Efficacy and Safety of High-Dose Mizoribine Combined With Cyclosporine, Basiliximab, and Corticosteroids in Renal Transplantation: A Japanese Multicenter Study.

Mizoribine (MZR) is an immunosuppressive agent that exhibits a less potent immunosuppressive effect at doses up to 3 mg/kg/d. We investigated whether high-dose MZR is effective and safe for renal transplant patients in conjunction with cyclosporine (CsA), basiliximab, and corticosteroids. Ninety Japanese renal transplant patients were administered MZR (6 mg/kg/d), CsA (7 mg/kg/d), prednisolone (maintenance dose, 10 mg/d), and basiliximab (20 mg/body). They were compared with a control group of 81 renal transplant patients who received mycophenolate mofetil (MMF; 1500 mg/d), CsA, prednisolone, and basiliximab. The 2-year patient and graft survival rates were 98.9% and 97.8% in the MZR group and 98.8% and 97.5% in the MMF group, respectively. The rejection rate within 2 years after transplantation was 21.1% in the MZR group and 16.0% in the MMF group; the difference was nonsignificant. None of the MZR group developed cytomegalovirus (CMV) disease, whereas 12.3% of the MMF group contracted CMV (P < .0001). CMV viremia developed in 28.9% of the MZR group vs 46.9% of the MMF group (P < .0001); their peak antigen levels were 20.4 ± 44.1 and 252.8 ± 527.0 (P < .01). Furthermore, the incidence of gastrointestinal disorder, hyperlipidemia, and blood disorder was significantly lower in the MZR group than in the MMF group. The combination of high-dose MZR with CsA, basiliximab, and corticosteroids not only provides satisfactory immunosuppression but is also associated with a low incidence of CMV infection and gastrointestinal and blood disorders.

Optical imaging of the propagation patterns of neural responses in the rat sensory cortex: comparison under two different anesthetic conditions.

Although many studies have reported the influence of anesthetics on the shape of somatic evoked potential, none has evaluated the influence on the spatio-temporal pattern of neural activity in detail. It is practically impossible to analyze neural activities spatially, using conventional electrophysiological methods. Applying our multiple-site optical recording technique for measuring membrane potential from multiple-sites with a high time resolution, we compared the spatio-temporal pattern of the evoked activity under two different anesthetic conditions induced by urethane or α-chloralose. The somatic cortical response was evoked by electrical stimulation of the hindlimb, and the optical signals were recorded from the rat sensorimotor cortex stained with a voltage-sensitive dye (RH414). The evoked activity emerged in a restricted area and propagated in a concentric manner. The spatio-temporal pattern of the evoked activity was analyzed using isochrone maps. There were significant differences in the latency and propagation velocity of the evoked activity, as well as the full width at half maximum of optical signal between the two anesthetic conditions. Differences in the amplitude and the slope of the rising phase were not significant.

Prefrontal unit activity of macaque monkeys during auditory and visual reaction time tasks.

During a simple reaction time task using auditory or visual stimuli, a total of 96 single units were recorded from the dorsolateral prefrontal cortex of macaque monkeys. These monkeys were trained to depress a lever for a fixed period which produced a tone burst or a small spot of light. After a variable period, the stimulus intensity changed, and then, the monkey released the lever. Eighty-one cue-related units were classified into 3 types according to their decay time; that is, phasic, tonic and mixed. Phasic units (n = 19) showed a transient increase of discharge rate with a relatively short peak latency (70-300 ms). Of these, 17 units responded exclusively to either visual or auditory stimuli and two to both. Tonic units (n = 55) showed enhanced or suppressed activity, with longer latencies, which was sustained as long as the cue period continued. The temporal pattern of the discharge in 23 tonic units was found to be similar for both the auditory and visual cues. Seven mixed-type units showed combined phasic and tonic patterns. Lever release-related units (n = 15) were activated only during the period of lever release with no distinction in cue modality. It is suggested that the dorsolateral prefrontal cortex receives sensory inputs fairly discretely on the phasic-type neurons and that these sensory activities are transmitted to the tonic-type neurons which lead to an initiation of the lever release behavior.

Possible representation of somatic pain in the rat insular visceral sensory cortex: a field potential study.

Vagus nerve stimulation evokes a potential in the dorsal insular cortex in rats. To determine whether this cortical visceral area, like the brainstem visceral nuclei, also receives somatic input, somatic potentials were examined. Subcutaneous electrical stimulation, regardless of the laterality and site, evoked a potential closely resembling the vagal potential in shape, surface distribution and depth profile. This somatic potential had a higher threshold and a longer latency than the potentials in the nearby somatosensory cortices, and was attributed to primary Adelta afferents based on conduction velocity measurements and the relationship to peripheral nerve activity. No Abeta afferent-related response was found. These results suggest that the insula receives convergent sensory input from both the viscera and body surface, and the latter probably conveys somatic nociceptive information.

Epidemiology of illness and injury among U.S. Navy and Marine Corps female training populations.

Evidence suggests that female military populations are at greater risk than their male counterparts for certain training- and combat-related illnesses and injuries. The objective of this prospective, multisite, epidemiological study was to define the patterns of illness and injury in military women during training. We developed a computer-based outpatient tracking system for prospective data collection of all outpatient encounters for use at (1) Officer Candidate School (OCS), Quantico; (2) Marine Corps Recruit Depot (MCRD), Parris Island; and (3) Recruit Training Command (RTC), Great Lakes. During the study period, 85.8% of OCS candidates (260 of 303), 72.4% of MCRD recruits (2,002 of 2,766), and 83.4% of RTC recruits (7,395 of 8,865) had at least one medical encounter during training. The most common category of medical encounters at all three sites was musculoskeletal injury, followed by respiratory and dermatological disorders. This study establishes high morbidity rates and identifies medical priorities for preventive interventions in Marine Corps and Navy female trainees.

Rhizosphere fungus Penicillium chrysogenum promotes growth and induces defence-related genes and downy mildew disease resistance in pearl millet.

Susceptible pearl millet seeds (cv 7042S) were treated with the plant growth promoting fungus Penicillium chrysogenum (PenC-JSB9) at 1 × 10(8) spores·ml(-1) to examine mRNA expression profiles of five defence responsive genes and test its ability to induce resistance to downy mildew caused by Sclerospora graminicola. PenC-JSB9 treatment at 1 × 10(8) CFU·ml(-1) for 6 h significantly enhanced seed germination (9.8- 89%), root length (4.08% to 5.1 cm), shoot length (18.9% to 7.77 cm) and reduced disease incidence (28%) in comparison with untreated controls. In planta colonisation of PenC-JSB9 showed that all three root segments (0-6 cm) and soil dilutions incubated on PDA produced extensive mycelial growth, however colonisation frequency of PenC-JSB9 was significantly higher in soil than in root segments. Spatiotemporal studies revealed that induction of resistance was triggered as early as 24 h and a minimum 2-3 days was optimal for total resistance to build up between inducer treatment and challenge inoculation in both experiments. In Northern blot analysis, transcript accumulation of resistant and PenC-JSB9 induced susceptible cultivars showed higher basal levels of defence gene expression than non-pretreated susceptible controls. Transcript accumulation in resistant seedlings challenge-inoculated with the pathogen showed maximum expression of CHS (3.5-fold increase) and Pr-1a (threefold increase) at 24 and 12 h, respectively. While PenC-JSB9 pretreated susceptible seedlings challenge-inoculated showed rapid and enhanced expression of LOX and POX at 48 h and for CHT at 24 h, whereas non-pretreated susceptible seedlings after pathogen inoculation showed weak expression of hybridised defence genes. Enhanced activation of defence genes by PenC-JSB9 suggests its role in elevated resistance against S. graminicola.

Carbamazepine-induced hypersensitivity syndrome associated with transient hypogammaglobulinaemia and reactivation of human herpesvirus 6 infection demonstrated by real-time quantitative polymerase chain reaction.

Drug-induced hypersensitivity syndrome (HS) is a rare but severe disease with multiorgan failure. Many different precipitating factors have been reported, but the pathophysiology of HS remains unknown. However, the association of the human herpesvirus (HHV) family, particularly of HHV-6, has recently been reported in patients with HS. We report a 14-year-old boy who was diagnosed as having carbamazepine-induced HS based on the clinical course, laboratory data and results of drug-induced lymphocyte stimulation tests. In addition, the reactivation of HHV-6 was demonstrated by real-time quantitative polymerase chain reaction and by significantly increased levels of the specific antibody in his paired sera. Furthermore, transient hypogammaglobulinaemia was detected in the early stage of the disease. In addition, serum levels of interferon-gamma, interleukin (IL)-6, IL-5 and eosinophil cationic protein, which were increased on admission, decreased dramatically after steroid therapy. This is the first report of carbamazepine-induced HS associated with reactivation of HHV-6, transient hypogammaglobulinaemia, increased serum levels of inflammatory cytokines and activated eosinophils. This case might contribute to the understanding of the pathophysiology of HS.

Prevention of sexually transmitted diseases and HIV in young military men: evaluation of a cognitive-behavioral skills-building intervention.

BACKGROUND: Military personnel deployed to foreign countries with high endemic rates of sexually transmitted diseases (STDs) are at risk. GOAL: To evaluate a cognitive-behavioral, skills-building intervention to prevent STDs in junior, enlisted, male US Marines deployed to the Western Pacific aboard ships with periodic liberty visits to foreign ports. STUDY DESIGN: This study, using a quasi-experimental design, assigned 584 men to a cardiopulmonary resuscitation training (n = 288) or a cognitive-behavioral intervention (n = 296). The intervention aimed to increase prevention knowledge, reduce high-risk psychosocial (motivation) factors, and build decision-making and communication skills to reduce risky sexual behaviors and alcohol consumption. RESULTS: Participation in the intervention was associated with increased knowledge regarding symptoms and treatment of STDs and HIV (P < 0.001), decreased alcohol use (P < 0.01), and sexual risk (P < 0.01) during liberty ports of call. CONCLUSION: A multiple-session, cognitive-behavioral, skills-building intervention can be successfully implemented for deployed military personnel.

The risk of human T cell leukemia virus and viral hepatitis infection among US Marines stationed in Okinawa, Japan.

The prevalence and incidence of human T cell leukemia virus type I/II (HTLV-I/II) and hepatitis A, B, and C virus infection were determined among US Marines stationed in Okinawa, Japan. Of 2875 personnel, 2 (0.07%) had antibody to HTLV-I/II. After 1-3 years, no HTLV seroconversions were observed, although 23% reported sexual contact with Okinawans. Of 1010 hepatitis-tested marines, 121 (12%) had antibody to hepatitis A virus (anti-HAV), 26 (2.6%) had antibody to hepatitis B core antigen (anti-HBc), and 2 (0.2%) had antibody to hepatitis C virus (anti-HCV). On follow-up, 1 subject seroconverted to anti-HAV, 8 to anti-HBc, and none to anti-HCV. Most marines with recent hepatitis B infection were young, single, and enlisted and had been on short deployments to other countries in Southeast Asia. Marines stationed in Okinawa are not at high risk for HTLV infection but are at increased risk for hepatitis B infection and should be considered for vaccination.

Detection of diverse HIV-1 genetic subtypes in the USA.

Of the nine genetic subtypes of HIV-1 that exist world wide, subtype B predominates in North America and Europe. Thus, most knowledge about HIV-1 and most vaccine development efforts are based on subtype B viruses. We document here the detection of HIV-1 subtypes A, D, and E in five US servicemen who acquired these non-subtype-B infections during overseas deployments. The dispersal of diverse HIV-1 subtypes into regions of the world with previously restricted genetic diversity may have important implications for the epidemiology of the epidemic and for the design and implementation of vaccine trials.

Initial low CD4 lymphocyte counts in recent human immunodeficiency virus infection and lack of association with identified coinfections.

Initial CD4 lymphocyte counts were studied in 244 patients with human immunodeficiency virus (HIV) seroconversion. The CD4 cell counts at initial presentation after seroconversion were normally distributed (mean, 579/mm3; SD, 252). The mean percentage of CD4 cells was 26.1% (SD, 5.6). CD4 cell counts were < 500/mm3 in 41% and < 200/mm3 in 4%. The mean calculated duration of HIV infection was 7.7 months, which was not significantly different between the highest and lowest CD4 count quartiles (8.1 vs. 7.9). Age, sex, race, and serologic evidence of toxoplasmosis, cytomegalovirus, hepatitis B, syphilis, and varicella-zoster virus were not associated with initial low CD4 cell counts; however, never-married men were significantly overrepresented in the lowest quartile. These findings suggest that extensive CD4 lymphocyte depletion is common in early HIV infection and that frequent screening is necessary to identify newly infected patients who would benefit from antiretroviral therapy.