Five‐year efficacy of finasteride in 801 Japanese men with androgenetic alopecia

Finasteride is standard medical treatment for androgenetic alopecia; however, no large studies with 5 years or more of follow up have been performed in Japan. The authors followed Japanese men with androgenetic alopecia treated with finasteride for 5 years to evaluate long‐term treatment efficacy. Of 903 men treated with finasteride (1 mg/day), 801 patients were evaluated over 5 years by modified global photographic assessment. Although the proportion of improvement was high (99.4%), modified global photographic assessment scores after 5 years of treatment were lower in patients with more advanced disease as measured by the modified Norwood–Hamilton scale. After separating patients into “sufficient” and “insufficient” efficacy groups according to the modified global photographic assessment score after 5 years (scores ≥6 and <6, respectively), multivariate analysis showed that independent risk factors of insufficient efficacy were age at start of treatment of 40 years or more (P = 0.021) and classification on the modified Norwood–Hamilton scale (P < 0.001), whereas presence of stress at start of treatment was a negative predictor (P = 0.025). In conclusion, continuous finasteride treatment for 5 years improved androgenetic alopecia with sustained effect among Japanese. Younger age and less advanced disease at start of treatment were the key predictors of higher finasteride efficacy.     

Activation of protein kinase C and nicotinamide adenine dinucleotide phosphate oxidase in leukocytes of spontaneously hypertensive rats.

The involvement of oxidative stress in polymorphonuclear leukocytes (PMN) in the pathogenesis of hypertension remains to be elucidated. We analyzed the generation of reactive oxygen species (ROS) by the circulating and peritoneally infiltrating PMN from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Flow cytometric analysis revealed that ROS generation by PMN from SHR was higher than that from WKY before (at 6 weeks of age) and after (at 16 weeks of age) the onset of hypertension. In vivo, ROS generation by PMN from SHR, but not that by PMN from WKY, was significantly suppressed by 10-week treatment with 50 mg/kg/day carvedilol, and this treatment did not affect blood pressure. Western blotting analysis revealed that protein kinase C alpha (PKCalpha), but not PKCbetaI or betaII, was activated more strongly in PMN from SHR than in PMN from WKY. Furthermore, expression of p47phox of nicotinamide adenine dinucleotide phosphate oxidase, but not of p67phox, in PMN from SHR was higher than that in PMN from WKY. These results suggest that ROS generation by PMN is principally enhanced in SHR through activation of PKCalpha and p47phox.     

Multiple sclerosis with higher cerebral dysfunction: a case report

Higher cerebral dysfunctions such as aphasia, apraxia and agnosia have seldom been reported in multiple sclerosis (MS). 12 year-old right-handed boy felt unsteadiness of the body and headache for several days. Two months later, he had the same episode and complained of visual disturbance, and weakness and sensory disturbance on the face and the extremities. Additionally, he showed amnestic aphasia, acalculia, ideomotor apraxia, finger agnosia and right-left disorientation. Cerebrospinal fluid examinations revealed increases IgG, myelin basic protein and neuron specific enolase (11%, 25 ng/ml and 28.8 ng/ml, respectively). X-ray CT scan and MRI-CT examinations revealed sclerotic lesions on the left parietal white matter and the right mid-brain. The diagnosis was made as MS. He was treated with m-PSL (methyl-prednisolone) pulse therapy for three weeks and consecutively treated with PSL for four weeks. He recovered gradually, but visual disturbance and facial palsy remained. After seven months MRI-CT showed a high signal intensity on the left parietal white matter in spite of the disappearance of the lesion on X-ray CT scan. We suggest that these higher cerebral dysfunctions may result from the lesion of the left parietal white matter which produces a disconnection between each cortical area.     

A case of autoimmune hepatitis needed to be differentiated from EBV hepatitis, in that the histology of liver biopsy specimen was useful for diagnosis]

A 10-year-old girl with autoimmune hepatitis (AIH) was reported. She was admitted to our hospital because of cholestasis and elevation of liver enzymes for 2 months. Laboratory examination revealed that EBV-DNA copy number in the PBMNC (peripheral mononuclear cells) was 1.2 x 10(3) copies/microg of DNA, hypergammaglobulinemia, and positive antinuclear antibody, positive anti-smooth muscle antibody. The histology of her liver biopsy specimen revealed interface hepatitis, dense mononuclear cell infiltrates, mild fibrosis, and negative for EBV in situ hybridization assay indicating AIH and not EBV-associated hepatitis. She was treated firstly with methylprednisolone pulses, then will prednisolone p.o.+azathioprine p.o.. Intravenous cyclophosphamide pulse therapy was introduced because of her abnormal immune pathology. All abnormal laboratory parameters improved to normal levels within 2 months, and EBV-DNA copy number in the PBMNC became negative after 4 months. The histology of liver biopsy specimen was useful for the diagnosis of AIH in such a difficult case needed to be differentiated from EBV hepatitis.     

A combined approach for purging multidrug-resistant leukemic cell lines in bone marrow using a monoclonal antibody and chemotherapy.

Selective removal of malignant cells (purging) from bone marrow (BM) is a concern in autologous BM transplantation (ABMT). Use of vincristine, etoposide, or doxorubicin for purging could be rendered ineffective by the presence of multidrug-resistant (MDR) tumor cells. To circumvent this particular problem, we investigated whether 17F9, a monoclonal IgG2b antibody directed against the cell surface product of the MDR gene, P-glycoprotein, is effective in selective removal of MDR cells from BM when used with rabbit complement (C'). Using two different cell lines we have demonstrated that 17F9 + C' selectively lyses MDR-positive cells. Three rounds of antibody + C' resulted in 96.4% +/- 3.6% kill of K562/DOX and 100% +/- 0% of CEM/VLB cells. Mixtures of malignant cells and normal BM resulted in 99.85% removal of K562/DOX and 99.91% removal of CEM/VLB clonogenic cells. This treatment did not affect normal committed precursors compared with C' alone. The addition of the cytotoxic agent etoposide (VP-16) following antibody purging results in a 4.6 log reduction of malignant cells. Furthermore, this antibody was effective when used against patients' leukemic blasts. These results suggest the use of 17F9 + C' is effective and selective for removal of MDR cells from BM before ABMT and the addition of VP-16 enhances the purging efficacy.     

The results of an investigation of the various factors influencing the late patency ratio of coronary bypass grafting

The purpose of this communication was to find out the factors influencing the late patency ratio of coronary artery bypass grafts of 42 patients in our institution. The following results were obtained: 1. The size of the measured diameters of coronary arteries and the graft flow rates were correlated well to the late patency ratio (p less than 0.05). 2. The regular physical exercise trainings were significantly important to keep patent grafts (p less than 0.01). 3. In blood serum studies, serum uric acid levels were significantly lower (p less than 0.05), the average mean HDL cholesterol levels were much higher (p less than 0.001) and the ratio of total cholesterol to HDL cholesterol were significantly lower in the group with late patent grafts than with grafts occluded. Therefore, we found out the variables affecting graft patency ratio which were examined by a stepwise method were the diameter of the coronary artery, regular physical exercise training, the average of lower serum uric acid levels and higher HDL cholesterol levels. The multiple coefficient for these four variables was 0.562 (p less than 0.001) and the contribution was 31.6%. According to the base of this studies, we have concluded that postoperative regular physical exercise, low fat and restricted calorie intake were very important to keep the late patent grafts in long-term follow up period after coronary bypass surgery.     

A surgical case of atrial septal aneurysm associated with rheumatic mitral and tricuspid disease and coronary-pulmonary artery fistula

A case of atrial septal aneurysm associated with combined valvular disease and coronary-pulmonary fistula (C-PA fistula) was presented. The patient successfully underwent mitral valve replacement, excision and closure of the aneurysm, tricuspid annuloplasty and closure of C-PA fistula. Atrial septal aneurysm is a rare anomaly and its natural course is thought to be generally good without significant clinical symptoms. However, complications such as cerebral and pulmonary embolism, or occlusion of the atrioventricular vales by the prolapsed aneurysm were reported to occur in small number of cases. In this case, diagnosis of the aneurysm was made by 2-D and Doppler echocardiography and further confirmed by cineangiography. Routine echocardiographic examinations will serve as useful noninvasive method for detection and follow up study of this anomaly.     

Satisfactory Remission Achieved by PUVA Therapy in Langerhans Cell Hisiocytosis in an Elderly Patient

Langerhans cell histiocytosis is currently regarded as a reactive proliferative process of Langerhans cells rather than a malignancy. The disease is characterized by Langerhans cell infiltration of skin, lung, bone and other organs. We report a 74-year-old man with Langerhans cell histiocytosis who had generalized hemorrhagic and crusted papules. He also had diabetes insipidus. Because he did not have any severe constitutional symptoms or failure of vital organs, we applied topical PUVA treatment to his skin lesions, which responded well to the therapy. Diabetes insipidus, however, remained, in spite of X ray radiotherapy for the pituiary lesion.     

Effects of minaprine and sulpiride injected into the amygdaloid nucleus on the duration of immobility in rats forced to swim

We examined the effects of minaprine and sulpiride injected into the medial amygdaloid nucleus on the duration of immobility in rats forced to swim. Minaprine (50 micrograms/microliter) significantly reduced the duration of immobility, while sulpiride (50 micrograms/microliters) remarkedly enhanced it. These results suggest that the medial amygdaloid nucleus might be involved in the suppressive effect of minaprine on the duration of immobility, as was seen with the tricyclic antidepressants. The pattern of behavior seen with sulpiride administrations differs considerably from that seen with the tricyclic antidepressants.     

Global bifurcation structure of chaotic neural networks and its application to traveling salesman problems

This paper studies global bifurcation structure of the chaotic neural networks applied to solve the traveling salesman problem (TSP). The bifurcation analysis clarifies the dynamical basis of the chaotic neuro-dynamics which itinerates a variety of network states associated with possible solutions of TSP and efficiently ‘searches’ for the optimum or near-optimum solutions. By following the detailed merging process of chaotic attractors via crises, we find that the crisis-induced intermittent switches among the ruins of the previous localized chaotic attractors underly the ‘chaotic search’ for TSP solutions. On the basis of the present study, efficiency of the ‘chaotic search’ to optimization problems is discussed and a guideline is provided for tuning the bifurcation parameter value which gives rise to efficient ‘chaotic search’.