Immunomodulatory properties of morphine and the hypothesised role of long-term opioid use in the immunopathogenesis of tuberculosis.

Epidemiological studies have shown high tuberculosis (TB) prevalence among chronic opioid users. Opioid receptors are found on multiple immune cells and immunomodulatory properties of opioids could be a contributory factor for ensuing immunosuppression and development or reactivation of TB. Toll-like receptors (TLR) mediate an immune response against microbial pathogens, including Mycobacterium tuberculosis. Mycobacterial antigens and opioids co-stimulate TLRs 2/4/9 in immune cells, with resulting receptor cross-talk via multiple cytosolic secondary messengers, leading to significant immunomodulatory downstream effects. Blockade of specific immune pathways involved in the host defence against TB by morphine may play a critical role in causing tuberculosis among chronic morphine users despite multiple confounding factors such as socioeconomic deprivation, Human immunodeficiency virus co-infection and malnutrition. In this review, we map out immune pathways involved when immune cells are co-stimulated with mycobacterial antigens and morphine to explore a potential immunopathological basis for TB amongst long-term opioid users.

Sex Difference in Risk Factors, GRACE Scores, and Management among Post-Acute Coronary Syndrome Patients in Sri Lanka.

OBJECTIVE: To assess sex-based differences in the prevalence of risk factor, their management, and differences in the prognosis among acute coronary syndrome (ACS) in Sri Lanka. METHODS: Patients diagnosed with ACS were recruited from hospitals throughout the island. The Joint European Societies guidelines were used to assess recommended targets for coronary heart disease risk factors, and the GRACE score was used to assess the post-ACS prognosis. Age-adjusted regression was performed to calculate odds ratios for men versus women in risk factor control. RESULTS: A total of 2116 patients, of whom 1242 (58.7%) were men, were included. Significant proportion of women were nonsmokers; OR = 0.11 (95% CI 0.09 to 0.13). The prevalence of hypertension (p < 0.001), diabetes (p < 0.001), and dyslipidemia (p=0.004) was higher in women. The LDL-C target was achieved in a significantly higher percentage of women (12.6%); OR = 0.33 (95% CI 0.10 to 1.05). When stratified by age, no significant differences were observed in achieving the risk factor targets or management strategies used except for fasting blood sugar (p < 0.05) where more men achieved control target in both age categories. Majority of the ACS patients had either high or intermediate risk for one-year mortality as per the GRACE score. In-hospital and 1-year mean mortality risk was significantly higher among men of less than 65 years of age (p < 0.05). CONCLUSIONS: Smoking is significantly lower among Sri Lankan women diagnosed with ACS. However, hypertension, diabetes, and dyslipidemia were more prevalent among them. There was no difference in primary and secondary preventive strategies and management in both sexes but could be further improved in both groups.

Management, characteristics and outcomes of patients with acute coronary syndrome in Sri Lanka.

BACKGROUND: Ischaemic heart disease is the leading cause of in-hospital mortality in Sri Lanka. Acute Coronary Syndrome Sri Lanka Audit Project (ACSSLAP) is the first national clinical-audit project that evaluated patient characteristics, clinical outcomes and care provided by state-sector hospitals. METHODS: ACSSLAP prospectively evaluated acute care, in-hospital care and discharge plans provided by all state-sector hospitals managing patients with ACS. Data were collected from 30 consecutive patients from each hospital during 2-4 weeks window. Local and international recommendations were used as audit standards. RESULTS: Data from 87/98 (88.7%) hospitals recruited 2177 patients, with 2116 confirmed as having ACS. Mean age was 61.4±11.8 years (range 20-95) and 58.7% (n=1242) were males. There were 813 (38.4%) patients with unstable angina, 695 (32.8%) with non-ST-elevation myocardial infarction (NSTEMI) and 608 (28.7%) with ST-elevation myocardial infarction (STEMI). Both STEMI (69.9%) and NSTEMI (61.4%) were more in males (P<0.001). Aspirin, clopidogrel and statins were given to over 90% in acute setting and on discharge. In STEMI, 407 (66.9%) were reperfused; 384 (63.2%) were given fibrinolytics and only 23 (3.8%) underwent primary percutaneous coronary intervention (PCI). Only 42.3 % had thrombolysis in <30 min and 62.5% had PCI in <90 min. On discharge, beta-blockers and ACE inhibitors/angiotensin II receptor blockers were given to only 50.7% and 69.2%, respectively and only 17.6% had coronary interventions planned. CONCLUSIONS: In patients with ACS, aspirin, clopidogrel and statin use met audit standards in acute setting and on discharge. Vast majority of patients with STEMI underwent fibrinolyisis than PCI, due to limited resources. Primary PCI, planned coronary interventions and timely thrombolysis need improvement in Sri Lanka.

Paraneoplastic limbic encephalitis with associated hypothalamitis mimicking a hyperdense hypothalamic tumor: a case report.

BACKGROUND: Paraneoplastic limbic encephalitis is an uncommon association of common malignancies such as small cell lung carcinoma, testicular teratoma, and breast carcinoma. The nonspecific nature of the clinical presentation, lack of freely available diagnostic markers, and requirement for advanced imaging techniques pose a great challenge in the diagnosis of this disease in resource-poor settings. CARE PRESENTATION: A 64-year-old previously healthy Sri Lankan man was admitted to the general medical unit with subacute memory impairment regarding recent events that had occurred during the previous 3 weeks. Initial noncontrast computed tomography of the brain revealed a hyperdensity in the hypothalamic region surrounded by hypodensities extending toward the bilateral temporal lobes; these findings were consistent with a possible hypothalamic tumor with perilesional edema. The patient later developed cranial diabetes insipidus, which was further suggestive of hypothalamic disease. Interestingly, gadolinium-enhanced magnetic resonance imaging of the brain showed no such lesions; instead, it showed prominent T2-weighted signals in the inner mesial region, characteristic of encephalitis. The possibility of tuberculosis and viral encephalitis was excluded based on cerebrospinal fluid analysis results. Limbic encephalitis with predominant hypothalamitis was suspected based on the radiological pattern. Subsequent screening for underlying malignancy revealed a mass lesion in the right hilum on chest radiographs. Histological examination of the lesion showed small cell lung cancer of the "oat cell" variety. CONCLUSION: We suggest that the initial appearance of a hyperdensity in the hypothalamus region on noncontrast computed tomography is probably due to hyperemia caused by hypothalamitis. If hypothalamitis is predominant in a patient with paraneoplastic limbic encephalitis, magnetic resonance imaging will help to differentiate it from a hypothalamic secondary deposit. Limbic encephalitis should be considered in a patient with computed tomographic evidence of a central hyperdensity surrounded by bitemporal hypodensities. This pattern of identification will be useful for early diagnosis in resource-poor settings.

Blindness in a Sri Lankan woman with bilateral breast lumps: a case report.

BACKGROUND: Granulomatosis with polyangiitis is a rare multisystemic autoimmune disorder predominantly affecting the upper and lower respiratory tracts and the kidneys, and rarely affecting other organ systems. Tuberculosis can mimic the presentation of granulomatosis with polyangiitis, and both can occur simultaneously in the same patient. Here we report what we believe to be the first case of concurrent granulomatous breast lesions and hemorrhagic retinal angiopathy in a Sri Lankan woman with refractory granulomatosis with polyangiitis complicated by probable tuberculosis. CASE PRESENTATION: A 48-year-old Sri Lankan Moorish woman presented with a 6-month history of ulcerating bilateral breast lumps, a 3-month history of non-healing painful ulcers on the palate, and sudden bilateral painless loss of vision. Retinoscopy confirmed left-sided retinal hemorrhages and bilateral panuveitis. An examination of her respiratory system showed bilateral coarse crepitations. Histologic examination of the palatal and breast lesions showed chronic granulomatous inflammation. Her levels of immune markers were elevated but her renal function was normal. Chest radiography showed bilateral mid-zone and lower-zone infiltrates with cavitation and small pleural effusions. Her serum proteinase 3 anti-neutrophil cytoplasmic antibody titer and the level of adenosine deaminase in her pleural fluid were significantly elevated. She was diagnosed with generalized granulomatosis with polyangiitis complicated with probable pulmonary tuberculosis, and was started on methylprednisolone and cyclophosphamide pulse therapy with anti-tuberculous treatment. She later developed cerebral vasculitis, indicating refractory disease, and was treated with second-line rituximab with excellent response. CONCLUSION: Proteinase 3 anti-neutrophil cytoplasmic antibody may be a valuable diagnostic marker in patients with atypical symptoms of granulomatosis with polyangiitis or in the presence of probable tuberculosis. Retinal vascular angiopathy needs to be diagnosed and treated early to prevent the development of complete blindness. Concomitant cytotoxic and anti-tuberculous treatments may be safe and effective in patients with simultaneous refractory disease with probable tuberculosis.

Seizures in an immunocompromised adolescent: a case report.

INTRODUCTION: Tuberculosis is a progressive and disabling infection predominantly seen in low-income and middle-income countries. Immunocompromised patients are at a higher risk of contracting tuberculosis than the healthy population. The presentation may also be atypical, leading to delay in diagnosis. We report the first case of tuberculous cerebral vasculitis presenting with epilepsia partialis continua. CASE PRESENTATION: A 17-year-old adolescent boy of Sri Lankan Moor heritage was taking long-term immunosuppressants for nephrotic syndrome. He presented to hospital with focal fits affecting his left arm. He later developed choreiform movements of the same arm, progressing to epilepsia partialis continua and weakness. The gradually evolving focal neurological signs and underlying immunosuppression raised the possibility of localized cerebral infection or inflammation. Analysis of his cerebrospinal fluid showed lymphocytosis with normal cellular morphology. Magnetic resonance imaging was suggestive of progressive vasculitic infarctions of the cerebral cortex and basal ganglia. There was no evidence of active autoimmune or viral disease on hematological investigations, but molecular amplification detected Mycobacterium tuberculosis in his cerebrospinal fluid. Although our patient had been established on isoniazid preventive treatment for eight months before the episode, tuberculosis was nonetheless considered to be the most likely cause of the cerebral vasculitis. He was treated with a trial of anti-tuberculosis treatment, including streptomycin and adjunctive steroids, and made an uneventful recovery. CONCLUSION: Clinicians should have a high index of suspicion for tuberculosis infection in patients with compromised immunity and other risk factors. The pathophysiological mechanisms underpinning cerebral vasculitis and epilepsia partialis continua are not completely understood. The efficacy of isoniazid prophylaxis in patients with immune suppression warrants further study. We present a regimen that successfully treated tuberculous cerebral vasculitis.

The concurrent association of inflammatory polymyositis and Crohn's ileo-colitis in a Sri Lankan man: a case report of a rare association and literature review.

BACKGROUND: Crohn's disease is a relapsing, systemic inflammatory disease affecting the gastrointestinal tract with associated extraintestinal manifestations and immune disorders. Among the few cases reported, the association of Crohn's disease with polymyositis varies in its complexity and severity. We report here the first known case of inflammatory polymyositis leading to rhabdomyolysis in a male patient diagnosed with Crohn's ileocolitis. CASE PRESENTATION: A 42-year-old previously healthy man presented with acute polymyositis leading to rhabdomyolysis. The acute nature of the illness raised the suspicion of an infective, toxic, or metabolic insult, which was excluded during further investigations. Prolonged low-grade fever and raised inflammatory markers led to the suspicion of inflammatory polymyositis, which was confirmed by electromyography and muscle histology. In the absence of an infective cause, the concurrent association of prolonged diarrhea containing blood and mucous after recovery from an acute phase of myositis proved a diagnostic challenge. Ileocolonoscopy findings of extensive aphthous ulceration with skip lesions extending to the terminal ileum, and histology showing polymorph infiltration of the lamina propria, transmural involvement, and micro abscess formation was suggestive of Crohn's disease. Sensory motor axonal peripheral neuropathy, which is another rare association of inflammatory bowel disease, was also present. CONCLUSION: An unrecognized genetic predisposition or altered gut permeability causing disruption of the gut immune barrier triggering an immune response against skeletal muscles may have contributed to this unique association. Both polymyositis and Crohn's ileocolitis responded well to corticosteroids and azathioprine, which is supportive of their immune pathogenesis. Myositis can be considered to be a rare extraintestinal manifestation of Crohn's disease and can be used in the differential diagnosis of corticosteroid or hypokalemia-induced myopathy in Crohn's disease.

Anatomical relations of the superficial sensory branches of the radial nerve: a cadaveric study with clinical implications.

BACKGROUND: Anatomically, it is difficult to give a systematic description of the superficial branch of the radial nerve (SBRN). Our aim was to describe the exact relationship of the SBRN to fixed bony points of radial styloid and Lister's tubercle, and to the cephalic vein. We also compared our data with other international studies. METHODS: The study was a descriptive anatomical study. Twenty-five forearms were dissected. Measurements were made from predefined fixed reference points. RESULTS: The mean distance to the point of emergence of the nerve from the radial styloid was 8.54 cm (SD = 1.32). The nerve branched at a mean distance of 5.57 cm (SD = 1.43) from the radial styloid. The mean distance to the point where the most medial and most lateral branches of the nerve crossing the wrist joint, measured from the Lister's tubercle were 2.51 cm (SD = 0.53) and 3.90 cm (SD = 0.64). In 17 specimens(68%) cephalic vein crossed the SBRN superficially once. Mean distance from the radial styloid to the most distal point where the vein crossed the nerve was 5.10 cm. Diffefrence between mean distance to the point of emergence and branching point, when compared with other international studies were not statistically significant. (P value > 0.05) CONCLUSIONS: We recommend avoiding transverse incisions in the snuffbox region between 2.51 cm and 3.90 cm from the Listers tubercle. We also recommend avoiding cannulation of the cephalic vein in the distal forearm.