AN ATYPICAL CASE OF ATYPICAL PNEUMONIA

SUMMARY A 23-year-old man, previously fit and well, presented with an atypical pneumonia, associated with microangiopathic anaemia, thrombocytopenia, rhabdomyolysis and renal impairment. Despite administration of intravenous fluids and antibiotics, his condition rapidly deteriorated, and the possibility of an aggressive connective tissue disorder was raised. Thus he was treated with high-dose oral steroids and plasma exchange until autoantibodies were shown to be negative. At this stage it transpired that the patient had swallowed water from a stream three weeks earlier, and leptospira antibody titres were subsequently found to be elevated. Antibiotics were continued, and after a protracted course he made a full recovery. Leptospirosis should be remembered as a rare cause of atypical pneumonia, particularly if there is associated hepatic or renal impairment.     

TDP‐43 pathology in Alzheimer's disease,dementia with Lewy bodies and ageing

Intracellular inclusions consisting of TAR DNA binding protein‐43 (TDP‐43 pathology) are present in up to 57% of Alzheimer's disease (AD) cases and follow a distinct topographical pattern of progression described in the TDP‐43 in AD staging scheme. This scheme has not been applied to the assessment of TDP‐43 pathology in dementia with Lewy bodies (DLB) and aged controls. We investigated TDP‐43 pathology prevalence and severity in AD, DLB, mixed AD/DLB (Mx AD/DLB) and aged controls. One hundred and nineteen human post‐mortem brains were included, neuropathologically diagnosed as AD: 46, DLB: 15, Mx AD/DLB: 19 and aged controls: 39. Paraffin sections inclusive of the amygdala, hippocampus, striatum and neocortex were immunohistochemically stained with antibodies against phosphorylated TDP‐43 and staged according to the TDP‐43 in AD staging scheme. TDP‐43 pathology was present in all groups: AD: 73.9%, DLB: 33.3%, Mx AD/DLB: 52.6% and controls: 17.9%. Prevalence of TDP‐43 pathology was significantly higher in AD and Mx AD/DLB compared to controls. In controls, higher age at death was associated with prevalence of TDP‐43 pathology and higher TDP‐43 in AD stage, suggesting that this type of TDP‐43 pathology may partly be an age‐associated phenomenon. Significantly higher prevalence of TDP‐43 pathology in the AD group indicates that AD pathology possibly triggers and aggravates TDP‐43 pathology. The validity of the TDP‐43 in AD staging scheme is not limited to AD and should be applied to assess TDP‐43 pathology in post mortem brains of aged individuals to further elucidate the role of TDP‐43 pathology in age associated neurodegeneration.     

Drug-induced endocytosis of neonatal erythrocytes

The erythrocytes of the newborn infant have many properties that distinguish them from those of adults, and their membranes are also different from those of adult erythrocytes. We compared the ability of adult and neonatal RBCs to undergo endocytosis on exposure to drugs. Using a quantitative method, we showed that neonatal erythrocytes undergo a greater degree of endocytosis than do adult RBCs in response to primaquine, vinblastine, and chlorpromazine, and are sensitive to lower concentrations of the drugs. Some forms of drug-induced endocytosis are red cell age-dependent; when RBCs were separated by density gradient centrifugation, the membranes of the younger, less dense populations of both the neonatal and adult RBCs were capable of more extensive internalization than those of the denser, older RBCs. Neonatal RBCs of a given density undergo more endocytosis than do adult RBCs of the same density, suggesting that the membrane of the neonatal RBC is less stable and capable of more of the reorganization reflected in endocytosis than is the adult RBC membrane.     

Seropositivity of Chlamydophila pneumoniae immunoglobulin G antibody of HIV/AIDS patients in Abuja,Nigeria

ObjectiveTo detect IgG antibody to Chlamydophila pneumoniae (CP) in sera of HIV/AIDS patients and provide rationale for inclusion of routine screening for anti-CP antibodies and anti-chlamydial agents in the Nigerian National HIV/AIDS Management Plan.MethodsSerum samples from 34 consenting HIV/AIDS patients attended a Government-approved Antiretroviral Treatment Facility in Abuja were screened by enzyme-linked immunosorbent assay for anti-CP IgG antibody using ImmunoComb® Chlamydia Bivalent IgG Test kit (Orgenics, Israel).ResultsAnti-CP IgG antibody was detected in 20 (58.8%) of 34 patients tested. The detection rate was higher among the males (8/13; 61.5%) than the females (12/21; 57.1%). Patients of the age group 16-30 years had the highest (7/10; 70%) detection of anti-CP IgG antibody.ConclusionsThe result of the present study suggests the presence of anti-CP antibodies in sera of the HIV/AIDS patients, and reinforces the need for routine screening for anti-CP antibodies as a necessary intervention to reduce the burden of Chlamydophila pneumoniae (C. pneumoniae) infections and to reduce HIV-positive morbidity in Nigeria. The outcome of this study also provides justification for the possible inclusion of anti-chlamydial agents in the National HIV/AIDS Management Plan to provide prophylaxis against or treat active C. pneumoniae infections.     

Autonomic dysfunction in dementia

Background

There are no studies of autonomic function comparing Alzheimer''s disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB) and Parkinson''s disease dementia (PDD).

Aims

To assess cardiovascular autonomic function in 39 patients with AD, 30 with VAD, 30 with DLB, 40 with PDD and 38 elderly controls by Ewing''s battery of autonomic function tests and power spectral analysis of heart rate variability. To determine the prevalence of orthostatic hypotension and autonomic neuropathies by Ewing''s classification.

Results

There were significant differences in severity of cardiovascular autonomic dysfunction between the four types of dementia. PDD and DLB had considerable dysfunction. VAD showed limited evidence of autonomic dysfunction and in AD, apart from orthostatic hypotension, autonomic functions were relatively unimpaired. PDD showed consistent impairment of both parasympathetic and sympathetic function tests in comparison with controls (all p<0.001) and AD (all p<0.03). DLB showed impairment of parasympathetic function (all p<0.05) and one of the sympathetic tests in comparison with controls (orthostasis; p = 0.02). PDD had significantly more impairment than DLB in some autonomic parameters (Valsalva ratio: p = 0.024; response to isometric exercise: p = 0.002). Patients with VAD showed impairment in two parasympathetic tests (orthostasis: p = 0.02; Valsalva ratio: p = 0.08) and one sympathetic test (orthostasis: p = 0.04). These results were in contrast with AD patients who only showed impairment in one sympathetic response (orthostasis: p = 0.004). The prevalence of orthostatic hypotension and autonomic neuropathies was higher in all dementias than in controls (all p<0.05).

Conclusion

Autonomic dysfunction occurs in all common dementias but is especially prominent in PDD with important treatment implications.Patients with autonomic failure experience disabling postural dizziness, syncope, falls, constipation and incontinence.¹ There is a need to identify symptomatic dysautonomia in dementia in order to ensure appropriate management and reduce risk of falls, which is particularly important as falls are a major cause of increased morbidity, institutionalisation and mortality in these individuals.²There are no previous prospective studies of autonomic function comparing the most common dementia subtypes in the elderly; Alzheimer''s disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB) and Parkinson''s disease dementia (PDD). A generalised deficit in cholinergic function would be expected to lead to autonomic dysfunction, and the common dementias have all been associated with underactivity of the cholinergic nervous systems.³ The Braak staging of Parkinson''s disease⁴ emphasises early involvement of the brainstem, including the dorsal vagal nucleus, and autonomic failure is a feature of Parkinson''s disease.⁵The only previous studies using standard bedside clinical autonomic tests have mainly included patients with AD only,^6,7,8,9,10 although two have included patients with multi‐infarct dementia or Binswanger''s encephalopathy,^11,12 and there is one retrospective report of clinical autonomic dysfunction in DLB patients.¹³ Studies using bedside tests require a level of cooperation by the subject which may not be possible in dementia. These data can be enhanced by measurements of heart rate variability,¹⁴ which requires less cooperation from the subject than other autonomic function tests and is suitable for use in patients with dementia.¹⁵We examined autonomic function using a combination of standardised bedside clinical testing and heart rate variability techniques, in an unselected series of patients with a range of dementia subtypes, diagnosed according to well validated diagnostic criteria, in comparison with appropriately matched elderly controls. Given the evidence of the retrospective study of DLB patients and data regarding autonomic dysfunction in Parkinson''s disease (PD),⁵ we hypothesised that autonomic dysfunction would be more severely impaired in DLB and PDD than in AD, and that the most severe impairment would be present in PDD because of the length of illness and severity of neurodegenerative disease.     

Duodenal Obstruction by Gallstone in the Absence of Cholecystoenteric Fistula,an Unusual Complication of Total Gastrectomy: Report of a Case

We present a case of gallstone obstruction of the duodenum in a post total gastrectomy patient without a cholecystoenteric fistula. The patient presented with epigastric pain. On abdominal computed tomography and percutaneous transhepatic choangiography imaging, the patient was found to have duodenal obstruction. At operation, the cause of obstruction was found to be a large gallstone in the third part of the duodenum, but there was no associated cholecystoenteric fistula. This report is the first to describe duodenal obstruction by a gallstone formed within the duodenum, in a patient post total gastrectomy with Roux-en-Y reconstruction, and highlights what can be a difficult diagnosis in such patients.     

Dementia with Lewy bodies

Synucleinopathies, with and without dementia, encompass a wide range of diseases including Parkinson's disease, multiple system atrophy, rapid eye movement (REM) sleep behavior disorder, and dementia with Lewy bodies (DLB). DLB is a neurodegenerative disorder resulting in slowly progressive and unrelenting dementia until death. Prevalence studies suggest that it is the second most common dementing illness in the elderly. The neuropathologic findings of DLB show a wide anatomic range. Lewy bodies and Lewy-related pathology are found from the brain stem to the cortex and, in many cases, associated with concurrent Alzheimer's disease pathology. A recent international consortium on DLB has resulted in revised criteria for the clinical and pathological diagnosis of DLB incorporating new information about the core clinical features and improved methods for their assessment. The presentation of DLB is typically one of cortical and subcortical cognitive impairments, with worse visuospatial and executive dysfunction than Alzheimer's disease. There may be relative sparing of memory especially in the early stages. Core clinical features of DLB include fluctuating attention, recurrent visual hallucinations, and parkinsonism. Suggestive features include REM sleep behavior disorder, severe neuroleptic sensitivity, and low dopamine transporter uptake in the basal ganglia on functional neuroimaging. Additional supportive features that commonly occur in DLB, but with lower specificity, include repeated falls and syncope, transient, unexplained loss of consciousness, severe autonomic dysfunction, hallucinations in other modalities, systematized delusions, depression, relative preservation of medial temporal lobe structures on structural neuroimaging, reduced occipital activity on functional neuroimaging, prominent slow wave activity on electroencephalogram, and low uptake myocardial scintigraphy. Management of DLB includes pharmacological and nonpharmacological interventions for its cognitive, neuropsychiatric, motor, and sleep disturbances.     

Genes harbouring susceptibility SNPs are differentially expressed in the breast cancer subtypes

Recently, genome-wide association studies of breast cancer revealed single nucleotide polymorphisms (SNPs) in five genes with novel association to susceptibility. While there is little doubt that the novel susceptibility markers produced from such highly powered studies are true, the mechanisms by which they cause the susceptibility remain undetermined. We have looked at the expression levels of the identified genes in tumours and found that they are highly significantly differentially expressed between the five established breast cancer subtypes. Also, a significant association between SNPs in these genes and their expression in tumours was seen as well as a significantly different frequency of the SNPs between the subtypes. This suggests that the observed genes are associated with different breast cancer subtypes, and may exert their effect through their expression in the tumours. Thus, future studies stratifying patients by their molecular subtypes may give much more power to classic case control studies, and genes of no or borderline significance may appear to be high-penetrant for certain subtypes and, therefore, be identifiable.