ABSTRACT
Taenia solium taeniasis/cysticercosis (TSTC) is a parasitic zoonotic disease that is endemic in several developing countries, causing serious public health and economic impacts. A cross-sectional study was conducted to assess knowledge, attitudes and practices (KAP) related to porcine cysticercosis (PCC) transmission, prevention and control among smallholder pig farmers in Kongwa and Songwe Districts in Tanzania. A semi-structured questionnaire was administered to 692 smallholder pig farmers from randomly selected households. STATA software version 17 was used to analyse quantitative data, summarize farmers' KAP about PCC and calculate performance scores. Nearly half (42%) of the respondents had little knowledge regarding PCC, only 17% of the respondents had good practices towards prevention/control of PCC and 72% had a positive attitude towards PCC- prevention/control measures. The majority (73%) of smallholder pig farmers admitted deworming their pigs regularly, whereas 76% reported deworming themselves and their family members regularly. Albendazole and ivermectin are the most commonly used medications for deworming people and pigs, respectively. According to the findings, the majority of smallholder pig farmers in Kongwa and Songwe Districts showed a good attitude towards PCC prevention/control measures but had limited knowledge of the PCC life cycle and control. In addition, only one in five farmers was engaged in good practices. The findings revealed further that farmers are engaged in risky behaviours that aid the spread and perpetuation of the T. solium parasite in the study area. It is recommended that farmers should be given proper health education on the T. solium transmission cycle and preventive/control practices to limit PCC transmission.
Subject(s)
Cysticercosis , Swine Diseases , Taeniasis , Swine , Animals , Humans , Cross-Sectional Studies , Tanzania/epidemiology , Farmers , Health Knowledge, Attitudes, Practice , Cysticercosis/epidemiology , Cysticercosis/prevention & control , Cysticercosis/veterinary , Taeniasis/veterinary , Swine Diseases/epidemiology , Swine Diseases/prevention & controlABSTRACT
BACKGROUND: Neurocysticercosis (NCC) is common in eastern Africa, but disease presentation varies considerably. Most patients have single or few NCC-typical lesions in their brain but some present with a large number of lesions. We present three patients with positive antibody-based serology for Taenia solium cysticercosis screened at the Vwawa district hospital, Mbozi district, southern Tanzania, in whom extensive NCC was confirmed by neuroimaging. CASE PRESENTATIONS: Patient 1 was a 55-year-old female from the tribe Malila smallholder farmer who has had four generalized tonic-clonic epileptic seizures over a period of 11 years and one episode of transient left hemiparesis one year before seizure onset. The patient also reported monthly to weekly episodes of severe, progressive, unilateral headache. The computed tomography (CT) scan of the brain showed 25 NCC lesions of which 15 were in the vesicular stage. Patient 2 was a 30-year-old male from tribe Nyha mechanic who reported monthly episodes of moderate to severe, progressive, bilateral headache, but no epileptic seizures. The CT scan showed 63 NCC lesions of which 50 were in the vesicular stage. Patient 3 was a 54-year-old female from the tribe Malila smallholder farmer who suffered from frequent generalized tonic-clonic epileptic seizures with potential signs of focal seizure onset. She also reported weekly to daily episodes of severe, progressive, unilateral headache. The CT scan showed 29 NCC lesions of which 28 were in the vesicular stage. CONCLUSIONS: Clinical presentation of NCC with multiple brain lesions varies considerably ranging from few epileptic seizures and severe headache to severe epilepsy with frequent epileptic seizures. Individuals with neurological signs/symptoms that may be due to NCC, based for example on epidemiological criteria or serological evidence of cysticercosis, are recommended to undergo neuroimaging before anthelminthic treatment is considered.
Subject(s)
Cysticercosis , Epilepsy , Neurocysticercosis , Male , Female , Humans , Middle Aged , Adult , Neurocysticercosis/diagnosis , Neurocysticercosis/diagnostic imaging , Tanzania , Brain/pathology , Seizures/etiology , Headache/etiologyABSTRACT
INTRODUCTION: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. METHODS: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6). RESULTS: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. CONCLUSION: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust.
Subject(s)
COVID-19 , Encephalitis , Guillain-Barre Syndrome , Nervous System Diseases , Humans , COVID-19/complications , COVID-19/diagnosis , SARS-CoV-2 , Observer Variation , Uncertainty , Nervous System Diseases/etiology , Nervous System Diseases/complications , Encephalitis/complications , Headache/diagnosis , Headache/etiology , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/complications , COVID-19 TestingABSTRACT
PURPOSE: Neurocysticercosis is common in regions endemic for Taenia solium. Active-stage neurocysticercosis can be treated with antiparasitic medication, but so far no study on efficacy and safety has been conducted in Africa. METHODS: We conducted a prospective cohort study on treatment of neurocysticercosis in Tanzania between August 2018 and January 2022. Patients were initially treated with albendazole (15 mg/kg/d) for 10 days and followed up for 6 months. Additionally in July 2021, all participants who then still had cysts were offered a combination therapy consisting of albendazole (15 mg/kg/d) and praziquantel (50 mg/kg/d). Antiparasitic treatment was accompanied by corticosteroid medication and anti-seizure medication if the patient had experienced epileptic seizures before treatment. RESULTS: Sixty-three patients were recruited for this study, of whom 17 had a complete follow-up after albendazole monotherapy. These patients had a total of 138 cysts at baseline, of which 58 (42%) had disappeared or calcified by the end of follow-up. The median cyst reduction was 40% (interquartile range 11-63%). Frequency of epileptic seizures reduced considerably (p < 0.001). Three patients had all active cysts resolved or calcified and of the remaining 14, eight received the combination therapy which resolved 63 of 66 cysts (95%). Adverse events were infrequent and mild to moderate during both treatment cycles. CONCLUSION: Cyst resolution was unsatisfactory with albendazole monotherapy but was very high when it was followed by a combination of albendazole and praziquantel.
Subject(s)
Anthelmintics , Cysts , Neurocysticercosis , Humans , Neurocysticercosis/drug therapy , Neurocysticercosis/complications , Neurocysticercosis/parasitology , Albendazole/adverse effects , Antiparasitic Agents/adverse effects , Praziquantel/adverse effects , Tanzania , Prospective Studies , Cysts/chemically induced , Cysts/complications , Cysts/drug therapy , Seizures/drug therapy , Seizures/chemically induced , Seizures/complications , Anthelmintics/adverse effectsABSTRACT
Human cysticercosis (CC) is a parasitic zoonosis caused by the larval stage (cyst) of the Taenia solium. Cysts can establish in the human central nervous system (neurocysticercosis, NCC) and other organs and tissues; they also develop in pigs, the natural intermediate host. Human taeniosis may be caused by T. solium, Taenia saginata and Taenia asiatica tapeworms; these infections are usually asymptomatic, but show a significant relevance as they perpetuate the parasites' life cycle, and, in the case of T. solium, they are the origin of (N)CC. In European Union (EU) member states and associated countries, the occurrence of autochthonous T. solium cases is debated, and imported cases have significantly increased lately; the status of T. asiatica has been never reported, whereas T. saginata is prevalent and causes an economic impact due to condemned carcasses. Based on their effects on the EU society, the specific diagnosis of these pathologies is relevant for their prevention and control. The aims of this study were to know the diagnostic tests used in European laboratories for human taeniosis/cysticercosis by means of a questionnaire, to determine potential gaps in their detection, and to obtain preliminary data on the number of diagnosed taeniosis/CC cases.
Subject(s)
Clinical Laboratory Techniques/methods , Cysticercosis/diagnosis , Molecular Diagnostic Techniques/methods , Animals , Cysticercosis/parasitology , Europe , Humans , Surveys and Questionnaires , Swine/parasitology , Taenia solium/embryologyABSTRACT
Nodding syndrome is a pediatric epileptic encephalopathy of apparent environmental origin that was first described in Tanzania, with recent epidemics in South Sudan and Uganda. Following a brief description of the medical geography, setting and case definition of this progressive brain disorder, we report recent advances relating to etiology, diagnosis and treatment described in papers given at the 2nd International Conference on Nodding Syndrome held in July 2015 in Gulu, Uganda. The target audience for this report includes: anthropologists, entomologists, epileptologists, health care workers, helminthologists, medical researchers, neuroepidemiologists, neurologists, neuroscientists, neuropathologists, nurses, nutritional scientists, primary health care physicians, psychiatrists, public health practitioners, toxicologists, and virologists.
ABSTRACT
BACKGROUND: Taenia solium metacestodes/cysts obtained from pig carcasses constitute a primary source for diagnostic tools used for the detection of human cysticercosis. Data on T. solium cyst preparation in Africa is still scarce but required to establish independent reference laboratories. OBJECTIVES: The aim of the present study is a) to present the likely yield of T. solium cyst material by the use of two different preparation methods in the field and b) to investigate its suitability for immunodiagnosis of human cysticercosis. METHODS: In Zambia, Uganda and Tanzania 670 pigs were screened for T. solium infection. Cysts were prepared by 'shaking method' and 'washing method'. Generated crude antigens were applied in a standard western blot assay. RESULTS: 46 out of 670 pigs (6.9%) were found positive for T. solium (Zambia: 12/367, 3.3%; Uganda: 11/217, 5.1%; Tanzania 23/86, 26.7%). Mean values of 77.7 ml whole cysts, 61.8 ml scolices/membranes and 10.9 ml cyst fluid were obtained per pig. Suitability of collected material for the use as crude antigen and molecular diagnostic techniques was demonstrated. CONCLUSION: This study clearly shows that T. solium cyst preparation in African settings by simple field methods constitutes an effective way to obtain high quality material as source for diagnostic tools and research purposes.
Subject(s)
Antibodies, Helminth/isolation & purification , Cysticercosis/diagnosis , Immunoblotting/methods , Taenia/chemistry , Animals , Antibodies, Helminth/blood , Cysticercosis/blood , Reproducibility of Results , Rural Population , Sensitivity and Specificity , Serologic Tests , Serum Globulins , Swine , Tanzania , Uganda , ZambiaABSTRACT
BACKGROUND: Onchocerciasis has been implicated in the pathogenesis of epilepsy. The debate on a potential causal relationship between Onchocerca volvulus and epilepsy has taken a new direction in the light of the most recent epidemic of nodding syndrome. OBJECTIVE: To document MRI changes in people with different types of epilepsy and investigate whether there is an association with O. volvulus infection. METHODS: In a prospective study in southern Tanzania, an area endemic for O. volvulus with a high prevalence of epilepsy and nodding syndrome, we performed MRI on 32 people with epilepsy, 12 of which suffered from nodding syndrome. Polymerase chain reaction (PCR) of O. volvulus was performed in skin and CSF. RESULTS: The most frequent abnormalities seen on MRI was atrophy (twelve patients (37.5%)) followed by intraparenchymal pathologies such as changes in the hippocampus (nine patients (28.1%)), gliotic lesions (six patients (18.8%)) and subcortical signal abnormalities (three patients (9.4%)). There was an overall trend towards an association of intraparenchymal cerebral pathologies and infection with O. volvulus based on skin PCR (Fisher's Exact Test p=0.067) which was most pronounced in children and adolescents with nodding syndrome compared to those with other types of epilepsy (Fisher's Exact Test, p=0.083). Contrary to skin PCR results, PCR of CSF was negative in all patients. CONCLUSION: The observed trend towards an association of intraparenchymal cerebral pathological results on MRI and a positive skin PCR for O. volvulus despite negative PCR of CSF is intriguing and deserves further attention.
Subject(s)
Brain Diseases/diagnosis , Central Nervous System Helminthiasis/diagnosis , Endemic Diseases , Epilepsy , Magnetic Resonance Imaging , Nodding Syndrome , Onchocerciasis/diagnosis , Onchocerciasis/epidemiology , Adolescent , Animals , Epilepsy/classification , Epilepsy/pathology , Female , Humans , Male , Onchocerca volvulus/isolation & purification , Onchocerciasis/cerebrospinal fluid , Polymerase Chain Reaction , Prospective Studies , Tanzania/epidemiology , Young AdultABSTRACT
Our aim was to assess the 1-year prevalence of migraine headache in a rural population within the catchment area of the Haydom Lutheran Hospital in northern Tanzania. From December 2003 until June 2004 a community-based door-to-door survey was carried out, using a questionnaire based on the criteria of the International Headache Society, including 1192 households with 7412 individuals selected by multistage cluster-random sampling. The overall 1-year prevalence of migraine headache was found to be 4.3% [316/7412, 95% confidence interval (CI) 3.8, 4.7] with an age-adjusted rate of 6.0% and a male : female ratio of 1:2.94 (P < 0.001). Of these individuals, 132 did not fulfil all criteria for migraine headache, hence, these patients had to be classified as migrainous disorders with a crude prevalence rate of 1.8% (132/7412. 95% CI 1.5, 2.1). The remaining 184 patients met all criteria for migraine resulting in a 1-year prevalence of 2.5% (184/7412, 95% CI 2.1, 2.9) and a male : female ratio of 1:2.51 (P < 0.001). The present survey shows that migraine headache is not uncommon in northern Tanzania. The recorded prevalence of migraine headache is located within the median of previous African prevalence surveys, which confirms the trend of lower migraine frequencies in rural Africa compared with western countries.
Subject(s)
Migraine Disorders/epidemiology , Rural Population/statistics & numerical data , Adolescent , Adult , Age Distribution , Aged , Child , Child, Preschool , Female , Health Surveys , Humans , Male , Middle Aged , Prevalence , Sex Distribution , Tanzania/epidemiology , Young AdultABSTRACT
PURPOSE: The study was conducted with the aim of assessing the hospital prevalence and aetiology of epileptic seizures with special emphasis on epilepsy and febrile convulsions in a rural African hospital. Symptomatic as well as unprovoked epileptic seizures have also been accounted for. METHODS: All patients admitted over a period of nine months to the Haydom Lutheran Hospital in Northern Tanzania were screened for neurological disorders. The present study focuses on epileptic seizures only. All patients with convulsions were seen prospectively in consecutive order by one of the authors (ASW). RESULTS: Of 8676 admissions 740 patients (8.5%) were given a neurological diagnosis. The most important neurological disorder was epileptic seizures. 272 patients (3.1%) had at least one seizure. Febrile convulsions were responsible for 30% (82 patients) of all epileptic seizures, followed by epilepsy with 24% (65 patients). Symptomatic (provoked) epileptic seizures made up for 27% (72 patients) and were caused by cerebral infections, eclampsia, strokes and head injuries. Seizures due to space-occupying lesions and alcohol withdrawal were also seen. In some cases, the reason remained obscure. The inpatient mortality of all seizures was 19%, being mainly due to the outcome of symptomatic seizures. The socioeconomic burden of hospital treatment of seizures was high corresponding to an average of US $ 20.2, paying for an average of 16.9+/-29.0 days in hospital. CONCLUSIONS: Contrary to developed countries, the most frequent neurological disorder amongst hospital inpatients was seizures. Febrile convulsions and epilepsy were major causes.
Subject(s)
Epilepsy/classification , Epilepsy/epidemiology , Rural Population , Adolescent , Adult , Age Distribution , Aged , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Risk Factors , Tanzania/epidemiologyABSTRACT
OBJECTIVES: Although epileptic seizures are an infrequent feature of acute attacks of the neuropsychiatric porphyrias, there are no significant reports of porphyria in chronic epilepsy. This paper attempts to redress the balance. METHODS: Three case reports, including detailed laboratory and molecular diagnostics. RESULTS: Two patients with variegate porphyria and one with acute intermittent porphyria, referred within 1 year to a specialist porphyria service, with a long history of chronic refractory epileptic seizures, are described. CONCLUSIONS: Porphyria may be an aetiological factor in some cases of chronic refractory partial or generalised epilepsy. Porphyria should also be considered if addition of a new anti-epileptic medication causes a major deterioration in the epilepsy.
Subject(s)
Epilepsy/complications , Porphyrias/etiology , Porphyrias/psychology , Acute Disease , Adult , Chronic Disease , Drug Resistance , Female , HumansABSTRACT
The anti-Hu antibody (HuAb) is directed against RNA-associated neuronal proteins and is known to cause paraneoplastic encephalomyelitis/sensory neuronopathy syndrome mostly when associated with small cell lung cancer (SCLC). Paraneoplastic encephalomyelitis/sensory neuronopathy syndrome with concurrent autonomic neuropathy has been reported to occur in paraneoplastic syndromes, although its occurrence concomitant with acute pandysautonomia is less frequent. The authors describe the clinical, neuropathologic, and serologic features of two cases with an anti-Hu-related paraneoplastic syndrome presenting with progressive autonomic neuropathy. Both patients showed features of dysautonomia, including postural dizziness, abdominal pain, and diarrhea, and symptoms of sensory neuropathy. Investigations disclosed severe sensory and autonomic neuropathy and positive HuAb titers. The disease of patient 1 had a very rapid progression, and the patient died of cardiac arrest within 2 months of the onset of symptoms. The autopsy revealed SCLC. In contrast, the disease of patient 2 had a less aggressive course. An extensive tumor search disclosed SCLC only 28 months after onset of symptoms, and the patient died 1 month later of cardiorespiratory arrest. Autopsies in both cases showed inflammation involving the intermediolateral columns and the dorsal root ganglia. These two cases illustrate the association of early dysautonomia with HuAb-related paraneoplastic syndrome and the variations of clinical, neuropathologic, and serologic findings in these types of cases.
Subject(s)
Nerve Tissue Proteins/immunology , Paraneoplastic Syndromes, Nervous System , RNA-Binding Proteins/immunology , Aged , Autoantibodies/blood , ELAV Proteins , Fatal Outcome , Ganglia, Spinal/pathology , Humans , Male , Nerve Tissue Proteins/genetics , Paraneoplastic Syndromes, Nervous System/genetics , Paraneoplastic Syndromes, Nervous System/immunology , Paraneoplastic Syndromes, Nervous System/pathology , Phenotype , RNA-Binding Proteins/geneticsSubject(s)
Anemia/physiopathology , Diabetes Mellitus, Type 1/physiopathology , Diabetic Neuropathies/physiopathology , Erythropoietin/therapeutic use , Hypotension, Orthostatic/drug therapy , Adult , Anemia/complications , Blood Pressure/drug effects , Erythropoietin/blood , Erythropoietin/deficiency , Female , Follow-Up Studies , Humans , Hypotension, Orthostatic/etiology , Hypotension, Orthostatic/physiopathology , Middle Aged , Recombinant Proteins , Time FactorsABSTRACT
OBJECTIVE: The normochromic normocytic anemia of erythropoietin (EPO) deficiency is recognized in advanced renal failure but not in early renal disease. The aim of this study was to determine whether anemia with EPO deficiency is found in type 1 diabetic patients with diabetic nephropathy in the absence of advanced renal failure and to compare them with patients with nondiabetic renal disease of similar severity. RESEARCH DESIGN AND METHODS: A total of 27 type 1 diabetic patients with diabetic nephropathy (DN), defined as having persistent proteinuria (mean 1,086 mg/day [CI 120-5,1901), a serum creatinine < or = 180 micromol/l, and retinopathy, were compared with 26 nondiabetic patients with glomerulonephritis (GN) and persistent proteinuria (1,874 mg/day [349-5,005]). The Hb concentration, red cell indexes, and serum EPO levels were measured, and other causes for the anemia were excluded. The EPO values were compared with a normal reference range obtained from nondiabetic patients with a microcytic anemia. The DN patients were tested for signs of diabetic peripheral and autonomic neuropathy. RESULTS: We found that 13 of the 27 DN patients were anemic (Hb 10.6 +/- 0.9 g/dl) in marked contrast to none of the GN patients (Hb 13.7 +/- 1.4 g/dl, P < 0.005). In the DN group, serum EPO concentrations failed to increase in response to anemia compared with the response seen in patients with microcytic anemia. Thus, the anemia of the DN group was associated with EPO deficiency. The anemic DN patients showed evidence of more severe proteinuria and diabetic neuropathy than the nonanemic DN patients. CONCLUSIONS: Anemia associated with EPO deficiency can occur early in DN before the onset of advanced renal failure, but does not normally occur in nondiabetic renal disease of similar severity. The pathogenesis requires elucidation.
Subject(s)
Anemia/complications , Diabetes Mellitus, Type 1/physiopathology , Diabetic Nephropathies/blood , Erythropoietin/blood , Adult , Anemia/blood , Biomarkers/blood , Blood Pressure , Diabetes Mellitus, Type 1/blood , Erythropoietin/deficiency , Female , Heart Rate , Hemoglobins/analysis , Humans , Male , Middle Aged , Proteinuria , Reference Values , Reproducibility of ResultsABSTRACT
Serum erythropoietin (EPO) levels are partially controlled by the sympathetic outflow to the kidney. We have studied whether patients with multiple system atrophy (MSA), known to be associated with dysautonomia, are EPO-deficient. Eighteen MSA patients were studied along with 32 idiopathic Parkinson's disease (PD) patients, 23 controls with iron-deficiency anaemia, and 18 healthy individuals. Serum creatinine was normal in all groups. Mean haemoglobin (Hb) concentration in MSA patients was 13.7 +/- 1.7 g/dL. Four MSA patients had unexplained anaemia (minimum Hb: 10.5 g/dL) and abnormal autonomic function tests including significant postural hypotension, whereas none of the PD patients was anaemic. Serum EPO levels were suppressed in relation to anaemia in MSA patients compared to elevated EPO levels in iron-deficiency anaemia patients (difference of regression lines P < 0.001), indicating EPO deficiency in the anaemic MSA patients. Serum EPO levels in PD patients were within normal range. A subset of MSA patients has anaemia and postural hypotension, which may be associated with EPO deficiency. This may have therapeutic implications.
Subject(s)
Anemia/metabolism , Erythropoietin/deficiency , Multiple System Atrophy/blood , Anemia/diagnosis , Autonomic Nervous System Diseases/diagnosis , Autonomic Nervous System Diseases/physiopathology , Cardiovascular System/physiopathology , Creatinine/blood , Enzyme-Linked Immunosorbent Assay , Erythropoietin/blood , Female , Heart Rate/physiology , Hemoglobins/analysis , Humans , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/epidemiology , Male , Middle Aged , Multiple System Atrophy/physiopathology , Severity of Illness IndexABSTRACT
AIMS: Clinical observation has led to the idea that there might be a distinctive form of selective sensory and autonomic neuropathy affecting patients with Type 1 diabetic mellitus with severe symptomatic autonomic neuropathy (Type 1-DAN) and this study was conducted to evaluate the presence of such a neuropathy in Type 1-DAN. METHODS: Nineteen Type 1 diabetic patients presenting for treatment of severe symptomatic autonomic neuropathy were examined (all had > or = 2 autonomic symptoms; age 39.3 +/- 10.2 years; duration of disease 25.6 +/- 10.5 years). For comparison, 19 Type 1 diabetic patients with neuropathic foot ulcers (age 44.5 +/- 6.6 years; duration of disease 26.7 +/- 9.2 years), 14 clinically uncomplicated Type 1 diabetic patients (age 39.9 +/- 5.6 years; duration of disease 22.9 +/- 9.3 years) and 16 non-diabetic healthy people as controls (age 39.3 +/- 10.7 years) were also examined. Results The large fibre modalities (light touch and vibration perception) were better preserved in the Type 1-DAN group than in the foot ulcer group. Thus, light touch sensation was normal in 11 out of 19 Type 1-DAN patients compared to only three out of 19 foot ulcer patients (P < 0.01), and vibration perception was 24.9 +/- 15.0 V and 40.5 +/- 7.9 V, respectively (P < 0.002) with some of the Type 1-DAN patients in the normal range. In contrast, the small fibre modalities, thermal perception and autonomic function, were grossly abnormal in both groups (hot thermal perception 14.1 +/- 2.5 degrees C and 12.6 +/- 3.7 degrees C; cold thermal perception 13.8 +/- 2.7 degrees C and 10.9 +/- 4. 7 degrees C; heart rate variation 2.9 +/- 1.5 beats/min and 4.8 +/- 4.0 beats/min, respectively). CONCLUSIONS: There is indeed a subgroup of Type 1 diabetic neuropathy patients who suffer from severe autonomic symptoms associated with a selective small fibre sensory and autonomic loss with relatively preserved large fibre sensory modalities.
Subject(s)
Diabetes Mellitus, Type 1/physiopathology , Diabetic Neuropathies/physiopathology , Sensation Disorders/physiopathology , Adult , Autonomic Nervous System/physiopathology , Diabetic Retinopathy/physiopathology , Female , Foot Ulcer/physiopathology , Heart Rate , Humans , Male , Neurologic Examination , Peripheral Nerves/physiopathology , Reference Values , Sensation Disorders/etiology , Valsalva ManeuverABSTRACT
Accumulation of arachidonic acid (AA) in the brain during ischaemia may contribute to development of brain oedema. In this study we investigated the effect of selected drugs on AA-induced cytotoxic brain oedema in C6 glioma cells. Suspended C6 glioma cells were preincubated with drugs and AA (0.1 mM) was added. When no drug was administered cell volume increased immediately after the addition of AA with a maximum cell swelling of 13.1+/-1.9% at 15 min (mean +/- S.E. M.). Preincubation of cells with BW 755C, a dual inhibitor of cyclo- and lipoxygenases, showed no reduction in cell swelling from AA, whereas superoxide dismutase, amiloride and the protein kinase inhibitor H-9370 led to a significant attenuation of volume increase (p<0.05). The role of Na(+) ions during cell swelling from AA was evaluated after pretreatment of C6 glioma cells with ouabain. This resulted in a reversal of cell swelling (p<0.01). We conclude that there is potential involvement of free radicals, signal transduction systems and intracellular accumulation of Na(+) ions in glial cell swelling from AA.
Subject(s)
Arachidonic Acid/pharmacology , Brain Edema , Neuroglia/cytology , 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine/pharmacology , Amiloride/pharmacology , Animals , Cell Size/drug effects , Enzyme Inhibitors/pharmacology , Glioma , Models, Neurological , Neuroglia/drug effects , Neuroglia/physiology , Ouabain/pharmacology , Superoxide Dismutase/antagonists & inhibitors , Tumor Cells, CulturedABSTRACT
AIMS: To discover whether Type 1 diabetic patients with autonomic neuropathy might be anaemic and erythropoietin (EPO)-depleted. METHODS: Fifteen Type 1 diabetic patients with serious complications (DM-COMP) were selected because of severe symptomatic autonomic neuropathy, including significant postural hypotension. All had proteinuria from nephropathy (three microalbuminuria and 12 macroalbuminuria), but a normal serum creatinine (< 122 micromol/l). They were compared to age and duration matched Type 1 diabetic controls without autonomic neuropathy (DM-controls) and non-diabetic patients with and without hypochromic, microcytic anaemia. RESULTS: The DM-COMP patients were anaemic (mean haemoglobin (Hb) 11.1+/-1.2 g/dl), sometimes severely (minimum Hb 9.2 g/dl), compared to non-neuropathic DM-controls (Hb 13.7+/-0.7 g/dl; P < 0.001). Furthermore, EPO failed to increase in association with anaemia in the DM-COMP group compared to the progressive increase in the non-diabetic, anaemic patients (difference of regression lines P < 0.001), indicating EPO depletion in the anaemic, diabetic patients. There was no other demonstrable cause for the anaemia. Treatment with EPO in 5 DM-COMP patients led to a rapid increase in haemoglobin (range 1.7-5.0 g/dl) with improvement in wellbeing. CONCLUSION: Some Type 1 diabetic patients with autonomic neuropathy present with an EPO-depleted anaemia, which responds to treatment with EPO. This observation supports the concept of autonomic neuropathy as a cause of anaemia with EPO depletion, although the role of established renal damage cannot be excluded.