma. Five patients with liver tumors associated with cirrhosis were treated from July 1993 to March 1994 with a microwave electrode (output 100 W, 3 to 4 cm long) devised for laparoscopic use. The tumors, all with diameters less than 3 cm and superficially located, were coagulated for a total radiation period of 20 to 30 min under laparoscopic, intraoperative ultrasonographic control. Postoperative complications were negligible, and laboratory values (glutamate-pyruvate transaminase, bilirubin, prothrombin time, platelet count) returned to preoperative levels within 7 days. Complete necrosis, including the surrounding liver tissue, was confirmed by a follow-up dynamic computed tomography scan during the follow-up period of 6 to 17 months (mean, 13 months). Laparoscopic microwave coagulonecrotic therapy can exert an effect on tumor equivalent to that obtained from a wedge resection but is noninvasive and may represent a new option for unresectable liver cancers.

To establish domiciliary treatment for cancer patients, following conditions must be settled. They are eligibility from clinical science, intentions of patients and their family, social and economical aspects, compatibility with medical service laws in Japan, and so on. Eligibility from clinical science should be the first matter to be settled among them. From the view of clinical science, medical care practices must be carried on in a correct manner even in patients' homes. In this study we focused on suitability from clinical science and examined possibility of domiciliary treatment for 111 inpatients in our hospital on April 6 th 1994. When the possibility was respectively judged by two nurses in our domiciliary cancer treatment committee, a difference appeared in the numbers of the candidates for domiciliary treatment. Finally the committee decided that 37 inpatients could receive medical care practices in their homes. The analysis of the reason in difference by two nurses made us recognize that the process of the selection of cancer treatment must be properly constructed for the well-qualified domiciliary treatment.

A 56-year-old female presented with end-stage renal disease. A CT scan of her kidneys demonstrated that the density of the renal parenchyma was quite low as compared with normal kidneys, and that corticomedullary demarcation was obscured. Magnetic resonance imaging (MRI) disclosed low intensity of the kidneys in T1-weighed images, and high intensity in T2-weighed images. In order to elucidate the etiology of her kidney disease, open renal biopsy was performed. The kidney surface was covered with numerous cysts with a diameter of less than 3 mm. Biopsy specimens from the cortical surface showed multiple cystic lesions. Serial sections of more than 200 slices of the biopsy material demonstrated that traces of collapsed glomeruli were present in most of the cysts. On electron microscopy, some epithelial cells lining the cysts were found to be round-shaped and contained a substantial amount of mitochondria, suggesting proximal tubules. These histological findings were compatible with glomerulocystic kidney disease (GCKD). An adult case of GCKD has rarely been reported, but the CT scan as well as MRI of the kidneys appeared to complement the diagnosis of GCKD. Although the cysts of GCKD have been considered to be dilatations of the Bowman's capsules, our observation suggested that part of the cells lining the cysts consisted of proximal tubular epithelium.

Myotonic dystrophy (DM) is the most common muscular dystrophy affecting adults among Caucasian and Japanese populations, with an average incidence of 12.5 in 100,000 in Caucasians and 5.5 in 100,000 in the Japanese. Recently the DM gene was cloned and characterized showing homology with the family of serine-threonine protein kinase. In DM patients expansion of an unstable trinucleotide CTG repeat, located within the 3' untranslated region of DM kinase gene, is involved. In this review we outline the molecular biological aspects of DM including DNA diagnosis, anticipation, differences between paternal and maternal transmission, founder chromosome and expression of the gene.

A case of mesangioproliferative glomerulonephritis (GN) associated with unique lesions of the juxtaglomerular apparatus (JGA) and interstitium is discussed. A 31-year-old Japanese woman who developed eyelid and pretibial edema with nephrotic-range proteinuria (4.8 g/day) and without hematuria, was admitted. Her proteinuria and edema quickly disappeared within 7 days after admission without treatment. Her blood examinations revealed hypocomplementemia on admission, but complement recovered to normal levels after 4 weeks. A renal biopsy specimen obtained on the 5th day of admission revealed moderate mesangioproliferative GN with marked periarteriolar inflammatory cell infiltrations in the JGA and occasionally in the tubular interstitium. Depositions of IgG, IgA, IgM and C3 were observed in the glomerular mesangial regions and some capillary walls, but not in the extraglomerular areas. Titers of GN-related viral antigens were not increased. Although the renal histology of this case was similar to that of experimental acute cytomegalovirus (CMV) GN in mice (described by Smith, R.D.), we could not detect CMV antigen by indirect immunofluorescent method or the virus-like particles by electron microscopy. Clinical cases of nephropathy combining lesions of the glomerulus, JGA, and interstitium are very rare. We herein report a patient with mesangioproliferative GN, who underwent an acute clinical course associated with unique inflammatory lesions of the JGA and/or interstitium.

The techniques and results of nine patients who underwent hepatic resections with surface and/or in situ perfusion cooling with hepatoprotective agents of PGE1 and Ulinastatin are described. Eight hepatocellular carcinomas associating chronic liver disease and one hemangioma are included in this report. Complete vascular exclusion technique with the centrifugal blood pump driven veno-venous bypass was employed on the three patients with giant liver tumors. The bypass technique with liver cooling made it possible to carry out otherwise impossible and risky resections, particularly in case with neoplastic involvement of the inferior vena cava. The other patients were subjected to segmentectomy of the right lobe under hemihepatic surface cooling or in situ hypothermic perfusion by chilled Lactate Ringer for vascular arrested right lobe. Liver tissue temperature dropped down to 19 degrees C to 26 degrees C during cooling. Postoperative physiologic changes were minimal irrespective of prolonged continuous vascular interruption of the cirrhotic liver for up to 60 min. There was no mortality and major morbidity in the present series. Liver cooling can be an useful hepatoprotective method for the cirrhotic liver in the hepatic resection with vascular occlusion.

So-called lethal midline granuloma is of great clinical and theoretical interest. The etiology of lethal midline granuloma is unknown and the pathogenesis is variable, with debate as to precise classification and natural history. In this study, we reported genotypic and immunopathological features in 3 cases of lethal midline granuloma. The histopathological diagnosis of their biopsy specimens was initially polymorphic reticulosis/midline malignant reticulosis. Immunohistologic study of the specimens revealed that immature or atypical cells had phenotypes of T-cells, CD2, CD3, CD4 (Case 1), CD4 (Case 2), and CD2, CD3 (Case 3). Those cells were also found to be positive for HLA-DR, which indicated that they were activated T-cells. Immunohistology in T-cells, however, was not able to give a similar clue to clonarity as it was possible within B-cell neoplasms by immunophenotyping the light chains. With the establishment of cDNA probes for the T-cell receptor genes it was possible to analyze neoplasms of lymphocyte origin for lineage and clonality. The Southern blot analysis of 3 cases showed rearrangement of TCR gene, TCR beta and TCR gamma chain (Cases 1 and 2) and TCR beta and TCR delta chain (Case 3), whereas none of them showed rearrangement of immunoglobulin heavy chain. These findings represented conclusive evidence for a monoclonal T-cell proliferation within lethal midline granuloma. On the ground of immunohistological and genotypic studies, lethal midline granuloma histologically diagnosed as polymorphic reticulosis/midline malignant reticulosis are proven to be a T-cell lymphoproliferative disorder.

A study was carried out to determine which factors contributed to the vowel and consonant recognition ability of recipients of the 22-channel cochlear implant system. On the basis of the statistical analysis, no isolated factor showed a strong correlation with vowel recognition score. On the other hand, negative correlations were found between patients' consonant recognition scores and postoperative psychophysical percepts such as threshold levels and maximum comfortable loudness levels. However, multiple regression analysis also showed that the combination of lower threshold levels, a larger number of usable electrodes, and wider dynamic ranges contributed to higher consonant recognition scores.

Clinical studies on S 6472, a longer lasting preparation of cefaclor (CCL), were performed and the following results were obtained. S 6472 was administered orally to 102 patients with urinary tract infections including 16 with acute uncomplicated pyelonephritis, 32 with acute uncomplicated cystitis, 31 with complicated pyelonephritis and 23 with complicated cystitis. 95 patients were treated with 375 mg of S 6472 2 times daily and 7 patients were treated with 750 mg of S 6472 2 times daily. The overall clinical efficacy was evaluated on the basis of the criteria proposed by the Japanese UTI Committee. 1. Clinical efficacies in 11 cases of acute uncomplicated pyelonephritis were excellent in 10 and moderate in 1, with an overall efficacy rate of 100%. Bacteriologically, all 12 strains identified in the acute uncomplicated pyelonephritis cases were eradicated, with an eradication rate of 100%. 2. Clinical efficacies in 21 cases of acute uncomplicated cystitis were excellent in 17, moderate in 3 and poor in 1, with an overall efficacy rate of 95%. As to bacteriological responses, 22 strains identified in the acute uncomplicated cystitis cases (except 1 of Escherichia coli) were eradicated, with an eradication rate of 95%. 3. Clinical responses in 43 cases of complicated urinary tract infections were excellent in 20, moderate in 15 and poor in 8, with an overall efficacy rate of 81%. Bacteriologically, 39 strains, including only one strain of P. aeruginosa, in the complicated urinary tract infection cases (except 4 of E. coli, 1 of Klebsiella pneumoniae, 1 of Enterococcus faecalis and 2 of Enterobacter cloacae) were eradicated, with an eradication rate of 83%. As side effects, slight stomatitis and gastric discomfort were noted in 1 patient each but we were able to continue the medication. Abnormal laboratory test values found were: 1 case of a slight and transient increase of lymphocytes in peripheral blood and 1 case of a slight and transient increase of serum creatinine level.

Anesthetic experience of 4 cases of hepatic resection using veno-venous bypass was reported. Non-forced bypass (passive shunt) was used in case 1. Hepatic resection was performed while supporting hemodynamic stability during the subsequent anhepatic phase using pump-driven veno-venous bypass (active shunt) in case 2-4. Various problems arose in each case. In the non-forced bypass case, hypotension during the bypass created a problem; whereas, hypothermia was pronounced during bypass in the pump-driven bypass cases. Massive transfusion due to bleeding, hypocalcemia, and unintentional hypothermia after veno-venous bypass precipitated heart failure. Attention should therefore be directed toward, (1) preparation for massive transfusion, (2) measurement and correction of the plasma calcium ion concentration, (3) maintenance of body temperature, and (4) hemodynamic control with a Swan-Ganz catheter and an inferior vena cava catheter. Extracorporeal bypass using a pump-driven veno-venous bypass (Bio-pump) and splanchnic decompression system via the portal system appear to be advantageous.

Endometriosis of the urinary tract is uncommon. A thirty-year-old woman was referred to our hospital, complaining of macrohematuria. Intravenous pyelography (IVP) showed bilateral hydro nephrosis. Cystoscopic examination revealed a mass around the bilateral ureteral orifice. Danazol therapy was commenced. After 6 months of therapy, IVP showed the improvement of hydronephrosis of left kidney and cystoscopy revealed the resolution of most of the mass in the bladder. For definite diagnosis and treatment, danazol therapy is considered to be effective for endometriosis, but if secondary fibrosis has occurred, surgical treatment may be necessary.

Seven patients with renal cell carcinoma, who had undergone uninephrectomy or who had only one functioning kidney were clinicopathologically studied. They were 5 males and 2 females, with ages ranging from 51 to 74 years (mean: 61 years). Of these cases, 4 had undergone uninephrectomy for renal cell carcinoma, and 1 had received uninephrectomy because of renal calculus. In the remaining 2 cases, one kidney did not function (hypoplastic kidney). Renal cell carcinoma was discovered by macroscopic hematuria in 2 cases, during the follow-up observation after a previous surgical treatment of renal cell carcinoma in 4 cases and by abdominal computed tomography during treatment of abdominal aneurysm in 1 case. Excluding one case with multiple metastases, all cases were surgically treated (3 with partial nephrectomy and 3 with enucleation). During surgery, renal blood vessels were clamped for 24-60 minutes (mean: 38 minutes). After operation, 5 cases showed an elevation in serum creatinine (greater than or equal to 2.0 mg/ml), which, however, was normalized rapidly by conservative treatment. They have been followed up for 6 months to 7 years and 8 months after operation (mean: 2 years and 11 months). The case which had undergone before and recently received enucleation (2 pieces) showed metastasis of cancer to the pancreas 2.5 years after the recent operation. Therefore, this case additionally received partial pancreatectomy. The results of this study suggest that conservative surgical treatments are appropriate for the treatment of renal cell carcinoma in patients with solitary kidney from viewpoint of the quality of life, so long as postoperative management is sufficiently made.

Nine myasthenia gravis patients (including 6 thymomas) with partial or no recovery were studied from 2 to 13 years after previous thymectomy, which had been carried out by the transsternal simple thymectomy in three, transretrothoratic simple thymectomy in three and extended thymectomy in three. X-ray CT and MRI of the mediastinum showed images compatible with residual thymic tissue in 8 of 9 patients. All patients underwent reoperation by extended thymectomy, and thymic tissue was found in 7 of 9 patients. There is no patients with recurrent thymoma localized to the mediastinum. After repeated thymectomy, 7 of 9 patients improved clinical including one patient without remnant and 2 patients were unchanged. Persistence of symptoms in patients with myasthenia gravis who have undergone the first surgery has been attributed to remnant thymic tissue. There is no correlation in the improvement and corticosteroid hormone therapy before the re-exploration. Therefore, it is quite reasonable to infer that incomplete removal of the thymus was responsible, at least partly, for failure of the first procedure.

Five cases of lethal midline granuloma were identified histologically and phenotypically as peripheral T-cell lymphomas. Epstein-Barr virus (EBV) DNA was detected in the nasal tumour biopsy specimens by Southern blotting and in-vitro hybridisation with simultaneous detection of EBV-determined nuclear antigen (EBNA) and T-cell surface markers by two-colour immunofluorescence. Further immunofluorescence and northern blotting revealed that EBNA2 gene and also latent membrane protein gene were expressed in the nasal tumour cells. The patients had high titres of antibodies to EBV. These findings suggest that lethal midline granuloma is causally associated with EBV.

Healing process of operative cardiac wounds was studied histopathologically in 14 patients who died 28 hours to 5 years after the operation of cardiac valve replacement. Repair of wounds in aorta and free wall of atrium was characterized by production of neointima and proliferation of collagen fiber at adventitia of aorta or epicardium of heart. Adhesion with granulation tissue at left ventricular venting wounds was observed in the case of 18th post-operative day. Reticulofibrosis of surrounding intracardiac muscle played an important role in development of granulation tissue. Cicatrix with collagen fiber was appeared from one month after the operation. In spite of attenuation of ventricular scar, aneurysmal bulging could not be observed. The basic healing pattern of wound in atrial septum was production and thickening of neointima. Granulation tissue rarely developed at the septum. Adhesion between sutured edges of atrial septal endocardium could not be observed and the dead space there remained over a period of 7 months after the operation. These findings indicated the continuous presence of unexpected weakness of the sutured septum until sufficient thickening of neointima had developed.

We experienced a case of reexpansion pulmonary edema during the fenestration of giant hepatic cyst. The patient was a 56 year-old female who had been suffering from dyspnea due to a large abdominal mass for 3 months. The preoperative chest X-ray revealed remarkable elevation of diaphragm (right third and left fifth intercostal spaces). The result of blood gas analysis showed hypoxemia and respiratory compensation for metabolic acidosis. By the drainage of 12L of the cyst fluid for 30 minutes during operation, bloody and foamy bronchial secretion spurted out. Vigorous respiratory management using PEEP was promptly started and continued postoperatively in ICU. The endotrachial tube was withdrawn on the 2nd postoperative day. The ratio of protein in airway secretion in to plasma protein was 0.78, and it appeared that the pulmonary edema was mainly caused by increased permeability of pulmonary capillary vessels.

A 68-year-old woman was hospitalized complaining of right flank pain. The excretory pyelogram revealed that the right kidney was hydronephrosis, and a retrograde pyelogram showed stringy filling defects in the middle portion of the right ureter. Suspecting a right ureter tumor, a right ureteronephrectomy was performed. The pathological diagnosis was ureteral cholesteatoma which is a rare condition with reports of only 9 cases in the Japanese literature. Although the possibilities of malignant change has been debatable, long term follow up would be mandatory.

Hyperthermia is a totally different modality from existing treatment modalities. Systemic hyperthermia (S-HT) is effective against advanced tumors which make resistance to conventional cancer therapies. In S-HT, it is essential and very important to manage cardio-pulmonary function in good condition. Especially, PEEP (about 7 cm H2O) is very effective to prevent lung edema. Fifty-four patients with a variety of neoplasms were subjected to S-HT, alone or in combination with chemotherapy, radiotherapy, and immunotherapy. S-HT was performed under general anesthesia by using extracorporeal circuit in corporating a heat exchanger. Usually, S-HT was given for 4-8 hours with 41.5-42.0 degrees C at 2 weeks intervals. Out of 25 evaluable cases, response was obtained in 11 cases (44%) including 2 cases of complete response. Cardio-pulmonary performance was evaluated using a flow directed pulmonary artery catheter (Swan-Ganz catheter). At treatment temperature, all patients showed hyperdynamic conditions and developed a two-fold mean increase in cardiac index. Altogether 172 treatment sessions were associated with sinus tachycardia and a reduction in diastolic pressures. Laboratory abnormalities included thrombocytopenia without sign of D.I.C., moderate hyperglycemia, mild degree of hypophosphatemia, hypolcalemia and transient elevations in liver enzymes. Serum creatinine levels were elevated in all treatment sessions without elevation of serum BUN. Serum levels of calcium and magnesium were stable. All of abnormalities and toxicities were decreased within 1 to 2 weeks after treatments. It is suggested that with carefully monitored conditions S-HT be performed safely without heart failure.