A case report of clonidine induced syncope: a review of central actions of an old cardiovascular drug.

BACKGROUND: Clonidine is an imidazoline sympatholytic, acting on both α2-adrenergic and imidazoline receptors in the brainstem to induce antihypertensive and negative chronotropic effects in the vasculature and heart respectively. CASE PRESENTATION: A 69-year-old gentleman with hypertension presented to the emergency department after multiple syncopal episodes over the past 12 months. Electrocardiogram demonstrated sinus bradycardia with a heart rate of 42 beats per minute. It was hypothesized that the antihypertensive agent clonidine was responsible for inducing symptomatic bradycardia. Clonidine was thus gradually tapered and then discontinued over five days restoring normal sinus rhythm rates while avoiding hypertensive rebound related to sympathetic surge. His heart rate and blood pressure remained within normal limits after the clonidine taper and subsequent adjustments to his other hypertensive medications and he was discharged. CONCLUSIONS: While clonidine has fallen out of favor for its indication as an antihypertensive, it remains a viable option for the use of opioid withdrawal, chronic pain, and smoking cessation, necessitating the appropriate clinical and pharmacological competencies for a physician to prescribe. A discussion of the clinical effects of clonidine brainstem receptor activation follows.

Microbiology of diabetic foot infections: from Louis Pasteur to 'crime scene investigation'.

Were he alive today, would Louis Pasteur still champion culture methods he pioneered over 150 years ago for identifying bacterial pathogens? Or, might he suggest that new molecular techniques may prove a better way forward for quickly detecting the true microbial diversity of wounds? As modern clinicians faced with treating complex patients with diabetic foot infections (DFI), should we still request venerated and familiar culture and sensitivity methods, or is it time to ask for newer molecular tests, such as 16S rRNA gene sequencing? Or, are molecular techniques as yet too experimental, non-specific and expensive for current clinical use? While molecular techniques help us to identify more microorganisms from a DFI, can they tell us 'who done it?', that is, which are the causative pathogens and which are merely colonizers? Furthermore, can molecular techniques provide clinically relevant, rapid information on the virulence of wound isolates and their antibiotic sensitivities? We herein review current knowledge on the microbiology of DFI, from standard culture methods to the current era of rapid and comprehensive 'crime scene investigation' (CSI) techniques.

Comparative analysis of severe pediatric and adult leptospirosis in Sao Paulo, Brazil.

Although leptospirosis may be fatal in childhood, the experience of many clinicians working in disease-endemic areas is that classic Weil's disease and death are less common among pediatric patients. The aim of the study was to ascertain disease spectrum and outcome differences in severe pediatric and adult leptospirosis in a large at-risk population. Epidemiologic, clinical, and laboratory data were obtained on hospitalized cases from São Paulo during 2004-2006. A total of 42 case-patients < 18 years of age and 328 case-patients ≥ 18 years of age were tested during the study. Compared with children, adults had higher rates of jaundice (P = 0.01), elevated serum bilirubin levels (P < 0.01), oliguria (P = 0.02), and elevated creatinine levels (P = 0.01) but not for thrombocytopenia or pulmonary involvement. The overall case-fatality rate was 27% (adult) versus 5% (pediatric) (P < 0.01). Severe pediatric leptospirosis may be less likely to show all classic features of Weil's disease and may be less fatal than in adults.

Outpatient follow-up of patients hospitalized for acute leptospirosis.

OBJECTIVE: The outcome of leptospirosis after the resolution of acute disease, either spontaneously or after treatment, is not well described. The aim of this study was to assess the possible sequelae of acute leptospirosis after hospital discharge. METHODS: We report here a prospective study carried out in São Paulo, Brazil in which patients hospitalized for leptospirosis were followed in the outpatient setting. RESULTS: Forty-seven patients were serially assessed: 32 severe and 15 mild cases. Early and late complications were not common in either group, but subjective complaints were common in the first few weeks after hospital discharge (53% of severe cases, 40% of mild cases). Two patients had continuing complaints: one had profound general malaise and the other developed new onset panic disorder. The sample analyzed represented 26% of the patients hospitalized with leptospirosis in the city of São Paulo during the study period. The duration of follow-up was an average of approximately 20 days at the first visit, and approximately 40 days at the second visit. Forty-seven patients came for one follow-up visit and 22 of the same patients had two follow-up visits. CONCLUSIONS: While two of 47 patients reported continuing symptoms after hospitalization for acute leptospirosis, no definitive, objective evidence of chronic sequelae due to this infection was proven. While preliminary, these observations point to the need for a prospective, rigorous and systematic study to definitively determine and characterize late complications and chronic disease after acute leptospirosis.

Leptospirosis-associated disturbances of blood vessels, lungs and hemostasis.

The frequency of massive pulmonary hemorrhages seems to be increasing in different geographic areas; however, there is no clear explanation for this trend. Although data on the pathogenesis of such complications are scarce, recent research indicates a potential role of autoimmunity and/or multifactorial mechanisms. However, much information is already available on the disturbance of hemostasis and blood vessels in leptospirosis-related literature, even if some contradictory concepts coexist. The purpose of this review is to integrate both new and classical information from human and animal studies on severe pulmonary forms of leptospirosis and disorders of hemostasis and blood vessels. We propose that the involvement of blood vessels in leptospirosis must be understood as a sepsis-like, diffuse process of endothelial activation/damage rather than as a classical systemic vasculitis. Pulmonary hemorrhages are most likely multifactorial and there has recently been evidence against the role of autoimmunity; however, further investigation of strain variations, exposure to hydrocarbons and association with renal dysfunction is required. Thrombocytopenia is a consistent feature of leptospirosis but it is not clear whether it is attributable to sepsis-related mechanisms. In addition, further investigation is required to define whether platelet function is activated or inhibited during severe leptospirosis.

Acute kidney injury in human leptospirosis: an immunohistochemical study with pathophysiological correlation.

Tubulointerstitial nephritis is a common clinicopathological finding in leptospirosis. Clinically, nonoliguric acute kidney injury (AKI), hypokalemia, sodium, and magnesium wasting frequently occur in leptospirosis. The exact mechanisms of renal involvement remain largely unclear. Immunohistochemistry to detect expression of the endogenous sodium/hydrogen exchanger isoform 3 (NHE 3), aquaporin 1 and 2, alpha-Na(+)K(+)ATPase, and sodium-potassium-chloride cotransporter in its NKCC2 isoform was performed on kidneys removed during autopsy of human leptospirosis cases and kidneys removed during autopsy of human non-leptospirosis cases with and without evidence of acute tubular necrosis (ATN). A decrease in NHE 3, aquaporin 1, and alpha-Na(+)K(+)ATPase expression occurred in proximal convoluted tubule cells. Expression of aquaporin 1 was preserved along the descending thin limb of the loop of Henle in the outer medulla. alpha-Na(+)K(+)ATpase expression was essentially preserved in the distal tubules, i.e., the thick ascending limb of the loop of Henle, macula densa, and distal convoluted tubule. Aquaporin 2 expression in the collecting tubules was enhanced compared to those of non-leptospirotic kidneys. NKCC2 cotransport isoform was expressed in the thick ascending limb of the loop of Henle and was essentially preserved in leptospirotic kidneys. Primary injury of the proximal convoluted tubules is regarded as the hallmark of the kidney in leptospirosis. Sodium and water transport are particularly affected with increased distal potassium excretion, hypokalemia, and polyuria. Enhanced expression of aquaporin 2 in medullary collecting tubules is probably an attempt to retain water during the nonoliguric phase of renal failure.

The contribution of bats to leptospirosis transmission in Sao Paulo City, Brazil.

The biodiversity of potential leptospiral reservoir hosts is lower in urban than in rural environments. Previous data indicate the potential for bats to act as carriers of Leptospira in regions such as the Amazon of South America and in Australia. Yet, little is known about the contribution of bats to leptospirosis in urban environments in South America. This study aimed to test the hypothesis that bats infected with Leptospira are sources of leptospirosis transmission to humans in São Paulo City, Brazil. Six of 343 bats caught in different districts within the city of Sao Paulo (182 insectivorous, 161 frugivorous or nectarivorous) were polymerase chain reaction (PCR) positive for pathogenic Leptospira; no seropositive bats were found. That few renal carriers of Leptospira were found in the city of Sao Paulo suggests that bats are not important in the transmission of leptospirosis to humans in this, and possibly other urban settings.

The contribution of bats to leptospirosis transmission in Sao Paulo City, Brazil

A biodiversidade de potenciais hospedeiros reservatórios leptospirose é menor em áreas urbanas do que em ambientes rurais. Os dados anteriores indicam o potencial de morcegos para agir como portadores de Leptospira em regiões como a Amazônia da América do Sul e na Austrália. No entanto, pouco se sabe sobre a contribuição dos morcegos para leptospirose em ambientes urbanos na América do Sul. Este estudo teve como objetivo testar a hipótese de que os morcegos infectados com Leptospira são fontes de transmissão da leptospirose para seres humanos na cidade de São Paulo, Brasil. Seis de 343 morcegos capturados em diferentes bairros dentro da cidade de São Paulo (182 insetívoros, frugívoros ou nectarívoros 161) foram de reação em cadeia da polimerase (PCR) positiva para Leptospira patogênica, sem morcegos soropositivos foram encontrados. Que poucos portadores de Leptospira renal foram encontrados na cidade de São Paulo sugere que os morcegos não são importantes na transmissão da leptospirose para seres humanos no presente, e possivelmente outras áreas urbanas.

Predictors of lethality in severe leptospirosis in urban Brazil.

To ascertain prognostic factors associated with fatal outcomes in severe leptospirosis, a retrospective case-control study was done using population-based surveillance data. Centralized death certificate reporting of leptospirosis mortality was combined with details of patients' hospitalizations, which were obtained from hospitals representing all sectors of São Paulo city. Among identified leptospirosis cases, 89 lethal cases and 281 survivor cases were analyzed. Predictors of death included age>40 years, development of oliguria, platelet count<70,000/microL, creatinine>3 mg/dL, and pulmonary involvement. The latter was the strongest risk factor with an estimated odds ratio of 6.0 (95% confidence interval: 3.0-12.0). Serologic findings with highest titer against Leptospira interrogans serovar Copenhageni did not show significant differences between survivors and non-survivors. Lung involvement was an important predictor of death in leptospirosis in São Paulo, of relevance in leptospirosis-endemic regions where this complication is common.

Case report: severe, symptomatic hypomagnesemia in acute leptospirosis.

We report a case of severe hypomagnesemia in non-oliguric acute renal failure caused by leptospirosis that required large doses of magnesium replacement during the acute phase of disease. Biochemical studies confirmed kidney-related magnesium wasting and the mechanisms of this defect are discussed. Magnesium imbalance with its attendant clinical complications occurs in leptospirosis and should be monitored and treated aggressively in cases of leptospirosis-induced non-oliguric acute kidney injury.

Renal involvement in leptospirosis--new insights into pathophysiology and treatment.

Acute renal failure (ARF) is one of the most common complications of leptospirosis although the causal mechanisms are still unclear. Diverse mechanisms are implicated in leptospiral nephropathy and new data supports the role of peculiar ion transport defects. Besides antibiotic therapy, ARF management in leptospirosis requires dialytic therapy which is most efficient when started early. Dialysis is the standard supportive therapy even though recent evidence suggests clinical benefit from alternative treatments such as plasmapheresis and hemofiltration. Renal recovery is achieved soon after clinical improvement. The comprehension of the primary mechanisms of renal dysfunction will be helpful in the development of additional therapeutic tools for improving supportive therapy for leptospiral nephropathy. This review discusses new insights into mechanisms implicated in leptospiral ARF and recent advances in treatment.

Renal involvement in leptospirosis: new insights into pathophysiology and treatment: [review]

Acute renal failure (ARF) is one of the most common complications of leptospirosis although the causal mechanisms are still unclear. Diverse mechanisms are implicated in leptospiral nephropathy and new data supports the role of peculiar ion transport defects. Besides antibiotic therapy, ARF management in leptospirosis requires dialytic therapy which is most efficient when started early. Dialysis is the standard supportive therapy even though recent evidence suggests clinical benefit from alternative treatments such as plasmapheresis and hemofiltration. Renal recovery is achieved soon after clinical improvement. The comprehension of the primary mechanisms of renal dysfunction will be helpful in the development of additional therapeutic tools for improving supportive therapy for leptospiral nephropathy. This review discusses new insights into mechanisms implicated in leptospiral ARF and recent advances in treatment.

Acute pancreatitis in fatal anicteric leptospirosis.

We report a fatal case of anicteric leptospirosis with pancreatitis (acute hyperglycemia and insulin requirement, elevated lipase and amylase levels), pulmonary infiltrates, and refractory shock. In disease-endemic areas, leptospirosis with pancreatitis should be considered in patients with fever and abdominal pain, and serum pancreatic enzymes, blood glucose, and serum electrolytes should be closely monitored.

Using death certificate reports to find severe leptospirosis cases, Brazil.

Severe leptospirosis with pulmonary hemorrhage is emerging globally. Measures to control leptospirosis through sanitation depend on accurate case finding and reporting. Rapid death certificate reporting, plus necropsy of persons who died of leptospirosis, facilitates public health intervention and could provide an important tool in assessing the global burden of leptospirosis.

Reversal of renal tubule transporter downregulation during severe leptospirosis with antimicrobial therapy.

Tubular dysfunction is a hallmark of severe leptospirosis. Antimicrobial therapy is thought to interfere on renal involvement. We evaluated the expression of a proximal tubule type-3 Na+/H+ exchanger (NHE3) and a thick ascending limb Na+-K+-2Cl(-) cotransporter (NKCC2) in controls and treated hamsters. Animals infected by a serovar Copenhageni isolate, were treated or not with ampicillin (AMP) and/or N-acetylcysteine (NAC). Leptospiral antigen(s) and expression of renal transporters were evaluated by immunohistochemistry, and serum thiobarbituric acid (TBARS) was quantified. Infected hamsters had high amounts of detectable leptospiral antigen(s) in target tissues while renal expression of NHE3 and NKCC2 decreased. Ampicillin treatment was associated with minimal or no detection of leptospiral antigens, normal expression of NHE3 and NKCC2 transporters, and reduced levels of TBARS. NAC effect was restricted to lowering TBARS. Early and late AMP treatment rescued tubular defects in severe leptospirosis disease, and there was no evidence of benefit from antioxidant therapy.

Peripheral nerve palsy in a case of leptospirosis.

We describe an unusual case of leptospirosis in a 54-year-old man presenting peripheral nerve palsy. The diagnosis of leptospirosis was confirmed by ELISA IgM and the microscopic agglutination test. Electrophysiological studies showed that no response could be obtained from the right fibular nerve. At 7 months after the initiation of treatment, additional electrophysiological studies and a neurological examination showed, respectively, a chronic axonal lesion of right fibular nerve with signs of re-innervation and a nearly complete clinical recovery. We feel that this case may serve to remind clinicians that peripheral nerve palsy is a potential clinical feature of leptospirosis.

Meningoencephalitis and new onset of seizures in a patient with normal brain CT and multiple lesions on MRI.

Toxoplasmic encephalitis is the most common cerebral mass lesion in patients with AIDS. The definitive diagnosis requires direct demonstration of the tachyzoite form of Toxoplasma gondii in cerebral tissue. The presumptive diagnosis is based on serology, clinical and radiological features, and on response to anti-Toxoplasma therapy. Typically, patients have a subacute presentation of focal neurological signs, with multiple lesions in computed tomography (CT) or magnetic resonance imaging (MRI). However, the neurological and CT scan spectrum is broad. We report a case of toxoplasmic encephalitis in a heterosexual man without prior history of HIV infection. He was admitted with four days of headache, confusion, and new onset of seizures. His brain CT disclosed no alterations and MRI revealed multiple lesions. Empirical specific anti-Toxoplasma therapy was initiated and the patient experienced excellent clinical and radiological improvement. His HIV tests were positive and the CD4+ cell count was 74 cells/ml (8.5 %). On follow up, three months later, the general state of the patient was good, without neurological sequelae and with a normal MRI. We concluded that toxoplasmic encephalitis should be considered in the differential diagnosis of meningoencephalitis in sexually active individuals, including cases without prior history or suspicion of HIV infection, and no abnormalities on CT scan.

Meningoencephalitis and new onset of seizures in a patient with normal brain CT and multiple lesions on MRI

Toxoplasmic encephalitis is the most common cerebral mass lesion in patients with AIDS. The definitive diagnosis requires direct demonstration of the tachyzoite form of Toxoplasma gondii in cerebral tissue. The presumptive diagnosis is based on serology, clinical and radiological features, and on response to anti-Toxoplasma therapy. Typically, patients have a subacute presentation of focal neurological signs, with multiple lesions in computed tomography (CT) or magnetic resonance imaging (MRI). However, the neurological and CT scan spectrum is broad. We report a case of toxoplasmic encephalitis in a heterosexual man without prior history of HIV infection. He was admitted with four days of headache, confusion, and new onset of seizures. His brain CT disclosed no alterations and MRI revealed multiple lesions. Empirical specific anti-Toxoplasma therapy was initiated and the patient experienced excellent clinical and radiological improvement. His HIV tests were positive and the CD4+ cell count was 74 cells/ml (8.5 percent). On follow up, three months later, the general state of the patient was good, without neurological sequelae and with a normal MRI. We concluded that toxoplasmic encephalitis should be considered in the differential diagnosis of meningoencephalitis in sexually active individuals, including cases without prior history or suspicion of HIV infection, and no abnormalities on CT scan.