A Rapid and Satisfactory Outcome with Combined Immunosuppressive Therapy in Acquired Haemophilia A with Underlying Tuberculosis.

Acquired haemophilia A (AHA) is a rare disorder with an incidence of 1.5 cases per million per year in the United Kingdom. The incidence could be underestimated due to difficulty in diagnosis and also due to the fact that people with low titre inhibitor levels are asymptomatic. It is usually a disease affecting elderly but a disease peak in the younger population is known. The common underlying diseases are autoimmune disorders, malignancies, infections, and drugs. However, approximately 50% of the cases do not have a specific aetiology and about 10% will not have bleeding manifestations. Therefore, an isolated prolongation of APTT should be evaluated, especially prior to any haemostatic challenges. We report a case of a middle-aged man who presented with bleeding due to AHA associated with high inhibitory titres and active pulmonary tuberculosis. He was treated with both antituberculous and combined-aggressive immunosuppressive therapy which resulted in satisfactory disease remission.

Non-mass versus mass-like ultrasound patterns in ductal carcinoma in situ: is there an association with high-risk histology?

AIM: To review the ultrasound (US) patterns of pure ductal carcinoma in situ (DCIS) using a non-mass-like (NML) versus mass-like (ML) classification and to investigate histopathological associations. MATERIALS AND METHODS: The present study was a retrospective analysis of sonographically evident pure DCIS lesions detected in a mammographic (MG) screening programme over a 7-year period from 2008. All lesions had undergone US-guided 14 G core biopsies with no upgrades to invasive disease on surgical histopathology. Lesions that were three-dimensional with convex margins were classified as ML and all others as NML. ML lesions were subdivided into solid, cystic, or mixed, and NML lesions into ductal and non-ductal. Imaging and pathological characteristics of NML versus ML lesions were investigated using logistic regression. RESULTS: There were 78 lesions in 75 participants. NML lesions accounted for 45 (58%) lesions, comprising 27 (60%) ductal and 18 (40%) non-ductal subtypes. There were 33 (42%) ML lesions; the largest subgroup being solid (n=21, 64%). Significant associations between lesion type and lesion size on US (<15 versus ≥15 mm), presence of US and mammographic calcification and posterior shadowing on sonography were identified. NML lesions had fivefold higher odds (OR=5.41 95% confidence interval [CI]: 2.03, 14.39, p=0.001) to be high grade and sevenfold higher odds (OR=7 95% CI: 1.75, 27.99, p=0.006) to have comedo necrosis on histopathology. CONCLUSION: DCIS lesions can be successfully classified using ML and NML lesion descriptors and NML morphology on US is associated with histological features of "high-risk" DCIS.

A case of warm autoimmune haemolytic anaemia with intravascular haemolysis: a rare presentation.

Autoimmune haemolytic anaemia (AIHA) is a rare (prevalence 0.2 -1.0 per 100,000 population) but a potentially fatal condition. Diagnosis of AIHA is based mainly on Direct Agglutination Test (DAT/Coomb's test). AIHA is classified into warm (optimal autoantibody reactivity at 37°C) and cold (optimal autoantibody reactivity at 4°C) types. Based on the presence or absence of an underlying cause, it is divided into primary (idiopathic) and secondary (secondary to lympho proliferative disorders, autoimmune disease, drugs and non-haematological malignancies). Warm type accounts for about 70% of cases with AIHA. It can occur at any age, but mostly after 40 years. Haemolysis in warm AIHA is mediated by IgG alone or IgG with complement. Once immunoglobulins are bound, the red cells are taken up by the macrophages of the reticulo-endothelial system which has receptors for the Fc fragments of the immunoglobulins. As the red cells are haemolysed extravascularly this occurs mainly in the spleen. Intravascular haemolysis is unusual in warm AIHA, although it can occur rarely, as warm autoantibodies can fix complements. We report severe warm AIHA in an adult with evidence of intravascular haemolysis, which is an unusual presentation.

Why are patients with progressive nonfluent aphasia nonfluent?

OBJECTIVE: To investigate the cognitive and neural basis for nonfluent speech in progressive nonfluent aphasia (PNFA). BACKGROUND: Nonfluent speech is the hallmark feature of PNFA, and this has been attributed to impairments in syntactic processing, motor-speech planning, and executive functioning that also occur in these patients. Patients with PNFA have left inferior frontal atrophy. METHODS: A large semi-structured speech sample and neuropsychological measures of language and executive functioning were examined in 16 patients with PNFA, 12 patients with behavioral-variant frontotemporal dementia (bvFTD), and 13 age-matched controls. Speech fluency was quantified as words per minute (WPM) in the semi-structured speech sample. Stepwise linear regression analyses were used to relate WPM to grammatic, motor-speech planning, and executive aspects of patient functioning. These measures were then related to cortical thickness in 8 patients with PNFA and 7 patients with bvFTD using structural MRI. RESULTS: WPM was significantly reduced in patients with PNFA relative to controls and patients with bvFTD. Regression analyses revealed that only grammatic measures predicted WPM in PNFA, whereas executive measures were the only significant predictor of WPM in bvFTD. Cortical thinning was significant in PNFA relative to controls in left inferior frontal and anterior-superior temporal regions, and a regression analysis related this area to reduced WPM in PNFA. Significant cortical thinning associated with limited grammatic processing also was seen in the left inferior frontal-superior temporal region in PNFA, and this overlapped with the area of frontal-temporal thinning related to reduced WPM. CONCLUSION: Nonfluent speech in PNFA may be due in part to difficulty with grammatic processing associated with left inferior frontal and anterior-superior temporal disease.

Neurocognitive contributions to verbal fluency deficits in frontotemporal lobar degeneration.

OBJECTIVE: To test the hypothesis that different neurocognitive networks underlie verbal fluency deficits in frontotemporal lobar degeneration (FTLD). METHODS: Letter ("FAS") and semantic ("animal") fluency tests were administered to patients with a behavioral/dysexecutive disorder (bvFTLD; n = 71), semantic dementia (SemD; n = 21), and progressive nonfluent aphasia (PNFA; n = 26). Tests measuring working memory, naming/lexical retrieval, and semantic knowledge were also obtained. MRI voxel-based morphometry (VBM) studies were obtained on a subset of these patients (bvFTLD, n = 51; PNFA, n = 11; SemD, n = 10). RESULTS: Patients with SemD were disproportionately impaired on the semantic fluency measure. Reduced output on this test was correlated with impaired performance on naming/lexical retrieval tests. VBM analyses related reduced letter and semantic fluency to anterior and inferior left temporal lobe atrophy. Patients with bvFTLD were equally impaired on both fluency tests. Poor performance on both fluency tests was correlated with low scores on working memory and naming/lexical retrieval measures. In this group, MRI-VBM analyses related letter fluency to bilateral frontal atrophy and semantic fluency to left frontal/temporal atrophy. Patients with PNFA were also equally impaired on fluency tests. Reduced semantic fluency output was correlated with reduced performance on naming/lexical retrieval tests. MRI-VBM analyses related semantic fluency to the right frontal lobe and letter fluency to left temporal atrophy. CONCLUSIONS: Distinct neurocognitive networks underlie impaired performance on letter and semantic fluency tests in frontotemporal lobar degeneration subgroups.

Systemic humoral immunity to non-typeable Haemophilus influenzae.

Non-typeable Haemophilus influenzae (NTHi) is a major cause of respiratory but rarely systemic infection. The host defence to this bacterium has not been well defined in patients with chronic airway infection. The aim of this study was to assess the effect of humoral immunity in host defence to NTHi. Responses were measured in control and bronchiectasis subjects who had recurrent bronchial infection. Antibody and complement-mediated killing was assessed by incubating NTHi with serum and the role of the membrane-attack complex and classical/alternate pathways of complement activation measured. The effect of one strain to induce protective immunity against other strains was assessed. The effect of antibody on granulocyte intracellular killing of NTHi was also measured. The results showed that both healthy control subjects and bronchiectasis patients all had detectable antibody to NTHi of similar titre. Both groups demonstrated effective antibody/complement-mediated killing of different strains of NTHi. This killing was mediated through the membrane-attack complex and the classical pathway of complement activation. Immunization of rabbits with one strain of NTHi resulted in protection from other strains in vitro. Antibody activated granulocytes to kill intracellular bacteria. These findings may explain why NTHi rarely causes systemic disease in patients with chronic respiratory mucosal infection and emphasize the potential importance of cellular immunity against this bacterium.

Large-cell calcifying sertoli cell tumour of the testis detected at screening of a family with Carney syndrome.

We report the detection of a large-cell calcifying Sertoli cell tumour (LCCSCT) in a 34-year-old male during screening of a family with Carney syndrome. The patient had ignored the testicular swelling for 7 years. He also had a cardiac myxoma. The LCCSCT in this patient had prognostically unfavourable features such as large size (>6 cm) and a high mitotic rate. There is only one previous report of a malignant LCCSCT in a patient with Carney syndrome.

The impact of repeated malaria attacks on the school performance of children.

The impact of repeated malarial infections on the school performance of children was investigated in 571 school children 6-14 years of age in a malaria-endemic area in southern Sri Lanka where both Plasmodium falciparum and P. vivax infections are prevalent. Malaria infections confirmed by microscopy were monitored over a six-year period. School performance was assessed by two specially designed, school grade-specific, test papers for Sinhala language and mathematics. The scores for Sinhala language and mathematics for each school term test for the year 1997 were obtained. Malarial infections were a major predictor of children's performance in language and mathematics after controlling for parent's education, monthly family income, and house type. The education of the father predicted language scores but not mathematics scores. A child who experienced more than five attacks of malaria scored approximately 15% less than a child who experienced less than three attacks of malaria. The data suggest that repeated attacks of malaria have an adverse impact on the school performance of children.

Audit of stroke care at the Institute of Neurology, National Hospital of Sri Lanka, 1994-1997.

OBJECTIVE: To audit the process of stroke care. DESIGN: Retrospective case record evaluation using an audit package designed by the Royal College of Physicians of London. SETTING: Institute of Neurology, National Hospital of Sri Lanka, Colombo. PATIENTS: 263 patients with stroke admitted over a period of 3 years. MEASUREMENTS: Documentation of 60 audit items related to 13 aspects of stroke care. RESULTS: The process of care was considered 'very good' for only 11 (18.3%), and 'good' for only 9 (15%) of the audit items. Care was 'average' for 5 (8.3%), 'poor' for 9 (15%) and 'very poor' for 26 (43.3%) of the items. CONCLUSIONS: Stroke care was suboptimal in many aspects. Care related to rehabilitation oriented neurological assessments, initiation of secondary preventive measures, rehabilitation planning and discharge planning were especially deficient. Competing interests: none declared. Some of the data reported in this paper have been presented at the Annual Scientific Sessions of the Sri Lanka Medical Association, 1998.

Use of routinely collected past surveillance data in identifying and mapping high-risk areas in a malaria endemic area of Sri Lanka.

Stratification of malaria endemic areas on eco-epidemiological criteria is an important step in planning and implementing malaria control programs. The uses of stratification of malaria endemic areas lead to better targeting of control measures such as residual insecticide spraying in countries where unstable malaria transmission occur. In this study, two methods that can be used for stratification of malaria endemic areas in Sri Lanka using routinely collected surveillance data over a period of 9 years are described. In the first method, the median Annual Parasite Incidence (API) was used as the criterion to classify an area as at risk for malaria while in the second method, the API and the Falciparum Rate (FR) were used as the criteria. Risk maps were produced by plotting the results of the analyses on maps generated by EPIMAP. The potential uses of risk maps are discussed.

Quantifying genetic and nongenetic contributions to malarial infection in a Sri Lankan population.

Explaining the causes of variation in the severity of malarial disease remains a major challenge in the treatment and control of malaria. Many factors are known to contribute to this variation, including parasite genetics, host genetics, acquired immunity, and exposure levels. However, the relative importance of each of these to the overall burden of malarial disease in human populations has not been assessed. Here, we have partitioned variation in the incidence of malarial infection and the clinical intensity of malarial disease in a rural population in Sri Lanka into its component causes by pedigree analysis of longitudinal data. We found that human genetics, housing, and predisposing systematic effects (e. g., sex, age, occupation, history of infections, village) each explained approximately 15% of the variation in the frequency of malarial infection. For clinical intensity of illness, 20% of the variation was explained by repeatable differences between patients, about half of which was attributable to host genetics. The other half was attributable to semipermanent differences among patients, most of which could be explained by known predisposing factors. Three percent of variation in clinical intensity was explained by housing, and an additional 7% was explained by current influences relating to infection status (e.g., parasitemia, parasite species). Genetic control of Plasmodium falciparum infections appeared to modulate the frequency and intensity of infections, whereas genetic control of Plasmodium vivax infections appeared to confer absolute susceptibility or refractoriness but not intensity of disease. Overall, the data show consistent, repeatable differences among hosts in their susceptibility to clinical disease, about half of which are attributable to host genes.

Churg-Strauss syndrome in patients receiving montelukast as treatment for asthma.

STUDY OBJECTIVES: We previously reported eight patients who developed Churg-Strauss syndrome in association with zafirlukast treatment for asthma and postulated that the syndrome resulted from unmasking of a previously existing condition due to corticosteroid withdrawal and not from a direct drug effect. The availability of montelukast, a new leukotriene receptor antagonist with a different molecular structure, permitted us to test this hypothesis. Our goals were to ascertain whether the Churg-Strauss syndrome developed in patients taking montelukast and other novel asthma medications, and to describe potential mechanisms for the syndrome. DESIGN: Case series. SETTING: Outpatient and hospital practices of pulmonologists in the United States and Belgium. PATIENTS: Four adults (one man, three women) who received montelukast as treatment for asthma; two women who received salmeterol/fluticasone therapy, but not montelukast. RESULTS: Churg-Strauss syndrome developed in the four asthmatic patients who received montelukast. In each case, there was a long history of difficult-to-control asthma characterized by multiple exacerbations that had required frequent courses of oral systemic corticosteroids or high doses of inhaled corticosteroids for control. Two other asthmatics who received fluticasone and salmeterol but not montelukast therapy developed the same syndrome with tapering doses of oral or high doses of inhaled corticosteroids. CONCLUSIONS: The occurrence of Churg-Strauss syndrome in asthmatic patients receiving leukotriene modifiers appears to be related to unmasking of an underlying vasculitic syndrome that is initially clinically recognized as moderate to severe asthma and treated with corticosteroids. Montelukast does not appear to directly cause the syndrome in these patients.

Malaria risk factors in an endemic region of Sri Lanka, and the impact and cost implications of risk factor-based interventions.

In an 18-month study of malaria in a population of 1,875 residents in 423 houses in an endemic area in southern Sri Lanka, the risk of malaria was found to be 2.5-fold higher in residents of poorly constructed houses than in those living in houses of good construction type. In residents of poorly constructed houses but not in others, the risk was even greater when the house was located near a source of water that could act as a potential breeding place for malaria vector mosquitoes (P = 0.0001). Based on previous findings that confirmed that house construction type was itself a risk determinant, and not merely a marker of other behavioral factors, we have estimated the potential impact of two feasible interventions to reduce the risk of malaria: 1) the imposition of a buffer zone of 200 meters around bodies of water from which houses of poor construction were excluded, which was estimated to lead to a 21% reduction of the malaria incidence in the overall population and a 43% reduction in the relocated community; and 2) the conversion of houses of poor construction type located in the buffer zone to those of a good construction type, which was estimated to lead to a 36% reduction in the incidence rates in the whole population and a 76% reduction in the residents of houses whose construction type was improved. Taking into consideration the cost to the Government of malaria prevention, we estimated the worth of a Government's investment in improving house construction type. The investment in housing was estimated to be offset in 7.2 years by savings to the Government on malaria costs alone, and beyond this period, to bring a return on the Government's investment by way of savings to the malaria control program.

Optimizing the malaria data recording system through a study of case detection and treatment in Sri Lanka.

The potential of using malaria incidence data routinely collected from endemic regions for disease control and research has increased with the availability of advanced computer-based technologies, but will depend on the quality of the data itself. We report here an investigation into the relevance of malaria statistics provided by the routine data collection system in Moneragala, a rural malaria-endemic region in Sri Lanka. All patients (n = 321) treated for malaria in 2 clusters of health care centres (HCCs) of both the private and the public sector in the administrative regions of Moneragala and Buttala Divisional Secretariat (D.S.). Divisions were studied in December 1995/ January 1996. The catchment area of these HCCs included a population resident in 53 Grama Niladhari (GN) areas, the smallest administrative units of the country. Almost equal numbers of malaria patients were detected and treated at Government and private health care institutions, and in 70% of them treatment was based on a diagnosis confirmed by microscopy. The routine data recording system, however, included only statistics from the Government sector, and only of patients whose diagnosis was microscopically confirmed. In compiling data, the origin of a case of malaria is attributed to the D.S. Division in which the institution (at which the patient was treated) was located, rather than the area in which the patient was resident, which was inaccurate because 90% of malaria patients sought health care at institutions located closest to their residence, thus crossing administrative boundaries. It also led to a loss of resolution of spatial data because patients' addresses recorded at the Government HCCs to the village-level are replaced in the statistics by the D.S. Division, which is a coarse spatial unit. Modifications to the system for malaria case recording needed to correct these anomalies are defined here. If implemented, these could result in major improvements to the quality of data, a valuable resource for the future of malaria control. The paper reiterates the call for the use of a standard spatial unit within a country to facilitate exchange of data among health and other sectors for the control of tropical diseases.

Psoriasis in Sri-Lanka--a computer analysis of 1366 cases.

A clinical and epidemiological study of psoriasis in Sri-Lanka is presented. The prevalence in the population is estimated to be over 0.4%. The clinic incidence was 8.7%; of these 53.2% were male, and 46.8% female and 8.3% reported a family history of the disease. The mean age at onset was 25.2 years. The frequency distribution for the age at onset was bimodal with peaks at the second and fifth decades. The age at onset was significantly low in females, in patients with a family history of the disease, in those affected by weather changes and in patients whose disease was precipitated by sore throats. The existence of natural subpopulations of patients is suggested. Clinical types and complications of the disease were not essentially different from those observed in the West.

The clinical spectrum of Sweet's syndrome (acute febrile neutrophilic dermatosis)-a report of eighteen cases.

Eighteen cases of Sweet's syndrome are described. This is the largest series so far reported and the first from the tropics. The essential features are the characteristic morphology, the histological appearances, the dramatic response to corticosteroids and the absence of scarring. Attention is drawn to the frequent involvement of the eyes and joints during the course of the illness. Fever and neutrophilia were found less frequently than a raised ESR or a preceding upper respiratory tract or skin infection. The term Sweet's syndrome is preferred to acute febrile neutrophilic dermatosis. The frequency of occurrence of different clinical manifestations is discussed.