Etiology of Chronic Liver Disease in Ethiopia: A Case Control Study with Special Reference to Viral Hepatitis and Alcohol.

INTRODUCTION: Chronic diseases of the liver are a global health problem with high morbidity and mortality. Viral hepatitis is the predominant cause for liver disease in low and middle-income countries. Viral hepatitis is also frequent in high-income countries but mainly as a complication to drug abuse or iatrogenic to treatment. In high-income countries non-fatty-liver-disease and complications to alcohol consumption are the most frequent etiology of liver disease. Viral hepatitis B and C is prevalent in Ethiopia but there are only few studies done in relation to chronic liver disease and a relationship between the increasing alcohol consumption and chronic liver disease. OBJECTIVE: A The aim of the study was to assess the association between chronic liver disease in Ethiopia and infection with viral hepatitis and possible relation to alcohol consumption. METHODS AND MATERIAL: An unmatched case control study was conducted in Addis Ababa. Cases were chronic liver disease patients (n = 812) and controls were patients without liver disease (n = 798). Data were collected from the records of patients treated at a specialized clinic of Gastrsoenterology and Hepatology in Addis Ababa from 1st January 2013 - 31st, December 2013. RESULTS: The odds of having hepatitis infection among chronic liver disease was AOR = 100.96, (95%CI: 62.15 - 164.02) for HBV and AOR = 59.2, (95%CI: 27.23 - 130.9) for HCV. Consumption of alcohol was associated with chronic liver disease (OR: 8.23 95%CI: 3.76 - 12.70). Liver enzymes were elevated significantly in patients with hepatitis and alcohol consumption compared to patients without alcohol consumption. CONCLUSION: Viral hepatitis infections are strongly associated with chronic liver disease. Prevention of viral hepatitis infections and control of alcohol consumption need to be strengthened in order to reduce the burden of chronic liver disease in Ethiopia.

Dependency of cerebral blood flow on mean arterial pressure in patients with acute bacterial meningitis.

OBJECTIVE: Patients with acute bacterial meningitis are often treated with sympathomimetics to maintain an adequate mean arterial pressure (MAP). We studied the influence of such therapy on cerebral blood flow (CBF). DESIGN: Prospective physiologic trial. SETTING: The Department of Infectious Diseases, Copenhagen University Hospital, Denmark. PATIENTS: Sixteen adult patients with acute bacterial meningitis. INTERVENTION: Infusion of norepinephrine to increase MAP. MEASUREMENTS: During a rise in MAP induced by norepinephrine infusion, we measured relative changes in CBF by transcranial Doppler ultrasonography of the middle cerebral artery, recording mean flow velocity (Vmean), and by the arterial to jugular oxygen saturation difference. In 10 out of 16 patients, serial measurements were performed until recovery or death. Individual autoregulation curves were analyzed by a computer program. Autoregulation was classified as impaired if Vmean increased by >10% per 30 mm Hg increase in MAP and if no lower limit of autoregulation was identified by the computer program; otherwise, autoregulation was classified as preserved. MAIN RESULTS: Initially, Vmean increased from a median value of 46 cm/sec (range, 30-87 cm/sec) to 63 cm/sec (33-105 cm/sec) (p < .0001), and arterial to jugular oxygen saturation difference decreased from 0.28 (0.16-0.51) to 0.21 (0.08-0.39) (p < .001) when MAP was raised from 69 mm Hg (55-102 mm Hg) to 110 mm Hg (93-129 mm Hg). CBF autoregulation was restored in eight of ten patients undergoing serial examination after 7 (range, 2-10) days. Six of these patients had an uncomplicated course, one had a protracted recovery, and one died. Autoregulation was not restored in two patients; one died and one had a protracted recovery. CONCLUSION: In patients in the early phase of acute bacterial meningitis, CBF autoregulation is impaired. With recovery from meningitis, the cerebral vasculature regains the ability to maintain cerebral perfusion at a constant level despite variations in MAP.

[A rare cause of osteomyelitis. A case of Mycobacterium bovis in a wrist]. / En sjaelden arsag til osteomyelit. Et tilfoelde af Mycobacterium bovis i et håndled.

A cases of longstanding infection with Mycobacterium bovis is described in 79 year-old retired butcher presenting with broad erosions of the right wristbones. Further investigations revealed a chronic infection with Mycobacterium bovis present for 58 years. The patient was treated with antibiotics. The importance of having tuberculosis in mind when investigating lytic bone destruction is discussed.

Meningitis caused by streptococci other than Streptococcus pneumoniae: a retrospective clinical study.

We reviewed the medical records of 26 patients (median age 62 years, range 5-76 years) admitted to our institution during 1978-98 with acute bacterial meningitis (ABM) caused by streptococci other than Streptococcus pneumoniae (comprising 1.9% of all patients with ABM). 19 cases were community-acquired and 7 were nosocomial. 73% had comorbid or predisposing conditions and 73% had an identifiable extracerebral focus; only in 2 patients no comorbid disease, primary focus or predisposing condition was present. Five patients had cerebral abscesses, and 5 had endocarditis. Beta-haemolytic streptococci were grown in 14 cases (serotype A: 4, B: 5, C: 1, G: 4) and were predominant among patients with endocarditis, whereas alpha- or non-haemolytic strains grew in 12 cases (S. mitis: 4, S. constellatus: 2, E. faecalis: 2, S. bovis: 1, unspecified: 3) and were predominant in patients with a brain abscess. Staphylococcus aureus grew together with a streptococcus in 2 cases. Blood culture was positive in 9 cases (35%). Neurologic complications occurred in 11 patients (42%) and extraneurologic complications in 18 patients (69%). Adverse outcomes occurred in 10 patients (38%), including 3 patients who died. Occurrence of seizures at any time of disease was significantly associated with an adverse outcome; no other clinical or paraclinical features appeared to affect outcome.

[Documentation of violence against civilians in a civil war. Examples from Kashmir]. / Dokumentation af overgreb mod civile i en borgerkrig. Eksempler fra Kashmir.

Physicians for Human Rights/Denmark visited Kashmir three times in 1993 and 1994. In Indian-held Kashmir we examined victims of torture and gunshots and we assessed similar evidence collected by local lawyers and doctors. In refugee camps for Indian Kashmiries we examined ten children, who were reported to have been tortured at the age of 5-14 years, and ten other children who allegedly had been ill-treated. Furthermore, 17 adults, who reported that they had been tortured, were examined. In nearly all cases there were physical findings in accordance with the histories of torture. In many cases, including those of the children, the findings were highly remarkable by their shape and localization. We interpret them as evidence of intentionally inflicted injuries. In the refugee camps we carried out a prevalence study of exposure to organized violence. Approximately 95% of all families had been exposed to violence; 35% reported that their children had been ill-treated. The physical findings indicate that intentional traumatization of civilians including children in Indian-held Kashmir takes place; the results of the prevalence study suggest that exposure to violence is widespread.

Acute meningococcal meningitis: analysis of features of the disease according to the age of 255 patients. Copenhagen Meningitis Study Group.

Clinical and laboratory features of acute meningococcal meningitis according to age were studied in 255 patients. Whereas males accounted for three out of five patients aged 0-4 years, females accounted for three out of four patients older than 50 years of age. All patients had clinical signs of nuchal rigidity and fever. Patients older than 30 years of age had less frequent petechiae (62%) than younger patients (81%). Furthermore, elderly patients above 50 years of age were prone to an obtunded mental state and a prolonged disease course with fever. Without relation to age, 2/3 had purulent meningitis and 2/3 had marked peripheral leucocytosis (> 15 x 10(9) cells/l); 90% of patients had at least one of these findings. The cellular inflammatory response in peripheral blood indicated a bacterial aetiology in > 95% of the cases. More than 80% of children and adults had abnormal CSF biochemical findings, but the level of protein and the glucose ratio (CSF/serum) were positively and negatively correlated to increasing age of the patient, respectively: thus, in children these biochemical markers may be unreliable in the differentiation between a bacterial and non-bacterial aetiology. Thrombocytopenia (< 100.000 x 10(9)/I) was not associated with age, though the lowest platelet count was found in elderly patients. The case fatality rate was 7.5%, but neither age, sex nor sign of septicaemia was associated with fatality. Thrombocytopenia, a lowered coagulation index (< 0.5, factors II, VII, X), a moderate anaemia (haemoglobin < 11 g/dl), an obtunded mental state and a history of convulsions were poor prognostic factors; only anaemia was independently correlated to fatality so this should be considered as an important prognostic marker in the acute phase of meningococcal meningitis.

A rat model of non-lethal bacterial infection.

The purpose of the study was to develop a small animal model of intraperitoneal infection without mortality and with a catabolic response to the infection, viz., to mimic the clinical situation in man. Intraperitoneal infection was induced in female Wistar rats by deposition of a gelatin capsule containing a mixture of Escherichia coli and Bacteroides fragilis and adjuvant substances. Seven groups of animals were infected with different bacterial inocula (0.2-4.3 x 10(6) CFU) to establish reproducible and dose-dependent changes in mortality, body weight in relation to food intake, blood cultures, peripheral blood leukocyte counts, and abscess formation on autopsy. No mortality was observed in animals with an inoculum below 2.2 x 10(6) CFU in spite of positive blood cultures. Initial weight loss was followed by weight gain in all animals except the group infected with the low inoculum (0.2 x 10(6) CFU). This group had no mortality, was in a catabolic state for three days, indicated by weight loss in spite of nearly normal food intake, and the infectious state was supported by intraperitoneal dissemination of small abscesses. The low-grade character of the infection was reflected by changes in peripheral blood lymphocyte and neutrophil granulocyte concentrations. In conclusion, this study presents a small animal model with a reproducible dose response to the bacterial challenge, allowing prolonged studies of metabolic changes following infection.

[Pneumococcal tricuspid valve endocarditis]. / Trikuspidalklapendocarditis med pneumokokker.

Endocarditis caused by pneumococci is a rare disease and cases that only affect the tricuspid valve represent less than 1% of all cases of endocarditis. A case presenting with a primary pneumonia and septicaemia is described. Due to persistent fever and the occurrence of a cardiac murmur echocardiography was done and demonstrated vegetations on the tricuspid valve. The course was complicated with septic pulmonary emboli before the patient recovered. Endocarditis with pneumococci may occur as a complication to a primary pneumonia and underestimation of the frequency with which it occurs is a possibility. Attention should be paid to patients with a primary pneumonia who do not respond to the initial treatment and to those who after an initial response show recurrent fever.

Acute meningitis of unknown aetiology: analysis of 219 cases admitted to hospital between 1977 and 1990.

Clinical and biochemical parameters in 219 patients with meningitis of unknown aetiology were analyzed according to their initial CSF leucocyte count. The male/female ratio was 1.1 and the median age 30 years,(males = 22 years/females = 42 years). Pre-admission antibiotic, which may inhibit bacterial growth, was given to 28% patients. On admission symptoms of meningitis were predominant: 96% had fever, 91% neck rigidity and 19% a severely affected mental state. In addition, 10% had a petechial rash. A bacterial aetiology was likely, as 91% had a predominance of polymorphonuclear leucocytes in the CSF and in 50% it was frankly purulent. The CSF leucocyte count correlated positively with age, the period of fever and the length of hospitalization, but did not relate to the 10.1% in-patient mortality rate. Mortality was related to advancing age, but not to the antibiotic regimen chosen. Patients admitted directly from their homes had the least complicated disease course and all survived. A low CSF leucocyte count, mainly found in young patients so admitted, could indicate either a non-bacterial self-limiting aetiology or diagnosis at an early stage of the disease. We found, however, that bacterial meningitis cannot be excluded on the basis of the CSF leucocyte count in combination with any clinical and biochemical parameters. Rapid hospital admission, regardless of age, is of major importance for prognosis. Improvement of non-cultural diagnostics tests and adjunctive therapy regimens are essential.

Evidence of physical torture in a series of children.

In a refugee camp for Kashmiris it was stated that children had been exposed to torture and ill-treatment; consequently, we decided to appraise the validity of such statements. Ten boys allegedly exposed to torture and 10 children who were said to have been ill-treated were interviewed and examined. The veracity of the individual statements about exposure was appraised through an assessment of the consistency between the history and the clinical findings. In all cases of alleged torture, the history was in agreement with clinical findings ascribed to torture. Torture methods included cuts with bayonets and burns with items easily available in any setting. In five of the 10 cases of torture, the scars were highly indicative of intentionally inflicted injuries, by their shapes, their presence in clusters and their localization in regions not normally exposed to traumatization. Nine of the 10 children allegedly exposed to ill-treatment had scars in accordance with their histories. In all cases, Indian security forces were said to have been responsible for the inflicted violence. The histories and the clinical findings were in accordance with results of examinations of adult victims of organized violence from the same region. On the basis of the physical evidence, in each case in agreement with the history, it is concluded that torture of children has occurred in Kashmir. Series of children with physical evidence of torture have not previously been described in the medical literature.

Characterization and quantification of plasma proteins excreted in faeces from healthy humans.

Faecal plasma protein loss was studied in 38 healthy adults. Using crossed immunoelectrophoresis and single radial immunodiffusion the most frequently found proteins were alpha 1-antitrypsin, IgA, alpha 1-antichymotrypsin (found in 97, 92, and 84% of subjects), prealbumin and IgM (both found in 55%). The major plasma proteins, albumin and IgG, were found in 37 and 13% of subjects, respectively, and in trace amounts only. alpha 2-macroglobulin could not be detected. There was no relation between the presence of proteins in faeces and their plasma concentration. When added to faeces, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and prealbumin were resistant to incubation (37 degrees C, 48 h), whereas albumin, IgG, IgM, and IgA were rapidly degraded (within 8-24 h). Some IgA was bound to secretory component, indicating enteric secretion. alpha 2-macroglobulin was semi-resistant to degradation, but its passage to the intestinal lumen may have been prevented by its molecular size. In conclusion, resistance to degradation, enteric secretion, and low molecular weight are the primary factors which favour the excretion of plasma proteins in faeces. The technique used in this study allows further studies in patients with inflammatory changes and protein-losing enteropathy.

Staphylococcus aureus meningitis: a review of 28 consecutive community-acquired cases.

From 1966 to 1989 a total of 1,830 cases of bacterial meningitis were recorded at the Department of Infectious Diseases, Rigshospitalet, Denmark. Staphylococcus aureus meningitis accounted for 44 (2.4%) of these cases. Among these, 28 cases were classified as community-acquired S. aureus meningitis. The mortality rate for these cases was 43%. A retrospective study of clinical features and parameters in these community-acquired cases showed the following conditions to be associated with a high mortality risk: advanced age, an underlying condition requiring artificial ventilation, cardiovascular disease and immune deficiencies. At admission, more than 75% of the patients had fever, nuchal rigidity and decreased consciousness. In 57% of cases the focus for the S. aureus infection was endocarditis, pneumonia or skin infections. All the patients had complications due to the meningitis, the major one being insufficient respiration. Autopsy performed in 9 of the 12 fatalities showed endocarditis in 5, pneumonia in 4, and pyelonephritis in 2. All of the brains examined at autopsy showed cerebral and subarachnoid hemorrhage.

Cerebrospinal fluid ferritin in patients with meningitis and cerebral infarction or bleeding.

The diagnostic value of cerebrospinal fluid (CSF) ferritin was assessed in 30 patients with meningeal reaction (viral meningitis 10; bacterial meningitis 6; meningism 14) and in 37 patients with cerebrovascular disease (cerebral infarction 29; transient ischaemic attacks 4; cerebral haemorrhage 4). The control group comprised 13 subjects with minor neurological disorders. CSF-ferritin levels were not significantly different in the various subgroups, most patients having values within the normal reference interval (2-7 micrograms/l). A clearly elevated CSF-ferritin was seen in one patient with bacterial meningitis and in one patient with intraventricular bleeding. In patients with meningeal reaction, CSF-ferritin was significantly correlated to CSF-protein. Patients with cerebrovascular disease displayed significant correlations between CSF-albumin and CSF-IgG and between CSF-ferritin, CSF-albumin and CSF-IgG. The present study indicates that measurement of CSF-ferritin is of no practical clinical relevance in the evaluation of patients with meningeal reaction and cerebrovascular disease.

Effects of omeprazole on neutrophil chemotaxis, super oxide production, degranulation, and translocation of cytochrome b-245.

The effects of omeprazole on polymorphonuclear neutrophil (PMN) chemotaxis, superoxide generation, degranulation and translocation of cytochrome b-245 were investigated. Omeprazole (10(-6) - 5 x 10(-3) mol/l) reduced chemotaxis under agarose in a dose dependent manner, and the effect was irreversible. Superoxide anion generation was inhibited 50% at a concentration of 2.5 x 10(-5) mol/l and completely abolished at 5 x 10(-3) mol/l. Acid degraded omeprazole also inhibited O2- generation. Omeprazole did not scavenge O2- generated in a cell free xanthin-xanthine oxidase system. Degranulation by PMNs was inhibited only by omeprazole in concentrations above 10(-4) mol/l. Translocation of cytochrome b-245, essential for generation of O2-, was not affected by omeprazole. In conclusion, the anti-ulcer agent omeprazole in concentrations obtained during intravenous administration may inhibit the function of PMNs in vitro.

Effects of sulphasalazine and its metabolites on neutrophil chemotaxis, superoxide production, degranulation and translocation of cytochrome b-245.

This study describes effects of sulphasalazine, 5-amino-salicylic acid (5-ASA) and sulphapyridine on polymorphonuclear neutrophils. Chemotaxis by polymorphonuclear neutrophils incubated with 5-ASA was reduced in a concentration dependent fashion (10(-5)-10(-4) M). Degranulation and release of lysozyme and beta-glucuronidase by activated polymorphonuclear neutrophils was inhibited by sulphasalazine but inhibited by sulphasalazine (IC50: 2 x 10(-4) M) and to a lesser extent by 5-ASA (IC50: 10(-3) M). Using a cell-free system sulphasalazine was found to be a strong scavenger and 5-ASA and sulphapyridine had only weak effects. Superoxide anion production requires translocation of a cytochrome b-245 and this translocation was reduced by sulphasalazine (P less than 0.01) but not by 5-ASA or sulphapyridine. In conclusion, the intact sulphasalazine molecule has an action of its own and marked differences exist between the action of sulphasalazine and 5-ASA, which may be important for the clinical activity.

Acyclovir in the prevention of duodenal ulcer recurrence.

This study tests the hypothesis that reactivation of a latent herpes simplex virus infection may be a cause of recurrent duodenal ulceration. Patients with recently healed duodenal ulcer were entered into a double blind, randomised study of maintenance treatment with the antiviral drug acyclovir (400 mg bid) versus placebo, to determine if suppression of herpes virus infection would influence the natural history of the ulcer disease. One hundred and fifteen patients entered the trial and 76 patients completed it according to the protocol. Endoscopy was performed when ulcer symptoms recurred and at the end of the 25 week trial period. In the acyclovir group the cumulated relapse rate was 63% compared with 56% in the placebo group (NS). This result suggests that reactivation of herpes simplex virus is not a cause of recurrent duodenal ulcer.

Polymorphonuclear leucocyte dysfunction during short term metabolic changes from normo- to hyperglycemia in type 1 (insulin dependent) diabetic patients.

Polymorphonuclear leucocyte (PMN) ingestion of particles coated with lipopolysaccharide (LPS) from Escherichia coli was compared to other PMN functions in seven patients with insulin dependent diabetes mellitus (IDDM) during short-term controlled metabolic changes from normo- to hyperglycemia without ketoacidosis. Factors known to interfere with PMN functions were excluded. PMN ingestion of particles coated with both LPS and bovine serum albumin became reduced from normo- to hyperglycemia. PMN motility was impaired in IDDM, but did not seem to be affected by short-term changes in metabolic control. PMN metabolism did not change from normo-to hyperglycemia. Particle-uptake by diabetic PMN is impaired after short term hyperglycemia in the range normally occurring in diabetics in every-day life.