Long-term vardenafil therapy improves hemodynamics in patients with pulmonary hypertension.

The phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, has been reported to produce sustained pulmonary vasodilatation in patients with pulmonary hypertension (PH). Recently, vardenafil, a more potent and selective PDE-5 inhibitor than sildenafil, has been approved for the treatment of erectile dysfunction. However, the long-term effects of oral vardenafil in patients with PH are unknown. We studied five consecutive patients with PH; one with primary pulmonary hypertension, two with chronic pulmonary thromboembolism, one with Eisenmenger syndrome (ventricular septal defect) and one with secondary pulmonary hypertension after a ventricular septal defect closure operation. In an acute hemodynamic trial, vardenafil (5 mg) significantly decreased both the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) with an increase in cardiac output. In a chronic hemodynamic trial, the maintenance dose of vardenafil (10 to 15 mg) for 3 months significantly decreased the PVR, but not the SVR, with a 20.7% reduction of the PVR/ SVR ratio. Plasma brain natriuretic peptide (BNP) levels were also significantly decreased after 3 months. This pilot study demonstrates that long-term oral vardenafil therapy may be a safe and effective treatment for patients with PH.     

Basic and clinical studies on norfloxacin in the pediatric field

Pharmacokinetic , bacteriological and clinical studies on norfloxacin (NFLX), a quinolone-carboxylic acid antibacterial agent, were conducted in the pediatric field. 1. Serum concentrations and urinary excretion of NFLX after single dose of 2.2 approximately 5.6 mg/kg (mean 4.4 +/- 1.2 mg/kg) were determined in 13 children with ages between 6 and 11 years. The mean peak serum concentration of the drug was 0.37 +/- 0.20 micrograms/ml at 2 hours after administration. The mean half-life of the drug in serum was 2.8 +/- 0.4 hours and the serum concentration at 8 hours was 0.11 +/- 0.06 micrograms/ml. The mean urinary concentration reached a maximum of 125.2 +2- 166.2 micrograms/ml in pooled urine from 0 to 2 hours and the mean urinary recovery rate in the first 8 hours after administration was 22.1 +/- 6.0%. A dose-response relationship was observed between doses/body weight and peak serum concentrations. 2. The clinical efficacy, bacteriological efficacy and the safety of NFLX were evaluated in 65 pediatric patients with ages between 2 years 10 months and 15 years 7 months with infections. In 62 assessable cases (acute purulent tonsillitis 9 cases, acute pneumonia 3 cases, chronic rhinitis 1 case, urinary tract infections 15 cases, and acute colitis 34 cases), clinical efficacies were excellent in 48 cases, good in 13 cases, and fair in 1 case with an overall efficacy rate of 98.4%. Staphylococcus aureus 1 strain, Staphylococcus epidermidis 1 strain, Escherichia coli 10 strains, Salmonella sp. 5 strains, Morganella morganii 1 strain, Pseudomonas aeruginosa 3 strains, Haemophilus parainfluenzae 1 strain and Campylobacter jejuni 12 strains were isolated from the patients as pathogens. Bacteriologically, all of these strains were eradicated except that 3 strains of C. jejuni only decreased. With regard to side effects, dizziness and nausea were observed in 1 case each but they were slight and the continuation of the treatment was possible. No abnormal laboratory test data were observed. From the above results, NFLX was considered to be a useful drug for the treatment of pediatric infections.     

A Case Report of Inflammatory Pseudosarcoma of the Urinary Bladder

A case of inflammatory pseudosarcoma of the urinary bladder in a 35 year-old Japanese male is presented. This benign lesion can easily be mistaken for spindle cell sarcoma since it consists of rhabdomyoblast like elongated strap cells showing infiltrative growth, and whether it is benign or malignant is difficult to determine by microscopic examination. In this case, spindle cell proliferation extended among bundles of the superficial muscle layer. However, no abnormal mitoses, severe nuclear atypia or cellular pleomorphism could be seen, thus indicating inflammatory pseudosarcoma. Although the lesion was not completely resected, no recurrent disease has been clinically observed for two years following transurethral resection. Urologists and surgical pathologists must be able to detect this lesion in order to avoid unnecessary surgical procedures. Acta Pathol Jpn 42: 760 765,1992.     

Ubiquitous Presence in Mammalian Cells of Enzymatic Activity Specifically Cleaving 8-Hydroxyguanine-containing DNA

Here we report the finding of enzymatic activity that specifically cleaves DNA containing 8-hydroxyguanine (oh⁸Gua) residues in various mammalian cells. To detect this activity, we used a synthetic double-stranded DNA containing a single oh⁸Gua at a defined position as the substrate, and analyzed the products of enzymatic digestion by polyacrylamide gel electrophoresis. Two cleavage sites near the oh⁸Gua residue were detected with partially purified fractions from cow brain and rat liver, and also with preparations from all mammalian tissues examined. These results suggest that enzymatic activity for the removal of oh⁸Gua from DNA is widely distributed in mammalian cells.     

Immunohistochemical study of bone GLA protein in primary bone tumors.

METHODS. The immunoreactivity of bone GLA protein (BGP) in primary bone tumors, including osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma of bone (MFH), and giant cell tumor of bone (GCT), was investigated with anti-BGP rabbit serum and peroxidase-antiperoxidase complex. RESULTS. As to intracellular localization, BGP antigenicity was detected in 33 of 35 cases of osteosarcoma and 12 of 25 cases of chondrosarcoma. However, there were no positive findings in all 15 cases of MFH or 20 cases of GCT. In chondrosarcoma, the frequency of positively stained cases increased according to pathologic grading (i.e., 3 of 14 cases of Grade 1, 7 of 9 cases of Grade 2, and 2 of 2 cases of Grade 3). Although the multinucleated cells in MFH or GCT were not immunostained, BGP antigenicity was observed in the multinucleated cells of osteosarcoma (12 of 15 cases). In the matrix of osteosarcoma, BGP immunoreactivity of the tumorous osteoid was observed in 28 of 32 cases. However, in the matrices of chondrosarcoma, MFH, and GCT, BGP immunoreactivity was not observed. CONCLUSION. These results suggest that the immunohistochemical study of BGP is useful for the differential diagnosis of bone tumors.     

Presynaptic Ca-antagonist omega-conotoxin irreversibly blocks N-type Ca-channels in chick sensory neurons

The present studies on electrophysiological and pharmacological differences of the three types of Ca-currents (N-, L- and T-types) in whole-cell clamped, cultured embryonic chick sensory neurons revealed that the majority (94%) of the Ca-currents in the nerve cells were the N-type, omega-Conotoxin (omega CTX, 5 microM), a blocker of transmitter release at the presynaptic terminals, induced a complete and irreversible blockage of Ca-currents elicited from the resting membrane potential (-60 mV) in 29 cells among 58. The Ca-currents thus irreversibly blocked by the omega CTX were determined as the N-type (neuronal), as they were insensitive to nifedipine (5 microM) or were reduced in amplitude by Bay K 8644 (5 microM). A small fraction (12%) of the total Ca-currents, which were still present after the omega CTX treatment (in the rest of 29 cells), were pure L-type (long-lasting) Ca-currents, as they were enhanced by the Bay K and were blocked by the nifedipine. omega CTX was a partial and reversible blocker of the L-type Ca-currents. Furthermore, T-type (transient) Ca-currents elicited in the hyperpolarized membrane (at -100 mV) were blocked by omega CTX in an incomplete and reversible manner. The N-type Ca-currents thus separated in the nerve cells exhibited various differences in features of the voltage-dependence and ionic selectivity from the L- and T-type Ca-currents.     

Antihypertensive effect of synthetic atrial natriuretic factor in vasopressin-infused rats

To assess the pathophysiological role of atrial natriuretic factors in the regulation of blood pressure, we studied the effect of chronic infusion of a synthetic atrial natriuretic factor of 25 amino-acid residues on blood pressure and sodium-water excretion. Experimental subjects were rats with hypertension made by chronic infusion of vasopressin on regular intakes of sodium or on sodium loading with 1% NaCl as drinking water. When a subdepressor dose (150 micrograms/kg/day) of synthetic atrial natriuretic factor was delivered via an osmotic minipump into the jugular vein simultaneously with 7.2 U/kg/day of vasopressin infused intraperitoneally by another osmotic minipump, the expected elevation of systolic blood pressure was completely inhibited. This was not accompanied by any changes in urine volume and urinary sodium excretion. The antihypertensive effect was sustained throughout the experimental period lasting 3 days in rats on regular sodium intake (p less than 0.01) or on sodium loading with 1% NaCl as drinking water (p less than 0.01). These results indicate that a subdepressor dose of synthetic atrial natriuretic factor can modulate the vasopressor effect of vasopressin. Therefore it is suggested that an atrial natriuretic factor may be involved in the regulation of blood pressure via its antagonizing effect to vasopressin.     

Statistical study of dermatomycosis - observations in Sendai National Hospital over a 30 year period]

A statistical 30-year study of dermatomycosis in Sendai National Hospital (1968-1997) revealed many changes in the prevalent diseases: Tinea pedis and tinea unguium constantly increased during this period, and the ratio of the former associated with nail infection finally reached 30% of all tinea pedis patients. On the contrary, tinea corporis and cruris showed a remarkable decreasing tendency. Patient age distribution of each disease also showed distinctive changes, generally increasing in the older generation and decreasing in the younger. The number of patients with tinea pedis and unguium gradually increased among the middle and older generations, with the peak of the age-distribution curve shifting upward year after year. On the other hand, cases of tinea cruris among the younger generation were few in the latest years, and middle-age patients remained at a low number. In the first stage of this study the kinds of atiologic dermatophytes consisted of multiple species, but after middle period the isolation of Epidermaphyton floccosum decreased. Microsporum canis appeared first in 1976 but in the recent several years has completely disappeared. In the last few years of the period studied Trichophyton rubrum and Trichophyton mentagrophytes were the only isolates found from among all types of dermatophytoses. Infantile candidiasis remarkably increased in 1970-1975 but thereafter decreased rapidlly. Candidial intertrigo also increased in the same period but did not decrease as much thereafter and continued at the same intermediate level. The number of other types of candidiases were not greatly changed throughout the 30-year period. Malassezia infection also showed no remarkable changes, and only 20 cases of sporothrichosis were found. One case of the deep seated form of cutaneous aspergillosis was found, and this was also true of chromomycosis caused by Fonceaea pedrosoi.     

Investigating endophenotype of endogeneous psychotic disorders]

Accumulated evidence from a number of previous structural MRI studies have revealed 1) the existence of abnormalities even at the brain structural level in subjects at an early stage of endogeneous psychotic illness, including schizophrenia and bipolar disorder, and 2) the existence of similar brain structural abnormalities to the patients even in individuals at high-risk of endogeneous psychotic illness. Recently, an increasing number of studies have investigated the associations between the functional polymorphism of candidate genes for susceptibility to schizophrenia and regional brain volume, a highly heritable trait marker, to uncover the linkage between the candidate genes and endophenotype of schizophrenia. Firstly, this review article overviewed recent literature examining the relationship between the candidate genes for susceptibility to schizophrenia and indices obtained from neuroimaging modalities. In contrast, a relatively limited number of previous studies examined associations between candidate genes for susceptibility to bipolar disorder and regional brain volume, although the high heritability of bipolar disorder has been reported as comparable to that of schizophrenia. Then, we discussed the possibility of endophenotyping of bipolar disorder and introduced our preliminary study. Finally, methodological considerations and future directions of endophenotyping of endogeneous psychosis were suggested.