Posterior Reversible Encephalopathy Syndrome and Fatal Cryptococcal Meningitis After Immunosuppression in a Patient With Elderly Onset Inflammatory Bowel Disease.

Advanced age and associated comorbidities are-recognized predictors of life-threatening adverse outcomes, such as opportunistic infection following immunosuppressive therapy. We describe the case of an elderly patient with stricturing colonic Crohn's disease and significant clinical comorbidities, initially controlled with corticosteroid induction followed by infliximab, whose course was complicated by fatal disseminated cryptococcal infection and posterior reversible encephalopathy syndrome. Our patient's case highlights rare, but serious, complications of immunosuppression. In applying modern treatment paradigms to the elderly, the clinician must consider the potential for more pronounced adverse effects in this potentially vulnerable group, maximizing benefit and minimizing harm.

Disseminated herpes simplex infection during pregnancy, rare but important to recognise.

Disseminated herpes simplex virus (HSV) infection during pregnancy is a rare, but potentially fatal condition. We present a case where prompt treatment with intravenous acyclovir resulted in a successful outcome for both mother and baby.

Mycobacterium bovis tenosynovitis.

Infectious tenosynovitis is a rare condition usually presenting with symptoms of joint pain, swelling and deformity. A large number of infectious organisms are known to cause tenosynovitis and prompt and accurate diagnosis is essential to ensure appropriate treatment is delivered before serious complications and functional impairment occurs. We report a case of Mycobacterium bovis tenosynovitis, a rare cause of infectious tenosynovitis; we discuss the clinical features and management of this condition and highlight the difficulties encountered in reaching the correct diagnosis and the importance of the appropriate use of biopsy to aid diagnosis.

A space occupying lesion masquerading as pancreatic carcinoma.

The coexistence of painless jaundice and a space-occupying lesion in the head of the pancreas usually signifies a diagnosis of pancreatic cancer. We present a case, where the cause of a pancreatic mass turned out to be related to tuberculosis. Tuberculosis affecting abdominal organs in isolation is uncommon, and more often forms part of disseminated disease. Pancreatic tuberculosis is very rare, especially in immunocompetent individuals. While every effort should be made to ensure that potentially operable pancreatic cancers undergo prompt surgical excision, the challenge for the future will be to make a preoperative diagnosis of pancreatic conditions that require medical rather than surgical therapy.

Utility of FDG-PETCT and magnetic resonance spectroscopy in differentiating between cerebral lymphoma and non-malignant CNS lesions in HIV-infected patients.

BACKGROUND AND PURPOSE: In HIV infected patients, MRI cannot reliably differentiate between central nervous system (CNS) lymphoma and non-malignant CNS lesions, particularly cerebral toxoplasmosis (CTOX). This study prospectively investigates the utility of FDG PET-CT and magnetic resonance spectroscopy (MRS) in discriminating CNS lymphoma from non-malignant CNS lesions in HIV infected patients, and assesses the ability of FDG PET-CT to guide the use of early brain biopsy. METHODS: 10 HIV patients with neurological symptoms and contrast enhancing lesions on MRI were commenced on anti-toxoplasmosis therapy before undergoing FDG PET-CT and MRS. Brain biopsies were sought in those with FDG PET-CT suggestive of CNS lymphoma, and in those with a negative FDG PET-CT scan who failed to respond to therapy. Final diagnosis was based on histology or treatment response. RESULTS: Two patients were confirmed to have CNS lymphoma and FDG PET-CT was consistent with this diagnosis in both. Six patients had cerebral toxoplasmosis in all of whom FDG PET-CT was consistent with non-malignant disease. One patient had progressive multifocal leukoencephalopathy (PML), FDG PET-CT was equivocal. One patient had a haemorrhagic brain metastasis and FDG PET-CT wrongly suggested non-malignant disease. MRS was performed successfully in eight subjects: three results were suggestive of CNS lymphoma (one true positive, two false positive), four suggested CTOX (two false negative, two true negative), one scan was equivocal. CONCLUSION: FDG PET-CT correctly identified all cases of CNS lymphoma and CTOX, supporting its use in this situation. MRS was unhelpful in our cohort.

Pharmacologic optimization of protease inhibitors and nonnucleoside reverse transcriptase inhibitors (POPIN)--a randomized controlled trial of therapeutic drug monitoring and adherence support.

We evaluated the feasibility and effectiveness of therapeutic drug monitoring (TDM) and adherence support (collectively, AT) vs standard of care (SOC) in patients receiving HIV protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) within a nurse-led clinic. Primary end points were failure to achieve viral load of <50 copies/mL at 24 weeks, viral rebound, or development of treatment limiting toxicity. One hundred twenty-two patients (AT 63 and SOC 59) were followed-up every 12 weeks, for a median of 72 weeks. No difference was observed between arms in risk of reaching a study end point or between groups of patients with abnormal vs "therapeutic" drug concentrations. Interindividual variabilities (coefficient of variation) were the following: efavirenz, 77.5%; nevirapine, 74.5%; lopinavir, 73.4%; nelfinavir, 83.7%; indinavir, 80.8%; saquinavir, 112.4%. Intraindividual variabilities (median coefficient of variation) were the following: NNRTIs, approximately 25%; PIs, 48.4%. Despite persistently abnormal results in 26 of patients in the AT arm (38%), dosage adjustment was only undertaken in 9 patients (35%).A significant proportion of patients had drug concentrations outside the therapeutic range. The Pharmacologic Optimization of PIs and NNRTIs (POPIN) study confirms that TDM trials are complex to interpret and statistically underpowered, with effectiveness better assessed through the clinical utility of a TDM result, whether normal or abnormal. Although TDM of PIs and NNRTIs may be useful in selected patients, routine and unselected use is not supported by current evidence.

Intracellular and plasma pharmacokinetics of nevirapine in human immunodeficiency virus-infected individuals.

BACKGROUND AND OBJECTIVE: Plasma concentrations of nevirapine have been linked to human immunodeficiency virus (HIV) treatment outcome. However, because the site of action of nevirapine is within HIV-infected cells, intracellular concentrations may better relate to antiviral exposure. Investigation of factors that alter the intracellular pharmacokinetics of nevirapine may also aid in our understanding of therapeutic failure. Our objective was to determine intracellular (or cell-associated) nevirapine concentrations over the full dosing interval and to relate protein binding and P-glycoprotein (P-gp) expression to intracellular exposure. METHODS: Plasma and peripheral blood mononuclear cells were isolated from blood samples taken from 10 HIV-infected patients at 0, 2, 4, 8, and 12 hours after dosing. Intracellular and plasma (total and unbound) concentrations were determined by liquid chromatography-tandem mass spectrometry, and the ratios of intracellular to total plasma exposure (area under the concentration-time curves) were calculated. P-gp expression was measured by flow cytometry. RESULTS: The median intracellular accumulation ratio was 0.005 (range, 0.001-0.054) and remained unchanged over the dosing interval. There was an association between higher plasma concentrations and lower cellular concentrations of nevirapine (total r(2) = 0.62, P = .007). There was no relationship between percent unbound nevirapine and intracellular nevirapine. There was a correlation between higher plasma nevirapine exposure and higher P-gp expression (r(2) = 0.77, P = .03), whereas intracellular nevirapine exposure decreased with higher P-gp expression (r(2) = 0.62, P = .01). CONCLUSIONS: The intracellular accumulation of nevirapine was low, did not change over the dosing interval, and was not related to protein binding. In this small study, cells with higher P-gp expression had lower cellular concentrations of nevirapine. Further studies are required to explore the influx and efflux transporter profile of this drug.