The purpose of this study was to clarify the adequate reduction rate of pituitary gonadotropins in ideal clinical management of shortterm hormone replacement therapy (ST-HRT) in postmenopausal women with undefined symptoms. Subjects included a total 324 postmenopausal patients between 48 and 61 years of age who visited the Department of Obstetrics and Gynecology at Osaka Medical College Hospital for the consult of menopausal symptoms. Administration of conjugated equine estrogen (0.625 mg/day) and progestin (2.5 mg/day) in the patients for 8 weeks. HRT was markedly effective in 28.7% of cases, effective in 40.7%, fairly effective in 21.9%, and ineffective in 8.6% of cases. The plasma concentration of FSH and LH after administration decreased significantly (P < 0.001) by 58.1% and 59.9% for markedly effective cases, and by 31.0% and 36.1% for effective cases. On the other hand, decreases in FSH and LH concentration were 14.1% and 1.3% for the fairly effective and 8.5% and -5.1% for ineffective cases, demonstrating a significantly greater decrease in plasma FSH and LH levels in the markedly effective and effective cases than those in ineffective cases (P < 0.001). There were significant differences in the reduction rates of plasma FSH and LH levels between in cases showing (59.9% and 53.2%) and not showing the side effects (24.8% and 25.9%), respectively (P < 0.0001). In conclusion, efficacy of ST-HRT was significantly correlated to the degree of decrease in plasma FSH and LH levels in patients with undefined symptoms. In addition, efficacy appeared to be correlated to the incidence of side effects. The degree of reduction of FSH (24.8-31.0%) and LH (25.9-36.1%) from the baseline may possibly be used as the suitable therapeutic window for hormone levels during HRT. The present results suggest that plasma gonadotropin levels could be a useful indicator for the management of patients undergoing short-term HRT for women with menopausal symptoms.

Eight female Macaca arctoides monkeys were given dimethylbenzanthracene (DMBA) directly into the milk ducts. During a 4-year observation period, ending with euthanasia and autopsy, no mammary cancers were noticed. However, one animal developed a superficial localized squamous cell carcinoma. DMBA is highly carcinogenic in rodents, e.g. producing a high incidence of breast cancer in C3H mice. It was concluded that carcinogenicity testing should be extended beyond testing in rodents to non-human primates in order to distinguish "primary rodent carcinogens" from those highly active in primates as well. Studies are in progress to study carcinogens in human cell lines transplanted into nu/nu mice.

A patient exposed to agent orange and a gunshot wound during the Vietnam War has developed multiple medical problems including nocardiosis, onychomycosis (Trichophyton rubrum), multiple thromboembolic episodes, hemochromatosis, diabetes mellitus type 2, diabetic neuropathy, activated protein C resistance (without Leyden V 1st mutation), degree A-V block, lung cancer (metastatic adenocarcinoma), carpal tunnel syndrome and arthritis.

Recurrent abdominal pain developed in a 74-year-old woman that chronically suffered from retrosternal pain and regurgitation. An erect abdominal plain film showed a fluid level in the ascending colon and an enlargement of the posterior lower mediastinum containing gas on the right. Unexpectedly, the patient reported that abdominal pain disappeared after meals. Double contrast enema and contemporaneous barium swallow showed herniation of the left colonic flexure into the left lower mediastinum and a gastric hernia within the right lower mediastinum, respectively. The hernias were in the same site of the enlargement of the mediastinum seen on the plain abdominal film. The colonic hernia partially reduced when the gastric hernia was filled with barium. We postulate that these findings could explain the disappearance of the colic obstruction and abdominal pain after meals.

To determine the genetic program mediating and maintaining the change from susceptibility to Crohn's disease (CD) to ongoing tissue destruction and loss of function, we utilized Affymetrix HG U95 AV2 Gene Chips and analyzed unpooled surgical CD colon specimens from adult patients. Using the patient as his own genetic filter we examined involved versus uninvolved adjacent areas, comparing results within one individual and then performing analysis comparing results between four individuals. Our results interrogated twice as many genes than the previous studies that used pooled unmatched specimens. We identified a limited set of nine genes upregulated in all four patients, and one gene (PTN) as downregulated. Several of the genes, including DEFA6, PAP, REG1A, REG1B, and phospholipase A2 had been implicated in previous studies, supporting their key role in CD. In 3 of 4 patients, 24 genes were upregulated in diseased areas, including DEFA5, IL-8, MMP-1, S100 calcium binding protein, and MGSA. Additional new candidate genes were identified, including DMT1, SERPINA1, GW112, and iNOS. The use of the unpooled samples allowed the detection of significant interindividual differences in expression of many other genes, supporting disease heterogeneity in CD. Results with select genes were confirmed with RT-PCR studies, as well as on biopsy samples from pediatric patients. We have determined a common profile of "late" CD, and also demonstrated the potential variability, suggesting possible differences in etiology, triggers, and the need for more individualized management. Additional studies to investigate protein expression of these candidate genes should be undertaken.

The diagnosis of mitral valve prolapse still remains a challenging proposition in some patients, particularly when the superior and posterior displacement of the mitral valve leaflets across the plane of the mitral valve annulus into the left atrium during systole is questionable. Therefore, additional reliable and reproducible echocardiographic criteria to improve the accuracy of mitral valve prolapse diagnosis would be ideal. In this small study, we proposed to assess the relationship between the systolic and diastolic contour of the mitral valve, as seen from the short axis views of the left ventricle, and compared to the currently used standard parasternal long axis view criteria. The apical views and the M-mode of the mitral valve were also assessed. From a total of 70 transthoracic echocardiograms that were prospectively examined, 50 echocardiograms were included for analysis. Nine patients met criteria for mitral valve prolapse using the parasternal long axis views standard definition. However, in these patients the concordance using M-mode and apical view criteria was 56% and 33%, respectively. None of the patients met M-mode criteria for mitral valve prolapse if the parasternal long axis criteria was not present, however 5 patients showed apical view mitral valve prolapse without meeting parasternal long axis views criteria. Conversely, a 100% concordance was noted between the parasternal long axis criteria for mitral valve prolapse and the contour of the mitral valve as seen from the short axis views. In all 9 patients with mitral valve prolapse, using the parasternal long axis criteria, a prominent buckling of the mitral valve was noted from the short axis views. Moreover, none of the 41 patients without mitral valve prolapse showed buckling in the short axis views. Therefore, buckling of the mitral valve, as seen from the short axis views, appears to provide a confirmatory role in diagnosing mitral valve prolapse, particularly in questionable cases; improving the overall accuracy. These findings should be validated in a double blind prospective study.

Prevalence rates of coronary artery bypass and valve surgery among Hispanics has not been well documented, particularly with regards to Puerto Ricans. Accordingly, we conducted a retrospective review of the surgical database in the Greater Buffalo Area of Western New York, serving a large Puerto Rican Hispanic community between January 1, 2001 and June 30, 2001, in order to determine if there is a particular trend in the utilization of these two surgical procedures among Caucasians, African Americans and Puerto Ricans. The results of this brief report shows that 95% of these surgical interventions, in the above mentioned time period, were done in Caucasians; while only 4.2% of these combined surgeries were performed in African Americans and in only 0.8% of Puerto Rican Hispanics. These results add to the growing evidence supporting lack of appropriate tool(s) or mechanism(s) to address health care issues among minorities, particularly Hispanic Puerto Ricans. This is the first report of this kind showing rates of coronary artery bypass and valve surgery involving this particular sector of the Hispanic community in the United States. It also emphasizes the need to promptly identify these deficiencies, particularly when considering that Hispanics are the most rapidly increasing minority ethnic population in the United States.

This is a brief review on studies of attacking HIV through a new angle. In previous studies, we have found that many patients with AIDS are resistant to interferon (IFN) therapy, and some develop resistance during therapy. Four factors were found to be responsible for the resistance of untreated patients: (a). release of free-circulating IFN-alpha/beta type 1 receptors, (b). a newly detected IFN inhibitory protein, (c). high prostaglandin E2, and (d). high levels of cAMP phosphodiesterases, particularly in AIDS-related neoplasms. This may interfere with intrinsic disease resistance and with the efficacy of IFN therapy. In an attempt to overcome this resistance, new compounds were synthesized which increase endogenous production of alpha, beta and gamma IFNs, have anti-template activity against DNA and RNA polymerases, inhibit reverse transcriptases and activates IFN-induced double-stranded RNA (dsRNA)-dependent protein kinase. It is expected that planned nonhuman primate and clinical studies will support preliminary findings. Preliminary in vitro and animal studies suggest that these new compounds may be effective against HIV, including multi-drug resistant strains.

Mitral valve prolapse (MVP) is closely related to myocardial sympathetic nerve function. This study evaluated the presence of impaired myocardial sympathetic nerve function by Iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy in ten patients with MVP. For comparison, 15 healthy subjects without heart disease were investigated (control group). Single photon emission computed tomography (SPECT) and anterior planar myocardial scintigraphy were performed 15 min (initial images) and 3 hours (delayed images) after injection of MIBG (111 MBq). The location and degrees of reduced tracer uptake were evaluated. Myocardial MIBG uptake was quantified by uptake ratio of the heart (H) to upper mediastinum (M) on the anterior planar images (H/M). Percentage washout of MIBG in nine sectors of all oblique slices along the short-axis was calculated. The washout rates were higher at the inferoposterior and septal segments in patients with anterior leaflet prolapse, and at inferoposterior and lateral segments in patients with posterior leaflet prolapse. The bull's eye map showed increased washout rate in the apical and posteroseptal basal segments. There was no significant difference in the H/M ratio between MVP patients and the control group. These results indicate that MIBG can be used to evaluate localized myocardial sympathetic nerve function in MVP.

We report a rare case of a 21-year-old man with leptospirosis mimicking acute pancreatitis and cholecystitis. This case report aims at pointing out the need of taking into consideration the possibility of leptospirosis in patients with an influenza-like syndrome, headache accompanied by acute abdominal pain and a suspicious exposure in order to prevent unnecessary surgical interventions.

Cells of human hepatocellular carcinoma (HCC) were morphologically different from those of normal liver. Intermediate filaments are important in building the architecture of liver cells and are proposed to interact with other cellular components. Synemin is one of intermediate filament associated proteins which can link between intermediate filament and other cytoskeletal structures. It was suggested that synemin might play some roles in tumorigenesis of hepatocellular cancinoma. In this study, we searched the synemin expression in 18 human HCCs by immunohistochemistry. The results revealed that synemin was modulated nearly in all human HCC cases. Many 0.4-0.8 microm-thick bundles were found in the IF extracts of liver and HCCs. These bundles were greater in diameter about 40 to 80 times of single IF. We speculated that the IFs were organized into the "filament bundles" to support the normal shape of the cells. That was, normal cell needed numerous synemin to lock the individual IF into stable "filament bundles". In cancer cells, the synemin was altered and this might lead to a loosened change of filament bundles, and the cancer cells would become pleomorphic.

A retrospective study was performed to determine the compliance of hormone replacement therapy (HRT), the reason for discontinuation. This study comprised 477 postmenopausal women who attended the women's psychosomatic and menopause clinic between January 1991 and December 2002. For the purposes of analysis, the women were classified into two groups. In Group A (242 subjects), subjects were allowed to decide whether or not to suspend or discontinue the drug, taking their condition into account, after their symptoms were alleviated. In Group B (235 subjects), all the women were informed as to the drug's excellent effects on osteoporosis and skin tissue before HRT was started and after their symptoms were alleviated. In Group A, the percentage of women who were still on this therapy was 77.7%, 34.3%, 21.1% and 8.7% at 3, 6, 12 and 24 months respectively after the start of therapy. Alternatively, in group B, the 24-month continuation rate was more than 50%. At 36 months (47.2%) and 60 months (38.7%) continuation rates were also significantly higher than those in group A (P < 0.0001). The leading reasons in the women's decision to discontinue HRT were improvement of symptoms (68.0% and 77.8% in group A and B, respectively, p = 0.408). The incidence in the women's decision to discontinue HRT by the reason of fear of cancer was significantly higher in group A (10.8%) than in group B (2.8%) (P = 0.008). In this study, the key factor affecting HRT compliance proved to be physician's advice. This means that when HRT is administered to Japanese women with the objective of alleviating menopausal symptoms and, high compliance can be expected provided individual patients are allowed to decide for themselves when HRT should begin end.

To evaluate the efficacy of the selective serotonin reuptake inhibitors (SSRIs) fluvoxamine and paroxetine in treating depression in the menopausal transition and to compare their efficacy, safety, side-effect profiles and drug compliance. One hundred and five perimenopausal patients (51.3 +/- 2.5 yr of age) were randomly assigned to receive a dosage of 50 mg/day of fluvoxamine (n=53) or 20 mg/day of paroxetine (n=52). The visual analog scale (VAS), Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) scores were evaluated before and after 3 months of therapy in the two groups of women. Significant reduction in HAM-D and HAM-A scores was observed in both groups of women, without significant difference between the two groups. VAS score in the fluvoxamine group (-62.6 +/- 5.2%) was significantly lower than that in the paroxetine group (-51.1 +/- 4.3%) (P < 0.0001). Although fluvoxamine compares favourably with paroxetine in rate of reduction of VAS score, this study suggests that both SSRIs are effective for and tolerated in depressed perimenopausal outpatients.

Tumor cells are morphologically different from normal cells. In this situation, we proposed that plectin, one of the intermediate filament associated proteins, might play some special roles in the tumorigenesis. Plectin exhibits a wide distribution spectrum among various tissues; however, it is scarcely investigated in tumor tissues including colorectal adenocarcinoma. In this study, we searched the plectin expression in 25 cases of colorectal adenocarcinoma and 10 cases of tubular adenoma with focal adenocarcinoma by immunohistochemical method. The results reveal that plectin is up-regulated in colorectal adenocarcinoma as well as in bizarre glands and locally invasive tumor nests in tubular adenoma, compared with normal colorectal mucosa. Over-expression of plectin in locally invasive tumor nests might help us in diagnosis of distinguish microinvasive foci from normal glands. The bizarre glands in adenoma might be precancerous lesions since the expression of plectin in them was identical to that of adenocarcinoma but in contrast to that of normal glands. The overexpression of plectin might affect the organization of cytoskeleton, which might further cause tumorigenesis and morphological change of colorectal epithelial cells.