Kidney biopsy in subsaharan Africa / Ponctions biopsies rénales en Afrique subsaharienne

Materials and methods: We carried out a retrospective and descriptive study on biopsies examined between January 2015 and December 2019, in the pathological departments of University Teaching Hospital of Bouaké and Cocody-Abidjan. The KB came from four countries (Côte d'Ivoire, Togo, Guinea-Conakry and Burkina Faso). Optical microscopy and/or direct immunofluorescence techniques were used. All biopsy samples including epidemiological, clinical and pathological data and an optical microscopy and/or direct immunofluorescence study were included. The parameters studied were indications for KB, epidemiological profile, clinic, proteinuria and pathological aspects. Results: Over the study period, we collected 179 KB, i.e. 35.8 KB/year. The mean age of the patients was 32.9 ±13.8 years (range 11-70 years). The sex ratio (M/F) was 1.03. Pure nephrotic syndrome was the main indication (64.2 %, n = 115) for KB, followed by impure nephrotic syndrome (11.7 %, n = 21), acute renal failure (ARF) (7.8 %, n = 14) and rapidly progressive glomerulonephritis (RPGN) (7.8 %, n = 14). Glomerulonephritis (GN) occurred in 86 % (n = 158), vascular nephropathy in 11.7 % (n = 21) and tubulointerstitial nephritis in 2.2 % (n = 4). The nephropathies were preferentially focal segmental glomerulosclerosis (34.6 %, n = 62), nephroangiosclerosis (10.6 %, n = 19), membranous GN (10 %, n = 18), post-infectious GN (8.9 %, n = 16) and lupus GN (7.3 %, n = 13). Conclusion: The KB is an essential step in the diagnosis of nephropathies. Focal segmental glomerulosclerosis is frequent in our study. The establishment of a Kidney registry would allow better knowledge of renal pathologies in sub-Saharan Africa.

La ponction biopsie rénale (PBR) constitue une avancée notable dans la prise en charge des néphropathies. En Afrique subsaharienne, peu d'études ont été réalisées. L'objectif de notre travail était d'évaluer les indications de la PBR et de déterminer les caractéristiques épidémiologiques et histologiques des néphropathies diagnostiquées en Afrique subsaharienne. Matériels et méthodes: Nous avons mené une étude rétrospective et descriptive portant sur les PBR examinées entre janvier 2015 et décembre 2019, dans les services d'anatomie et cytologie pathologiques des CHU de Cocody-Abidjan et de Bouaké. Les PBR provenaient de quatre pays africains (Côte d'Ivoire, Togo, Guinée-Conakry et Burkina Faso). Les techniques de microscopie optique et/ou d'immunofluorescence directe ont été utilisées. Nous avons inclus l'ensemble des PBR contributives sur cette période et pour lesquelles nous disposions de données cliniques et biologiques. Les paramètres étudiés étaient les données cliniques et biologiques, l'indication de la PBR et les résultats histologiques. Résultats: Sur la période d'étude, nous avons colligé 179 PBR, soit 35,8 PBR/an. L'âge moyen des patients était de 32,9 ± 13,8 ans (extrêmes de 11 à 70 ans). Le sex ratio (H/F) était de 1,03. Le syndrome néphrotique pur était la principale indication (64,2 %, n = 115) à la réalisation d'une PBR, suivi du syndrome néphrotique impur (11,7 %, n = 21), de l'insuffisance rénale aiguë (IRA) (7,8 %, n = 14) et de la glomérulonéphrite rapidement progressive (GNRP) (7,8 %, n = 14). Les glomérulonéphrites (GN) s'observaient dans 86 % des cas (n = 158), les néphropathies vasculaires dans 11,7 % (n = 21) et les néphrites tubulo-interstitielles dans 2,2 % (n = 4). Les néphropathies les plus fréquentes étaient la hyalinose segmentaire et focale (34,6 %, n = 62), la néphroangiosclérose (10,6 %, n = 19), la GN extramembraneuse (10 %, n = 18), la GN post-infectieuse (8,9 %, n = 16) et la GN lupique (7,3 %, n = 13). Conclusion: La PBR est un geste capital pour le diagnostic des néphropathies. La hyalinose segmentaire et focale est la principale nosologie retrouvée dans notre cohorte. La mise en place d'un registre Rein permettrait une meilleure connaissance et prise en charge des pathologies rénales en Afrique subsaharienne.

Antimicrobial activity of the volatile compound 3,5-dichloro-4-methoxybenzaldehyde, produced by the mushroom Porostereum spadiceum, against plant-pathogenic bacteria and fungi.

AIMS: In this study, volatile compounds released from mycelia of some aromatic mushrooms were investigated for their inhibitory activity against plant-pathogenic bacteria and fungi. METHODS AND RESULTS: A screening revealed that volatile compounds from mycelia of Porostereum spadiceum remarkably inhibited the colony formation of plant-pathogenic bacteria, including Clavibacter michiganensis subsp. michiganensis and Ralstonia solanacearum while also inhibiting the conidial germination of plant-pathogenic fungi including Alternaria brassicicola and Colletotrichum orbiculare. The volatile compounds were isolated from the culture filtrate of P. spadiceum, and 3,4-dichloro-4-methoxybenzaldehyde (DCMB) was identified as a major compound. DCMB significantly inhibited bacterial colonization at 10 µg ml-1 and fungal conidial germination at 0·1-1 µg ml-1 as a vapour. CONCLUSIONS: This is the first report on the production of the volatile compound DCMB by P. spadiceum and on the antimicrobial activity of DCMB against plant-pathogenic bacteria and fungi at low concentrations. It may be possible to use the compound as an agent for protecting crops from bacterial and fungal diseases during cultivation and storage. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides an understanding of antimicrobial activity of the mushroom volatile compound that may be useful as a novel biological control agent for protecting various plant diseases.

Severe Phlebitis Accompanying Vascular Rejection Type Acute T Cell-Mediated Rejection in Renal Transplantation.

PURPOSE: Renal transplant patients with vascular rejection type acute T cell-mediated rejection (ATCMR) grade II have a poor prognosis. Vascular lesions in those cases are thought to randomly occur, thus we searched for a novel pathological marker related to vascular rejection in kidney transplantation. METHODS: We determined pathological characteristics in 14 ATCMR grade II patients treated during an acute phase from 2004 to 2013. We then examined whether those findings appeared in transplant kidney biopsy specimens, except for cases of vascular rejection, in patients examined from 2010 to 2014. RESULTS: In 9 of the 14 ATCMR grade II patients, phlebitis was accompanied by inflammatory cells that formed polypoid projections in the venous lumen and partial disappearance of vascular endothelium. Further investigation showed those inflammatory cells to be T cells and macrophages. Histological findings revealed coexisting phlebitis in 2 of 13 patients with ATCMR grade I, 3 of 24 with borderline changes, and none with normal findings. Phlebitis occurred at a significantly greater rate than the other findings in cases of vascular rejection (P < .05). However, there was no significant difference in regard to graft survival between patients with and without phlebitis (P = .1829). CONCLUSION: Our results suggest severe phlebitis as a novel finding associated with the pathology of vascular rejection in patients with a renal allograft.

Transitional correlation between inner-membrane potential and ATP levels of neuronal mitochondria.

The importance of highly active mitochondria and their contribution to neuronal function has been of recent interest. In most cases, however, mitochondrial activity is estimated using measurements of mitochondrial inner membrane potential (IMPmito), and little is known about the dynamics of native mitochondrial ATP (ATPmito). This study conducted simultaneous imaging of IMPmito and ATPmito in neurons to explore their behaviour and their correlation during physiological mitochondrial/neuronal activity. We found that mitochondrial size, transport velocity and transport direction are not dependent on ATPmito or IMPmito. However, changes in ATPmito and IMPmito during mitochondrial fission/fusion were found; IMPmito depolarized via mitochondrial fission and hyperpolarized via fusion, and ATPmito levels increased after fusion. Because the density of mitochondria is higher in growth cones (GCs) than in axonal processes, integrated ATPmito signals (density × ATPmito) were higher in GCs. This integrated signal in GCs correlated with axonal elongation. However, while the averaged IMPmito was relatively hyperpolarized in GCs, there was no correlation between IMPmito in GCs and axonal elongation. A detailed time-course analysis performed to clarify the reason for these discrepancies showed that IMPmito and ATPmito levels did not always correlate accurately; rather, there were several correlation patterns that changed over time.

Decreased expression of Met during differentiation in rat lung.

Organ-specific stem cells play key roles in maintaining the epithelial cell layers of lung. Bronchioalveolar stem cells (BASCs) are distal lung epithelial stem cells of adult mice. Alveolar type 2 (AT2) cells have important functions and serve as progenitor cells of alveolar type 1 (AT1) cells to repair the epithelium when they are injured. Hepatocyte growth factor (HGF) elicits mitogenic, morphogenic, and anti-apoptotic effects on lung epithelial cells through tyrosine phosphorylation of Met receptor, and thus is recognized as a pulmotrophic factor. To understand which cells HGF targets in lung, we identified the cells expressing Met by immunofluorescence assay. Met was strongly expressed in BASCs, which expressed an AT2 cell marker, pro-SP-C, and a club cell marker, CCSP. In alveoli, we found higher expression of Met in primary AT2 than in AT1 cells, which was confirmed using primary AT2 cells. We further examined the mitogenic activity of HGF in AT2-cell-derived alveolar-like cysts (ALCs) in 3D culture. Multicellular ALCs expressed Met, and HGF enhanced the ALC production. Taking these findings together, BASCs could also be an important target for HGF, and HGF-Met signaling could function more potent on cells that have greater multipotency in adult lung.

Gene therapy with neurogenin3, betacellulin and SOCS1 reverses diabetes in NOD mice.

Islet transplantation for type 1 diabetes is limited by a shortage of donor islets and requirement for immunosuppression. We approached this problem by inducing in vivo islet neogenesis in non-obese diabetic (NOD) diabetic mice, a model of autoimmune diabetes. We demonstrate that gene therapy with helper-dependent adenovirus carrying neurogenin3 (Ngn3), an islet lineage-defining transcription factor, and betacellulin (Btc), an islet growth factor, leads to the induction of periportal insulin-positive cell clusters in the liver, which are rapidly destroyed. To specifically accord protection to these 'neo-islets' from cytokine-mediated destruction, we overexpressed suppressor of cytokine signaling 1 (SOCS1) gene, using a rat insulin promoter in combination with Ngn3 and Btc. With this approach, about half of diabetic mice attained euglycemia sustained for over 4 months, regain glucose tolerance and appropriate glucose-stimulated insulin secretion. Histological analysis revealed periportal islet hormone-expressing 'neo-islets' in treated mouse livers. Despite evidence of persistent 'insulitis' with activated T cells, these 'neo-islets' persist to maintain euglycemia. This therapy does not affect diabetogenicity of splenocytes, as they retain the ability to transfer diabetes. This study thus provides a proof-of-concept for engineering in vivo islet neogenesis with targeted resistance to cytokine-mediated destruction to provide a long-term reversal of diabetes in NOD mice.

Gene therapy for rhesus monkeys heterozygous for LDL receptor deficiency by balloon catheter hepatic delivery of helper-dependent adenoviral vector.

Autosomal dominant familial hypercholesterolemia (FH) is a monogenic life-threatening disease. We tested the efficacy of low-density lipoprotein receptor (LDLR) gene therapy using helper-dependent adenoviral vector (HDAd) in a nonhuman primate model of FH, comparing intravenous injection versus intrahepatic arterial injection in the presence of balloon catheter-based hepatic venous occlusion. Rhesus monkeys heterozygous for mutant LDLR gene (LDLR+/-) developed hypercholesterolemia while on a high-cholesterol diet. We treated them with HDAd-LDLR either by intravenous delivery or by catheter-based intrahepatic artery injection. Intravenous injection of ⩽1.1 × 10(12) viral particles (vp) kg(-1) failed to have any effect on plasma cholesterol. Increasing the dose to 5 × 10(12) vp kg(-1) led to a 59% lowering of the plasma cholesterol that lasted for 30 days before it returned to pre-treatment levels by day 40. A further increase in dose to 8.4 × 10(12) vp kg(-1) resulted in severe lethal toxicity. In contrast, direct hepatic artery injection following catheter-based hepatic venous occlusion enabled the use of a reduced HDAd-LDLR dose of 1 × 10(12) vp kg(-1) that lowered plasma cholesterol within a week, and reached a nadir of 59% pre-treatment level on days 20-48 after injection. Serum alanine aminotransferase remained normal until day 48 when it went up slightly and stayed mildly elevated on day 72 before it returned to normal on day 90. In this monkey, the HDAd-LDLR-induced trough of hypocholesterolemia started trending upward on day 72 and returned to pre-treatment levels on day 120. We measured the LDL apolipoprotein B turnover rate at 10 days before, and again 79 days after, HDAd-LDLR treatment in two monkeys that exhibited a cholesterol-lowering response. HDAd-LDLR therapy increased the LDL fractional catabolic rate by 78 and 50% in the two monkeys, coincident with an increase in hepatic LDLR mRNA expression. In conclusion, HDAd-mediated LDLR gene delivery to the liver using a balloon catheter occlusion procedure is effective in reversing hypercholesterolemia in a nonhuman primate FH model; however, the unsustainability of the hypocholesterolemic response during 3-4 months of follow up and heterogeneous response to the treatment remains a challenge.

Arthroscopic debridement in the treatment of patients with osteoarthritis of the elbow, based on computer simulation.

We retrospectively assessed the value of identifying impinging osteophytes using dynamic computer simulation of CT scans of the elbow in assisting their arthroscopic removal in patients with osteoarthritis of the elbow. A total of 20 patients were treated (19 men and one woman, mean age 38 years (19 to 55)) and followed for a mean of 25 months (24 to 29). We located the impinging osteophytes dynamically using computerised three-dimensional models of the elbow based on CT data in three positions of flexion of the elbow. These were then removed arthroscopically and a capsular release was performed. The mean loss of extension improved from 23° (10° to 45°) pre-operatively to 9° (0° to 25°) post-operatively, and the mean flexion improved from 121° (80° to 140°) pre-operatively to 130° (110° to 145°) post-operatively. The mean Mayo Elbow Performance Score improved from 62 (30 to 85) to 95 (70 to 100) post-operatively. All patients had pain in the elbow pre-operatively which disappeared or decreased post-operatively. According to their Mayo scores, 14 patients had an excellent clinical outcome and six a good outcome; 15 were very satisfied and five were satisfied with their post-operative outcome. We recommend this technique in the surgical management of patients with osteoarthritis of the elbow.

Carbohydrate response element-binding protein (ChREBP) plays a pivotal role in beta cell glucotoxicity.

AIMS/HYPOTHESIS: This study was aimed at the elucidation of the pathogenesis of glucotoxicity, i.e. the mechanism whereby hyperglycaemia damages pancreatic beta cells. The identification of pathways in the process may help identify targets for beta cell-protective therapy. Carbohydrate response element-binding protein (ChREBP), a transcription factor that regulates the expression of multiple hyperglycaemia-induced genes, is produced in abundance in pancreatic beta cells. We hypothesise that ChREBP plays a pivotal role in mediating beta cell glucotoxicity. METHODS: We assessed the role of ChREBP in glucotoxicity in 832/13 beta cells, isolated mouse islets and human pancreas tissue sections using multiple complementary approaches under control and high-glucose-challenge conditions as well as in adeno-associated virus-induced beta cell-specific overexpression of Chrebp (also known as Mlxipl) in mice. RESULTS: Under both in vitro and in vivo conditions, ChREBP activates downstream target genes, including fatty acid synthase and thioredoxin-interacting protein, leading to lipid accumulation, increased oxidative stress, reduced insulin gene transcription/secretion and enhanced caspase activity and apoptosis, processes that collectively define glucotoxicity. Immunoreactive ChREBP is enriched in the nucleuses of beta cells in pancreatic tissue sections from diabetic individuals compared with non-diabetic individuals. Finally, we demonstrate that induced beta cell-specific Chrebp overexpression is sufficient to phenocopy the glucotoxicity manifestations of hyperglycaemia in mice in vivo. CONCLUSIONS/INTERPRETATION: These data indicate that ChREBP is a key transcription factor that mediates many of the hyperglycaemia-induced activations in a gene expression programme that underlies beta cell glucotoxicity at the molecular, cellular and whole animal levels.

Intramural bronchogenic cyst of the oesophagus.

Bronchogenic cysts are relatively common mediastinal cysts. Here, we report removal of a rare paraoesophageal-type bronchogenic cyst by video-assisted thoracoscopic surgery in a 52-year-old male patient. The defect of the oesophageal wall was successfully reinforced with an intercostal muscle flap.

Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia.

Glycogen storage disease type Ia (GSD-Ia) stems from glucose-6-phosphatase (G6Pase) deficiency and causes hypoglycemia, hepatomegaly, hypercholesterolemia and lactic acidemia. Three dogs with GSD-Ia were initially treated with a helper-dependent adenovirus encoding a human G6Pase transgene (HDAd-cG6Pase serotype 5) on postnatal day 3. Unlike untreated dogs with GSD-Ia, all three dogs initially maintained normal blood glucose levels. After 6-22 months, vector-treated dogs developed hypoglycemia, anorexia and lethargy, suggesting that the HDAd-cG6Pase serotype 5 vector had lost efficacy. Liver biopsies collected at this time revealed significantly elevated hepatic G6Pase activity and reduced glycogen content, when compared with affected dogs treated only by frequent feeding. Subsequently, the HDAd-cG6Pase serotype 2 vector was administered to two dogs, and hypoglycemia was reversed; however, renal dysfunction and recurrent hypoglycemia complicated their management. Administration of a serotype 2 HDAd vector prolonged survival in one GSD-Ia dog to 12 months of age and 36 months of age in the other, but the persistence of long-term complications limited HDAd vectors in the canine model for GSD-Ia.

[Thymic cancer with superior vena cava invasion reconstructed by ready-made Y-graft].

A 57-year-old woman was admitted to our hospital with a complaint of left supraclavicular lymph node's swelling in January 2007. Computed tomography (CT) showed the lobulated tumor suspected of superior vena cava (SVC) invasion, located in the anterior mediastinum, 5 x 3 cm in size. The patient underwent thymectomy, resection of SVC, and partial resection of the right upper lobe. SVC was reconstructed by ready-made Y-graft (Hemashied phi 18 x 9 mm). Histopathological diagnosis was thymic cancer, poorly differentiated squamous cell carcinoma. The patient was discharged on 21st postoperative day. Postoperative radiotherapy (RT : 12.6 Gy) was canceled for the side effect. Alternatively, adjuvant chemotherapy [carboplatin (CBDCA) +paclitaxel (PTX)] was administered. Additional RT (50 Gy) was given to the lesion of local recurrence 1 and half year after the operation. The patient was alive without any signs of recurrence after RT. Left side bypass graft was patent at 8 months postoperatively, but was obliterated thereafter. Right side bypass is patent at more than 2 years postoperatively. Ready-made Y-graft can be one of the choices of SVC reconstruction.

Laser ion source: a direct plasma injection scheme for two-beam type interdigital-H radio frequency quadrupole linac.

We developed a laser ion source using a direct plasma injection scheme (DPIS) as an injection system for a two-beam type radio frequency quadrupole (RFQ) linac with an interdigital-H (IH) type cavity. The laser ion source in the DPIS is directly connected to the RFQ cavity without the low energy beam transport system. We achieved a high current C(2+) beam above 60 mA per beam channel from the ion source. The beam will be injected to the two-beam type IH-RFQ linac, and the linac will generate a beam current of approximately 44 mA per beam channel.

Clinicopathological study of expression of lymphatic vessels in renal allograft biopsy after treatment for acute rejection.

BACKGROUND: Lymph vessel expression is related to inflammatory cell infiltration, around renal tubules in acute rejection episodes (ARE) of transplanted kidneys. However, there is little information on the lymph vessels after treatment of an ARE, particularly in relation to renal function and histological findings. PATIENTS AND METHODS: We investigated 13 cases of ARE diagnosed by kidney transplant biopsy performed from 1997 to 2005 within 3 years of transplantation. Treatment of the ARE lead to an improved serum creatinine level in all cases. There was neither an ABO-incompatible nor an acute humoral rejection case. Lymphatic vessels in re-biopsies were examined using immunohistochemical staining with D2-40 antibody that detected lymphatic endothelium. Re-biopsy cases in which the baseline creatinine had increased by more than 20% despite treatment were considered the severe group; the others, as the stable group. The relation between lymphatic vessel density (LVD) and renal function was examined using Banff scores. RESULTS: LVD was significantly higher in the severe than the stable group. The expression of lymph vessels versus the Banff score showed a direct relation: greater Banff scores showed higher expressions of lymph vessels. CONCLUSIONS: The expression of lymph vessels in renal allograft specimens after treatment of an ARE was related to deterioration of renal function and inflammatory cell invasion. We plan a further examination of the relationship between the expression of lymph vessels and long-term prognosis.

Benign metastasizing leiomyoma of the lung: potential role of low-grade malignancy.

We report here 2 cases of multiple metastatic lung tumors after hysterectomy for leiomyoma. One patient was diagnosed as having a benign metastasizing leiomyoma (BML), while the other patient simultaneously developed a left pelvic tumor and multiple lung tumors, both of which were finally diagnosed as low-grade endometrial stromal sarcomas (ESSs). The metastatic potential of BML is not completely understood, but previously reported cases of BML may include low-grade ESS, which may play a significant role in the metastasis of benign uterine tumors.

Immediate radical fang mark ablation may allow treatment of japanese viper bite without antivenom

Administration of antivenom is currently the standard treatment for snake envenomation. However, it can sometimes cause anaphylactic reactions including urticaria, bronchospasm and hypotension. Furthermore, it may also provoke life-threatening complications, even though the mortality rate is less than 1 percent. In this study, we present a new treatment - immediate radical fang mark ablation - that was successfully performed on five victims of Japanese viper bites without antivenom use. In these five victims of venomous snakebites, surgical debridement was immediately performed. Two patients received a free-skin graft to resurface their wounds while three of them healed conservatively (i.e. by ointment treatment without surgery). After treatment, all patients could return to work. Immediate radical ablation is a recommended procedure that can reduce the amount of venom in tissues, which consequently decreases inflammatory reactions and reduces the necessity for antivenom.(AU)

[Subdural hematoma following cardiac surgery].

We report 3 cases of subdural hematoma following open heart surgery under cardiopulmonary bypass. In 2 patients, emergency removal and drainage of a subdural hematoma was performed by neurosurgeons, and conservative management was performed in the remaining one. All patients belonged to a high risk group of bleeding due to anticoagulation therapy, and they had no episode of head trauma. Subdural hematomas may have been due to rapid alterations in cerebral volume, leading to a tearing of the dural bridging veins under cardiopulmonary bypass. Although early diagnosis and prompt treatment is very important, it is often difficult to examine neurological findings after cardiac surgery. We consider that patients who need long-term sedation under anticoagulation therapy must have their neurological status checked at least once in a few days.

A clinicopathologic study of p27(kip1) expression in renal allograft biopsy.

BACKGROUND: P27 (Kip1) is an inhibitor of cyclin-dependent kinases/cyclin complex that keeps mature cells growth-arrested. In IgA nephropathy, a decreased p27kip1 expression in podocytes has been reported to be related to lesion formation of focal segmental glomerulosclerosis and renal dysfunction. We reviewed the p27kip1 expression in transplanted kidneys. METHODS: p27kip1 expression was examined immunohistochemically in 26 allograft biopsy specimens. RESULTS: p27kip1 expression was recognized in podocytes. Patients with more than 0.5 g proteinuria showed fewer p27kip1-positive cells than those with less than 0.5 g proteinuria. The decreased p27kip1 expression in podocytes was related to cg and ah of the Banff 97 classification. In the two cases in which p27kip1 expression was remarkably decreased, elevation of the serum creatinine level was recognized at the time of biopsy, resulting in kidney transplant loss. The histological findings were chronic/sclerosing allograft nephropathy grade II-(b) in both cases. CONCLUSION: In conclusion, decreased p27kip1 expression in podocytes suggested a significant role in proteinuria among renal transplant recipients.