Increased microglial activation and protein nitration in white matter of the aging monkey

Activated microglia are important pathological features of a variety of neurological diseases, including the normal aging process of the brain. Here, we quantified the level of microglial activation in the aging rhesus monkey using antibodies to HLA-DR and inducible nitric oxide synthase (iNOS). We observed that 3 out of 5 white matter areas but only 1 of 4 cortical gray matter regions examined showed significant increases in two measures of activated microglia with age, indicating that diffuse white matter microglial activation without significant gray matter involvement occurs with age. Substantial levels of iNOS and 3-nitrotyrosine, a marker for peroxynitrite, increased diffusely throughout subcortical white matter with age, suggesting a potential role of nitric oxide in age-related white matter injury. In addition, we found that the density of activated microglia in the subcortical white matter of the cingulate gyrus and the corpus callosum was significantly elevated with cognitive impairment in elderly monkeys. This study suggests that microglial activation increases in white matter with age and that these increases may reflect the role of activated microglia in the general pathogenesis of normal brain aging.     

Clinical presentation,viral kinetics,and management of human monkeypox cases from New Delhi,India 2022

We describe the clinical and demographic characteristics, virological follow-up, and management of five confirmed monkeypox cases from New Delhi, India without any international travel history. The viral load kinetics and viral clearance were estimated in oropharyngeal swabs (OPS), nasopharyngeal swabs (NPS), EDTA blood, serum, urine, and various lesion specimens on every fourth day of follow-up ranging from 5 to 24 post onset day (POD) of illness. All five cases presented with mild to moderate-grade intermittent fever, myalgia, and lesions on the genitals, groins, lower limb, trunk, and upper limb. Four cases had non-tender firm lymphadenopathy. No secondary complications or sexually transmitted infections were recorded in these cases except for the presence of viral hepatitis B infection marker hepatitis B virus surface antigen (HBsAg) in one case. All the cases were mild and had a good recovery. A higher viral load was detected in lesion fluid (POD 9), followed by lesion roof (POD 9), urine (POD 5), lesion base (POD 5), and OPS/NPS (POD 5). The monkeypox virus (MPXV) DNA was detected in clinical samples from 5th to 24th POD. These monkeypox cases without international travel history suggest the underdiagnosed monkeypox infection in the community. This emphasizes the need for active surveillance of MPXV in the high-risk population such as men having sex with men and female sex workers.     

Normal heterophoric changes: 20 years' follow-up

Background: Evaluation of changes in the heterophoric condition of 100 normal individuals over a 20-year period. Methods: A reprospective study was undertaken. Charts of 100 normal men were reviewed. Individual changes in the heterophoric status were recorded over a 20-year period. The average value of the phoria at age 18–22 years was compared with the average value at age 34–38 years. Measurements were taken for near and distance fixation. No one was heterotropic. Changes in convergence and accommodation were also calculated. Results: A 0.9 ± 1.7 prism diopter increase in esophoria for distance fixation and a 0.6±2.5 prism diopter increase in exophoria for near fixation were found. These changes were statistically significant (P<0.001 andP<0.02 respectively). The near point of convergence receded by 0.5 ± 1.1 cm (P<0.001), and a decrease in accommodation over time of 2.8 ± 1.4 diopters was found (P<0.001). Conclusion: An increase in esophoria for distance fixation and a exophoria for near fixation was found in a 20-year follow-up of 100 normal subjects.     

Interphase nucleolar organizer region distribution in the tissues of oral leukoplakia, oral submucous fibrosis and oral cancer

The AgNOR technique, was applied to oral tissue sections of 185 oral cancer, 42 oral leukoplakia, 37 oral submucous fibrosis and 10 normal subjects to investigate whether any correlation held good in these different tissues. Compared to the AgNOR counts in normal oral epithelium, there was a gradation in increase in the mean AgNOR counts from oral leukoplakia to oral submucous fibrosis to oral carcinoma (P<0.01). This suggests that AgNOR count parallels with the degree of neoplastic transformation of oral epithelium. Three oral submucous fibrosis patients who showed very high AgNOR counts as that of oral cancer patients, later developed oral carcinoma. Among the oral cancer tissues, the moderately and poorly differentiated subtypes showed higher AgNOR counts and scattered distribution pattern than the well differentiated subtype which showed a clustered distribution pattern. These results suggest that AgNOR technique can be utilised as a diagnostic and prognostic indicator in premalignant and malignant oral tissues.     

Correlation of quantitative measures with the modified Ashworth scale in the assessment of plantar flexor spasticity in patients with traumatic brain injury

This study of plantar flexor spasticity describes relationships among a traditional qualitative spasticity scale, three potential quantitative spasticity measures and a measure of voluntary ankle muscle function. Thirty-four volunteer adult patients with traumatic brain injuries participated. There were 28 males and 6 females; the mean age was 30.3 years. A battery of five randomly sequenced tests was performed for each subject on one ankle. Tests were: modified Ashworth scale (MAS) scoring; H-reflex testing with and without Achilles tendon vibration; H-reflex testing with and without dorsiflexor contraction; reflex threshold angle and timed toe tapping (TTT). Twenty-six subjects returned to have the second ankle tested, resulting in 60 ankles for the analyses. Spearman's coefficients for correlation of quantitative spasticity measures with MAS scores ranged from 0.39 to 0.49 with associated probabilities 0.002. Pearson coefficients for correlation of quantitative spasticity measures with TTT scores were lower but also significant (P 0.07). Multiple correlation for the set of quantitative measures yieldedR = 0.614 (P < 0.001) with MAS scores andR = 0.365 (P = 0.045) with TTT scores. These findings reveal statistically significant relationships of low to moderate strength among potential quantitative spasticity measures, a traditional qualitative spasticity scale and a simple measure of voluntary ankle muscle function. Understanding these relationships is an essential part of the ongoing search for quantitative spasticity measures.The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.     

Impact of Treatment for Childhood Obesity on Parental Risk Factors for Cardiovascular Disease

Background. Family-based approaches using the parents as agents of change to treat childhood obesity are superior to programs targeting only children in achieving weight reduction and have a lower dropout rate.Objective. The aim of this study was to compare the impact of two behavioral approaches (parents only vs children only) for the treatment of childhood obesity on parental weight, eating, and activity habits as well as cardiovascular risk factors.Design. A randomized 1-year clinical intervention study was performed.Methods. Sixty obese children (≥20% over ideal weight for age, height, and sex), ages 6–11 years, were randomly allocated to the experimental (parents as sole agents of change) or conventional groups (children as sole agents of change). Fourteen (1-h-long) support/educational sessions were conducted by a clinical dietitian for the parents in the experimental group and 30 sessions for children in the conventional group. Anthropometric and biochemical measurements were determined at the start and end of the program.Results. The experimental approach, when compared to the conventional intervention, was found to be superior in the reduction of fathers overweight (P < 0.05). The former approach resulted also in improved profile of risk factors for cardiovascular disease in both parents. These changes could be ascribed to a greater improvement in eating and activity behaviors observed in parents belonging to the experimental intervention group who participated in a family-based intervention to treat their children's obesity.Conclusions. Treatment of childhood obesity targeting the parents as the sole agent of change, which is more effective for the treatment of childhood obesity when compared to a children-oriented program, may in addition award parents with the benefit of changing their own eating and activity patterns, thus making this program ideal for treatment of obesity in children and their overweight parents.     

Osteosarcoma of the sella

Primary osteosarcoma of the skull is rare. Osteosarcoma arising from the sellar region is extremely uncommon. The case of a 38-year-old man with osteosarcoma of the sella is described, and the literature is reviewed. The patient was treated with surgery followed by aggressive chemotherapy and radiotherapy. Currently he is in remission at 12 months.     

Progression of steroid-associated osteoporosis after heart transplantation

BACKGROUND: Osteoporosis has been recognized as an important side effect of long-term and of pulsed steroid application after heart transplantation. METHODS: In June 1989 a prospective clinical trial was started to study bone demineralization by quantitative computed tomographic scan. All patients received vitamin D and calcium. In group I (n = 30) synthetic calcitonin (40 Medical Research Council Standard Units subcutaneously per day was administered in 14-day cycles, whereas group II patients (n = 31) received a placebo preparation. Repeat trabecular and cortical quantitative computed tomographic scans of the thoracic (T12) and lumbar spine (L1, L2, L3) were obtained within 48 weeks after heart transplantation. RESULTS: Expressed as the means of T12, L1, L2, and L3, trabecular bone density decreased significantly from 100+/-24 to 79+/-29 mg/mL within 3 weeks after heart transplantation, followed by a further reduction to 67+/-29 mg/mL after 3 months in the calcitonin group. The values for cortical bone density decreased significantly from 229+/-37 to 202+/-40 mg/mL (calcitonin) 3 weeks after heart transplantation. Comparable results were obtained in the placebo group. In both groups bone density remained stable thereafter. Intergroup differences were not of statistical significance. CONCLUSIONS: In heart transplant recipients progressive trabecular bone demineralization is limited to the first 3 postoperative months. Thereafter, bone density remained stable. A positive effect of synthetic calcitonin in addition to prophylactic calcium and vitamin D application could not be proved by repeat quantitative computed tomography.     

Management of degenerative disc disease above an L5-S1 segment requiring arthrodesis.

Clear guidelines exist for treating spondylolisthetic deformity and instability. How the surgeon handles adjacent-level degenerative disease is not as well established. Because magnetic resonance imaging now provides us with far more information on the "health" of radiographically normal intervertebral discs, the treatment of dehydrated or degenerated discs adjacent to a fusion is becoming more problematic. In this discussion, two experts discuss their approach to symptomatic lumbosacral spondolisthesis accompanied by adjacent-level disc degeneration. Drs. Herkowitz and Abraham believe strongly that the adjacent segment should be left alone, whereas Dr. Albert recommends extending the fusion in many instances.     

Inhibition of allergen-induced pulmonary responses by the selective tryptase inhibitor 1,5-bis-[4-[(3-carbamimidoyl-benzenesulfonylamino)-methyl]-phenoxy]-pen tane (AMG-126737)

Emerging evidence suggests that mast cell tryptase is a therapeutic target for the treatment of asthma. The effects of this serine protease are associated with both pathophysiologic pulmonary responses and pathologic changes of the asthmatic airway. In this study, the tryptase inhibitor 1,5-bis-[4-[(3-carbamimidoyl-benzenesulfonylamino)-methyl]-p henoxy]-pentane (AMG-126737) was evaluated for its pharmacologic effects against allergen-induced airway responses. AMG-126737 is a potent inhibitor of human lung mast cell tryptase (Ki = 90 nM), with greater than 10- to 200-fold selectivity versus other serine proteases. Intratracheal administration of AMG-126737 inhibited the development of airway hyperresponsiveness in allergen-challenged guinea pigs with an ED50 of 0.015 mg/kg. In addition, the compound exhibited oral activity in the guinea pig model. The in vivo activity of AMG-126737 was confirmed in a sheep model of allergen-induced airway responses, where the compound inhibited early and late phase bronchoconstriction responses and the development of airway hyperresponsiveness. These results support the proposed role of tryptase in the pathology of asthma and suggest that AMG-126737 has potential therapeutic utility in this pulmonary disorder.