Presenting Symptoms of Nonerosive and Erosive Esophagitis in Pediatric Patients

Children and adolescents with symptomatic gastroesophageal reflux disease (GERD) and erosive esophagitis (EE) of grade ≥2 (n=45) or nonerosive esophagitis (NEE) (n=45) were assessed to determine the relationship between presenting symptoms, esophagitis severity, and patient age. Overall, regurgitation/vomiting, abdominal pain, and cough were the most frequent symptoms. The prevalence and severity of anorexia/feed refusal was significantly greater in EE versus NEE children; this symptom was also significantly more prevalent in younger (1–5 years) children (both NEE and EE groups) compared to older children. Cough was significantly less severe in NEE adolescents than in younger children. Cough, anorexia/feed refusal, and regurgitation/vomiting were more severe and heartburn was less severe in EE children aged 1–5 years compared with older patients. In conclusion, GERD in children manifests differently than that in adults and symptoms vary with patient age. Symptoms were not predictive of presence or lack of mucosal damage.     

Immunocytochemical localization of heat-shock protein 60-related protein in Beta-cell secretory granules and its altered distribution in non-obese diabetic mice

Summary Immuno-electron microscopy technique was employed to investigate the cellular distribution of 60 kDa heat-shock protein (HSP60) in pancreatic Beta cells of control and non-obese diabetic mice. In thin sections prepared from control mice, antibody to mammalian HSP60 cross-reacted with protein(s) located to mitochondria and secretory granules. In particular, prominent binding of the antibody was seen to the insulin core of the mature insulin-secreting granules. In comparison, very little immunoreactivity was observed with immature secretory granules or with the Golgi apparatus. No binding to secretory granules or mitochondria was observed with normal mouse serum or with unrelated sera. On Western blots, HSP60 antibody specifically interacted with a single 62 kDa islet cell protein. These results suggest the existence of an HSP60-related protein with a novel location in mature secretory granules of Beta cells. The preferential association of the HSP60-related protein with the insulin core was gradually lost in Beta cells of pre-diabetic non-obese diabetic mice, and correlated with the progression of insulitis. The decrease in the granular binding of the HSP60 antibody was accompanied by an increase in cytoplasm staining, and was concomitant with a significant expansion of the insulin core diameter. The altered distribution of the HSP60-related protein in prediabetic mice, together with our observation that immature secretory granules accumulate in these animals indicate that the presence of HSP60-related protein in secretory granules might be associated with the secretory function of Beta cells.     

Treatment of Postmenopausal Osteoporosis

Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration with a resulting increase in bone fragility and hence susceptibility to fracture. Calcium and vitamin D are the most commonly used therapies for osteoporosis, although their efficacy in osteoporotic fracture prevention remains uncertain. Biphosphonates are the most frequently prescribed medication for treatment of osteoporosis and are often considered as first-line therapy for the treatment of osteoporosis. Currently, hormone replacement therapy is only approved by the Food and Drug Administration (FDA) for short-term treatment of severe postmenopausal symptoms with the lowest dose used for the shortest time. In view of its lack of effect on the prevention of nonvertebral fractures, the use of raloxifene should be limited to women with spinal osteoporosis. Most experts agree that it is preferable to treat osteoporosis with a more potent agent than calcitonin and manage the pain separately. Currently, the FDA recommends the use of parathyroid hormone for treatment of osteoporosis for a maximum of 2 years because of the concern of development of osteosarcoma. Drs. Gupta and Aronow have no real or apparent conflicts of interest relating to the subject under discussion.     

Exercise-induced pulmonary vasoconstriction during combined blockade of nitric oxide synthase and beta adrenergic receptors.

We studied the effects of inhibition of nitric oxide (NO) (endothelium-derived relaxation factor) synthase in combination with alpha and beta adrenergic receptor blockade on pulmonary vascular tone during exercise. In paired studies, we exercised sheep on a treadmill at a speed of 4 mph, and measured blood flow and pressures across the pulmonary circulation with and without inhibition of NO synthase (N omega-nitro-L-arginine 20 mg/kg intravenous [i.v.]), alpha receptor blockade (phentolamine 5 mg i.v.), beta receptor blockade (propranolol 1 mg i.v.), and combined alpha and beta receptor blockade. Activation of both types of adrenergic receptors occurs with exercise, and because increased release in NO is hypothesized to occur during exercise, these studies were designed to determine the magnitude of effect and interactions of these competing dilator and constrictor influences. We found that inhibition of NO synthase raised pulmonary vascular resistance (PVR) at rest and that, although a reduction in PVR occurred with exercise from this new baseline, vasoconstriction persisted. Combined beta blockade and NO synthase inhibition unmasked unopposed alpha vasoconstriction; PVR rose at rest and continued to rise with exercise; and mean pulmonary arterial pressures approached very high levels, 43.8 +/- 4.4 cmH2O. Using a distal wedged pulmonary artery catheter technique, most of the vasoconstriction was found to be in vessels upstream from small pulmonary veins. During exercise in sheep there appears to be a high degree of alpha and beta adrenergic-mediated tone in the pulmonary circulation. Endogenous production of NO actively dilates pulmonary vessels at rest and opposes potent alpha-mediated pulmonary vasoconstriction during exercise.     

Post-stroke depression

Stroke is considered mainly as a physical disability, and stroke-related depression is under-recognised. Cognitive, language and functional impairment complicates the recognition of post-stroke depression. The pathophysiology of post-stroke depression is poorly understood, but several risk factors have been identified. Depression following stroke can impede recovery and rehabilitation and is associated with higher mortality Randomised trials show that antidepressants, especially selective serotonin uptake inhibitors, are effective in the treatment of this condition. Despite the evidence available, a large number of patients remain undertreated. Early identification and treatment can reduce the functional impairment and mortality related to post-stroke depression.     

Efficacy of clarithromycin for treatment of experimental Lyme disease in vivo.

Clarithromycin provided effective therapy against arthritis induced by Borrelia burgdorferi infection in the hamster. In vitro, clarithromycin was at least 1 log more potent than tetracycline against two isolates of B. burgdorferi from human sources, as measured by MICs and 50% inhibitory concentrations. Clarithromycin was effective in preventing the onset of B. burgdorferi-induced arthritis, as determined by several parameters of paw swelling. When administered after the onset of arthritis, clarithromycin therapy reduced the degree of swelling and decreased recovery time. These results suggest that clarithromycin has potential as an effective therapy for Lyme disease.     

Reversal of daunorubicin resistance in P388/ADR cells by itraconazole.

Itraconazole is a recently developed triazole antifungal agent that inhibits cell membrane sterol biosynthesis. Itraconazole, in a dose-dependent manner, enhanced intracellular accumulation of daunorubicin and reversed the drug resistance in murine leukemia P388/ADR cells. In addition, itraconazole corrected the altered plasma membrane potentials of P388/ADR cells. The concentrations of itraconazole that reversed drug resistance are comparable to the plasma levels achieved by therapeutic dosage used in the treatment of fungal infections. Therefore, itraconazole is a potential candidate for in vivo use to reverse multidrug resistance in cancer with added benefit of its antifungal property.     

Left ventricular volume: an optimal parameter to detect systolic dysfunction on prospectively triggered 64-multidetector row computed tomography: another step towards reducing radiation exposure

In this study, we define the correlation between LV volumes (both LV end-diastolic volume [LVEDV] and LV end-systolic volume [LVESV]) and ejection fraction (EF) on 64 slice multi-detector computed tomography (MDCT). We also determine the accuracy of all the LV volume (LVV) parameters to detect LV systolic dysfunction (LVSD) and investigate the feasibility of using LVV as a surrogate of LVSD on prospectively gated imaging to prevent the radiation exposure of retrospective imaging. 568 patients undergoing 64-detector MDCT were divided into 2 groups: Group 1—subjects without any heart disease and LVEF ≥ 50%; and Group 2—patients with coronary artery disease and LVEF < 50% (defined as LVSD). The LVV (LV cavity only) and Total LV volume (cavity + LV mass) at end-systole and end-diastole (LVESV, Total LVESV, LVEDV and Total LVEDV) were measured. The upper limit values (mean + 2 SD) of all LVV parameters in Group 1 were used as the reference criterion to diagnose LVSD in Group 2. An exponential correlation was found between LVEF and all the LVV parameters. The specificity to detect LVSD in Group 2 was >90% and the sensitivity was 88.9, 83.3, 61.3 and 74.9% by using LVESV, Total LVESV, LVEDV and Total LVEDV, respectively. Systolic and diastolic LV volumes had a high correlation with LVEF and a high accuracy to detect LVSD. Thus, on prospectively triggered imaging, ventricular volumes can predict patients with reduced LVEF, and appropriate referrals can be made.