In-vivo studies of targeted and localized cancer drug release from microporous poly-di-methyl-siloxane (PDMS) devices for the treatment of triple negative breast cancer.

Triple-negative breast cancer (TNBC) treatment is challenging and frequently characterized by an aggressive phenotype and low prognosis in comparison to other subtypes. This paper presents fabricated implantable drug-loaded microporous poly-di-methyl-siloxane (PDMS) devices for the delivery of targeted therapeutic agents [Luteinizing Hormone-Releasing Hormone conjugated paclitaxel (PTX-LHRH) and Luteinizing Hormone-Releasing Hormone conjugated prodigiosin (PG-LHRH)] for the treatment and possible prevention of triple-negative cancer recurrence. In vitro assessment using the Alamar blue assay demonstrated a significant reduction (p < 0.05) in percentage of cell growth in a time-dependent manner in the groups treated with PG, PG-LHRH, PTX, and PTX-LHRH. Subcutaneous triple-negative xenograft breast tumors were then induced in athymic female nude mice that were four weeks old. Two weeks later, the tumors were surgically but partially removed, and the device implanted. Mice were observed for tumor regrowth and organ toxicity. The animal study revealed that there was no tumor regrowth, six weeks post-treatment, when the LHRH targeted drugs (LHRH-PTX and LHRH-PGS) were used for the treatment. The possible cytotoxic effects of the released drugs on the liver, kidney, and lung are assessed using quantitative biochemical assay from blood samples of the treatment groups. Ex vivo histopathological results from organ tissues showed that the targeted cancer drugs released from the implantable drug-loaded device did not induce any adverse effect on the liver, kidneys, or lungs, based on the results of qualitative toxicity studies. The implications of the results are discussed for the targeted and localized treatment of triple negative breast cancer.

[Epidemiology and outcome of Congolese children who had surgery for heart defects]. / Épidémiologie et devenir des enfants congolais opérés pour cardiopathies congénitales.

AIMS: to determine the principal heart defects for which children underwent surgery and to determine the survival rate. PATIENT AND METHODS: this retrospective cohort study involves Congolese babies treated surgically from September 1989 to September 2010 in France for congenital heart defects (through "Mécénat chirurgie cardiaque" and "Chaîne de l'espoir"). It includes only 110 of the 182 recorded patients during the study period. RESULTS: The sex ratio for the 110 subjects included in the analysis was 1. Their mean age at surgery was 77.4 ± 57.6 months old (range: 8 to 204 months). The main congenital heart defects for which surgery was performed were ventricular septal defect (21.9%), tetralogy of Fallot either isolated (22.8%) or associated with patent foramen ovale (1.8%) or coronary anomalies (1.8%), atrial septal defect associated with other malformations (8.2%), pulmonary atresia with ventricular septal defect (5.5%), aortic stenosis (3.7%), atrioventricular septal defect (0.9%), and Laubry-Pezzi syndrome (0.9%). The median length of follow-up was 42.4 ± 35.6 months (range, 3-240 months). Patients' mean age at the study's end was 121.1 ± 86.3 months (range 20-372 months). The 5-year survival rate was 90% and the 20-year survival, 83.3%. CONCLUSION: Heart surgery for congenital heart defects has improved survival.

[Short-term prognosis of heart diseases managed at the pediatric intensive care unit of the Brazzaville University Hospital]. / Pronostic immédiat des cardiopathies prises en charge dans le service des soins intensifs pédiatriques du CHU de Brazzaville.

OBJECTIVE: To determine the main heart diseases of children admitted to our pediatric intensive care unit. PATIENTS AND METHODS: This cross-sectional study was conducted in 2011 (January to December) in the pediatric intensive care of the Brazzaville University Hospital. RESULTS: The study included 42 children, 27 of them girls (64.3%). Their mean age was 2.6 ± 3.4 years, and the mean age of their mothers 26.6 ± 5.1 years. The reasons for admission were dyspnea (n = 34, 81%), fever (n = 21, 50%), edema syndrome (n = 8, 19%), squatting (n = 5, 12%), impaired consciousness (n = 4), seizures (n = 3, 7.1%), shock (n = 2, 4.8%), and malaise (n = 1, 2%). Associated signs included coughing (n = 30, 71.4%), impaired general condition (n = 14, 33.3%), cyanosis (n = 9, 21.4%), and chest deformity (n = 15, 35.7%). Heart failure was found in 28 cases (66.7%), as was congenital heart disease. The main heart diseases were ventricular septal defects (n = 13), cardiomyopathy (n = 9), and the tetralogy of Fallot (n = 6). The most common factors of decompensation were anemia (n = 12, 28.6%) and bronchopneumonia (n = 11, 26.2%). The immediate mortality rate was 23.8%. CONCLUSION: The heart diseases in children admitted in critical situations usually required surgical care, not available in our country. Rapid treatment is possible by strengthening South-South cooperation with neighboring countries where cardiac surgery is available.

[Priapism in children and adolescents with homozygous sickle cell disease in Brazzaville]. / Priapisme chez l'enfant et l'adolescent drépanocytaire homozygote à Brazzaville.

OBJECTIVE: To determine the prevalence of priapism, assess knowledge and appreciate its characteristics in childhood sickle cell disease. METHODOLOGY: A case-control study was conducted at the University Hospital of Brazzaville (Department of Pediatrics, Hematology and Clinical Urology). The cases consisted of 202 sickle cell anemia who are at least 5 years. Witnesses consisted of 112 children with sickle cell disease not of the same age from the same family as the previous. RESULTS: Priapism was found in 68 (34%) affected children, divided into 54 cases (79.4%) of chronic intermittent priapism and 14 cases (20.6%) of acute priapism. In the control group no cases were observed (p=0.001). Priapism was known by six (3%) patients in the group of children with sickle cell disease. In the control group, it was known by 25 (22.3%) children. It was seen in the group of sickle cell disease as any: 113 children (56%), a natural phenomenon that can occur in life: 57 children (28%), a complication of sickle cell disease: 26 children (13%). In the control group, it was considered a natural phenomenon that can occur in life: 60 children (53.6%), a complication of sickle cell disease: 52 children (46.4%). The average age of priapism occurred in the first episode was 10.4±9.5 years. CONCLUSION: The importance of the prevalence of priapism, and insufficient knowledge needed strengthening information, education and communication with children and their parents.

[Tooth decay in school environment at Brazzaville (Congo)]. / La carie dentaire en milieu scolaire a Brazzaville (Congo).

AIM: To determine the frequency of dental caries and habits that can be the cause of this disease in Brazzaville. METHODS: A prospective study was conducted in primary schools between February and May 2010. This study involved a sample of 307 students of both sexes, aged 4-15 years from school in the city of Brazzaville. RESULTS: Prevalence of dental caries was 53.4% and the index of DMFT 2.06. Use of toothbrush was 99.4%. Two children (0.7%) brushed their teeth three times a day. There was a statistical link between regularity of brushing and occurrence of caries. The prevalence of caries was of 53% in children who brushed once a day and 12.8% in those who brushed twice a day. No decay was noted in those who brushed three times a day (p = 0.001). The DMFT was 2.06 in children who used non-fluoridated toothpaste and 1.13 in those who used the fluoridated toothpaste (p = 0.002). CONCLUSION: To ensure students a better oral hygiene and healthier teeth, a module in oral health education in schools is one of the way to fight against this public health problem.

[Determinants of cerebral malaria in Congolese children]. / Déterminants du neuropaludisme en milieu pédiatrique congolais.

Malaria still constitutes a worrying problem of public health. It remains an important cause of infant mortality. To determine the determinants of severe malaria a case control study was carried out from July to December 2011 in the pediatric intensive care department of the university hospital of Brazzaville. The group included 230 children hospitalised for severe malaria, and the control group consisted of children followed up for non-severe malaria. Cases and controls were compared using statistical tests for matched group. The young age of the mother (OR=4.13), her poor education level (OR=2.36), the low socioeconomic level of parents (OR=5.90), the malnutrition (OR=2.67), the delay of consultation (OR=13.69) and parasitemia were associated with significantly higher risk of severe malaria. The importance of identified determinants imposes the implementation of primary prevention measures, which pass through the amelioration of socioeconomic and cultural conditions of populations, the reinforcement of sanitary education, and also a secondary prevention consisting of an early and accurate management of ordinary malaria.

Time resolved chromatograms in ultra-thin layer chromatography.

Ultrathin-layer chromatography (UTLC) is a recently developed analytical method intended for compact, rapid separations of nanolitre analyte volumes. Optimizing this method's performance requires new measurement techniques compatible with the millimetre length scales and rapid separation dynamics observed in UTLC. We have designed, implemented and characterized a measurement system which records UTLC separations in full color with 32 µm spatial resolution and 33 ms temporal resolution. Our code analyzes multiple tracks per plate, filters analyte spots by color, and automatically generates time-resolved figures of merit. The instrument presented here captures a wealth of information from a UTLC separation, and should provide insight into UTLC physics and improved analytical performance.

Morphological modification of nanostructured ultrathin-layer chromatography stationary phases.

Ultrathin-layer chromatography (UTLC) provides the high sensitivities and rapid separations over short distances desirable in many analytical applications. The dependence of these performance benefits on UTLC layer microstructure motivates continued stationary phase engineering efforts. A new method of modifying the elution behaviours of nanostructured thin film UTLC stationary phases is investigated in this report. Macroporous normal phase silica thin films ∼5 µm thick were fabricated using glancing angle deposition (GLAD). Reactive ion etching (RIE) and a subsequent annealing treatment modified stationary phase morphology to tune migration velocity, analyte retention, and overall separation performance. Combining this technique with a RIE shadow mask enabled fabrication of adjacent concentration and separation zones with markedly different elution properties. Although produced using an entirely new approach, GLAD UTLC concentration zone media behaved in a manner consistent with traditional thin-layer chromatography (TLC) and high-performance TLC (HPTLC) concentration zone plates. In particular, these new media focused large volume, low concentration dye mixture spots into narrow bands to achieve high-quality separations. The described approach to modifying the morphology and resultant elution behaviours of nanostructured stationary phases expands the capabilities of the GLAD UTLC technique.

Analyte migration in anisotropic nanostructured ultrathin-layer chromatography media.

We investigate the performance of highly anisotropic nanostructured thin film ultrathin-layer chromatography (UTLC) media with porosity and architecture engineered using the glancing-angle deposition (GLAD) process. Our anisotropic structures resemble nanoblades, producing channel-like features that partially decouple analyte migration from development direction, offering new separation behaviours. Here we study GLAD-UTLC plate performance in terms of migration distance, plate number, retention factor and a figure of merit specific to GLAD-UTLC, track deviation angle. Migration distances increase with porosity by a factor of two for all feature orientations (up to a maximum of 22 mm) over the range of porosities considered in this study. Plate numbers approaching 1100 are observed for GLAD-UTLC plates when the nanoblade features are aligned with the development direction. We present a theoretical model describing mobile phase flow in anisotropic GLAD-UTLC media, and find good agreement with experimental results. Our plates provide channel features that reduce transverse spot broadening while providing the wide pores required for rapid migration and high separation performance. These improvements may enable a greater number of parallel separations on miniaturized GLAD-UTLC plate formats. Their small sizes should also make them compatible with the Office Chromatography concept in which office peripherals (inkjet printers and flatbed scanners) replace conventional TLC instruments. Equipped with a better understanding of the unique GLAD-UTLC elution behaviours, we expect to further improve performance in the future.

[Childhood laterocervical abscess fistulized in the pharynx: a case study]. / Abcès latérocervical de l'enfant fistulisé dans le pharynx: à propos d'un cas.

Cervical adenophlegmon is frequently encountered in children. We report on a case of an exceptional direct communication between a retropharyngeal abscess and a cervical adenophlegmon, observed in a 25-month-old child. Treatment comprised double antibiotic therapy and retropharyngeal drainage, which led to the subsidence of the laterocervical abscess. The progression was uncomplicated.

[Pathological fracture revealing an osseous histoplasmosis. A case report on a 60-year patient]. / Fracture pathologique révélant une histoplasmose osseuse. A propos d'une observation chez une patiente de 60 ans.

The authors report a new case of African Histoplasmosis in a 60-year-old patient. It was an humeral localization revealing a pathological fracture which grew into an extension of osteolysis and a cutaneous fistulization likely to be a malignant bone tumor. The case has been diagnosed by surgical biopsy and histological analysis. Its antifungal treatment in progress resulted in the drainage of the out-flow that should permit the bone reconstruction by graft. The authors stress on the need to focus on this affection whenever, in a tropical area, one is faced with any chronic bone fistula that cannot positively be cured in spite of sound medical cares.

Effects of angiotensin IV and angiotensin-(1-7) on basal and angiotensin II-stimulated cytosolic Ca2+ in mesangial cells.

This study analyzed the influence of two main metabolites of angiotensin II, angiotensin IV and angiotensin-(1-7), on basal and angiotensin II-dependent [Ca2+](i) in rat mesangial cells. Angiotensin IV behaved as a weak agonist. Its effects were abolished by angiotensin AT(1) receptor antagonists. Treatment with angiotensin II abolished the effect of a subsequent treatment with angiotensin IV whereas two successive angiotensin IV-dependent [Ca2+](i) peaks were obtained. Angiotensin II increased [Ca2+](i) in a Ca2+-free medium whereas angiotensin IV was inactive. Leucine-valine-valine-hemorphin 7, a hemorphin specific for the angiotensin AT(4) receptor, was devoid of any agonistic or antagonistic effect. In contrast, angiotensin-(1-7), if without influence on basal [Ca2+](i), inhibited angiotensin II- and angiotensin IV-dependent [Ca2+](i) increases. Total inhibition of the angiotensin IV effect was obtained whereas association of angiotensin-(1-7) to 8-(NN-diethylamino)-octyl-3,4,5-trimethoxybenzoate, an inhibitor of inositol phosphate-mediated Ca2+ release, was necessary to suppress the effect of angiotensin II. These results provide evidence that angiotensin II metabolites may participate in the control of [Ca2+](i) in mesangial cells at the initial stage of binding to the angiotensin AT(1) receptors.

[Post-transplant nephropathy and arterial hypertension]. / Nadcisnienie tetnicze a przewlekla nefropatia potransplantacyjna.

The introduction of new immunosuppressive regimens results in the significant improvement in the outcome of patients after kidney transplantation. However, about 5 percent of renal transplants are lost every year. Not only immunological (alloantigendependent) but also nonimmunological (alloantigen-independent) factors are involved in late graft loss. Among them, hypertension, hyperlipidemia, proteinuria, genetic predisposition, viral infection and nephrotoxicity of immunosuppressive drugs contribute to the development and to the progression of chronic post-transplant nephropathy. Hypertension can be both the cause and the consequence of chronic allograft failure. Hypertension is frequently observed before transplantation, persists after grafting and increases the risk of chronic allograft nephropathy. Hypercholesterolemia, obesity, atheromatosis, polycythemia, and excessive salt intake are factors contributing in post-transplant hypertension. However, in some cases, hypertension can be transferred with the grafted kidney, as observed in normotensive patients before renal transplantation. In 1 to 12 percent of cases, the cause of post transplant hypertension is the stenosis of the transplant artery. Sometimes the presence of hypertension in renal recipients may result from the recurrence of glomerulonephritis or from the development of glomerulonephritis de novo in the graft. Also immunosuppressive treatment with corticosteroids and cyclosporine A contributes to the increased prevalence of hypertension by 20-30 percent. The development of the graft nephroarteriolosclerosis as a consequence of hypertension accelerates the progression of the post-transplant nephropathy. Adequate control of the arterial pressure (< 140/90) should be achieved in all renal transplant recipients. Reduction in protein and salt intake is important to reduce hyper-filtration and slows the progression of transplant nephropathy. However, pharmacological treatment is usually needed. Angiotensin-converting-enzyme inhibitors, angiotensin II type I receptor antagonists exhibit beneficial hemodynamic effect leading to the reduction of glomerular hypertension and proteinuria. Calcium antagonists besides their systemic antihypertensive effect, can protect renal grafts from vascular and renal toxicity of CyA. Sometimes, combined therapy with these and other antihypertensive drugs and diuretics is necessary.

[A case of rapidly progressive glomerulonephritis in the course of Wegener's granulomatosis]. / Przypadek gwaltownie postepujacego klebuszkowego zapalenia nerek w przebiegu choroby Wegenera.

Wegener's granulomatosis (WG) is characterized by granulomatous vasculitis of the respiratory tract and glomerulonephritis (GN). Prognosis of this disease is poor and about 20% of untreated patients die after one year from the onset. WG was recognized in 45-year-old patient on the basis of: 1) clinical symptoms (joint pain and swollen, purpura on the skin which appeared one week after respiratory tract infection, ulceration of the tonsils and lingula), 2) results of additional testing (X-chest-ray-infiltrates of both lungs), positive results of the cANCA (titre 1:640) and rapidly progressive renal failure [the increase of serum creatinine level (Pcr) from 123.7 to 707 mumol/l (1.4 to 8.0 mg/dl) during one week]. Renal biopsy revealed extracapillary GN (cellular crescents in 7 out of 8 glomeruli and scattered foci of fibrinoid necrosis of capillary walls in all). At the beginning of the treatment Pcr raised to 884 mumol/l (10 mg/dl) and the patient required hemodialysis. He was treated with methylprednisolone (M) at flash doses of 1000 mg/24 h by three days followed by 125 mg/24 h i.v.--because of peptic ulcer, with cyclophosphamide (C-150 mg/24 h p.p.), with trimetoprim/sulphametoxazole, with pentoxifylline and omeprazol. After six weeks of the treatment in the control kidney biopsy sclerotic changes in 10 out of 13 glomeruli and diffuse interstitial fibrosis were found. However, during the same time, we observed clinical remission of the disease and the decrease of Pcr to 176.8 mumol/l (2 mg/dl). The M dosis was reduced by 5 mg every weeks and the C dosis--to 50 mg (because of the increase of aminotransferase levels) After six months of the treatment Pcr was 132.6 mumol/l (1.5 mg/dl) and CANCA titer was 1:16. In this case of RPGN, despite off the progression of the morphological changes in the kidney, we obtained the clinical remission of the disease and significant decrease of Pcr level. These results suggest that aggressive treatment of WG is justified even in patients with advanced renal failure requiring dialysis and in such patients clinical remission is possible to occur.

[Comparative study of two immunosuppressive treatment methods in patients with focal segmental glomerulosclerosis]. / Porównanie dwóch metod leczenia immunosupresyjnego u chorych na ogniskowa segmentalna sklerotyzacje klebuszków nerkowych.

Focal segmental glomerulosclerosis (FSGS) is a glomerular disease of varying severity. Most patients, however, develop end-stage renal failure within 10 years from clinical onset. In this retrospective study, the outcome of immunosuppressive treatment in 22 adult patients with biopsy-proven primary FSGS was evaluated. Eleven patients were treated with prednisone, azathioprine and chlorambucil (group A) and 11 with prednisone and pulse cyclophosphamide (group B). The nephrotic syndrome (NS) was found in 4 patients from the group A and in 3 patients from the group B, arterial hypertension in 8 and 9 patients, respectively. During the follow-up lasting about 50 months as the mean, 70% of the patients did not respond to the treatment and complete remission was obtained only in 3 patients from the group B. On the other hand, 7 patients progressed into CFR. Among them, 5 out of 7 patients with NS (4 from the group A) needed dialysis treatment or doubled their Pcr after a mean of 38 months. This study confirms poor outcome of immunosuppressive treatment in patients with FSGS. However, of the two forms of treatment used in the study, the response appeared to be better and more lasting with cyclophosphamide than with azathioprine and chlorambucil. Corticosteroids associated with pulse cyclophosphamide therapy seems to improve the chances of remission and to protect from renal dysfunction.