A Double-blind, Placebo-controlled, Multicenter, Prospective, Randomized Study of Beraprost Sodium Treatment for Cats with Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is a common progressive and irreversible disease in cats. The efficacy and safety of beraprost sodium (BPS) in cats with CKD have not been evaluated. HYPOTHESIS/OBJECTIVES: To evaluate the efficacy and safety of BPS in the treatment of cats with CKD, as compared to placebo. ANIMALS: Seventy-four client-owned cats with naturally occurring CKD. METHODS: Double-blind, placebo-controlled, multicenter, prospective, randomized trial. The cats received BPS (55 µg/cat) or a placebo PO q12 h for 180 days. The primary endpoint was prospectively defined as a change in the serum creatinine (sCr), serum phosphorus-to-calcium ratio or urine specific gravity (USG). RESULTS: The sCr increased significantly (P = 0.0030) in the placebo group (mean ± SD: 2.8 ± 0.7 to 3.2 ± 1.3 mg/dL) but not in the BPS group (2.4 ± 0.7 to 2.5 ± 0.7 mg/dL). The difference between the groups at day 180 was significant (0.8 mg/dL, 95% CI: 0.2 to 1.3 mg/dL, P = 0.0071). The serum phosphorus-to-calcium ratio was significantly (P = 0.0037) increased in the placebo group (0.46 ± 0.10 to 0.52 ± 0.21 mg/dL) but not in the BPS group (0.50 ± 0.08 to 0.51 ± 0.11 mg/dL). There was no significant change in the USG in either group. An adverse event judged as being treatment-related included vomiting that occurred in 1 case in the placebo group. No clinically relevant change was observed in the CBC and other blood chemistry tests. CONCLUSIONS AND CLINICAL IMPORTANCE: Beraprost sodium treatment was well tolerated and safe in cats with CKD. BPS inhibited the reduction in renal filtration function as measured by sCr increase.

The metabolism of IgE in patients with immunodeficiency states and neoplastic conditions.

Serum IgE concentrations were determined and IgE turnover studies were performed in control individuals as well as in patients with several disease states. Patients with common variable hypogammaglobulinemia, thymoma and hypogammaglobulinemia, ataxia telangiectasia, and selective IgA deficiency had significantly decreased mean serum IgE concentrations. In turnover studies, this was found to be due to decreased IgE synthesis. In spite of these depressed mean values, some patients with common variable hypogammaglobulinemia had normal serum IgE concentrations and synthetic rates. Patients with the Wiskott-Aldrich syndrome had a significantly elevated mean serum IgE concentration. In one of four patients studied with the turnover technique, a strikingly high IgE concentration was present and was associated with an elevated IgE synthetic rate. Three other patients had both normal serum IgE concentrations and synthetic rates. Patients with chronic lymphocytic leukemia had significantly decreased mean serum concentrations and synthetic rates for IgE. The depressed IgE synthesis was associated with a significantly prolonged IgE half-life. Patients with Hodgkin's disease had significantly increased serum IgE concentrations. One of three patients studied had a high serum IgE concentration and synthetic rate of IgE. The two other patients had normal serum IgE concentrations associated with normal synthetic rates. Finally patients with protein-losing enteropathy or familial hypercatabolic hypoproteinemia had normal IgE concentrations associated with normal IgE metabolic parameters. In these cases, the disorder in the catabolic rate was not severe enough to affect the total amount of circulating IgE because IgE normally has a very high fractional catabolic rate. In general, IgE levels in a variety of disease states were correlated with IgE synthetic rates and abnormalities in the catabolic rate of IgE in disease did not exert an important effect on IgE concentration.

Major risk factors for atherosclerosis are manifested in experimental Ca-deficiency.

The eggshell is the major source of Ca required during growth of chick embryos. Therefore, chick embryos placed ex ovo for long-term (SL) are rendered severe systemic calcium deficiency. We report here that SL chick embryos express Ca-deficiency related atherogenic disorders, and that in vitro Ca-deficiency induces dedifferentiation, i.e. loss of cell-type specific features and accelerated proliferative activities, in the various types of cultured cells. Systemic blood pressure is significantly higher and an accelerated weight gain of the heart is noted in SL compared to normal embryos (NL) at the incubation Day-14. Plasma cholesterol was lower, while triglyceride and glucose were higher in SL. Varying Ca in the culture medium (FCa, 1.8 mM; HCa, 2.8 mM; Ca/2, 0.9 mM) clearly affected the phenotype of the cultured cardiomyocytes and vascular cells isolated from the chick embryos. The cell number and total DNA were significantly larger and the level of LDH and proliferating cell nuclear antigen (PCNA) was elevated in Ca/2 compared to FCa. On the contrary, the level of CPK and contractile proteins were lowered in Ca/2. Thus, it is indicated that Ca-deficiency induces atherogenic disorders in vivo, and accelerates cell proliferation and decelerates sarcomeric protein expression in vitro. Taken together, it is suggested that the atherogenic, developmental disorders in SL may be the integrated result of the phenotype alteration in the various cell types directly induced by Ca-deficiency.

A unified design algorithm of two-dimensional digital filters for radioisotope image processing.

A unified design algorithm of two-dimensional digital filters for radioisotope image processing based on the Fourier-Bessel transform and the weighted least-squares method is described. The algorithm presented here can treat the various kinds of two-dimensional digital filters in a unified approach. Design examples are presented and several graphs are included to show the relationships between the design parameters as an aid in practical applications. The application of the method in radioisotope image processing is also presented. Several low-pass, Wiener and band-pass filters were designed using the method and applied to some clinical data in nuclear medicine including SPECT images. The digital filter design technique proposed here is considered to provide a powerful tool for extraction of additional qualitative information and improvement of the quality of nuclear medicine images both in research and in routine clinical work.

ECG-gated thallium-201 myocardial SPECT in patients with old myocardial infarction compared with ECG-gated blood pool SPECT.

We evaluated one of the merits of ECG-gated thallium-201 single photon emission computed tomography (g-T1 SPECT), i.e., the ability to appreciate left ventricular (LV) wall motion. LV wall motion assessed by g-T1 SPECT and by ECG-gated Blood Pool SPECT (g-BP SPECT) was classified into three grades and compared segment by segment. T1-201 uptake by g-T1 SPECT was also classified into three grades and compared with those of wall motion in g-BP SPECT. Fifty patients with prior myocardial infarction were injected intravenously at rest with 111 to 185 M Bq (3 to 5 mCi) of Tl-201. The left ventricular regions were divided into anterior, septal, inferior and lateral segments (50 patients X 4 segments = 200 segments in total). The grades of wall motion and Tl-201 uptake detected by g-Tl SPECT correlated well with those of wall motion in g-BP SPECT (94.5% and 85%, respectively). With g-Tl SPECT it was possible to evaluate left ventricular wall motion, providing clear perfusion images.

Assessment of hepatic excretory function in chronic liver disease by hepatobiliary scintigraphy.

Hepatobiliary scintigraphy was performed in 23 normal subjects and 47 patients with chronic liver disease (chronic hepatitis; n = 27, liver cirrhosis; n = 20) to evaluate its availability as a test of liver function. After intravenous administration of Tc-99m N-pyridoxyl-5-methyl-tryptophan, the data were acquired for 60 min and the time-activity curves of ROIs (the heart and liver) were generated. In two compartment model simulation, the early blood clearance rate (kl), late blood clearance rate (km), hepatic uptake rate (ku) hepatic excretion rate (ke), and hepatic excretion T 1/2 were calculated. There was no significant difference in those four k values in normal and chronic hepatitis. However, in liver cirrhosis each of them, except km, was lower than in normal subjects. The kl value correlated closely with the indocyanine green plasma clearance test, whereas the ke and T 1/2 values were closely correlated with the level of serum bilirubins. Only hepatobiliary scintigraphy showed the excretory function of the liver quantitatively and the ke value was helpful in detecting hepatic excretory dysfunction early in chronic liver disease before serum bilirubins increased.

Diffuse gallium-67 uptake in radiation pneumonitis.

To evaluate the clinical usefulness of Ga-67 imaging for the assessment of radiation pneumonitis, 12 patients who had developed radiation pneumonitis after receiving radiotherapy alone for non-small-cell lung cancer from 1979 through 1988 were reviewed. Diffuse bilateral Ga-67 uptake occurred in 5 out of the 12 cases; in the other 7 cases, Ga-67 uptake was confined to the irradiation lung. Conversely, chest radiography showed infiltrates only in the irradiated lung. Histopathology of the lung in four out of the five cases that showed diffuse Ga-67 uptake in the lung, however, revealed that the lung outside the radiation field with Ga-67 uptake was consistent with interstitial pneumonitis induced by radiation. These results suggest that radiation pneumonitis could extend beyond the irradiated lung and that Ga-67 imaging is more useful than chest radiography for the assessment of the spatial extent of radiography pneumonitis.

[Evaluation of serum pepsinogen I and II of patients with gastric cancer].

Serum pepsinogen levels were examined by immunoradiometric assay method for evaluating its clinical usefulness in gastric cancer. In patients with gastric cancer, serum PG-I tended to decrease but PG-II stayed normal level, resulting in low PG-I/PG-II ratio. Combination of PG-I and PG-I/PG-II discriminated 53.7% of gastric cancer, 70.6% of scirrhous type gastric cancer, and 66.7-100% of those arisen in the upper portion of the stomach, but 13.7% of normal subjects. As the aged normal subjects tended to show decreased PG-I/PG-II ratio (about 30% of the normal subjects aged over 40 years were discriminated as abnormal), the usefulness for detection of gastric cancer seems to be limited, but some types of gastric cancer such as scirrhous type or one arisen in the upper portion may be discriminated by this method. It is also suggested that this method may detect the recurrence of the cancer in some patients.

Role of anti-oncomirs miR-143 and -145 in human colorectal tumors.

We examined the expression levels of microRNAs (miRNAs (miRs)) in colorectal tumors (63 cancer specimens and 65 adenoma specimens) and paired non-tumorous tissues. Decreased expression of miR-143 and -145 was frequently observed in the adenomas and cancers tested, compared with miR-34a downregulation and miR-21 upregulation. Expression profiles of miR-143 and -145 were not associated with any clinical features. As the downregulation of miR-143 and -145 was observed even in the early phase of adenoma formation, the decreased expression of both miRs would appear to contribute mainly to the initiation step of tumorigenesis, not to the progression stage, and not to clinical prognostic factors. For clinical application, we changed the sequences of the passenger strand in the miR-143 duplex and performed chemical modification at the 3'-overhang portion of miR-143, leading to greater activity and stability to nuclease. The cell growth inhibitory effect of the chemically modified synthetic miR-143 in vitro was greater than that of endogenous miR-143. The miR-143 showed a significant tumor-suppressive effect on xenografted tumors of DLD-1 human colorectal cancer cells. These findings suggest that miR-143 and -145 are important onco-related genes for the initiation step of colorectal tumor development and that the chemically modified synthetic miR-143 may be a hopeful candidate as an RNA medicine for the treatment of colorectal tumors.