The Vanishing Adrenal Glands: A transient regression of adrenal lymphoma after a single dose of 1 mg dexamethasone

Objective: Dexamethasone is a known treatment for lymphoma, but it’s potency and rapidity of its effect has not been recognised. Our objective is to present a case of bilateral adrenal lymphoma, which significantly reduced in size after a single dose of dexamethasone. Methods: Clinical course and investigations including Adrenocorticotropic hormone (ACTH), cortisol, short synacthen test, computed tomography (CT) and adrenal biopsy are presented. Results: A 52-year-old man had a fall and was incidentally found to have bilateral adrenal masses (6 cm on left and 5 cm on right) on CT. His adrenal function tests included plasma metanephrines (normetanephrine 830 pmol/L (0-1180); metanephrine <100 pmol/L (0-510); 3-methoxytyramine <100 pmol/L (0-180), aldosterone 270 pmol/L( 90-700) and random cortisol 230 nmol/L (160-550). Overnight dexamethasone suppression test (ONDST), with 1 mg of dexamethasone, showed cortisol of <28 nmol/L (0-50).. A repeat CT, eight days following ONDST, showed adrenal masses of 4.5 cm and 3.5 cm on left and right respectively. He had a follow-up CT three months later, which showed adrenal lesions measuring 8 cm (left) and 9 cm (right). He subsequently presented with fatigue and dizziness. Morning cortisol of 201 nmol/L (160-550) with ACTH of 216 ng/L (10-30) indicated primary adrenal insufficiency. Mineralocorticoid and glucocorticoid replacement was commenced. Adrenal biopsy showed abnormal enlarged B-cells consistent with a diagnosis of diffuse large B-cell lymphoma. Conclusion: A diagnosis of lymphoma should be considered when adrenal lesions shrink, following even a single low dose of dexamethasone administered as a part of a diagnostic test

COVID-19 catalysing assessment transformation: A case of the online open book examination

Under COVID-19 lockdown conditions, the imposition of social distancing and restricted mobility, disrupted the traditional way of assessment in higher education. The closed book examination, conducted under proctored conditions, had to be substituted for the online open book examination (OOBE), posing challenges to both conventional and Open Distance Learning (ODL) institutions. The OOBE became a new experience to lecturers and students. Considering COVID-19 as a potential catalyst for educational transformation, the experiences gained in this format of assessment presents a valuable frame of reference for future learning. The aim is to extract lessons from this innovative learning experience to inform future assessment practices. The study is set in the context of a B.Ed. (Hons) compulsory module, offered at an Open Distance Learning (ODL) institution in South Africa. It is guided by the research question: “what were students’ experiences of their first online, open-book final examination and what are the implications for policy, practice and research?” This is a qualitative study, using as data, student emails on their experiences of the OOBE. The results show that the OOBE is an innovative assessment practice in higher education, in need of deeper understanding and (re)training. We conclude that the OOBE offers transformational opportunities in higher education assessment practices, to replace the traditional closed-book examination. We make recommendations to assist lecturers and students in approaching the OOBE in future

Pharmacological Evaluation of Leaves Extract from Rivea Ornata Roxb.

From the study entitled "Pharmacological Evaluation of Leaves Extract from Rivea ornata Roxb., the following conclusion could be drawn. ❖ The present study has thus duly supported the traditional use of methanolic Extract of Rivea ornata Roxb. have scientifically proved the antihyperlipidemic, antidiabetic, analgesic, antipyretic and wound healing activity. ❖ Apart from the suggested actions listed in discussion part absence of acute toxicity and sub acute toxicity may also offer a new hope for safe treatment in future. ❖ Preliminary phytochemical study of methanolic extract of Rivea ornata Roxb. was found to contain Carbohydrates, Steroids, Alkaloids, Glycosides, Tannins, Phenolic compounds, Gums and mucilage are present. ❖ Presence of Alkaloids, Tannins and Glycosides in the methanolic extract of Rivea ornata Roxb. was observed in IR & HPTLC analysis. Though present in small quantities, it was found to produce considerable effects. ❖ The results of acute toxicity study indicate that the methanolic extract of Rivea ornata was non-toxic up to dose level of 2000mg/kg body weight in albino rats as per acute oral toxicity studies. 1/10th of the LD50 Dose is 200mg/kg is used for Pharmacological screening. ❖ The results of subacute toxicity study indicate that the methanolic extract of Rivea ornata was non-toxic in chronic administration. ❖ The methanolic extract of Rivea ornata at a dose of 200mg/kg exhibited significant hypolipidemic activity in Triton X 100 induced hyperlipidemic rats. This is showed by the reduction of serum lipid parameters such as triglycerides, total cholesterol, LDL, VLDL with an increase in HDL concentration in the group treated with 200mg/kg of methanolic Extract of Rivea ornata. ❖ The methanolic extract of Rivea ornata at a dose of 200mg/kg showed significant antidiabetic activity in Alloxan induced hyperglycemic rats. This is showed by the reduction of blood glucose level in the group treated with 200mg/kg of methanolic extract of Rivea ornata. ❖ The methanolic extract of Rivea ornata was subjected to the Tail immersion and hot plate method Analgesic test, showed a significant analgesic effect. ❖ The methanolic extract of Rivea ornata was subjected to the Antipyretic activity against Brewer’s yeast induced hyperpyrexia showed a significant reduce in body temperature of the animals treated with 200mg/kg of methanolic extract of Rivea ornata. ❖ The methanolic extract of Rivea ornata was subjected to the wound healing activity, showed a significant wound healing effect on excision wound in rats. ❖ In future, further investigation might provide an insight to identify the functional groups in the methanolic extract of Rivea ornata responsible for the antihyperlipidemic, antidiabetic, analgesic, antipyretic and wound healing activity and to elucidate the exact mechanism of action, which is responsible for the observed significant activity with low toxicity and better therapeutic index

A clinical study on Aan Maladu (Male Infertility) with the evaluation of siddha drug Veeriya Viruthi Chooranam

The aim of the study is to increase the sperm count and sperm motility in male infertility patient. The trial medicine Veeriya viruthi Chooranam was prepared as per literature. The duration of the trial period is 48 days. The trial dose is Veeriya viruthi Chooranam 1 gm. twice a day with cow’s milk. I had selected 20 patients for the trial based on Inclusion and Exclusion criteria. Before treatment routine blood, urine and semen analysis taken in all 20 patients. Siddha methods like udal thathukkal, Envagai thervu, Neerkuri and Neikuri were noted in case sheet proforma. Patients were instructed to come for next review once in 7 days. Age: Most of the patients were in the age group between 31-40 years. Pithavaatham naadi was most common naadi felt. Thinai: Most of the patients were from Neithal Thinai 70%. Kaalam: seasonal Variances do not have any impact for affecting the people. Occupation: The disease is more common in people working in hot atmosphere like Drivers and Labourers. Diet & Personal habits: People with habit of taking Vegetarian and Mixed Diet, smoking, Alcoholic has more incidence of the disease. Mukkutrum: In Vali, Abaanan, Koorman, Viyanan and Devathathan, In Pitham Anal, Sadhagam, Aalosagam, and in Iyyam Tharpagam and Sandhigam were affected in most of the cases. Udal Thathugal: Saaram, and sukkilam were affected in all the patients. Naadi: Pithavaatham naadi was most common naadi felt. RESULTS AFTER TREATMETNT: Veeriya viruthi Chooranam showed good results with relieving symptoms in almost 70% patients. 55% of patients shows good improvement, 30% of patients shows moderate improvement and in 15% of patients shows poor improvement was observed. The pharmacological studies Veeriya Viruthi Chooranam had good spermatogenesis effect in rats. The Toxicity study revealed that there were no signs of toxicity as could be judged by the absence of undesirable clinical manifestations and no alteration in bio chemical markers. The bio-statistical report of the clinical trial shows significant result. CONCLUSION: AAN MALADU (Male infertility) is primarily due to the derangement of pitham. Veeriya viruthi Chooranam predominating with Inippu and Thuvarppu taste respectively neutralizes the pitham. From the pre-clinical pharmacological studies it is evident that the medicine was significant Spermatogenic activity. The Veeriyaviruthi Chooranam does not produce any toxicity in preclinical study. So it is non-toxic and safe drug for Aan maladu. From the preclinical study Veeriyaviruthi Chooranam increase the sperm motility. No adverse effect was reported during the course of the treatment. The trial medicine gave maximum relief from the symptoms of Aan maladu. The preparation of trial drug is too easy and the cost effect is economically. Therefore the author concluded that the trial medicine VEERIYA VIRUTHI CHOORANAM should be a very good remedy for Aan Maladu (Male Infertility)

Silymarin Protects Epidermal Keratinocytes from Ultraviolet Radiation-Induced Apoptosis and DNA Damage by Nucleotide Excision Repair Mechanism

Solar ultraviolet (UV) radiation is a well recognized epidemiologic risk factor for melanoma and non-melanoma skin cancers. This observation has been linked to the accumulation of UVB radiation-induced DNA lesions in cells, and that finally lead to the development of skin cancers. Earlier, we have shown that topical treatment of skin with silymarin, a plant flavanoid from milk thistle (Silybum marianum), inhibits photocarcinogenesis in mice; however it is less understood whether chemopreventive effect of silymarin is mediated through the repair of DNA lesions in skin cells and that protect the cells from apoptosis. Here, we show that treatment of normal human epidermal keratinocytes (NHEK) with silymarin blocks UVB-induced apoptosis of NHEK in vitro. Silymarin reduces the amount of UVB radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane pyrimidine dimers (CPDs) and as measured by comet assay, and that ultimately may lead to reduced apoptosis of NHEK. The reduction of UV radiation-induced DNA damage by silymarin appears to be related with induction of nucleotide excision repair (NER) genes, because UV radiation-induced apoptosis was not blocked by silymarin in NER-deficient human fibroblasts. Cytostaining and dot-blot analysis revealed that silymarin repaired UV-induced CPDs in NER-proficient fibroblasts from a healthy individual but did not repair UV-induced CPD-positive cells in NER-deficient fibroblasts from patients suffering from xeroderma pigmentosum complementation-A disease. Similarly, immunohistochemical analysis revealed that silymarin did not reduce the number of UVB-induced sunburn/apoptotic cells in the skin of NER-deficient mice, but reduced the number of sunburn cells in their wild-type counterparts. Together, these results suggest that silymarin exert the capacity to reduce UV radiation-induced DNA damage and, thus, prevent the harmful effects of UV radiation on the genomic stability of epidermal cells

Understanding concepts of generalism and specialism amongst medical students at a research-intensive London Medical School

Background Many prominent UK medical organisations have identified a need for more generalist clinicians to address the complex requirements of an aging society. We sought to clarify attitudes towards “Specialists” and “Generalists” amongst medical students and junior doctors at Imperial College School of Medicine. Methods A survey exploring medical students’ beliefs was followed up by qualitative analysis of focus groups of medical students and Imperial-graduate foundation year doctors. Results First year medical students associated specialists with academia and higher income, and generalists with ease of training and job availability. Senior (Years 5/6) medical students associated specialists even more firmly with broader influence and academic work, whilst generalists were assigned lower prestige but the same workload as specialists. The medical student focus group discussed concepts of Generalism pertaining only to Primary Care. In contrast, the foundation year doctor focus group revealed that Generalism was now seen to include some hospital care, and the perception that generalists sat lower in a knowledge hierarchy had been challenged. Conclusion Perceptions that Generalism is associated with lower prestige in the medical profession are already present at the very start of medical school and seem to be reinforced during undergraduate training. In early postgraduate clinical practice, the perceived knowledge and prestige hierarchy lessens. These findings can help inform curriculum redesign and the promotion of Generalism as a rewarding career aspiration

Bioactive Dietary Supplements Reactivate ER Expression in ER-Negative Breast Cancer Cells by Active Chromatin Modifications

Breast cancer is the most common cancer and the leading cause of cancer death in women. Although tamoxifen therapy is successful for some patients, it does not provide adequate benefit for those who have estrogen receptor (ER)-negative cancers. Therefore, we approached novel treatment strategies by combining two potential bioactive dietary supplements for the reactivation of ERα expression for effective treatment of ERα-negative breast cancer with tamoxifen. Bioactive dietary supplements such as green tea polyphenols (GTPs) and sulforaphane (SFN) inhibit DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), respectively, which are of central importance to cancer prevention. In the present study, we have observed that treatment of ERα-negative breast cancer cells with GTPs and SFN alone or in combination leads to the reactivation of ERα expression. The combination of 20 µg/mL GTPs and 5 µM SFN was found to be the optimal dose of ERα-reactivation at 3 days in MDA-MB-231 cells. The reactivation of ERα expression was consistently correlated with ERα promoter hypomethylation and hyperacetylation. Chromatin immunoprecipitation (ChIP) analysis of the ERα promoter revealed that GTPs and SFN altered the binding of ERα-transcriptional co-repressor complex thereby contributing to ERα-reactivation. In addition, treatment with tamoxifen in combination with GTPs and SFN significantly increased both cell death and inhibition of cellular proliferation in MDA-MB-231 cells in comparison to treatment with tamoxifen alone. Collectively, our findings suggest that a novel combination of bioactive-HDAC inhibitors with bioactive-demethylating agents is a promising strategy for the effective treatment of hormonal refractory breast cancer with available anti-estrogens

Regulating environmental responsibility for the multinational oil industry: continuing challenges for international law

States utilise international law to create opportunities within global markets for private transnational economic actors, such as multinational oil companies, to invest and/or operate within foreign jurisdictions. However, there is a lack of directly enforceable international mechanisms against these private actors when they cause environmental damage abroad. International law responses to this problem range from the establishment of international compulsory compensation schemes, the proposed expansion of the doctrine of State responsibility to include liability for private actors and more recently, through litigation in the home States of multinational oil companies. However, both international jurisprudence and US, Dutch and British domestic case law reveal an ambivalence towards holding such private transnational economic actors legally accountable in their home State jurisdictions for violations committed abroad. Certain States (the USA and France) have responded to this ambivalence by reasserting their domestic regulatory powers to require immediate clean-up and compensation, prior to domestic judicial litigation, whereas other States (Nigeria) are unable to achieve the same level of effective enforcement due to their weaker political and economic bargaining positions