A locus for spondylocarpotarsal synostosis syndrome at chromosome 3p14

Spondylocarpotarsal synostosis syndrome is a rare autosomal recessive disorder characterised by vertebral fusions, frequently manifesting as an unsegmented vertebral bar, as well as fusions of the carpal and tarsal bones.

In a study of three consanguineous families and one non-consanguineous family, linkage analysis was used to establish the chromosomal location of the disease gene. Linkage analysis localised the disease gene to chromosome 3p14. A maximum lod score of 6.49 (q = 0) was obtained for the marker at locus D3S3532 on chromosome 3p. Recombination mapping narrowed the linked region to the 5.7 cM genetic interval between the markers at loci D3S3724 and D3S1300. A common region of homozygosity was found between the markers at loci D3S3724 and D3S1300, defining a physical interval of approximately 4 million base pairs likely to contain the disease gene.

Identification of the gene responsible for this disorder will provide insight into the genes that play a role in the formation of the vertebral column and joints.

     

Potential predictors of the onset of focal intestinal perforation in extremely low birth weight infants based on an analysis of coagulation and fibrinolysis markers at birth: A case-control study based on ten years of experience at a single institution

Purpose: We aimed to investigate potential predictors of focal intestinal perforation (FIP) in extremely low birth weight infants (ELBWIs) among coagulation and fibrinolysis markers at birth.Methods: We reviewed the medical records of FIP patients and their coagulation and fibrinolysis markers at birth between 2010 and 2019, and matched patients according to gestational age. FIP was diagnosed based on macroscopic intestinal perforation with a punched-out lesion without necrosis. Patient characteristics and blood test results, including coagulation and fibrinolysis marker levels, were compared between the groups.Results: Two hundred forty ELBWIs were enrolled in this study (FIP, n = 18; controls, n = 222). In the FIP group, the gestational age at birth was significantly younger (p = 0.023) and the birth weight was significantly lower (p = 0.007) in comparison to the control group. Furthermore, the FIP group showed significantly lower levels of fibrinogen (p = 0.027) and factor XIII (F-XIII) (p = 0.007). The receiver operating characteristics curves for fibrinogen and F-XIII revealed that the 95% confidence intervals of fibrinogen and F-XIII were 0.530–0.783 (p = 0.027), and 0.574–0.822 (p = 0.007), respectively.Conclusions: This is the first report focusing on coagulation and fibrinolysis markers in FIP patients at birth. The fibrinogen and F-XIII values at birth are potential predictors of FIP in ELBWIs.Type of Study: Study of Diagnostic Test (Case Control Study)Level of Evidence: Level IV     

Tacrine hydrochloride treatment IND: methods for rapid physician and patient enrollment and data retrieval

A Treatment IND (TIND) is a mechanism available to the Food and Drug Administration (FDA) in the United States by which promising new drugs can be provided to patients with life-threatening illnesses. In many instances, the illness is life-threatening but of relatively low incidence, making the demand for the new treatment limited. However, if the disease is more prevalent and incidence is increasing, the demand for access to an experimental therapy may be substantially greater. Novel approaches and technologies would help manage recruitment of physicians, enrollment of patients and retrieval and timely analysis of data. Such was the case in the TIND for tacrine hydrochloride (Cognex), a cholinesterase inhibitor which was under development for the treatment of patients with Alzheimer's Disease (AD). There were an estimated 4 million prevalent cases of AD in the US for which no approved therapeutic option was available at the time this TIND was initiated. We anticipated that there could be a large demand by both physicians and patients to enroll in the TIND. Therefore, to meet this demand, various mechanisms were employed to allow rapid enrollment and drug shipments to the patient. In addition, physicians who participated in the TIND were able to use a telephone touch-tone data entry system for reporting data and ordering new supplies of tacrine for their patients. Serious adverse events were reported directly to trained operators and summarized on a weekly basis for reporting to the FDA. At the time the programme was terminated, nearly 2000 physicians had enrolled to participate in the TIND and nearly 10,000 patients had received tacrine under the programme. The methods employed in this study to collect clinic visit and safety data met both regulatory and good clinical practice guidelines. In summary, a large volume of data was handled rapidly and efficiently in this programme.     

Lethal persistent pulmonary hypertension of the newborn in Bohring–Opitz syndrome

Bohring–Opitz syndrome (BOS) is a rare disease with a number of characteristic features, including hypertelorism, prominent metopic suture, exophthalmos, cleft palate, abnormal posture, and developmental retardation. Here, we report a BOS patient presenting with lethal persistent pulmonary hypertension of the newborn (PPHN) and inspiratory respiratory failure. The female infant was treated with nitric oxide and vasodilator, which did not improve her condition. The inspiratory respiratory failure required management with deep sedation. She died on postnatal day 60 due to progressed heart failure. Whole exome sequencing revealed de novo mutation in the ASXL1 gene, c.1934dupG, p.Gly646TrpfsTer12.     

Étude de la relation entre le reflux gastro-oesophagien (RGO) et l’infection à helicobacter pylori (H.pylori) à Kinshasa

Background

Relationship between gastro esophageal reflux disease (GERD) and H. pylori infection is controversial.

Aim

To study the relationship between GERD and H. pylori infection in Kinshasa where the prevalence of this infection is high.

Patients and Methods

Two hundred consecutive patients underwent an upper gastro-intestinal tract endoscopy with gastric biopsies. Data were collected on patient’s age, sex, weight, alcohol and NSAIDs intake, symptoms, endoscopy and histopathology of gastric biopsies. The endoscopic esophagitis was scored using the Los Angeles classification. Two biopsy specimens were obtained from the antrum and two from the corpus for histological assessment. Giemsa method was used for H. pylori research.

Results

Two hundred patients were included. There were 77 (38,5%) men and 123 (61,5%)women with a mean age of 47, 5±14, 3 years. A statically significant relation was found between heartburn, regurgitation, eructation and GERD. Prevalent rate of GERD was 32%. No association was found between H. pylori infection and GERD.

Conclusion

GERD is frequent in Kinshasa. There is no relationship between GERD and H. pylori infection.     

Expression of vascular endothelial growth factor and its receptors after mandibular distraction osteogenesis

During distraction osteogenesis, angiogenic activity is essential for new bone formation. This study examined the expression of vascular endothelial growth factor (VEGF) and two of its receptors, Flt-1 (VEGFR-1) and Flk-1 (VEGFR-2), in cellular components after mandibular distraction osteogenesis. Unilateral mandibular distraction (0.5 mm twice per day for 10 days) was performed in six mongrel dogs. Two animals each were killed on days 7, 14 and 28 after completion of distraction. The distracted mandibular segments and contralateral undistracted control segments were harvested and processed for immunohistochemical examination. Seven days after distraction, there was a significant increase in the expression levels of VEGF and its receptors in the osteoblasts, osteocytes and immature fibroblast-like cells compared to control specimens. These levels were maintained for 14 days after distraction in the osteoblasts and fibroblast-like cells. Twenty-eight days after distraction, VEGF and VEGFR-1 were expressed only moderately/weakly in the osteoblasts, and no VEGFR-2 expression was detected in the cellular component of the distracted bone. Throughout the observation period, VEGFR-1 expression was stronger than that of VEGFR-2. The expression patterns of VEGF and its receptors suggest that it plays an important role in osteogenesis, and that osteoblasts and immature fibroblast-like cells of the distracted bone may have an autocrine growth effect during distraction osteogenesis.     

Un angiome géant révélé par une volumineuse masse abdominopelvienne

Hemangioma is the most frequent benign tumor of the liver. Being asymptomatic, it is often discovered accidentally on echography. The hemangioma is said to be giant when its diameter exceeds 4 cm, and may pose diagnostic problems. We report the medical observation of a 31-yearold patient presenting with huge angioma of the liver revealed by a huge abdominopelvic mass with no sign or other compressive complications. Abdominal echography and CT scan were not able to make with certitude the diagnosis of the mass. Laparotomy allowed excision of the mass and the diagnosis of huge angioma.     

Experimental and clinical studies on BRL 25000 (clavulanic acid-amoxicillin) granules in the pediatric field

Fundamental and clinical studies have been performed on BRL 25000 (clavulanic acid 1 part-amoxicillin 2 parts) granules in the pediatric field. The antibacterial activities of BRL 25000 and amoxicillin (AMPC) were investigated against clinically isolated and laboratory stocked strains. BRL 25000 was superior to AMPC against strains of E. coli, Salmonella sp. and Klebsiella sp., and similar against Gram-positive cocci. Serum concentrations of AMPC and clavulanic acid (CVA) were measured 0.25, 0.5, 1, 2, 4 and 6 hours after administration of BRL 25000 granules at dose levels of 7.5, 10, 15 and 20 mg/kg. At 7.5 mg/kg peak level of AMPC of 2.69 micrograms/ml was achieved about 2 hours after dosing with a biological half-life of 1.64 hours; corresponding value for CVA was 0.53 micrograms/ml at 1 hour with a T 1/2 of 1.46 hours. At 10 mg/kg, AMPC also peaked after 2 hours (3.82 micrograms/ml) and the T 1/2 was 1.63 hours, whilst for CVA the value was 0.56 micrograms/ml with a T 1/2 of 1.24 hours. Value for AMPC at 15 mg/kg was 5.18 micrograms/ml at 1 hour post dose with a T 1/2 of 1.48 hours, and for CVA 4.01 micrograms/ml at 1 hour with a T 1/2 of 0.89 hour. At the highest dose of 20 mg/kg, AMPC level reached 4.21 micrograms/ml after 2 hours with a T 1/2 of 2.39 hours, and the CVA peak was 1.64 micrograms/ml at 1 hour with a T 1/2 of 1.01 hours. The 6 hours urinary recovery of AMPC and CVA following administration of the BRL 25000 granules ranged from 38-64% and 2-33%, respectively. In the clinical studies, the BRL 25000 granules are administered to 15 cases with pediatric infections and the clinical response was excellent or good in all cases treated (100%). Bacteriological investigation was performed on 13 strains from 12 cases and all strains were eradicated (100%). Regarding side effects, elevation of eosinophil was observed in 1 case and vomiting in 3 cases.