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.     

High incidence of nitrosamine-induced tumorigenesis in mice lacking DNA repair methyltransferase

The enzyme O6-methylguanine-DNA methyltransferase repairs alkylation- induced DNA damage, O6-methylguanine and O4-methylthymine, the former being formed more frequently. Previously, by means of gene targeting, we generated mice in which alleles for methyltransferase were disrupted. We now use these mouse lines, which are totally deficient in methyltransferase activity, to examine protective effects of the enzyme against tumor formation. In gene-targeted female mice given an i.p. injection of 5 mg/kg of dimethylnitrosamine, a larger number of liver and lung tumors occurred, as compared with normal female mice treated in the same manner. In male mice given a lower dose of carcinogen, the difference between normal and gene-targeted mice was statistically insignificant although more tumors did form in the gene-targeted mice. Methyltransferase apparently afforded protection from nitrosamine- induced tumorigenesis.      

Evaluation of cerebral perfusion from bypass arteries using selective intraarterial microsphere tracer after vascular reconstructive surgery.

BACKGROUND AND PURPOSETo detect areas of cerebral perfusion from bypass arteries after vascular reconstruction, we administered selective intraarterial microsphere tracer into the external carotid arteries and determined (via single-photon emission computed tomography [IA-SPECT]) whether the distribution of radiotracer matched the arteriographic distribution of contrast material as shown on external carotid angiograms.METHODSWe compared the extent of regional distribution of tracer after external carotid artery injection of 20 to 40 MBq of 99mTc-HMPAO or 99mTc-ECD with that of contrast medium on the external carotid angiograms in 582 cortical regions in 12 patients with atherosclerotic occlusive disease and in 18 patients with moyamoya disease.RESULTSMarked accumulation of tracer was found only in the expected, specific, newly developed areas of cerebral perfusion from bypass arteries. The regional distribution of tracer corresponded to that of contrast medium in 523 regions (90%) and did not correspond in 59 regions (10%). Significant overestimation of the distribution of contrast material relative to that of tracer was observed in the patients with moyamoya disease.CONCLUSIONSPECT showed slightly different distribution of tracer from that predicted by conventional angiography. IA-SPECT should enhance the analysis of newly developed areas of cerebral perfusion from the bypass arteries.     

The effect of MS-818, a pyrimidine compound,on the regeneration of peripheral nerve fibers of mice after a crush injury

One of the pyrimidine compounds, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4-d]pyrimidine (MS-818), has neurotropic effects in vitro. Therefore, we studied the effect of MS-818 on the regeneration of the peroneal nerve in C57BL/6J mice after a crush injury. Two test groups, which received a daily intraperitoneal injection of 5 mg/kg or 10 mg/kg MS-818, respectively, were compared with controls, which received daily intraperitoneal injections of physiological saline, over a 14-day period. The maximum foot-width ratio (crushed side/uncrushed side) was obtained on days 1, 8 and 14 after the crush injury, and the various morphometric parameters were evaluated at both 5 and 10 mm distal to the proximal portion of the crush site. The significant effects of MS-818 included a larger maximum foot width (P<0.04) and a greater number of unmyelinated axons per nerve at both levels (P<0.003) in both test groups than in controls. MS-818 had no significant effects on body weight, the increase of total transverse fascicular area after the crush injury, the total number of myelinated fibers with their size distributions, or the number of nuclei of Schwann cells and macrophages. Therefore, we conclude that MS-818 promotes axonal sprouting and elongation after a crush injury in mice.     

The effect of intraosseous graft length on tendon-bone healing in anterior cruciate ligament reconstruction using flexor tendon

The current study was performed to understand the relationship between graft length placed within the bone tunnel and intraosseous graft healing in anterior cruciate ligament (ACL) reconstruction. Twenty-four adult beagle dogs were divided into two groups of 12 animals each. In each animal, ACL reconstruction using a 4-mm diameter autogenous flexor tendon graft was done in the left knee. In groups I and II, the graft having a length of 15 and 5 mm, respectively, was placed within the tibial tunnel. The proximal end of the graft was placed through the over-the-top route in all animals. In each group, five animals were sacrificed immediately after surgery, and the remaining seven were sacrificed at 6 weeks postoperatively. Biomechanical and histologic evaluations were performed. In pull out testing, the ultimate failure load and the linear stiffness of the graft-tibia complex harvested at 6 weeks were significantly greater than those harvested at the time-zero period. There were no significant differences in those parameters between groups I and II at 6 weeks. In each group, the perpendicular collagen fibers connecting the tendon to the bone tunnel wall were observed only in the narrow area located close to the intra-articular tunnel outlet. In conclusion, excessively long placement of the flexor graft within the bone tunnel does not result in an additional increase of anchoring strength and stiffness of the graft in ACL reconstruction.     

Functions of microglia in immune mechanisms in the central nervous system]

Microglia are only one type of professional immune cells in the central nervous system, functioning as scavenger cells that remove pathogens, and as antigen presenting cells that present brain-specific antigens to invading T cells. They also play a critical role in the pathophysiology of various CNS disorders as effector cells to destroy neural cells by secreting inflammatory cytokines, radicals, and glutamate. At the same time, they can protect neural functions by producing neurotrophic factors. Thus, to study the mechanisms for regulation of microglial functions may be useful for understanding the etiology and future therapeutic strategy for intractable neurological disorders.     

Meaning in measurement of bone mineral content as preoperative evaluation of aged patients

Recently, mean span of life has been prolonged, and extensive operations are performed on aged patients. However, there are cases which have a difference between their chronological and actual ages. Bone mineral content (BMC) decreases with age and the decrease in BMC might suggest deterioration of immunological competence as observed in osteoporosis. Whether BMC can be an index for evaluation of geriatric patients' actual age from the aspect of immunological competence was investigated. Subjects were 54 cases aged more than 60. Twenty-one healthy young males and females were enrolled as the control group. Quantitative CT is used for assessment of BMC. The value obtained by dividing BMC by the standard BMC of the same age and sex, was defined as BMC index. BMC indices of normal BMC group were more than 0.8 and those of decreased BMC group were less than 0.8. Some immunological markers were investigated. Lymphocyte subset OKT3+ was reduced and juvenile lymphocytes expressed by OKT6+ and OKT3+-(OKT4+ + OKT8+) increased (corrected). Increased in juvenile lymphocyte and decrease in lymphocyte blast transformation and competence of generating interleukin 2 were observed in decreased BMC group. BMC is useful as preoperative evaluation for geriatric operative cases and patients of BMC index below 0.8 need to be paid attention to postoperative infection.