Rituximab has a myriad of clinical uses, ranging from its disease modifying action in rheumatoid arthritis, to its role in chemotherapy for cancer. Being an anti CD20 monoclonal antibody, it controls inflammation by targeting peripheral B cells including those present in the synovium. The use of Rituximab is associated with some side effects such as cytopenias and increased risk of infections such as JC virus reactivation leading to multifocal encephalopathy. The role of Rituximab as an immunosuppressant has been established. However, its association with tuberculosis in endemic countries like India is yet to be understood well. The study was a cross sectional study of the two cases reported about the incidence of tuberculosis in patients receiving infusions of rituximab for rheumatoid diseases. These adverse drug reactions were reported to the nearest pharmacovigilance center through the Vigiflow portal of WHO and were assessed for their causality as per the WHO scale. A 45 year old male patient, a known case of Systemic Lupus Erythematosus, presented to a tertiary care hospital with high grade fever with chills and rigors after which he was diagnosed with pleural effusion due to tuberculosis. The patient was on immunosuppressants which included Rituximab, Mycophenolate Sodium, Prednisolone and Hydroxychloroquine. Rituximab was withdrawn and the remaining medications were continued as per the initial plan. A 19 year old male patient, a known case of dermatomyositis and dilated cardiomyopathy, presented to a tertiary care hospital with complaints of fever with chills and rigors, and breathlessness on exertion which was followed by the diagnosis of miliary tuberculosis. Earlier, the patient was on Rituximab, Cyclophosphamide, Hydroxychloroquine and Prednisolone. Plan of further infusions of Rituximab and Cyclophosphamide was terminated while the remaining medications were continued. Both the patients were put on anti tubercular therapy and are now improving. The association of bacterial infections like tuberculosis with the use of Rituximab is not well understood. However, Rituximab being an immunosuppressant can be considered to be related to this infection. In our case series we readdress this association through a literature review.
The betaine/GABA transporter (BGT1) is important for osmoprotection in kidney medullary cells. We previously reported an acute (30 min) increase in extracellular Ca caused dose‐dependent inhibition of BGT1 in renal MDCK cells (AJP Renal 291:F305‐12, 2006). To determine if extracellular Ca might be a local regulator of BGT1, we tested the response to low Ca serum‐free growth medium (LCM, 0.09 mM Ca2+). Na+/GABA cotransport in MDCK monolayers was activated within 30 min after transfer from standard culture medium to LCM. Activation was significant after 60–90 min (n=3–5) and was independent of medium osmolarity. Peak transport was increased 50% in isotonic LCM and 100% in hypertonic (500 mOsm) LCM over controls. Hypertonic LCM also activated Na+/betaine cotransport by 400% within 60 min (n=3). The system A amino acid transporter showed a similar 4‐fold activation in hypertonic LCM. Perfusion of Fura‐ 2‐loaded MDCK cells with LCM decreased intracellular Ca2+ by 31% (n=22) within 6–7 min. Confocal imaging of ZO‐1 protein showed a marked change in distribution within 45 min exposure to LCM, consistent with disruption of tight junctions. Trafficking pathways may be disrupted by loss of tight junctions and cell polarity, and activation of BGT1 and system A transport by LCM could be due to increased membrane insertion or decreased retrieval.
Background: India has the highest burden of acute coronary syndrome (ACS) in the world. This research is to evaluate prescriptions pattern and extent of adherence to American College of Cardiology (ACC)\American Heart Association (AHA) guidelines in the management of ACS with patient outcome.Methods: Case record form containing patient’s demographic, clinical profile, diagnosis, prescription drugs (with dose, duration and frequency) were noted. Pharmacotherapy was compared to ACC/AHA guidelines, to evaluate adherence, guideline adherence index (GAI-5) was used for 5 major drug groups for ACS. GAI was calculated as: number of patients using the prescribed medications/number of eligible patients multiplied by 100.Results: A total of 172 patients diagnosed with ACS. 64 (37.20%) Patients with the highest preponderance to ACS belonged to 51-60 years age group with a 4.73:1 male to female ratio. ST-elevation myocardial infarction (STEMI) (44.77%) was the most common diagnosis and an average of 14.66±4.34 drugs were prescribed. Majority of the patients opted for percutaneous coronary intervention (PCI) with or without having received fibrinolytic therapy at onset. Adherence to the ACC/AHA guidelines being 93.75% and 118 prescriptions being 100% adherent to the guidelines. A positive correlation between adherence and number of drugs was statistically significant.Conclusions: The success of evidence-based medicine (EBM) was well noted with a 0% in hospital mortality rate i.e. all of the 172 patients were discharged with therapeutic success. Despite the concept of EBM and its proven effectiveness, there is a paucity of availability of such guidelines in India, so this study, a first of its kind can serve as a starting point of generating national as well as local guidelines.
The betaine/GABA transporter (BGT1) is important for osmoprotection in kidney medullary cells. We previously reported an acute (30 min) increase in extracellular Ca caused dose‐dependent inhibition of BGT1 in renal MDCK cells (AJP Renal 291:F305‐12, 2006). To determine if extracellular Ca might be a local regulator of BGT1, we tested the response to low Ca serum‐free growth medium (LCM, 0.09 mM Ca2+). Na+/GABA cotransport in MDCK monolayers was activated within 30 min after transfer from standard culture medium to LCM. Activation was significant after 60–90 min (n=3–5) and was independent of medium osmolarity. Peak transport was increased 50% in isotonic LCM and 100% in hypertonic (500 mOsm) LCM over controls. Hypertonic LCM also activated Na+/betaine cotransport by 400% within 60 min (n=3). The system A amino acid transporter showed a similar 4‐fold activation in hypertonic LCM. Perfusion of Fura‐ 2‐loaded MDCK cells with LCM decreased intracellular Ca2+ by 31% (n=22) within 6–7 min. Confocal imaging of ZO‐1 protein showed a marked change in distribution within 45 min exposure to LCM, consistent with disruption of tight junctions. Trafficking pathways may be disrupted by loss of tight junctions and cell polarity, and activation of BGT1 and system A transport by LCM could be due to increased membrane insertion or decreased retrieval.
Deriphyllin is a combination of etophylline and theophylline (1,3-dimethylxanthine) from methylxanthine group. These are extensively prescribed in developing countries like ours because it is inexpensive. It is a nonselective phosphodiesterase inhibitor, an effect that could simulate beta receptor stimulation by increasing intracellular levels of cyclic-AMP. [1] It can indirectly stimulate both β 1 and β 2 receptors through release of endogenous catecholamines. [2] Theophylline has narrow therapeutic index and a large pharmacokinetic variability between patients which makes toxicity a common problem. Adverse effects may be evident within the normal therapeutic range. [3] Drug-induced hallucination is a relatively common symptom, with a prevalence of 4%-38%. [4] Scientific literature is also scarce, reporting hallucinations in children occurring with deriphyllin. To our knowledge, this is the first report which associates deriphyllin use with hallucinations in adults. case reportAn 83-year-old male patient with a history of fall 20 days back with head injury arrived in emergency department with drowsiness, altered sensorium, and left side weakness, along with urine and stool incontinence. On examination, his Glasgow Coma Scale was E3V4M6 with bilateral pupil 1.5 mm and reactive. Power on his right side was found to be 5/5 and left side 2/5. The patient is a known case of recent onset asthma and was on tablet deriphyllin 150 mg BD and salbutamol nebulization BD. The patient was started on antibiotics, analgesics, and antiepileptics. Computed tomography (CT) scan brain was done which showed right frontotemporoparietal subdural hematoma. He underwent emergency drainage of subdural hematoma. The patient's condition improved by evening, and no neurological deficit was found, with movement of all four limbs (power grade 5/5 on the right side and 4/5 on the left side). He was shifted to the ward next day, but he again developed weakness of left side for which CT scan was done which showed recurrent subdural clots for which he again underwent burr holes and evacuation of clots. Within 2 days, left side hemiparesis improved and then the patient
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