The spectrum of genetic mutations in breast cancer.

Breast cancer is the most common malignancy in women around the world. About one in 12 women in the West develop breast cancer at some point in life. It is estimated that 5%-10% of all breast cancer cases in women are linked to hereditary susceptibility due to mutations in autosomal dominant genes. The two key players associated with high breast cancer risk are mutations in BRCA 1 and BRCA 2. Another highly important mutation can occur in TP53 resulting in a triple negative breast cancer. However, the great majority of breast cancer cases are not related to a mutated gene of high penetrance, but to genes of low penetrance such as CHEK2, CDH1, NBS1, RAD50, BRIP1 and PALB2, which are frequently mutated in the general population. In this review, we discuss the entire spectrum of mutations which are associated with breast cancer.

Clinical profile and complication of malaria hepatopathy.

BACKGROUND: This study was designed to study the patient characteristics, presenting features and complications of malaria in patients with elevated liver enzymes and to compare these data to those of patients with normal liver enzymes. METHODS: A convenient sample of 100 patients with malaria was selected from three tertiary care referral hospitals. Study subjects were divided into two groups: (1) patients (controls) with normal liver enzymes and (2) patients (cases) with >3 times the normal liver enzymes in the absence of an alternate explanation for such elevation. Patient characteristics, presenting features and complications of malaria in these two groups were studied. Data were collected using a semi-structured pretested proforma and were analyzed using the statistical analysis program SPSS, version 11.5 (SPSS, Inc., Chicago, IL). RESULTS: The mean ages were 38.12 years for the cases and 35.20 years for the controls with a non-significant p value of 0.289. Males composed 82% of the cases that were diagnosed with malarial hepatopathy; the remaining 18% were females. Falciparum malaria was present in 56% of the cases, compared to 12% of the controls. Icterus was present in 66% of cases of malarial hepatopathy, compared to 32% of the controls. Of the 66% of these cases, 18.18% had serum bilirubin >3mg%, whereas out of the 32% of the controls presenting with icterus, only 5.55% had serum bilirubin >3mg% (p=0.003). Of the cases with malarial hepatopathy, 38% suffered from hypoglycemia, compared to 0% of the controls (p<0.001); 84% of the cases presented with thrombocytopenia, compared to 70% of the controls (p<0.001); 12% of the cases suffered from renal failure with serum creatinine levels >2mg%, compared to 2% of the controls (p=0.060). CONCLUSION: Plasmodium falciparum infection (either alone or along with P. vivax) is the leading cause of malarial hepatopathy. Jaundice is a common clinical manifestation among these patients. Patients with malarial hepatopathy have increased incidences of hypoglycemia and thrombocytopenia. Malarial hepatopathy occurs in relation to severe infection, most of which are treated with parenteral artesunate.

Statistical modelling and forecasting of cervix cancer cases in radiation oncology treatment: a hospital based study from Western Nepal.

BACKGROUND: To estimate the numbers and trends in cervix cancer cases visiting the Radiotherapy Department at Manipal Teaching Hospital, Pokhara, Nepal, statistical modelling from retrospective data was applied. MATERIALS AND METHODS: A retrospective study was carried out on data for a total of 159 patients treated for cervix cancer at Manipal Teaching Hospital, Pokhara, Nepal, between 28th September 2000 and 31st December 2008. Theoretical statistics were used for statistical modelling and forecasting. RESULTS: Using curve fitting method, Linear, Logarithmic, Inverse, Quadratic, Cubic, Compound, Power and Exponential growth models were validated. Including the constant term, none of the models fit the data well. Excluding the constant term, the cubic model demonstrated the best fit, with R2=0.871 (p=0.004). In 2008, the observed and estimated numbers of cases were same (12). According to our model, 273 patients with cervical cancer are expected to visit the hospital in 2015. CONCLUSIONS: Our data predict a significant increase in cervical cancer cases in this region in the near future. This observation suggests the need for more focus and resource allocation on cervical cancer screening and treatment.

Autopsy discoveries of death from malaria.

Malaria inflicts a huge health care burden in terms of mortality and morbidity worldwide. There has been evidence in the literature where many unexpected/unexplained deaths turned out to be related to malaria on autopsy. The aim of this study is to review autopsy diagnosed malaria related deaths in the literature with due stress to its biologic and forensic aspects. A meticulous literature search was performed for "sudden malaria death", "malaria death postmortem diagnosis" and "unexplained death malaria" across PubMed, SCOPUS, Cochrane Database of Systematic Reviews, Allied and Complementary Medicine, British Nursing Index, CINAHL, EMBASE, Ovid-MEDLINE and Google Scholar. All the literature was thoroughly reviewed and analyzed with reference to the type of study, location, travel history, age, gender, circumstance of death, method of diagnosis, species involved, chemoprophylaxis usage and take home message from the particular study. Plasmodium falciparum was responsible in most of the cases. The symptoms mimicked influenza in most of the case reports. Travel to endemic areas was common to most of the victims. The travelers were from all over the world including USA, France, Switzerland, Spain, Portugal, Germany and Asia (China and Japan). Vascular congestion with the presence of malarial pigment laden RBCs in capillaries of various organs was the major histopathology finding. Such lesions were found in the brains of all subjects (100%), liver of 78% of the cases, spleen in 67%, lungs in 56% and myocardium in 43% of the cases. Peripheral smear and rapid diagnostic test was of great aid to the autopsy in many cases. PCR was used for diagnosis as well as exclusion of possibility of co-infection with other species in case of Plasmodium knowlesi related death. The postmortem and histopathology findings in this case were similar to P. falciparum except for the fact that brain sections were negative for intracellular adhesion molecule-1. Chemoprophylaxis was not taken by the victims except for two in whom history of chloroquine based chemoprophylaxis was mentioned. Given the worldwide prevalence of the disease, increasing international travel and rapidly developing drug resistance, malaria will continue to be an important disease and should be considered in all cases of unexpected deaths particularly in malaria endemic regions or in presence of travel history to endemic regions.

Carbamzepine-induced toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a widespread life-threatening mucocutaneous disease where there is extensive detachment of the skin and mucous membrane. Many factors involved in the etiology of TEN including adverse drug reactions. Here we are reporting a case of toxic epidermal necrolysis in an adult male patient after receiving carbamazepine in a 38 year old male. On the 18(th) day of carbamazepine, patient developed blisters which first appeared on the trunk, chest and arms. The erythematous rash was covering almost all over the body with epidermal detachment of 70% body surface area. There was loss of eye lashes, congestion of conjunctiva with mucopurulent discharge and exposure keratitis. The clinical impression was TEN induced by carbamazepine. Carbamazepine was stopped immediately. He was treated with high dose intravenous betamethasone and systemic and topical antibiotics. After one month, the progression of the skin lesions halted and he was discharged.

Suicidal plant poisoning with Colchicum autumnale.

Colchicum autumnale is commonly known as autumn crocus, and as 'gowri gedde' in the southern region of Karnataka State in South India. It contains an alkaloid called colchicine, which blocks the cell division by inhibiting mitosis. We present a sporadic case of suicidal plant poisoning wherein a 24-year-old man consumed 'gowri gedde' to end his life. Initially he presented with severe vomiting, diarrhoea and epigastric pain. He died on the third day of ingestion due to multiorgan failure. Chemical analysis of blood and viscera obtained postmortem confirmed the presence of colchicine. Colchicine poisoning is potentially life threatening because of its high toxicity and unavailability of specific antidotal treatment. It classically presents with gastroenterocolitis, and may result in multiorgan failure in fatal cases.