Plurihormonal pituitary adenoma with concomitant adrenocorticotropic hormone (ACTH) and growth hormone (GH) secretion: a report of two cases and review of the literature

Plurihormonal pituitary adenomas are tumours that show immunoreactivity for more than one hormone that cannot be explained by normal adenohypophysial cytodifferentiation. The most common combinations in these adenomas include growth hormone (GH), prolactin (PRL) and one or more glycoprotein hormone sub-units (β-TSH, β-FSH, β-LH and αSU). The authors report two cases of a plurihormonal pituitary adenoma expressing the rare combination of ACTH and GH. They both underwent successful transphenoidal hypophysectomy (TSH). Long-term post-operative follow-up revealed no evidence of tumour recurrence. Due to the multiple secretions and plurihormonal characteristics clinical diagnosis of composite pituitary adenomas can be difficult. The authors discuss the diagnosis and management of composite pituitary adenomas and review the literature regarding this rare phenomenon.     

Founder effects of the homogentisate 1,2-dioxygenase (HGD) gene in a gypsy population and mutation spectrum in the gene among alkaptonuria patients from India

Clinical Rheumatology - Alkaptonuria (AKU) is a rare metabolic disease. The global incidence is 1:100,000 to 1:250,000. However, identification of a founder mutation in a gypsy population from...     

Primary Prevention of Falls: Effectiveness of a Statewide Program

Objectives. We examined a population-wide program, Pennsylvania’s Healthy Steps for Older Adults (HSOA), designed to reduce the incidence of falls among older adults. Older adults completing HSOA are screened and educated regarding fall risk, and those identified as being at high risk are referred to primary care providers and home safety resources.Methods. From 2010 to 2011, older adults who completed HSOA at various senior center sites (n = 814) and a comparison group of older adults from the same sites who did not complete the program (n = 1019) were recruited and followed monthly. Although participants were not randomly allocated to study conditions, the 2 groups did not differ in fall risk at baseline or attrition. We used a telephone interactive voice response system to ascertain the number of falls that occurred each month.Results. In multivariate models, adjusted fall incidence rate ratios (IRRs) were lower in the HSOA group than in the comparison group for both total (IRR = 0.83; 95% confidence interval [CI] = 0.72, 0.96) and activity-adjusted (IRR = 0.81; 95% CI = 0.70, 0.93) months of follow-up.Conclusions. Use of existing aging services in primary prevention of falls is feasible, resulting in a 17% reduction in our sample in the rate of falls over the follow-up period.The public health significance of falls among older adults is clear. As noted by the National Council on Aging,

falls are the leading cause of injury related deaths of older adults, the primary reason for older adult injury emergency department visits, and the most common cause of hospital admissions for trauma.1

In 2011, the rate of nonfatal fall injuries requiring emergency department care was 2301 per 100 000 among people aged 50 to 54 years but 14 159 per 100 000 among people 85 years or older.2Self-report measures from health surveys confirm that there is a high prevalence of falls (30%–40%) among people 65 years or older and that the prevalence increases with age (40%–50% among those 80 years or older), as does the inability to get up from falls.3,4 Even noninjurious falls are disabling in that they are associated with activity restriction, isolation, deconditioning, and depression.5–8 In 2005, medical care costs associated with falls in the United States among people 50 years or older totaled about $13.5 billion (including deaths, hospital care, and emergency department admissions).2 A challenge for public health is to decrease the risk of falls without encouraging reduced physical activity, which carries other risks.Risk factors for falls include sedative use, cognitive impairment, lower extremity weakness, poor reflexes, balance and gait abnormalities, foot problems, and environmental hazards.9,10 Community-level efforts have adapted clinical interventions in addressing such risk factors. A review of 5 prospective but nonrandomized community trials involving matched control communities suggested that fall-related fractures could potentially be reduced by 6% to 33%,11 and meta-analyses and systematic reviews provide support for the effectiveness of multifactorial assessments and management of fall risk.12 The Centers for Disease Control and Prevention (CDC) has compiled a compendium of successful interventions that can be used by public health practitioners and community-based organizations.13,14Recommendations for optimal means of preventing falls are still evolving.15,16 A Cochrane review reported that exercise and home safety programs reduce the rate of falls and risk of falling but did not reveal any benefits of interventions that increase knowledge regarding fall prevention without additional components.3Pennsylvania’s Department of Aging has opted for a hybrid program in which older adults can take advantage of an intervention that offers, within the current aging service infrastructure, risk screening for falls and education regarding prevention. This voluntary program, Healthy Steps for Older Adults (HSOA), is available to all adults 50 years or older. Those identified as having a high risk for falls are referred to primary care providers and encouraged to complete home safety assessments. Because it relies on referrals to physician care rather than direct clinical interventions, the program may be less effective among people at high risk for falls; however, it is scalable across the state and reaches large numbers of people. In the case of some public health challenges, such a strategy may be more effective than more intensive interventions targeting high-risk individuals.17There is a lack of evidence regarding the effectiveness of this short-term, low-cost, population-wide program in reducing the incidence of falls among its participants, however. Here we report the results of a statewide evaluation of HSOA, which uses the state’s network of providers of aging services in its primary prevention efforts.     

Green-synthesized gold nanoparticles from black tea extract enhance the chemosensitivity of doxorubicin in HCT116 cells via a ROS-dependent pathway

Green gold nanoparticles (GNPs) were prepared from black tea extract (BTE) and used to examine the chemosensitivity of doxorubicin in colon cancer cell line HCT116. BTE-GNPs were prepared by a single-step method and characterized by UV-Vis spectroscopy, FTIR spectroscopy, SEM, DLS and zeta-potential. The MTT assay was performed to determine the cytotoxicity of HCT116 cells and also normal kidney cells HEK293. Apoptosis and ROS generation were investigated by flow cytometry. The inhibition of ROS levels by the inhibitor NAC was determined by both spectrofluorimetry and confocal microscopy. Expression levels of pro- and anti-apoptotic proteins were determined by a western blot technique. BTE-GNPs significantly enhanced the cytotoxic effect of DOX with its co-treatment in HCT116 cells. The cytotoxic effect of BTE-GNP + DOX was involved in apoptosis via a ROS-dependent pathway by enhancing the pro-apoptotic protein expression. Therefore, our results indicated that green gold nanoparticles of black tea extract (BTE-GNP) may be potent chemosensitizers of doxorubicin.

Green gold nanoparticles (GNPs) were prepared from black tea extract (BTE) and used to examine the chemosensitivity of doxorubicin in colon cancer cell line HCT116.     

Changes in the antioxidant defense and hepatic drug metabolizing enzyme and isoenzyme levels, 8-hydroxydeoxyguanosine formation and expressions of c-raf.1 and insulin-like growth factor II genes during the stages of development of hepatocellular carcinoma in rats.

This is an extensive study in a defined initiation-promotion hepatocellular carcinoma model of hepatocarcinogenesis (in rats) in which many important marker enzymes and isoenzymes and 8-hydroxydeoxyguanosine formation have been studied together with two very important cellular proliferating genes, insulin-like growth factor II and c-raf.1, known for their role in hepatocellular cancer development. Experiments were carried out on hepatic tissues of male Sprague-Dawley rats. Variations in different enzyme/isoenzyme activities/contents/expression pattern and 8-hydroxydeoxyguanosine-positive cells were studied. Insulin-like growth factor II and c-raf.1 gene expressions were monitored. A direct shift with increase in size and numbers of lesions was found to occur in different experimental groups. In this study, glutathione peroxidase (1.14 and 1.46-fold) and reduced triphosphopyridine nucleotide (TPNH)-cytochrome-c-reductase (1.94 and 2.94-fold) activities, cytochrome b5 (1.57 and 3.28-fold) and P-450 contents (1.45 and 1.22-fold), glutathione content (1.27 and 1.45-fold) and superoxide dismutase and catalase (1.16 and 1.39-fold) activities in group A animals were found to be lower than those in initiation and promotion studies, respectively. 8-Hydroxydeoxyguanosine-positive nuclei count showed that oxidative damage of nuclear DNA enhanced with the progress of the disease. The insulin-like growth factor II expression was found to be predominant in hepatocellular carcinoma and in early preneoplastic lesions. Unlike insulin-like growth factor II, c-raf.1 expression was located in the late basophilic lesions associated with hepatocellular carcinoma. During the various stages of the development of hepatocellular carcinoma, the enzymes played a significant role in metabolizing carcinogens and thereby scavenging various toxic metabolites or free radicals produced. A sequence of cellular changes starting from the appearance of glycogen storage foci to basophilic foci leading to hepatocellular carcinoma via mixed cell foci varied the activity/content or expression pattern of the enzymes and isoenzymes and in 8-hydroxydeoxyguanosine formation. It has been established that c-raf.1-induced signaling pathways activated by insulin-like growth factor II is implicated in the late stage of development of cancer.     

Aspirin in acute gastroenteritis: a clinical and microbiological study

Soluble aspirin given by mouth in divided dosage decreased intestinal fluid loss in infants and young children with acute gastroenteritis. The treated group had significantly less diarrhea, which ceased earlier and needed less intravenous therapy, than a randomly selected control group given an indistinguishable placebo. This effect of aspirin occurred with diarrhea caused by Salmonella, Aeromonas, Escherichia coli producing heat-labile toxin, and rotavirus, but not with diarrhea associated with strains of E. coli producing heat-stable toxin.     

Tuberculosis in renal transplant recipients: Rifampicin sparing treatment protocol

The reactivation of mycobacterium infection inrenal transplant recipients in developingcountries is a common therapeutic dilemma,especially in those patients receivingcyclosporin immunosuppression. The inclusion ofrifampicin in the antituberculosis protocolincreases the risk of precipitating acuteallograft rejection due to its interaction withcyclosporin and also increases the financialburden. We successfully treated 16 patients whodeveloped mycobacterial infection post renaltransplant with a rifampicin sparingantituberculosis drug regimen. Pyrexia ofunknown origin was the most common manifestationobserved and a therapeutic trial withantituberculosis drugs is justified. De novodiabetes mellitus appears to be an added riskfactor and increases the susceptibility tomycobacterial infection.