Percutaneous thermal ablation for renal cell carcinoma in patients with Birt-Hogg-Dubé syndrome.

PURPOSE: The purpose of this study was to analyze the outcome of patients with Birt-Hogg-Dubé (BHD) syndrome who underwent percutaneous thermal ablation of renal cell carcinoma (RCC). MATERIALS AND METHODS: Six patients with genetically proven BHD syndrome who underwent one or more sessions of percutaneous thermal ablation for the treatment of RCC were included. There were 4 men and 2 women, with a mean age of 57.3±7.5 [SD] years (range: 44-67years). A total of 29 RCCs (1-16 tumors per patient) were treated during 20 thermal ablation sessions (7 with radiofrequency ablation and 13 with cryoablation). Outcomes of thermal ablation therapy were assessed, including technical success, adverse events, local tumor progression, development of metastases, survival after thermal ablation, and changes in renal function. RESULTS: Technical success was achieved in all ablation sessions (success rate, 100%). No grade 4 or 5 adverse events were observed. All patients were alive with no distant metastasis during a median follow-up period of 54months (range: 6-173months). No local tumor progression was found. The mean decrease in estimated glomerular filtration rate during follow-up was 10.7mL/min/1.73m2. No patients required dialysis or renal transplantation. CONCLUSION: Radiofrequency ablation and cryoablation show promising results for the treatment of RCCs associated with BHD syndrome. Percutaneous thermal ablation may be a useful treatment option for this rare hereditary condition.

Review of renal anastomosing hemangioma with focus on clinical and pathological aspects.

Renal anastomosing hemangiomas (RAH) has been recently proposed as a new entity. In this article, we summarize the clinicopathologic features of this tumor. RAH usually develops on a background of end-stage renal disease. Macroscopically, tumors are well-defined and their cut surface shows mahogany brown spongy tissue with epicenter in the renal medulla. Tumors are usually small, but larger lesions are reported. On microscopic examination, the tumor consists of sinusoid-like vascular channels lined by cuboidal endothelial cells with occasional hobnail-like appearance of endothelial cells closely mimicking splenic sinusoids. Eosinophilic hyaline globules may be present in the cytoplasm of neoplastic endothelial cells. Extramedullary hematopoiesis containing erythroid precursor and megakaryocytes may be present in the vascular lumens. Immunohistochemically, endothelial cells are positive for CD31 and CD34, but negative for D2-40, GLUT-1 and HHV8. The surrounding stroma around endothelial cells demonstrates positivity for  smooth muscle action. To date, there are no studies on molecular genetic aspects of RAH. This tumor is indolent based on site and size of the lesion, partial or nephrectomy is sufficient as a therapeutic modality.

The detection of toxigenic Corynebacterium ulcerans from cats with nasal inflammation in Japan.

Corynebacterium ulcerans (toxigenic C. ulcerans) produces the diphtheria toxin, which causes pharyngeal and cutaneous diphtheria-like disease in people, and this bacterium is commonly detected in dogs and cats that are reared at home. It is considered dangerous when a carrier animal becomes the source of infection in people. To investigate the carrier situation of toxigenic C. ulcerans of cats bred in Japan, bacteria were isolated from 37 cats with a primary complaint of rhinitis in 16 veterinary hospitals in Osaka. Toxigenic C. ulcerans was detected in two of the cats. By drug sensitivity testing, the detected bacterium was sensitive to all investigated drugs, except clindamycin. It appears necessary to create awareness regarding toxigenic C. ulcerans infection in pet owners because this bacterium is believed to be the causative organism for rhinitis in cats.

Identification of novel tumour-associated antigens in canine mammary gland tumour.

UNLABELLED: Canine mammary gland tumour (MGT) is the most common neoplasm in female dogs and has similar biological characteristics to human MGT. Spontaneous canine MGT is a more attractive clinical model in oncological research than that of the murine experimental model. Tumour-associated antigens (TAAs), which are produced in tumour cells, are applied as tumour markers, tumour vaccine antigens and molecular targets of therapeutic drugs. In this study, we have primarily identified 13 different TAAs of canine MGT by serological immunoscreening of cDNA expression library. The results of serological mini-arrays of identified antigens showed that CCDC41 antigen specially reacted with 35% of sera from MGT-dogs and did not react with control sera. We also found that HSPH1 mRNA expression levels increased significantly in MGT tissues. These findings will contribute to the development of diagnostic technologies and translational target therapies for dogs. CLINICAL RELEVANCE: HSPH1, which is strongly expressed in the tumour tissue, will be a possible vaccine antigen of canine MGT.

Review of renal tumors associated with Birt-Hogg-Dubé syndrome with focus on clinical and pathobiological aspects.

Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant inherited disorder characterized by clinical features of skin lesions, pulmonary lesions and renal tumor. The gene responsible for this syndrome is located on chromosome 17p11.2 and designated as FLCN. In this article, we review renal tumors associated with BHDS with a focus on clinical and pathobiological aspects. Renal tumors often occur multifocally or bilaterally in the imaging analyses or gross examination. Histological examination of renal tumors includes a variety of subtypes such as hybrid oncocytic tumor, chromophobe renal cell carcinoma (RCC), oncocytoma, clear cell RCC and papillary RCC. The histologic discordance in multiple tumors seems to be characteristic of this syndrome. Oncocytosis is observed histologically in about half of the cases. Several investigations have elucidated that folliculin may be involved in the mammalian target of rapamycin (mTOR) pathway recently. Renal tumors composed of clear cells may behave in an aggressive fashion. However, renal tumors including hybrid oncocytic tumor, chromophobe RCC and oncocytoma behave mostly in an indolent fashion.

Metabolic features of rats resistant to a high-fat diet.

OBJECTIVE: We assessed the metabolic characteristics of high-fat-diet-resistant (DR) rats. METHODS: Body weight, energy intake, locomotor activity, oxygen consumption, plasma leptin and lipid levels, size of visceral-fat adipocytes, and mRNA levels of genes related to lipid metabolism were measured in control rats fed standard chow and in obesity-prone (high-fat-diet-induced obesity, DIO) and DR rats fed a high-fat diet. Glucose tolerance and insulin tolerance tests were also performed. RESULTS: DIO rats gained weight more rapidly than did DR and control rats; DR rats gained less weight than did DIO rats despite similar energy intake. Energy expenditure did not differ among the three groups. The diameter of visceral-fat adipocytes was similar in DR and control rats. mRNA levels of genes involved in lipogenesis, such as fatty acid synthase and acetyl-CoA carboxylase, tended to be lower in DR than in control and DIO rats, whereas those of carnitine palmitoyltransferase 1a, which is involved in fatty acid ß-oxidation, were greater in DR rats than in the other groups. DIO rats showed hyperinsulinemia and glucose intolerance, whereas DR rats had high sensitivity to insulin. CONCLUSION: DR rats show suppression of lipogenesis and acceleration of fatty acid ß-oxidation in the visceral fat. These characteristics likely contribute to the anti-obesity phenotype of DR rats.

Comparative validity of the WHO-5 Well-Being Index and two-question instrument for screening depressive symptoms in patients with type 2 diabetes.

A simple tool consisting of two questions for screening depressive symptoms has been shown to be useful in primary care settings, but its validity in patients with diabetes has yet to be evaluated. We compared the test performance of this two-question instrument with that of WHO (The World Health Organization)-5. We consecutively enrolled 153 patients with type 2 diabetes who visited a diabetes clinic in Japan. Using the Center for Epidemiologic Studies Depression Scale as a reference standard of depressive symptoms, we calculated the sensitivity and specificity of the two-question instrument and WHO-5, and compared the area under the ROC curves of these tests. The two-question instrument had a sensitivity of 53.6% (95% CI, 39.7-67.0%) and specificity of 67.7% (95% CI, 58.1-74.9%). With the conventional cutoff point equal to or less than 13 points, the WHO-5 had a sensitivity of 57.1% (95% CI, 43.2-70.3%) and specificity of 82.5% (95% CI, 81.9-94.9%). The area under the ROC curve for the WHO-5 and two-item questionnaire, an indicator of discriminatory power, was 0.81 and 0.73, respectively, showing a statistically significant difference (P = 0.0453). The two-question instrument had statistically lower discriminatory power than the WHO-5 in screening depressive symptoms in patients with diabetes. We do not recommend the use of the two-question instrument for screening depressive symptoms in patients with diabetes.

Prognostic significance of L-type amino-acid transporter 1 expression in surgically resected pancreatic cancer.

BACKGROUND: The expression of L-type amino-acid transporter 1 (LAT1) is tumour-specific and has been shown to have essential roles in cell growth and survival. However, little is known regarding the clinical significance of LAT1 expression in pancreatic cancer. This study was conducted to determine the prognostic significance of LAT1 expression. METHODS: A total of 97 consecutive patients with surgically resected pathological stage I-IV pancreatic ductal adenocarcinoma were retrospectively reviewed. Tumour sections were stained by immunohistochemistry for LAT1, CD98, Ki-67 and vascular endothelial growth factor (VEGF), and microvessel density was determined by CD34 and p53. RESULTS: L-type amino-acid transporter 1 and CD98 were highly expressed in 52.6% (51/97) and 56.7% (55/97) of cases, respectively (P=0.568). The expression of LAT1 within pancreatic cancer cells was significantly associated with disease stage, tumour size, Ki-67, VEGF, CD34, p53 and CD98. L-type amino-acid transporter 1 expression was confirmed to be a significant prognostic factor for predicting poor outcome by multivariate analysis. CONCLUSION: L-type amino-acid transporter 1 expression is a promising pathological marker for the prediction of outcome in patients with pancreatic cancer.

Circadian variability of pulse oximetry in healthy children under the age of 7.

BACKGROUND: Peripheral oxygen saturation (SpO(2)) measured by pulse oximetry is widely used in clinical practice, but its fluctuations over the course of the 24 h of a day have not been explored at length. Recently, we reported that children hospitalized due to non-cardiopulmonary causes had a circadian variation in SpO(2). This finding needed to be corroborated in healthy children, which is the objective of the present study. PATIENTS AND METHODS: Healthy children residing in a state foster home were studied with pulse oximetry every 2h for 24h. RESULTS: Eighty two children were included in the study, ranging in age from one month to 6.5 years (average ± standard error of 3.06 ± 0.16 years), with a weight-for-length/height percentile of 65.5 ± 2.9. In 65 (79.3%) children, the SpO(2) levels followed a sinusoidal curve suggesting circadian rhythm. The total group of sinusoidal curves in this population had a mesor of 95.10 ± 0.08% SpO(2), period of 21.05 ± 0.54 h (in 53.8% of these children, the period was between 20 and 28 h). The maximum SpO(2) was reached at 3:14 pm ± 16 min, and the minimum at 5:16 am ± 48 min. When the 24 h were divided into four periods, it was demonstrated that the highest SpO(2) levels were reached between 2 pm and 8 pm. CONCLUSIONS: In this population of clinically healthy children, there was a circadian variation in pulse oximetry, with maximum values in the late afternoon and minimal values in the early morning.

Morphological changes and viability of Cryptosporidium parvum sporozoites after excystation in cell-free culture media.

Cryptosporidium parvum, belonging to the phylum Apicomplexa, is a major cause of waterborne gastroenteritis throughout the world. The sporozoites are thought to invade host enterocytes using an active process termed gliding motility. However, the biological and morphological changes within the sporozoites during this process are not fully understood. In the present study, excysted sporozoites of C. parvum were analysed ultrastructurally in vitro and their viability was evaluated using fluorescent dyes. The sporozoites excysted from oocysts changed morphologically from banana-shaped to rod-shaped and finally to a rounded shape, in culture media in 3 h. Transmission microscopy revealed that the distance between the apical end and the nucleus was markedly reduced, dense granules were present close to the rhoptry in the apical region, amylopectin granules were absent, and membranes of round sporozoites were less clear. A fluorescent assay showed that the rate of survival decreased from 89% to 56% at 0-3 h (84.3% for banana-shaped and 49.2% for rod-shaped sporozoites). Therefore, post-excysted sporozoites in vitro underwent morphological changes and a rapid loss of viability. This staining method is useful, inexpensive and provides an alternative to more costly and intensive flow cytometric assays or infectivity assays with host cells in vitro.

Decreased pregnancy rate is linked to abnormal uterine peristalsis caused by intramural fibroids.

BACKGROUND: The relationship between fibroids and infertility remains an unsolved question, and management of intramural fibroids is controversial. During the implantation phase, uterine peristalsis is dramatically reduced, which is thought to facilitate embryo implantation. Our aims were to evaluate (i) the occurrence and frequency of uterine peristalsis in infertile women with intramural fibroids and (ii) whether the presence of uterine peristalsis decreases the pregnancy rate. METHODS: Ninety-five infertile patients with uterine fibroids were examined using magnetic resonance imaging (MRI). Inclusion criteria were as follows: (i) presence of intramural fibroids, excluding submucosal type; (ii) no other significant infertility factors (excluding endometriosis); and (iii) regular menstrual cycles, and MRI performed at the time of implantation (luteal phase day 5-9). The frequency of junctional zone movement was evaluated using cine-mode-display MRI. After MRI, patients underwent infertility treatment for up to 4 months, and the pregnancy rate was evaluated prospectively. RESULTS: Fifty-one patients fulfilled the inclusion criteria, and 29 (57%) and 22 (43%) patients were assigned to the low (0 or 1 time/3 min) or high frequency (≥ 2 times/3 min) uterine peristalsis group, respectively. Endometriosis incidence was the same in both groups. Ten out of the 29 patients (34%) in the low-frequency group achieved pregnancy, compared with none of the 22 patients (0%) in the high-frequency group (P< 0.005). Comparing pregnant and non-pregnant cases, 4 of 10 patients (40%) and 9 of 41 patients (22%), respectively, had endometriosis (not significant). CONCLUSIONS: A higher frequency of uterine peristalsis during the mid-luteal phase might be one of the causes of infertility associated with intramural-type fibroids.

Guidelines for diagnosing and treating pulmonary infiltrates in children with acute leukaemia: impact of timely decisions.

AIM: Children with leukaemia are at increased risk of pulmonary complications, often with unspecific clinical data, delayed diagnosis and a high mortality rate. We evaluated the usefulness of diagnostic-therapeutic guidelines (DTG) in which specific times for decision making were incorporated. METHODS: Clinical charts of children with acute leukaemia and suspicion of pulmonary involvement were reviewed. Patients were allocated to group I if their diagnostic and therapeutic decisions were in accordance with the DTG, and to group II if not. RESULTS: Children from group I (n=32) and group II (n=28) did not differ with respect to age (9.3+/-0.5 years old, mean+/-SEM), gender, type, risk and stage of leukaemia, anaemia and neutropenia. Total length of hospital stay and hospitalization due to the pulmonary disease were shorter in group I than in group II (14.8+/-2.1 vs. 28.5+/-3.7 days, p=0.0016; and 10.8+/-1.0 vs. 18.4+/-1.8 days, p=0.0003, respectively). Two patients (6.3%) died due to the pulmonary pathology in group I, and nine (32.1%, p=0.016) in group II. CONCLUSIONS: Diagnostic-therapeutic guidelines that incorporate timely decisions constitute a useful algorithm to reduce the length of hospital stay and mortality in children with acute leukaemia and pulmonary infiltrates. A prospective study is needed to validate these results.

p19/Arf and p53 suppress sentinel lymph node lymphangiogenesis and carcinoma metastasis.

The ability of tumor cells to metastasize is increasingly viewed as an interaction between the primary tumor and host tissues. Deletion of the p19/Arf or p53 tumor suppressor genes accelerates malignant progression and metastatic spread of 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced squamous cell carcinomas, providing a model system to address mechanisms of metastasis. Here, we show that benign pre-metastatic papillomas from wild-type mice trigger lymphangiogenesis within draining lymph nodes, whereas there is no growth of primary tumor lymphatic vessels. Lymph node lymphangiogenesis is greatly accelerated in papilloma-bearing p19/Arf- or p53-deficient mice, which coincides with the greater propensity of these tumors to progress to carcinomas and to metastasize. The extent of accumulation of B cells within the tumor-draining lymph nodes of wild-type mice predicted the level of lymph node lymphangiogenesis and metastatic potential. Arf or p53 deficiency strongly accelerated lymph node immune cell accumulation, in a manner that was associated with the extent of lymph node lymphatic sinus growth. This immune cell accumulation and lymph node lymphangiogenesis phenotype identifies host anti-tumor responses that could drive metastatic spread of cancers via the lymphatics.

GER1, a GDSL motif-encoding gene from rice is a novel early light- and jasmonate-induced gene.

The reaction of the rice mutant HEBIBA differs from that of wild-type rice in that the mutant responds inversely to red light and is defective in the light-triggered biosynthesis of jasmonic acid (JA). Using the wild type and the HEBIBA mutant of rice in a differential display screen, we attempted to identify genes that act in or near the convergence point of light and JA signalling. We isolated specifically regulated DNA fragments from approximately 10 000 displayed bands, and identified a new early light- and JA-induced gene. This gene encodes an enzyme containing a GDSL motif, showing 38 % identity at the amino acid level to lipase Arab-1 in Arabidopsis thaliana. The GDSL CONTAINING ENZYME RICE 1 gene (GER1) is rapidly induced by both red (R) and far-red (FR) light and by JA. The results are discussed with respect to a possible role for GER1 as a negative regulator of coleoptile elongation in the context of recent findings on the impact of JA on light signalling.

Detailed images of asteroid 25143 Itokawa from Hayabusa.

Rendezvous of the Japanese spacecraft Hayabusa with the near-Earth asteroid 25143 Itokawa took place during the interval September through November 2005. The onboard camera imaged the solid surface of this tiny asteroid (535 meters by 294 meters by 209 meters) with a spatial resolution of 70 centimeters per pixel, revealing diverse surface morphologies. Unlike previously explored asteroids, the surface of Itokawa reveals both rough and smooth terrains. Craters generally show unclear morphologies. Numerous boulders on Itokawa's surface suggest a rubble-pile structure.

Effect of altitude on the frequency of pulmonary tuberculosis.

SETTING: Pulmonary tuberculosis (PTB) incidence greatly varies around the world, a phenomenon usually attributed to socio-economic factors or health service availability. A recent study, however, indicated that PTB was inversely related to altitude. OBJECTIVE: To evaluate factors associated with PTB notification rates in Mexico. METHODS: Annual notification rates (1998-2002) of PTB in each of the 32 Mexican states were analysed, and likely factors were assessed through correlation and multiple regression analyses. RESULTS: Most variables lacked association with PTB rates, including percentage of population aged > or = 65 years, population density, percentage of population with < or = 2 minimum salaries, percentage of population with social security, level of education, diabetes incidence, percentage of immigration, percentage of rural population and a global marginalisation index. Only altitude above sea level correlated with tuberculosis incidence (r = -0.74, P < 0.0001). Likewise, in the multiple regression analysis only altitude reached a statistically significant association. CONCLUSION: Our results showed that altitude had a strong inverse relationship to PTB notification rates in Mexico, which might be related to the well known changes in alveolar oxygen pressure at different altitudes. Interestingly, several factors traditionally considered as predisposing conditions for the development of PTB did not correlate with the disease.

Diabetes modifies the male:female ratio in pulmonary tuberculosis.

SETTING: Socio-cultural factors have been invoked to explain the male predominance among patients with pulmonary tuberculosis, but there is no conclusive evidence of their role. OBJECTIVE: To assess male predominance in a group of diabetics with pulmonary tuberculosis compared with patients with pulmonary tuberculosis alone. DESIGN: Clinical records of in-patients with pulmonary tuberculosis and with (TBDM group, n = 202) or without (TB group, n = 226) diabetes mellitus were reviewed, and the male percentages in each of six age groups (15-29, 30-39, 40-49, 50-59, 60-69, > or = 70 years) calculated. RESULTS: In the TB group, no gender difference (51% males) was found in the first age period, followed by a male predominance thereafter (71%, 68%, 75%, 63% and 58%). The TBDM group showed a similar pattern in the first two age groups (56% and 74%), followed by a steadily decline (r(S) = -0.90, P = 0.04) in male percentage (60%, 44%, 45%, 27%), leading to a female predominance after age 50. The association of age and gender was also corroborated by logistic regression in TBDM (P = 0.02), but not in TB (P = 0.19) patients. CONCLUSIONS: Diabetes was associated with a progressive shift of male predominance in pulmonary tuberculosis. Because diabetes is a disease that affects social activities similarly in men and women, our results suggest that factors other than socio-cultural ones are also important for determining the male predominance in pulmonary tuberculosis.