Supraphysiological 25-hydroxy vitamin D3 level at admission is associated with illness severity and mortality in critically ill patients.

We studied the association between admission serum 25-hydroxy vitamin D3 level and in-hospital mortality in a prospective cohort of critically ill patients admitted to the medical intensive care unit of a tertiary care referral center. Of the 180 patients enrolled, 129 were included. Vitamin D3 deficiency was observed in 37% (n = 48) and supra-physiological levels (≥250 nmol/L) in 15.5% (n = 20). Patients with supraphysiological vitamin D3 levels were grouped as outliers. There was no difference in mortality (p = 0.41) between vitamin D3 deficient (21/48) and non-deficient (36/81) patients in analysis with and without outliers. Patients with vitamin D3 ≥250 nmol/L had a significantly higher (p = 0.02) Simplified Acute Physiology Score (SAPS) II and mortality (p = 0.003) [mean (SD) 60.1 ± 17.1 and 75% (15/20), respectively] when compared with the rest [45.6 ± 18 and 38.5% (42/109), respectively]. The sensitivity, specificity and SAPS II independent odds ratio to predict mortality in patients with supraphysiological vitamin D3 levels were 26.3, 93.1 and 3.7% (95% confidence interval 1.2-11.4; p = 0.03), respectively. In conclusion, vitamin D3 deficiency in our cohort was not associated with mortality. A patient subset with supra-physiological vitamin D levels had higher illness severity scores and mortality. Extrinsic factors interfering with test results were ruled out. A biological hypothesis to explain this observation is proposed. Further clarification of mechanisms leading to this observation is warranted.

Central nervous system involvement in scrub typhus.

Scrub typhus is an emerging infectious disease in India. Among its protean clinical manifestations, central nervous system involvement is common. In this prospective observational study, altered sensorium, headache, seizures and aseptic meningitis were found to be common central nervous system manifestations. Prompt treatment with doxycycline reduces morbidity and mortality.

Clinico-epidemiological profile of seven adults with spotted fever from a tertiary care hospital in South India.

Spotted fever (SF), a tick-borne rickettsial infection, is being increasingly reported from mainly northern Indian states. A lack of awareness and confirmatory laboratory tests underestimate the incidence of this infection which, in India, is predominantly seen during the rainy season. Many patients diagnosed with viral exanthematous illnesses may be suffering from SF, which is treatable if detected early. There is very little data on SF in adults in southern India. We present seven patients with SF treated between January 2007 and January 2008 in a tertiary care hospital in South India. All presented during the rainy season, with rash (100%) and generalized oedema (71%) being the most common features. There was one death due to type I respiratory failure. Renal failure, shock, aseptic meningitis and hepatitis were other significant abnormalities detected in these patients. Clinicians need to be aware of SF and suspect it in appropriate patients.

Cleistanthus collinus poisoning.

Cleistanthus collinus, a toxic shrub, is used for deliberate self-harm in rural South India. MEDLINE (PUBMED) and Google were searched for published papers using the search/ MeSH terms "Cleistanthus collinus," "Euphorbiaceae," "Diphyllin," "Cleistanthin A," Cleistanthin B" and "Oduvanthalai." Non-indexed journals and abstracts were searched by tracing citations in published papers. The toxic principles in the leaf include arylnaphthalene lignan lactones - Diphyllin and its glycoside derivatives Cleistanthin A and B. Toxin effect in animal models demonstrate neuromuscular blockade with muscle weakness, distal renal tubular acidosis (dRTA) and type 2 respiratory failure with conflicting evidence of cardiac involvement. Studies suggest a likely inhibition of thiol/thiol enzymes by the lignan-lactones, depletion of glutathione and ATPases in tissues. V-type H+ ATPase inhibition in the renal tubule has been demonstrated. Mortality occurs in up to 40% of C. collinus poisonings. Human toxicity results in renal tubular dysfunction, commonly dRTA, with resultant hypokalemia and normal anion gap metabolic acidosis. Aggressive management of these metabolic derangements is crucial. Acute respiratory distress syndrome (ARDS) is seen in severe cases. Cardiac rhythm abnormalities have been demonstrated in a number of clinical studies, though the role of temporary cardiac pacemakers in reducing mortality is uncertain. Consumption of decoctions of C. collinus leaves, hypokalemia, renal failure, severe metabolic acidosis, ARDS and cardiac arrhythmias occur in severe poisonings and predict mortality. Further study is essential to delineate mechanisms of organ injury and interventions, including antidotes, which will reduce mortality.

Cartap hydrochloride poisoning: A clinical experience.

Cartap hydrochloride, a nereistoxin analog, is a commonly used low toxicity insecticide. We describe a patient who presented to the emergency department with alleged history of ingestion of Cartap hydrochloride as an act of deliberate self-harm. The patient was managed conservatively. To our knowledge this is the first case report of Cartap hydrochloride suicidal poisoning. Cartap toxicity has been considered to be minimal, but a number of animal models have shown significant neuromuscular toxicity resulting in respiratory failure. It is hypothesized that the primary effect of Cartap hydrochloride is through inhibition of the [(3)H]-ryanodine binding to the Ca(2+) release channel in the sarcoplasmic reticulum in a dose-dependent manner and promotion of extracellular Ca(2+) influx and induction of internal Ca(2+) release. This results in tonic diaphragmatic contraction rather than paralysis. This is the basis of the clinical presentation of acute Cartap poisoning as well as the treatment with chelators namely British Anti Lewisite and sodium dimercaptopropane sulfonate.

Acute myocardial injury and rhabdomyolysis caused by multiple bee stings.

Massive envenomation by honey bees is capable of causing multiorgan dysfunction as a result of direct toxic effect of massive envenomation and secondary to systemic anaphylactic reactions. Acute myocardial ischemia due to bee envenomation is a rare event. We report the case of a 65 year old lady who presented with acute myocardial ischemia, severe rhabdomyolysis and angioedema following massive bee envenomation.

Acute kidney injury in tropical acute febrile illness in a tertiary care centre--RIFLE criteria validation.

BACKGROUND: Acute febrile illnesses are a common cause of tropical acute kidney injury (AKI). The incidence and severity of AKI in tropical febrile illnesses and validity of RIFLE classification are unclear. METHODS: Consecutive adult inpatients of a tertiary hospital in southern India with tropical acute febrile illness between January 2007 and January 2008 were prospectively studied for the incidence and severity of AKI based on RIFLE classification and its association with mortality and dialysis requirement. RESULTS: The 367 patients (mean age 39.7±16.9 years; 60% males) with tropical acute febrile illness due to scrub typhus (51.2%), falciparum malaria (10.4%), enteric fever (8.7%), dengue (7.6%), mixed malaria (6.5%), leptospirosis (3.3%), undifferentiated acute febrile illness (8.4%) and others (3.8%) (spotted fever, vivax malaria and Hantaan virus infection) had an overall mortality rate of 12.3%. The incidence of AKI was 41.1%; of which, 17.4%, 9.3% and 14.4% were in the Risk, Injury and Failure classes, respectively. Of the patients, 7.9% required dialysis. Among the Risk, Injury and Failure groups, there was an incremental risk of mortality (OR 6.9, 20.2 and 25.6; P<0.001) and dialysis requirement (OR 3.4, 28.8 and 178.8; P<0.001). CONCLUSIONS: The incidence of AKI in the common tropical acute febrile illnesses in our study such as scrub typhus, falciparum malaria, enteric fever, dengue and leptospirosis is 41.1%. RIFLE classification is valid and applicable in AKI related to tropical acute febrile illnesses, with an incremental risk of mortality and dialysis requirement.

Clinical profile and outcome of patients hospitalized with dimethyl and diethyl organophosphate poisoning.

UNLABELLED: The two major classes of organophosphate compounds, dimethyl and diethyl organophosphates, have different toxicokinetic properties. This study evaluated the clinical profile and outcomes in patients admitted with poisoning with these two classes of organophosphates. METHODS: This retrospective study spanned 6 years (2002-2007). Patients were treated with atropine and supportive care including ventilation, as required, and followed up until death or hospital discharge. Oximes were not administered. Of the 422 charts retrieved, 396 fulfilled inclusion criteria. Data on the clinical profile, ventilation, length of hospital stay, incidence of intermediate syndrome and mortality were extracted. RESULTS: The mean (± standard deviation) age was 31.4 ± 12.7 years with a male preponderance (2.6:1). The median (interquartile range (IQR)) admission pseudocholinesterase level of 317 (222-635) U/L indicated significant inhibition of cholinesterase activity. The median lag-time to presentation to our hospital was 5 (IQR 3-8.5) hours. Oximes were administered at a primary center in 33 patients (8.3%). Dimethyl organophosphate was ingested by 141 patients, diethyl organophosphate by 108, S-alkyl organophosphate by 2, and an un-identified organophosphate by 145 patients. Ventilation was required in 260 patients (65.7%); the median duration of ventilation being 7.5 (IQR 3-12) days. Overall mortality was 13.1%. There was a significant difference between dimethyl and diethyl organophosphate compounds in ventilatory requirement (76% vs. 56%, adjusted odds ratio (OR) 2.37, 95% CI 1.01-5.57, p=0.047), duration of ventilation (11 (4-15) vs. 5 (2-9) days, adjusted OR 1.12, 95%CI 1.04-1.21, p=0.002) and incidence of intermediate syndrome (72/125 (58%) vs. 24/92 (26%), adjusted OR 2.84, 95%CI 1.38-5.86, p=0.004). Mortality was similar in the two groups (20/141 (14%) vs. 7/108 (6%), dimethyl vs. diethyl organophosphate, adjusted OR 1.29, 95%CI 0.43-3.94, p=0.65). CONCLUSIONS: Patients admitted with dimethyl organophosphate poisoning have a worse outcome compared with diethyl organophosphate poisoning for clinically relevant patient outcomes.

Mixed connective tissue disorder and Castleman's disease.

We present a 16-year-old girl who presented with polyarthritis in association with Raynaud's phenomenon, malar rash, oral ulcers, photosensitivity and alopecia of 6 months duration. On evaluation, it emerged that she had a mixed connective tissue disorder with a mesangio-proliferative glomerulonephritis. Her Chest radiograph revealed a well defined left mid and lower zone opacity with evidence of a hilar mass on CT Thorax. Histopathological examination following CT guided biopsy of the mass revealed a hyaline vascular type of Castleman's disease. Mixed Connective Tissue Disorder with Castleman's Disease is a rare association; the patient presenting with varied and interesting manifestations. It is important to understand this association in view of management. The exact etio-pathogenesis of the autoimmune manifestations in patients with Castleman's disease is not clear. Treatment with immunosuppression can suppress both immune manifestations and result in tumour regression as well.

Acute undifferentiated febrile illness in adult hospitalized patients: the disease spectrum and diagnostic predictors - an experience from a tertiary care hospital in South India.

Local prevalences of individual diseases influence the prioritization of the differential diagnoses of a clinical syndrome of acute undifferentiated febrile illness (AFI). This study was conducted in order to delineate the aetiology of AFI that present to a tertiary hospital in southern India and to describe disease-specific clinical profiles. An 1-year prospective, observational study was conducted in adults (age >16 years) who presented with an undifferentiated febrile illness of duration 5-21 days, requiring hospitalization. Blood cultures, malarial parasites and febrile serology (acute and convalescent), in addition to clinical evaluations and basic investigations were performed. Comparisons were made between each disease and the other AFIs. A total of 398 AFI patients were diagnosed with: scrub typhus (47.5%); malaria (17.1%); enteric fever (8.0%); dengue (7.0%); leptospirosis (3.0%); spotted fever rickettsiosis (1.8%); Hantavirus (0.3%); alternate diagnosis (7.3%); and unclear diagnoses (8.0%). Leucocytosis, acute respiratory distress syndrome, aseptic meningitis, mild serum transaminase elevation and hypoalbuminaemia were independently associated with scrub typhus. Normal leukocyte counts, moderate to severe thrombocytopenia, renal failure, splenomegaly and hyperbilirubinaemia with mildly elevated serum transaminases were associated with malaria. Rash, overt bleeding manifestations, normal to low leukocyte counts, moderate to severe thrombocytopenia and significantly elevated hepatic transaminases were associated with dengue. Enteric fever was associated with loose stools, normal to low leukocyte counts and normal platelet counts. It is imperative to maintain a sound epidemiological database of AFIs so that evidence-based diagnostic criteria and treatment guidelines can be developed.

The clinical profile and association of delirium in geriatric patients with hip fractures in a tertiary care hospital in India.

INTRODUCTION: Delirium is common in hospitalized geriatric patients with hip fractures. A number of peri-operative predisposing and postoperative precipitating factors have been identified in Western literature but data regarding this problem within the Indian context is scarce. METHOD: The objectives of the study were to ascertain the incidence of delirium in geriatric patients admitted for the treatment of hip fractures in the Department of Orthopaedics of a tertiary care referral centre in South India, to delineate their clinical profile and identify probable contributing factors for development of delirium in this group of patients. The study was a prospective, cohort study design that was conducted on patients above the age of 60 years, admitted to the orthopaedic ward with hip fracture and who underwent hip surgery. A total of 81 patients were recruited from May 1st 2004 to April 30th 2005 (total duration of one year). RESULTS: Of the 81 patients 17 (21%) of the patients developed post-operative delirium. On multivariate analysis the presence of underlying dementia (OR 16.97), duration of surgery > 2.5 hrs (OR 8.23) and preoperative packed cell volume < 25 (OR 8.07) were found to be independent predisposing risk factors that were associated with the development of postoperative delirium. Postoperative infections, metabolic abnormalities and vascular events were found to be important detected medical causes for precipitating post-operative delirium. Patients who had delirium had longer hospital stays and poor ambulation at discharge. CONCLUSIONS: Delirium in geriatric patients undergoing hip fracture surgery results in poor postoperative outcomes and increased cost. The etiology of delirium is multi-factorial. A number of potentially modifiable factors have been identified as risk factors for delirium. Appropriate intervention strategies involving physicians and geriatricians need to be implemented within the Indian context to reduce the incidence of delirium.

A clinical study of renal tubular dysfunction in Cleistanthus collinus (Oduvanthalai) poisoning.

INTRODUCTION: Self-poisoning through the ingestion of Oduvanthalai is common in South India. Mortality may occur because of arrhythmias, renal failure, shock, and respiratory distress. The mechanisms of toxicity are unclear. This prospective, clinical study was designed to assess renal tubular dysfunction because of Oduvanthalai poisoning. METHODS: Thirty-two consecutive patients admitted with Oduvanthalai poisoning at a tertiary care hospital in South India, from June 2007 to August 2009 (26 months), were evaluated through history, physical examination, and laboratory studies. Following an interim analysis, additional studies of renal tubular function were performed on a subcohort of eight patients. These included the following: (1) urinary pH, daily serum, and urine anion gap; (2) 24-h urine protein and potassium; and (3) assessment of urine hexosaminidase and amino acid levels. RESULTS: Metabolic acidosis (100%), which persisted at discharge (65.6%), hypokalemia (62.5%), and renal failure (15.6%), was apparent in the total cohort. Tests of renal tubular function on the subcohort revealed a normal anion gap, hyperchloremic, metabolic acidosis of renal etiology, defective urinary acidification, and hypokalemia with kaliuresis, indicative of distal renal tubular acidosis in six patients. Urinary hexosaminidase and amino acid levels, markers of proximal tubular dysfunction, were elevated in seven and two patients, respectively. CONCLUSIONS: Distal renal tubular acidosis is an important feature of Oduvanthalai poisoning. Proximal tubular injury and, in more severe forms, global tubular dysfunction with diminished glomerular filtration rate may occur.

Scrub typhus: an unrecognized threat in South India - clinical profile and predictors of mortality.

Scrub typhus is an important cause of acute undifferentiated febrile illnesses in the Indian subcontinent. Delay in diagnosis and in the initiation of appropriate treatment can result in severe complications such as acute respiratory distress syndrome (ARDS), septic shock and multisystem organ failure culminating in death. We conducted a prospective, observational study to delineate the clinical profile and predictors of mortality in scrub typhus in adults admitted to the medical wards of a tertiary care, referral hospital in South India over a one-year period. The case fatality rate in this study was 12.2%. Metabolic acidosis (odds ratio [OR] 6.1), ARDS (OR 3.6), altered sensorium (OR 3.6) and shock (OR 3.1) were independent predictors of mortality. It appears that scrub typhus has four possible overlapping clinical presentations: mild disease; respiratory predominant disease; central nervous system predominant disease (meningoencephalitis); or sepsis syndrome. Given the telltale presence of an eschar (evident in 45.5%), the characteristic clinical profile and the dramatic therapeutic response to a cheap, yet effective, drug such as doxycycline, medical practitioners in the region should have ample opportunity to reach an early diagnosis and initiate treatment which could, potentially, reduce the mortality and morbidity associated with scrub typhus.

Hair dye poisoning--an emerging problem in the tropics: an experience from a tertiary care hospital in South India.

Super-Vasmol, a cheap, freely-available hair dye is emerging as a major cause of suicidal poisoning in India. It contains potential toxins including paraphenylene diamine, resorcinol, sodium ethylenediaminetetraacetic acid and propylene glycol which can result in multiorgan dysfunction. A retrospective study was conducted over 3.5 years (January 2006-July 2009) of 13 consecutive patients with Super-Vasmol poisoning admitted to a tertiary care, referral hospital in South India. A chart review including records of clinical presentations, laboratory findings and treatment details was carried out. Eleven of the patients were women and the mean age was 27.2 years. The predominant clinical features were cervico-facial oedema and pain, cola-coloured urine and oliguria. Laboratory investigations revealed elevated hepatic transaminases (100%), leucocytosis (92.3%), elevated creatinine phosphokinase (92.3%), metabolic acidosis (84.6%), hypocalcaemia (61.5%), hyperphosphataemia (46.2%) and renal failure (38.5%). Eight of the patients were discharged with complete recovery. Trends towards a poor outcome were evident among the following patients: late presentation at our centre; when no gastric lavage was done at the primary-care centre; those requiring tracheostomy/intubation at the primary centre; presentation with a low Glasgow Coma Score or seizures; established renal failure; and those who subsequently require dialysis, mechanical ventilation or intensive care. Hair dye poisoning classically presents with cervico-facial oedema, severe rhabdomyolysis and renal failure. Early therapy with tracheostomy and aggressive forced diuresis are essential in order to prevent the high mortality associated with this toxin. It is imperative to raise public awareness of the potential toxicity of the dye as well as to educate physicians about the need for aggressive and early treatment.

The clinical profile and predictors of mortality in patients with melioidosis in South India.

Melioidosis is an underdiagnosed and underreported disease in India with protean clinical manifestations. Mortality in this study population was 17%. The predominant risk factor for melioidosis was diabetes mellitus. Multifocal disease was present in 66% and pulmonary involvement in 61% of patients. In a country like India where the conditions are conducive for endemic melioidosis and due to the clinical similarity of melioidosis to diseases like tuberculosis, it is essential for clinicians to have a high degree of suspicion and pursue suitable diagnostic strategies for melioidosis in the appropriate clinical setting.

Acute febrile illness caused by hantavirus: serological and molecular evidence from India.

Study of hantavirus infections in India is in its early stages. As early symptoms of hantavirus disease can be non-specific and the diagnosis confirmed only by laboratory testing, use of appropriate diagnostic tools is important. To improve the diagnosis of hantavirus infections in India, commercial ELISA systems followed by indirect immunofluorescence assays were used to detect anti-hantavirus IgM and IgG in samples from patients with acute febrile illness. Of 347 patients tested, 5.2% showed serological evidence of hantavirus infection. Sequences obtained from patients showing molecular evidence of hantavirus infection were related to Hantaan virus. In the absence of mu-capture ELISA, we recommend the use of combination testing systems in areas non-endemic for hantavirus infections. In India there is an increased risk of rodent-borne infections and the differential diagnosis of undifferentiated febrile illness should include hantavirus infection.

A bizarre appearance of a common disease, tuberculous dactylitis, involving multiple digits in an adult.

Tuberculosis is a common illness in developing nations. Tuberculous dactylitis is an unusual manifestation of tuberculous osteomyelitis seen predominantly in children. A woman presented with painless, fusiform swelling of multiple digits of the hand. Synovial biopsy revealed granulomatous inflammation and the pus smear was positive for acid-fast bacilli. She underwent debridement of the involved digits and was initiated on antituberculous therapy. This is an unusual presentation of tuberculous dactylitis in an immunocompetent host which involved multiple digits in a single hand.

Sternal tuberculous osteomyelitis presenting as a pulsatile swelling.

Primary sternal tuberculous osteomyelitis is a rare form of tuberculous osteomyelitis. We report a case of a young adult with primary tuberculous osteomyelitis of the sternum who presented with a pulsatile anterior chest wall swelling. Computed tomography of the thorax revealed a hypodense lytic lesion in the body of the sternum that had eroded into the anterior mediastinum where it lay in close contact with the right ventricle, resulting in the clinically evident transmitted pulsations. Among the protean manifestations of tuberculosis this case illustrates a unique presentation as a pulsatile chest wall mass.