Prevalence and Characteristics of Hepatitis Delta Virus Infection in a Tertiary Hospital Setting in Cameroon.

BACKGROUND/AIMS: Hepatitis B virus (HBV) and hepatitis D virus (HDV) coinfection is associated with more severe liver disease than HBV alone. More knowledge on the epidemiology and clinical impact of HDV-infected individuals is needed in Cameroon.We aimed at determining the frequency of anti-HDV antibody testing in hepatitis B surface antigen (HBsAg) positive patients, the proportion of anti-HDV positivity, and the characteristics of anti-HDV positive compared to anti-HDV negative patients in a tertiary hospital setting in Cameroon. METHODS: A cross-sectional study was conducted. Clinical records of chronic HBV-infected patients attending the gastroenterology unit at the Douala General Hospital from 2010 to 2014 were reviewed. RESULTS: Of 365 files of HBsAg-positive patients defined as chronic HBV infection, 80.5% (294) were tested for anti-HDV antibodies, among whom 10.5% (31/294) were positive. Median aspartate aminotransferase (P < 0.0001), alanine aminotransferase (P < 0.0001), and gamma glutaryl transpeptidase (P < 0.0001) were significantly higher while platelets count (P < 0.002) and prothrombin time (P < 0.0001) were significantly lower in anti-HDV positive compared to anti-HDV negative patients. Liver necroinflammation (P < 0.0001), fibrosis score (P < 0.0001), and decompensated cirrhosis (P < 0.0001) were also significantly associated with anti-HDV positivity. CONCLUSION: The proportion of anti-HDV antibody positivity remains high in this setting and was significantly associated with more severe liver disease compared to those who were anti-HDV negative. More studies are needed to evaluate rates of HDV testing in other centers in Cameroon and the subregion. Preventive strategies for HBV prevention, which also apply to HDV, must still be reinforced by healthcare providers and policy makers.

[Significance of the urine strip test in case of stunted growth]. / Intérêt de l'examen des urines à la bandelette en cas de retard de croissance.

Observation of stunted growth in children usually leads the general practitioner to refer the patient to endocrinologists or gastroenterologists. In most cases, after a complementary check-up, the diagnosis is made and treatment is initiated. However, certain cases remain undiagnosed, particularly renal etiologies, such as proximal tubulopathy. The urine strip test at the initial check-up would be an easy and inexpensive test to avoid delayed diagnosis. The aim of the present paper is to increase general physicians' and pediatricians' awareness of the significance of questioning the parents and using the urine strip test for any child presenting stunted growth. We report a patient case of a 20-month-old child admitted to the emergency department for severe dehydration. He had displayed stunted growth since the age of 5 months and showed a negative etiologic check-up at 9 months of age. Clinical examination at admission confirmed stunted growth with loss of 2 standard deviations and signs of dehydration with persistent diuresis. Skin paleness, ash-blond hair, and signs of rickets were also observed and the urine strip test showed positive pads for glycosuria and proteinuria. Polyuria and polydipsia were also revealed following parents' questioning, suggesting proximal tubulopathy (Fanconi syndrome). Association of stunted growth, rickets, polyuria and polydipsia, glycosuria (without ketonuria and normal glycemia), and proteinuria suggest nephropathic cystinosis. Ophthalmic examination showed cystine deposits in the cornea. The semiotic diagnosis of nephropathic cystinosis was confirmed by leukocyte cystine concentrations and genetic investigations. This case report clearly illustrates the significance of the urine strip test to easily and quickly concentrate the diagnosis of stunted growth on a renal etiology (glycosuria, proteinuria), especially on proximal tubulopathy for which the most frequent cause is nephropathic cystinosis. Specificity of nephropathic cystinosis treatment is that the age of treatment initiation is crucial and determinant for the prognosis of the disease and the onset of final stage renal failure. Therefore, the urine strip test should be included in the systematic check-up of stunted growth to identify any renal etiology.

Interstitial fibrosis evolution on early sequential screening renal allograft biopsies using quantitative image analysis.

Screening renal biopsies (RB) may assess early changes of interstitial fibrosis (IF) after transplantation. The aim of this study was to quantify IF by automatic color image analysis on sequential RB. We analyzed RB performed at day (D) 0, month (M) 3 and M12 from 140 renal transplant recipients with a program of color segmentation imaging. The mean IF score was 19 ± 9% at D0, 27 ± 11% at M3 and 32 ± 11% at M12 with a 8% progression during the first 3 months and 5% between M3 and M12. IF at M3 was correlated with estimated glomerular rate (eGFR) at M3, 12 and 24 (p < 0.02) and IF at M12 with eGFR at M12 and 48 (p < 0.05). Furthermore, IF evolution between D0 and M3 (ΔIFM3-D0) was correlated with eGFR at M24, 36 and 48 (p < 0.03). IF at M12 was significantly associated with male donor gender and tacrolimus dose (p = 0.03). ΔIFM3-D0 was significantly associated with male donor gender, acute rejection episodes (p = 0.04) and diabetes mellitus (p = 0.02). Thus, significant IF is already present before transplantation. IF evolution is more important during the first 3 months and has some predictive ability for change in GFR. Intervention to decrease IF should be applied early, i.e. before 3 months, after transplantation.

[Fabry disease and cystinosis, two lysosomal diseases: similarities and differences]. / Maladie de Fabry et cystinose, deux maladies lysosomales: similitudes et différences.

Fabry disease and cystinosis are both lysosomal diseases. Some clinical features (such as renal and corneal involvement) are shared by both diseases whereas many other features are different (mode of inheritance, rate of progression, mechanism of lysosomal storage, therapeutic modalities etc.). Intermediary mechanisms that lead from lysosomal overload to lesions and disease are still incompletely understood.

Interstitial fibrosis quantification in renal transplant recipients randomized to continue cyclosporine or convert to sirolimus.

Conversion from cyclosporine (CsA) to sirolimus at week 12 after kidney transplantation is associated with a significant improvement in renal function. The aim of this analysis was to investigate the effect of this conversion on interstitial fibrosis (IF), a hallmark of chronic allograft injury, in patients taking part in the CONCEPT trial. This multicenter, prospective, trial included 193 renal recipients randomized at week 12 to switch from CsA to sirolimus or to continue CsA, with mycophenolate mofetil. Routine biopsy with automated, quantified assessment of IF by a program of color segmentation was performed at 1 year in 121 patients. At 1 year, renal function was significantly improved in the conversion group as assessed by estimated GFR (MDRD) and measured GFR. Biopsy results, however, showed no between-group difference in percentage of IF. Calculated GFR at 1 year was significantly associated with the percentage of IF (p = 0.004, R(2)= 0.07). By multivariate analysis diabetic patients had more fibrosis than non-diabetic patients. In conclusion, although kidney transplant patients converted from CsA to sirolimus showed significant improvement in renal function, we found no difference of IF on 1-year biopsies.

Quantification of interstitial fibrosis by image analysis on routine renal biopsy 1 year after transplantation in patients managed by C2 monitoring of cyclosporine microemulsion.

BACKGROUND: Renal interstitial fibrosis (IF), the main histopathologic feature of chronic allograft nephropathy (CAN), may be an important surrogate endpoint for patient follow-up. IF is currently assessed by semiquantitative analysis, but automatic color image analysis may be a more reliable, reproducible method to evaluate IF. We performed a retrospective analysis to calculate IF on routine renal biopsies 1 year after transplantation. METHODS: Data were obtained from MO2ART, a prospective multicenter trial in which the cyclosporine microemulsion dose was adjusted based on C(2) levels. We included 26 patients in whom routine renal biopsy at 1 year was available from two centers. For each biopsy, a section was analyzed by a program of color segmentation image that automatically extracted green-colored areas characteristic of IF. Results were expressed as percent IF and grade namely grade I, <25%; grade II, 25% to 50%; and grade III, >50%. The results were compared according to clinical and biological data. RESULTS: The 26 patients had a mean IF score of 0.35 +/- 0.04. We observed 34.6% CAN grade I; 46.1%, grade II; and 19.2%, grade III. Serum creatinine at 3 years was greater in the higher grade of automated IF by repeated ANOVA. CONCLUSION: Automatic quantification of IF on routine biopsy at 1 year after transplantation was predictive of renal outcome. This technique may provide an interesting tool for the early diagnosis of CAN after renal transplantation.

[Pheochromocytoma: 25 years of experience. Report of 199 cases]. / Phéochromocytomes: 25 ans d'expérience. A propos de 199 cas.

The methods for diagnosing pheochromocytoma have progressed in 25 years, so changing the clinical, biological and tumoral presentations. The authors compare the features of 199 patients with pheochromocytoma operated between 1975 and 2001 by quartiles. The frequency and known duration of hypertension, plasma adrenaline, the tumour size and proportion of cases which were malignant from the outset, have decreased over the observation period (p < 0.01). The average age and proportion of familial cases or associated with diabetes or those of asymptomatic patients (with incidentaloma), has not changed significantly. The pheochromocytoma were adrenal (104 right, 60 left, 12 bilateral) or ectopic (23) and 13 were malignant from the outset. Over a median 5 year follow-up, 35 pheochromocytomas recurred either in the benign or malignant forms. Recurrences of tumours of the right adrenal were more common than those of the left adrenal gland (p = 0.03). In conclusion, pheochromocytomas are diagnosed earlier, at a stage when the tumours are smaller and less secreting. The higher incidence and recurrence rate of right adrenal pheochromocytoma remain unexplained.

Separation, identification and quantitation of ceramides in human cancer cells by liquid chromatography-electrospray ionization tandem mass spectrometry.

Ceramides are important intracellular second messengers that play a role in the regulation of cell growth, differentiation and programmed cell death. Qualitative and quantitative analysis of these second messengers requires sensitive and specific analytical methods to detect endogenous levels of individual ceramide species and to differentiate between them. Nine synthetic ceramides were separated by liquid chromatography coupled to tandem mass spectrometry on a C18 bonded silica column. The lipids were eluted in gradient elution mode using a mixture of water, acetonitrile and 2-propanol as mobile phase. They were detected by reaction monitoring performed on positive ion electrospray generated ions. Collision-induced fragmentations conducted on ceramides produced a well characteristic product ion at m/z 264, making multiple reaction monitoring (MRM) well suited for various ceramides quantitative measurements. After optimization of the extraction step, the proposed methodology was able to identify and quantify different ceramide species issued from human cancer cells. The method could be validated for C16, C18 and C20 ceramides, quantified at the nanogram level. The validation exhibits good results with respect to linearity, accuracy and precision.

Autoimmune pancreatitis mimicking cancer of the head of pancreas: report of two cases.

Autoimmune pancreatitis has been characterised in 1995, but only a few cases have been published since then, most of them from Japan. This report describes the cases of two Belgian male patients who presented with isolated obstructive jaundice. Radiological imaging studies were highly suggestive of carcinoma of the head of pancreas and both patients underwent uneventful cephalic pancreaticoduodenectomy with portal vein resection. Pathological analysis of the removed tissues suggested an autoimmune process in both cases. Both patients had hyper-gammaglobulinemia and antinuclear antibodies, but failed to show evidence of any other autoimmune disease or cause of chronic pancreatitis. In both cases final diagnosis was autoimmune pancreatitis. Preoperative clinical suspicion of this diagnosis is mandatory and may avoid unnecessary surgery in future cases.

[Clinical case of the month. Von Hippel-Lindau disease]. / Le cas clinique du mois. Maladie de Von Hippel-Lindau.

VHL disease is a rare genetical disease with a poor long-term prognosis. Clinical features include retineous angiomas, CNS hemangioblastomas, pheochromocytomas and renal cysts. Renal cysts are bilateral and frequently lead to malignant transformation. Surgical treatment of renal cysts is preferably delayed until a minimum of 3 cm diameter has been reached. Treatment has to be as conservative as possible, knowing that uni- or bilateral nephrectomy often has to be carried out later.

Structural studies on human glutathione S-transferase pi. Substitution mutations to determine amino acids necessary for binding glutathione.

In order to identify amino acids involved in binding the co-substrate glutathione to the human glutathione S-transferase (GST) pi enzyme, we assembled three criteria to implicate amino acids whose role in binding and catalysis could be tested. Presence of a residue in the highly conserved exon 4 of the GST gene, positional conservation of a residue in 12 glutathione S-transferase amino acid sequences, and results from published chemical modification studies were used to implicate 14 residues. A bacterial expression vector (pUC120 pi), which enabled abundant production (2-26% of soluble Escherichia coli protein) of wild-type or mutant GST pi, was constructed, and, following nonconservative substitution mutation of the 14 implicated residues, five mutants (R13S, D57K, Q64R, I68Y, L72F) showed a greater than 95% decrease in specific activity. A quantitative assay was developed which rapidly measured the ability of wild-type or mutant glutathione S-transferase to bind to glutathione-agarose. Using this assay, each of the five loss of function mutants showed a greater than 20-fold decrease in binding glutathione, an observation consistent with a recent crystal structure analysis showing that several of these residues help to form the glutathione-binding cleft.