Leptospirosis from the clinical viewpoint

Epidemiological, clinical and microbiological data of 27 patients suffering from leptospirosis are presented. Because of the sporadic occurrence of the disease, diagnosis on admission was correct in only 18% of the patients. As proved by the agglutination test, most of the infections were due to serotype icterohaemorrhagiae, but in only one case could the leptospires be detected directly in the blood culture. In most of the cases the course of the disease was moderately severe with one fatality. Symptomatology and treatment are discussed.     

Biochemical characterization of mutant phenylalanine hydroxylase enzymes and correlation with clinical presentation in hyperphenylalaninaemic patients

Summary  The biochemical properties of mutant phenylalanine hydroxylase (PAH) enzymes and clinical characteristics of hyperphenylalaninaemic patients who bear these mutant enzymes were investigated. Biochemical characterization of mutant PAH enzymes p.D143G, p.R155H, p.L348V, p.R408W and p.P416Q included determination of specific activity, substrate activation, V _max, K _m for (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (BH₄), K _d for BH₄, and protein stabilization by BH₄. Clinical data from 22 patients either homozygous, functionally hemizygous, or compound heterozygous for the mutant enzymes of interest were correlated with biochemical parameters of the mutant enzymes. The p.L348V and p.P416Q enzymes retain significant catalytic activity yet were observed in classic and moderate PKU patients. Biochemical studies demonstrated that BH₄ rectified the stability defects in p.L348V and p.P416Q; additionally, patients with these variants responded to BH₄ therapy. The p.R155H mutant displayed low PAH activity and decreased apparent affinity for l-Phe yet was observed in mild hyperphenylalaninaemia. The p.R155H mutant does not display kinetic instability, as it is stabilized by BH₄ similarly to wild-type PAH; thus the residual activity is available under physiological conditions. The p.R408W enzyme is dysfunctional in nearly all biochemical parameters, as evidenced by disease severity in homozygous and hemizygous patients. Biochemical assessment of mutant PAH proteins, especially parameters involving interaction with BH₄ that impact protein folding, appear useful in clinical correlation. As additional patients and mutant proteins are assessed, the utility of this approach will become apparent. Competing interests: None declared References to electronic databases: Online Mendelian Inheritance in Man: . Enzyme Commission: . PAH Mutation database: .     

Leptospirosis in northern India: a clinical and serological study

A total of 400 serum samples collected from patients, clinically suspected of leptospirosis, were evaluated for antibodies by LEPTO dipstick and microscopic agglutination test (MAT). Twenty of these patients (5%) had serological evidence of leptospirosis. Leptospira interrogans serovars Autumnalis and Icterohaemorrhagiae, Canicola and Javanica were serogroups recorded serologically. Fever and jaundice were the most common clinical presentations. Male preponderance was seen in the leptospirosis cases. Outdoor activities, agricultural activities, contact with animals were significantly associated with seropositivity for Leptospira. This study highlights that leptospirosis is a significant health problem in northern India, though grossly under reported due to the absence of routine laboratory diagnostic facilities for this disease.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

Cowden syndrome: clinical case presentation with oral lesions

Cowden syndrome is an autosomal-dominant inheritance disease, characterized by the presence of skin and oral mucosa multiple hamartomas and nodules, together with thyroid and breast anomalies and polyposis of the gastrointestinal tract, which tend to undergo malignant transformation, especially in breast and thyroids. Therefore, the oral lesions early diagnosis facilitates the identification of asintomatic lesions, in other parts of the body. This is the case in the report we are to present, in which the patient, probably with the Cowden Syndrome, because of the presence of multiple hamartomas in the oral mucose diagnosed a breast carcinoma, and other alterations such as thyroid calcifications and polyposis of the gastrointestinal tract.     

Ischemic hepatitis: clinical presentation and pathogenesis

BACKGROUND: The pathophysiology of ischemic hepatitis, otherwise known as "shock liver," is poorly understood, although it is believed to be the result of a reduction in systemic blood flow as typically occurs in shock. The aim of this study was to investigate the importance of this phenomenon as well as other clinical features in patients with ischemic hepatitis.METHODS: We identified a cohort of 31 patients (case group) who met the most commonly accepted definition of ischemic hepatitis (an acute reversible elevation in either the serum alanine or aspartate aminotransferase level of at least 20 times the upper limit of normal, excluding known causes of acute hepatitis or hepatocellular injury, in an appropriate clinical setting). We also evaluated the clinical features and serum aminotransferase levels in a cohort (the control group) of 31 previously healthy patients who sustained major nonhepatic trauma at San Francisco General Hospital, a major trauma center. Both groups of patients had documented systolic blood pressures <75 mm Hg for at least 15 minutes. Clinical and hemodynamic (invasive and noninvasive) data were recorded.RESULTS: Despite the marked reduction in blood pressure, no patient in the control group developed ischemic hepatitis. The mean (+/- SD) peak serum aspartate aminotransferase level in the control group was only 78 +/- 72 IU, in contrast with a mean peak of 2,088 +/- 2,165 IU in the case group. All 31 patients with ischemic hepatitis had evidence of underlying organic heart disease, 29 (94%) of whom had right-sided heart failure.CONCLUSIONS: Systemic hypotension or shock alone did not lead to ischemic hepatitis in any patient. The vast majority of patients with ischemic hepatitis had severe underlying cardiac disease that had often led to passive congestion of the liver. These data lead us to propose that right-sided heart failure, with resultant hepatic venous congestion, may predispose the liver to hepatic injury induced by a hypotensive event.     

Changing presentation of seizures with aging: clinical and etiological factors

BACKGROUND: The historically higher incidence of seizures in children has changed, the elderly now have a higher incidence than any age-group, 2-3 times of that found in children. Classical teachings on etiologies, clinical presentation and progression of seizures are based on observations of a younger population and need to be revised in view of features unique to this age-group. The findings of two large VA cooperative studies show that even in sophisticated medical environments, up to 30% of patients 60 years and older with recurrent partial seizures go undiagnosed for more than 1 year of seizure onset. OBJECTIVE: (a) To characterize the manifestations of auras, seizures and postictal states in the elderly and the relevance of various etiologies to these presentations. (b) To identify and discuss factors that contribute to the difficulties in the diagnosis of seizures in this population. METHODS: A review of our experience in treating a large population of elderly patients in a university epilepsy center and a review of the literature relating to the problem. CONCLUSIONS: Seizures in the elderly are both overdiagnosed and underdiagnosed: either situation can have serious adverse consequences. Diversity of etiologies and atypical presentations make recognition of seizures difficult. Histories are frequently inadequate: complaints of multiple physical symptoms confuse the picture, unwillingness of elderly patients to admit to problems they believe are physiological in nature by the fear others may think they are 'losing their mind' and high staff turnover result in erratic identification of problems. The significant morbidity and mortality associated with poorly controlled seizures in this population are in large part preventable since excellent response to treatment can be achieved in more than 80% of individuals. The correct diagnosis of seizures is more likely if both physician and patients are familiar with the nuances of epilepsy in the elderly.     

Leptospirosis: A clinical review of evidence based diagnosis,treatment and prevention

Leptospirosis is a zoonotic disease with worldwide distribution and increasing prevalence. Infection is caused by the spirochete Leptospira, with common exposure being contaminated fresh water. Most infections are asymptomatic, but symptoms range from a mild, self-limiting, non-specific febrile illness to fulminant respiratory and renal failure with a high mortality rate. The combination of jaundice, renal failure, and hemorrhage is known as Weil’s disease and is the most characteristic pattern associated with severe leptospirosis. Clinical suspicion alone may be enough to warrant empiric antibiotic treatment in many cases. Serological methods are the most commonly used means of confirming a diagnosis of leptospirosis. The “gold standard” is the microscopic agglutination test. Typical treatment for mild causes is oral doxycycline, though azithromycin and oral penicillins are reasonable alternatives. Intravenous penicillin G has long been the standard of care for severe cases though limited studies show no benefit compared to third generation cephalosporins. We review the clinical presentation, diagnosis, treatment and prevention of leptospirosis.     

Autonomic neuropathy: clinical presentation and differential diagnosis

Autonomic neuropathy (AN) may occur in the elderly in connection with other common illnesses afflicting this age group, such as diabetes or Parkinson's disease, or even as the primary illness. Symptoms of AN are numerous, but syncope, with its risk for fractures and head trauma, is the most serious. The clinical presentation and differential diagnosis of AN are discussed, as are a group of diseases associated with AN. Treatment guidelines are outlined.     

Intussusception: trends in clinical presentation and management

BACKGROUND: The association of a rotavirus vaccine and intussusception has renewed interest in understanding the incidence, clinical presentation and outcome of intussusception. METHODS: A retrospective chart review of all patients diagnosed with intussusception at Royal Children's Hospital, Melbourne over a 6.5-year period (1 January 1995-30 June 2001) was conducted using patients identified by a medical record database (ICD-9-CM code 560.0 1993-1997; ICD-10-CM code 56.1 1998-2001). Patient profile, clinical presentation, diagnosis methods, treatment and outcome were analyzed and compared to data previously reported on children with intussusception at the same hospital during 1962-1968. RESULTS: The hospitalization rate for primary idiopathic intussusception increased marginally from 0.19 to 0.27 per 1000 live births during the period 1962-1968 to 1995-2001. Most patients (80%) were <12 months of age (median age 7 months, range 2-72 months). The combination of abdominal pain, lethargy and vomiting was reported in 78% of infants. Air enema confirmed the diagnosis of intussusception in 186 of 191 cases (97%) and air reduction was successful in most cases (82%). Factors associated with increased risk of intestinal resection included abdominal distension (32%), bowel obstruction on abdominal X-ray (27%) and hypovolemic shock (40%). No mortality was observed in the present study. CONCLUSIONS: Over the past 40 years at Royal Children's Hospital, Melbourne the hospitalization rate due to primary idiopathic intussusception has marginally increased from 0.19 to 0.27 per 1000 live births. Diagnosis and treatment using air enema has been highly successful, resulting in a reduction in patients requiring surgery and reduced hospital stays.     

Tako-tsubo-like syndrome with atypical clinical presentation: case report and literature review

A 78-year-old woman presented herself at emergency for the appearance of severe dyspnea. An electrocardiogram showed signs of inferior and anterior necrosis, and laboratory tests showed a small increase of myocardial cytonecrosis enzymes. An echocardiogram detected a reduction of global systolic function (ejection fraction [EF] approximately 40%) as well as akinesia of the apex, interventricular septum middle segments, and anterior and anterolateral walls, with basal segments showing compensatory hyperkinesia. The coronarography showed a coronary tree substantially free from significant lesions. The patient was transferred to the cardiology unit of our hospital. Based on the contained increase of the cardiac enzymes, the absence of coronary lesions, and the presence of typical echocardiography alterations, we suspected a Tako-tsubo-like syndrome. On deeper anamnestic investigation, an event of strong emotional stress emerged preceding the hospital admission that confirmed the pathology, even though it is atypical to see clinical presentation a long time after a stressful event.     

Leptospirosis in Istanbul, Turkey: a wide spectrum in clinical course and complications

Patients with high fever and multiorgan involvement were investigated for the determination of frequency, clinical course and complications of leptospirosis in Istanbul. Leptospirosis was determined in 22 cases among the 35 hospitalized patients that were pre-diagnosed as leptospirosis according to 'Probable Leptospirosis Diagnosis and Follow-up' form. Among the leptospirosis cases 19 were male and 16 were military staff. Mean age was 35.6 y. Dark field examination (DFE), latex agglutination test (LAG), ELISA IgM, leptospirosis culture (LC) and microscopic agglutination test (MAT) were performed to confirm the diagnoses. The most frequent initial symptoms and findings were fever, fatigue, headache, nausea-vomiting and increased muscle sensitivity. Jaundice was noted only in 2 cases. A 74-y-old female patient died after the recurrence of the disease with severe rhabdomyolysis and pulmonary failure. Sagittal sinus thrombosis, perimyocarditis and chronic renal failure were major complications in another 3 patients. ELISA IgM, LC, DFE, LAG and MAT tests were positive in 68, 72, 82, 100 and 100% of the patients, respectively. As a conclusion, diagnosis of leptospirosis is usually overlooked. Clinical awareness, use of probable leptospirosis diagnosis forms and the application of different laboratory methods in the diagnosis of suspected cases may offer the chance to diagnose the leptospirosis accurately.     

Infective endocarditis in patients with end-stage renal disease: clinical presentation and outcome

BACKGROUND: Infective endocarditis is a common complication of vascular access in patients undergoing long-term hemodialysis. However, available data are either dated or gathered from small samples. The goal of this study was to investigate the clinical characteristics and outcome of infective endocarditis occurring in patients with end-stage renal disease. METHODS: Patients were identified by computerized discharge diagnosis and manual chart review at 3 major hospitals in Honolulu, Hawaii. The search covered an 11-year period, through December 2001. Modified Duke criteria were retrospectively applied. Patients fulfilling criteria for definite endocarditis were included in this study. RESULTS: Forty patients were identified. Average age was 59.4 years, and average duration of hemodialysis before endocarditis was 3.3 years; arteriovenous fistulas were the most commonly used access sites. Predominant organism was Staphylococcus aureus in 20 (50%) of the 40 cases. The mitral valve was affected in 29 cases (73%); aortic and mitral valve endocarditis was seen in 8 cases (20%). Overall in-hospital mortality was 52% (21/40). Patients with an unfavorable outcome more often had fever on admission, fewer negative blood cultures, and bivalvular infective endocarditis, and more often underwent valve replacement surgery. The perioperative mortality in patients undergoing valve replacement was 73% (11/15). CONCLUSIONS: Mortality of infective endocarditis in patients with end-stage renal disease remains high and has been essentially unchanged during the past decade. If patients require valve replacement surgery, mortality is even higher. A randomized, controlled trial is needed to clarify whether the increased mortality is due solely to more severe disease in patients requiring valve replacement surgery.