Estrogen receptor alpha-negative and progesterone receptor-positive breast cancer: lab error or real entity?

Aretrospective study comparing the estrogen receptor (ER) alpha subtype and progesterone receptor (PR) profile of breast carcinomas amongst 1625 cases over 2.5 years was carried out. Strictly speaking it is generally believed that breast carcinomas can biochemically express PR only if they are ER-positive. However, a few ERalpha-PR+ cases do exist paradoxically. This class of tumors was the focus of our study in which we looked at the possible reasons for such an immunophenotype and compared it with a group of ERalpha+PR+ breast carcinomas. An internationally recognized immunohistochemical method employing monoclonal antibodies against estrogen and progesterone receptors was used. Correlations with established risk factors i.e. menopausal status, grade, tumor size and lymph node status were analyzed for our study group (ERalpha-PR+) and compared with a control (ERalpha+PR+). Out of the total 1625 cases, 29.91% (486) were ERalpha+PR+, 5.11% (83) were ERalpha+PR-, 56.86% (924) were ERalpha-PR- and 8.12% (132) were ERalpha-PR+. Patients\u27 age was significantly lower in the ERalpha-PR+ group (P=0.002). Statistical analysis of the grading between the two study groups revealed no significant difference (P=0.091), although the ERalpha-PR+ group contained significantly more poorly differentiated tumors than the ERalpha+PR+ one (P=0.032). Tumor size was also significantly larger in the ERalpha-PR+ than in the ERalpha+PR+ group (P=0.046). The frequency of lymph node metastases was independent of receptor profile. In conclusion, our study group does exhibit characteristics which are suggestive of a distinct breast cancer phenotype (ERalpha-PR+) with a different etiology and prognosis

Coping styles in patients with anxiety and depression

Different individuals use different coping styles to cope with their problems. In patients with anxiety and/or depression, these have important implications. The primary objective of our study was to estimate the frequency of different coping mechanisms used by patients with symptoms of anxiety and depression. A descriptive, cross-sectional survey was conducted and patients with symptoms of anxiety and depression were identified using the Aga Khan University\u27s Anxiety and Depression Scale (AKUADS). Coping styles were determined by using the 28-item Brief COPE inventory. We were able to recruit 162 people. The prevalence of anxiety and depression was found to be 34%. Females were more than 2 times likely to have anxiety and depression (P value = 0.024, OR = 2.62). In patients screening positive for AKUADS, religion was the most common coping mechanism identified. Acceptance , Use of instrumental support , and Active coping were other commonly used coping styles. Our findings suggest that religious coping is a common behavior in patients presenting with symptoms anxiety and depression in Pakistan. Knowledge of these coping styles is important in the care of such patients, as these coping methods can be identified and to some extent modified by the treating clinician/psychiatrist

Medicinal importance of grapefruit juice and its interaction with various drugs

Grapefruit juice is consumed widely in today's health conscious world as a protector against cardiovascular diseases and cancers. It has however, been found to be an inhibitor of the intestinal cytochrome P – 450 3A4 system, which is responsible for the first pass metabolism of many drugs. The P – glycoprotein pump, found in the brush border of the intestinal wall which transports many of these cytochrome P – 450 3A4 substrates, has also been implicated to be inhibited by grapefruit juice. By inhibiting these enzyme systems, grapefruit juice alters the pharmacokinetics of a variety of medications, leading to elevation of their serum concentrations. Most notable are its effects on the calcium channel antagonist and the statin group of drugs. In the case of many drugs, the increased serum concentration has been found to be associated with increased frequency of dose dependent adverse effects. In this review, we have discussed the phytochemistry of grapefruit juice, the various drugs involved in the drug – grapefruit juice eraction with their mechanisms of action and have presented the clinical implications of these interactions

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Outcomes of primary percutaneous coronary intervention at a joint commission international accredited hospital in a developing country -- can good results, possibly similar to the west, be achieved?

Background: Primary percutaneous coronary intervention (PCI) is the treatment of choice following ST-elevation myocardial infarction (STEMI). There is limited adoption and a paucity of data on outcomes following primary PCI in developing countries. The objective of this study was to describe the procedural and clinical outcomes of patients undergoing PCI for STEMI at a Joint Commission InternationalAccreditation (JCIA) certified hospital in Pakistan and make a comparison with outcomes from the West. Methods: We conducted a retrospective cohort study at a tertiary care university hospital in Karachi, Pakistan. A total of 277 consecutive patients undergoing primary PCI between January 2001 and December 2005 were reviewed. Exclusion criteria included preceding fibrinolytic therapy and STEMI due to stent thrombosis. Cox proportional hazards models were constructed. The primary outcome was mortality. Results: Procedural success was 97.1%. Inhospital mortality was 8.3% (43.9% in cardiogenic shock, 2.1% in non-shock patients), comparing very favorably with the published literature from developed countries. Multivariate predictors of death included (hazards ratio, 95% confidence interval) age (1.42 [1.14-1.76]), mechanical ventilation (8.35 [2.82-24.73]), cardiogenic shock (2.80 [1.04-7.55]), prior CABG (9.78 [1.15-83.13]) and ejection fraction (0.96 [0.92-0.99]). Conclusion: We conclude that excellent outcomes for a critical illness like STEMI can be achieved in a developing country at a JCIA-certified hospital, possibly similar to those seen in the West. There is a strong need for making the practice of primary PCI more widespread in developing nations. More outcomes data are needed from similar hospitals in the region to determine whether our results are generalizable

Chemical composition and mechanisms underlying the spasmolytic and bronchodilatory properties of the essential oil of Nepeta cataria L.

Aim of the study: The study was aimed to investigate the chemical composition and pharmacological basis for traditional use of essential oil of Nepeta cataria L (Limiaceae) (Nc.Oil]) in gastrointestinal and respiratory disorders. Materials And Methods: Chemical analysis was carried out through GC-EIMS, (13)C NMR and Kovats Retention Indices while pharmacological study was carried out in isolated tissues preparations. Results: Four major components, 1,8-cineol (21.00%), alpha-humulene (14.44%), alpha-pinene (10.43%) and geranyl acetate (8.21%) were identified among the 27 compounds in Nc.Oil. In isolated rabbit jejunum, Nc.Oil, papaverine and verapamil inhibited spontaneous and high K(+)(80 mM) precontractions, as well as shifted the Ca(++) concentration-response curves (CRCs) to right, indicating calcium channel blocking activity. In isolated guinea-pig trachea, Nc.Oil and papaverine inhibited carbachol (1 mu M) and K(+) precontractions with similar potency, while verapamil was more potent against K(+). Nc.Oil also potentiated isoprenaline inhibitory CRCs, similar to papaverine, indicating papaverine-like PDE inhibitor activity. In isolated guinea-pig atria, Nc.Oil caused cardiodepression at around 25-80 times higher concentrations, similar to papaverine. Conclusions: These data indicate that Nepeta cataria possesses spasmolytic and myorelaxant activities mediated possibly through dual inhibition of calcium channels and PDE, which may explain its traditional use in colic, diarrhea, cough and asthma