Outcome of uncorrected CSF leak and consequent recurrent meningitis in a patient: a case presentation and literature review.

Purpose: Post-traumatic CSF leaks are a complication in 2% of all head injuries. Majority of these patients will recover spontaneously. Whilst recent literature has predominantly centred on CSF leaks and their general investigations and management thereof, there is a paucity of information when it comes to those patients who have persistent post-traumatic CSF leaks, as well as the complication of recurrent meningitis. We present a patient with a persistent post-traumatic CSF leak who presented with recurrent bacterial meningitis thirteen times- the highest documented amount in an adult. We reviewed the literature with regards to the above as well.Material and Methods: We reviewed a vast array of journal articles on the topic of CSF leaks from the PubMed resource, and focused this review specifically on those that documented patients who had uncorrected CSF leaks and their outcomes.Results: Complications include meningitis and rhinorrhoea with brain abscesses and pneumocephalus occurring less frequently. Mortality has been documented to be 9% after 1 year. The rates of persistent CSF leaks were within the same range with an average calculated rate of 21%. Whilst meningitis was recorded and is common, it was not stipulated whether the incidences were recurrent.Conclusion: Post-traumatic persistent CSF leaks remain a therapeutic challenge and continued follow-up with early surgical intervention is highly recommended to prevent complications. One of the more serious complications of a persistent leak is meningitis. The long-term outcomes of recurrent meningitis could include cumulative focal neurological deficitis and cognitive impairment.

Burden and predictors of hypertension in India: results of SEEK (Screening and Early Evaluation of Kidney Disease) study.

BACKGROUND: Hypertension (HTN) is one of the major causes of cardiovascular morbidity and mortality. The objective of the study was to investigate the burden and predictors of HTN in India. METHODS: 6120 subjects participated in the Screening and Early Evaluation of Kidney disease (SEEK), a community-based screening program in 53 camps in 13 representative geographic locations in India. Of these, 5929 had recorded blood pressure (BP) measurements. Potential predictors of HTN were collected using a structured questionnaire for SEEK study. RESULTS: HTN was observed in 43.5% of our cohort. After adjusting for center variation (p < 0.0001), predictors of a higher prevalence of HTN were older age ≥ 40 years (p < 0.0001), BMI of ≥ 23 Kg/M2 (p < 0.0004), larger waist circumference (p < 0.0001), working in sedentary occupation (p < 0.0001), having diabetes mellitus (p < 0.0001), having proteinuria (p < 0.0016), and increased serum creatinine (p < 0.0001). High school/some college education (p = 0.0016), versus less than 9th grade education, was related with lower prevalence of HTN. Of note, proteinuria and CKD were observed in 19% and 23.5% of HTN subjects. About half (54%) of the hypertensive subjects were aware of their hypertension status. CONCLUSIONS: HTN was common in this cohort from India. Older age, BMI ≥ 23 Kg/M2, waist circumference, sedentary occupation, education less, diabetes mellitus, presence of proteinuria, and raised serum creatinine were significant predictors of hypertension. Our data suggest that HTN is a major public health problem in India with low awareness, and requires aggressive community-based screening and education to improve health.

Cur(Que)min: a neuroactive permutation of curcumin and quercetin for treating spinal cord injury.

Among Spinal Cord Injury (SCI) intervention the administration of high-dose high-potency steroidal drugs such as methylprednisolone or dexamethasone is used to reduce the inflammation associated with primary injury and prevention of the subsequent secondary injury. The administration of steroids has several side-effects that jeopardize their use and therefore safer chemical neuro-entities are required. Natural compounds such as curcumin (anti-oxidant) and quercetin (anti-inflammatory) have been investigated as alternative neuroactive, but are not as potent as the steroids. Hence, they are required in very high doses which may lead to significant toxicity causing an increase in cellular levels of reactive oxygen species, active iron chelation, inhibiting the activity of the cytochrome P450 enzymes such as glutathione-S-transferase and UDP-glucuronosyltransferase. A reduction in the dose of these neuroactives is possible with the administration of a 'chemically-variant' permutation with additive or synergistic therapeutic benefits. Therefore, we hypothesize that curcumin and quercetin, both natural polyphenolic flavonoids, can "additively and synergistically" improve the physiological outcome after traumatic SCI when used in combination and termed 'Cur(Que)min' - thereby decreasing the dose levels and hence reducing the inherent high dose-cytotoxicity of the individual neuroactives. This hypothesis provides the first-account of a curcumin-quercetin combination for SCI intervention theorizing the possible biomolecular-mechanism that may provide the scientific community with a novel neuroprotective and neurotherapeutic treatment option for SCI.

Relationship between the neuroprotective effects of insulin-like growth factor-1 and 17ß-oestradiol in human neuroblasts.

Insulin-like growth factor-1 (IGF-1) and oestrogens interact with each other as neuroprotective factors. We have previously demonstrated that 17ß-oestradiol protects against ß-amyloid and oxidative stress toxicity and increases the amount of cell cholesterol in human foetal neuroblasts (FNC). The present study aimed: (i) to assess the protective effects of IGF-1 in FNC cells; (ii) to investigate the relationship between IGF-1 and 17ß-oestradiol; and (iii) to determine whether cholesterol was a major mediator of the effects of IGF-1, similarly to 17ß-oestradiol. We found that IGF-1 effectively exerts neuroprotective effects in FNC cells. We also demonstrated that the IGF-1 receptor (IGF-1R) pathway is needed to maintain oestrogen-mediated neuroprotection. Finally, we found that, opposite to 17ß-oestradiol, IGF-1 did not cause a significant increase in cell cholesterol. These findings indicate that a cross-talk between IGF-1 and 17ß-oestradiol occurs in FNC cells. In particular, the activation of the IGF-1R cascade appears to be fundamental to warrant 17ß-oestradiol-mediated neuroprotection, even though cell cholesterol does not play a major role as an effector of this pathway.

Non-traumatic myelopathy at the Chris Hani Baragwanath Hospital, South Africa--the influence of HIV.

BACKGROUND: Non-traumatic myelopathy from developing regions has been described widely. In these regions infections, mainly tuberculosis, followed by acute transverse myelitis and neoplasms, dominate. These are also regions of high HIV prevalence. In developed regions, the most prominent reported spinal cord disease in HIV/AIDS is vacuolar myelopathy (VM). Other myelopathy causes in HIV/AIDS include opportunistic infections, neoplasms, vascular lesions and metabolic disease. In developing regions, opportunistic infections are more commonly encountered with VM occurring less frequently. AIM: To determine the influence of HIV on the myelopathy spectrum in an HIV endemic region. DESIGN: Prospective case series. METHODS: Hundred unselected consecutive in-patients admitted with myelopathy were studied. Myelopathy aetiologies were established by collating information obtained from magnetic resonance imaging (MRI) scans, CSF and blood studies, CXR findings, non-neurological illness and response to treatment. Data were analysed in terms of two cohorts, HIV positive and HIV negative. RESULTS: Approximately 50% of the patients presenting and admitted to our hospital with non-traumatic myelopathy are HIV positive. The HIV positive myelopathy patients were younger (20-40 years) and had infectious aetiologies. Tuberculosis was the most frequently identified cause of myelopathy. The majority of HIV-positive patients had advanced HIV infection. Anti-retroviral treatment did not influence myelopathy aetiologies. The HIV-negative patients were older and had neoplasms, followed by degenerative spondylosis as the main myelopathy causes. CONCLUSION: HIV influences the non-traumatic myelopathy spectrum in regions with high HIV prevalence. Empiric treatment of HIV-myelopathy patients with anti-tuberculous medications where resources are severely limited has merit.

Computational molecular modeling and structural rationalization for the design of a drug-loaded PLLA/PVA biopolymeric membrane.

The purpose of this study was to design, characterize and assess the influence of triethanolamine (TEA) on the physicomechanical properties and release of methotrexate (MTX) from a composite biopolymeric membrane. Conjugated poly(L-lactic acid) (PLLA) and poly(vinyl alcohol) (PVA) membranes were prepared by immersion precipitation with and without the addition of TEA. Drug entrapment efficiency (DEE) and release studies were performed in phosphate buffered saline (pH 7.4, 37 degrees C). Scanning electron microscopy elucidated the membrane surface morphology. Computational and structural molecular modeling rationalized the potential mechanisms of membrane formation and MTX release. Bi-axial force-distance (F-D) extensibility profiles were generated to determine the membrane toughness, elasticity and fracturability. Membranes were significantly toughened by the addition of TEA as a discrete rubbery phase within the co-polymer matrix. MTX-TEA-PLLA-PVA membranes were tougher (F = 89 N) and more extensible (D = 8.79 mm) compared to MTX-PLLA-PVA (F = 35 N, D = 3.7 mm) membranes as a greater force of extension and fracture distance were required (N = 10). DEE values were relatively high (>80%, N = 5) for both formulations. Photomicrographs revealed distinct crystalline layered morphologies with macro-pores. MTX was released by tri-phasic kinetics with a lower fractional release of MTX from MTX-TEA-PLLA-PVA membranes compared to MTX-PLLA-PVA. TEA provided a synergistic approach to improving the membrane physicomechanical properties and modulation of MTX release. The composite biopolymeric membrane may therefore be suitable for the novel delivery of MTX in the treatment of chronic primary central nervous system lymphoma.

Human immunodeficiency virus associated intracranial aneurysms: report of three adult patients with an overview of the literature.

BACKGROUND AND PURPOSE: Aneurysms have been described in HIV infected patients. These involve predominantly extracranial blood vessels with specific histological and clinical features. Intracranial aneurysms are rare and have been identified mainly in children. METHODS: Case reports and literature review. RESULTS: Three black South African HIV positive adult patients with intracranial aneurysms were identified. The clinical, laboratory and radiological features are described. CONCLUSIONS: Intracranial aneurysms occur in both adults and children infected with HIV. More information is required on this association. The frequency in terms of numbers of cases indicates that it is an uncommon association or manifestation of HIV. The characteristics of the aneurysms suggest that they are distinctive and not a chance or coincidental co-occurrence of congenital or arteriosclerotic aneurysms.

Reduced risk of toxoplasma encephalitis in HIV-infected patients--a prospective study from Gauteng, South Africa.

Toxoplasma seroprevalence was determined in 307 consecutive HIV-infected medical inpatients at the Helen Joseph Hospital, Johannesburg, South Africa, using an enzyme linked immunosorbent assay to detect immunoglobulin G (IgG) and IgM antibodies. The mean age of patients was 36 years, with a female to male ratio of 1.3 to 1. The mean CD4 count was 109 cells/mL. Toxoplasma antibodies were detected in 25 patients (8%). Twenty-two of these patients were IgG positive and IgM negative, i.e. reactivation toxoplasmosis. Only two patients (0.65%) had clinical manifestations of toxoplasmosis (one toxoplasma encephalitis and one retinitis). The risk for toxoplasma encephalitis (TE) was 0.33%. These results indicate that the toxoplasma seroprevalence and the TE risk in this population is low. The implication from this study is that in HIV-infected populations where the toxoplasma seroprevalence is low, the TE risk will be low and empiric treatment of focal brain lesions with anti-toxoplasma therapy may be inappropriate.

The incidence of end-stage renal disease in India: a population-based study.

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are emerging public health problems in developing countries, and need changes in health-care policy. ESRD incidence data are not available from large parts of the developing world including South Asia. We report the ESRD incidence in a large urban population in India. ESRD incidence was estimated for four consecutive calendar years (2002-2005) among 572 029 subjects residing in 36 of the 56 wards of the city of Bhopal. These subjects are beneficiaries of free health care in a hospital established after the 1984 Union Carbide Industrial Accident. Crude and age-adjusted incidence rates were calculated. A total of 346 new ESRD patients were diagnosed during the study period; 86 in 2002, 82 in 2003, 85 in 2004, and 93 in 2005. Average crude and age-adjusted incidence rates were 151 and 232 per million population, respectively. The mean age was 47 years, and 58% were males. Diabetic nephropathy was the commonest (44%) cause of ESRD. This study provides the first population-based ESRD incidence data from India and reveals it to be higher than previously estimated. Diabetic nephropathy is the leading cause of ESRD. Changes are required in health-care policy for optimal care of CKD patients and efficient resource utilization for management of those with ESRD.

Blood pressure-measuring devices in rural South Africa: an audit conducted by the SASPI team in the Agincourt field site.

BACKGROUND: Cardiovascular disease is an important cause of morbidity and mortality in South Africa. The Southern Africa Stroke Prevention Initiative (SASPI) found a high prevalence of stroke in the rural Agincourt subdistrict, Limpopo province. Hypertension is the commonest vascular risk factor in our population and it is essential that primary care services be adequately equipped to detect and treat hypertension. The aim of this study was to assess the number, accuracy and working condition of blood pressure measuring devices (BMD) in the clinics that serve the field site, and to assess the clinic sisters' perceptions of the availability of antihypertensive medication and aspirin. METHODS: In each of the clinics serving the site we assessed the BMDs and cuffs using the following criteria: general condition, bladder size, state of rubber components, operation of the inlet valve and control of valve operation. The legibility of the gauge, level and condition of the mercury, and the condition of the glass tube were checked when relevant. The performance of the BMD was then assessed both with the cuff used in the clinic and with a new functioning cuff, against an accurate mercury sphygmomanometer. By interviewing the clinic sister we could assess the availability of antihypertensive medication and aspirin, as well as the state of the drug delivery system. RESULTS: All BMDs were mercury sphygmomanometers. Four clinics had one BMD each, one clinic had two, and one clinic had four. In one clinic the device was not functional at all until the study cuff was used. None of the clinics had spare cuffs and only one clinic had access to a large cuff. Nine out of 10 (90%) cuffs tested had unsatisfactory valve function, and none was of the size recommended by the guidelines. Although the condition of the mercury was only considered satisfactory in 40% of BMDs, once a new cuff had been fitted to the BMDs all of them were accurate to within 4 mmHg between 50 and 250 mmHg. Fifty per cent of clinic sisters felt they always had sufficient stock of hydrochlorothiazide and alpha-methyldopa, but the supply of more expensive medication was less reliable. Only one clinic always had sufficient aspirin. CONCLUSION: Although none of the primary care clinics had fully functioning BMDs, almost all the defects related to malfunctioning and inappropriately sized cuffs, which would be inexpensive to repair or replace. A procedure for routine servicing or replacement of both BMDs and cuffs is needed, as well as optimisation of medication delivery to remote areas.

Protein S deficiency in HIV associated ischaemic stroke: an epiphenomenon of HIV infection.

The purpose of the study was to determine the relevance of protein S deficiency in HIV infected patients with ischaemic stroke. In total, 33 HIV positive patients with ischaemic stroke, previously described by us, were prospectively compared with control groups for occurrence of protein S deficiency. The control groups comprised an equal number of consecutive matched HIV positive and negative patients without and with stroke respectively. Data were analysed in contingency tables using Fisher's exact test. Protein S deficiency occurred significantly more frequently in HIV positive compared with HIV negative stroke patients (p < 0.001). However, by including HIV positive patients without stroke as a control group and comparing this group with the HIV positive stroke group we found that protein S deficiency is statistically related to HIV infection and not stroke occurrence. Our data indicate that the presence of protein S deficiency in HIV positive patients with stroke is an epiphenomenon of HIV infection.

Management of HIV-associated focal brain lesions in developing countries.

BACKGROUND: HIV-associated focal brain lesions (HFBL) are caused by opportunistic infections, neoplasms, or cerebrovascular diseases. In developed countries, toxoplasma encephalitis (TE) is the most frequent cause, followed by primary CNS lymphoma (PCNSL). Guidelines based on these causes however are poorly suited to developing countries, where treatable infections predominate as causes of HFBL. AIM: To determine a practical approach to the management of HFBL in developing countries. DESIGN: Case series. METHODS: Patients (n = 32) were managed based on presumed aetiologies of the focal brain lesions, determined by collating information from CT scans, CSF and blood studies, concurrent non-neurological illness and response to treatment. RESULTS: The principal presumed cause of HFBL was tuberculosis (69%). The therapeutic response was good in 69% of patients. DISCUSSION: In developing countries, infections are the predominant cause of HFBL, the principal causes being infections that are endemic to the populations being studied. Empiric treatment based on limited investigations should be directed according to the nature of such infections. A modified algorithm is proposed.

Hepatitis C virus related cryoglobulinemic glomerulonephritis.

A 46 years male presented with skin rash and acute nephritic syndrome. He had history of jaundice four months back. Rheumatoid factor and cryoglobulins were present in the serum. Although anti-HCV antibodies were negative, HCV RNA was detected by polymerase chain reaction. Kidney biopsy showed membranoproliferative glomerulonephritis and thrombi in the lumen of the glomerular capillary loops. His renal functions improved with steroids.

Hemodialysis in acute renal failure: does the membrane matter?

Patients who develop hospital-acquired acute renal failure (ARF) that require dialytic support have high mortality rates. The potential impact of dialyzer membrane biocompatibility on clinical outcomes in ARF has been a subject of ongoing controversy. This article summarizes the clinical trials published to date that have examined the effect of dialyzer membrane biocompatibility on clinical outcomes of patients with ARF who require intermittent hemodialysis. A redirection of research endeavors in the field of dialysis in ARF is also argued.

The salivary adenosine/AMP content of Phlebotomus argentipes Annandale and Brunetti, the main vector of human kala-azar.

Adenosine and AMP in the salivary glands of the sand fly Phlebotomus argentipes were characterized by reversed-phase high-pressure liquid chromatography with diode-array detection and mass spectrometry. AMP and adenosine were measured in individual salivary gland pairs, yielding 76.8 +/- 8.6 and 380 +/- 25 pmoles per pair of salivary glands, respectively (mean +/- SE, n = 12). These values decrease to 45 +/- 7 and 181 +/- 21 pmoles following a blood meal, indicating that AMP and adenosine were secreted. Because adenosine and AMP have anti-platelet, vasodilatory, and immunomodulatory properties, it is proposed that these salivary nucleotides help the fly to blood feed and may affect Leishmania transmission.

Effects of lithium chloride on induction and expression of methylphenidate sensitization.

Repeated administration of psychomotor stimulants produces an enduring and progressively enhanced behavioral response known as behavioral sensitization, which has been implicated as a model for psychiatric disorders such as mania, schizophrenia, and drug addiction. The objective of the study was to determine whether lithium chloride (LiCl), an anti-manic agent, is effective in blocking the development and/or the expression of behavioral sensitization to methylphenidate. Male Sprague-Dawley rats (n=64) weighing 170-190 g were randomly divided into seven treatment groups. A computerized animal activity monitor system continuously recorded locomotor activity for 16 days. Effects of LiCl on induction of methylphenidate sensitization were studied by giving LiCl before or during six daily methylphenidate administrations. Effects of LiCl on the expression of methylphenidate sensitization were studied by injecting LiCl after sensitization to methylphenidate was induced. It was shown that LiCl treatment modulated the acute methylphenidate effects by transiently attenuating the locomotor response to methylphenidate during the six daily methylphenidate administrations but neither single nor multiple treatments with LiCl blocked the development or the expression of behavioral sensitization.