Case Report: Novel Pathogenic Variant Detected in Two Siblings with Type 1 Gaucher Disease.

BACKGROUND: Gaucher disease (GD) is an autosomal recessive lysosomal storage disease. The disease develops due to glucocerebrosidase enzyme deficiency caused by biallelic pathogenic variants in the glucosylceramidase beta 1 (GBA1) gene, which encodes the glucocerebrosidase enzyme. The GBA1 gene is located at chromosomal location 1q22 and consists of 11 exons. In this article, we report a novel pathogenic variant in the GBA1 gene. CASE PRESENTATIONS: A 32-year-old female patient with no known chronic disease was admitted with complaints of weakness, bone pain, and abdominal pain. Her evaluation included hepatosplenomegaly, thrombocytopenia, osteoporosis, and anemia. The clinical suspicion of Gaucher disease was confirmed by glucocerebrosidase enzyme level and genetic testing. In her family screening, her sister also had hepato-splenomegaly, osteoporosis, thrombocytopenia, and anemia. Both sisters had no neurological symptoms. As a result of GBA1 gene sequence analysis in two of our patients, a missense variant was detected in the c.593C>A homozygous genotype. This variant has not been reported in any previously published case. CONCLUSION: In this case report, we aimed to contribute to the literature by reporting a new novel pathogenic variant in the GBA1 gene leading to type 1 Gaucher disease that has not been described before.

Effects of a psychoeducation program on disease burden, depression, and anxiety levels in relatives of psychotic patients in a community mental health center.

PURPOSE: This study evaluates the effect of a 10-week psychoeducation program (PP) on disease burden, depression, and anxiety levels in relatives of psychotic patients. DESIGN AND METHODS: The participants were 43 relatives of patients attending a community mental health center. The Zarit Caregiver Burden Scale (ZCBS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) were used to collect psychometric data. FINDINGS: Administering the PP to caregivers significantly reduced their ZCBS, BAI, and BDI scores. PRACTICE IMPLICATIONS: We recommend integrating the PP into treatment and rehabilitation programs within the scope of psychiatric-care services.

Impact of Everolimus and Low-Dose Cyclosporin on Cytomegalovirus Replication and Disease in Pediatric Renal Transplantation.

In order to investigate the hypothesis that the mammalian target of rapamycin inhibitor everolimus (EVR) shows anticytomegalovirus (CMV) activity in pediatric patients, we analyzed the impact of EVR-based immunosuppressive therapy on CMV replication and disease in a large cohort (n = 301) of pediatric kidney allograft recipients. The EVR cohort (n = 59), who also received low-dose cyclosporin, was compared with a control cohort (n = 242), who was administered standard-dose cyclosporin or tacrolimus and an antimetabolite, mostly mycophenolate mofetil (91.7%). Multivariate analysis revealed an 83% lower risk of CMV replication in the EVR cohort than in the control cohort (p = 0.005). In CMV high-risk (donor+/recipient-) patients (n = 88), the EVR-based regimen was associated with a significantly lower rate of CMV disease (0% vs. 14.3%, p = 0.046) than the standard regimen. In patients who had received chemoprophylaxis with (val-)ganciclovir (n = 63), the CMV-free survival rates at 1 year and 3 years posttransplant (100%) were significantly (p = 0.015) higher in the EVR cohort (n = 15) than in the control cohort (n = 48; 1 year, 75.0%; 3 years, 63.3%). Our data suggest that in pediatric patients at high risk of CMV, an EVR-based immunosuppressive regimen is associated with a lower risk of CMV disease than a standard-dose calcineurin inhibitor-based regimen.

Treatment of an unusual complication of transfemoral TAVI with a new technique: successful occlusion of ventricular septal defect by opening the closure device in the ascending aorta.

Ventricular septal defect (VSD) is a rare complication of transcatheter aortic valve implantation (TAVI) via the transfemoral approach. Aetiological factors leading to VSD have been reported as post-balloon dilatation, oversized prosthesis implantation, and severe calcification of the aorta. However, we present a case of VSD occurring after TAVI with an Edwards Sapien XT prosthesis without any distinct aetiological factors. We used a new technique for closure of the significant VSD; opening the left ventricular disc of the closure device in the ascending aorta and successfully implanting the device without any damage to the bioprosthetic valve.

Evaluation of smoking genotoxicity in Turkish young adults.

BACKGROUND: For the past few decades, it has been widely known in developed countries that tobacco is dangerous, but it is still insufficiently realized how big these dangers really are. AIMS: To determine and evaluate micronuclei (MN) frequencies of young smokers and nonsmokers in three different tissues (peripheric blood lymphoctes, buccal mucosa, and exfoliative urothelial cells) at the same time. MATERIALS AND METHODS: MN assay was performed on buccal mucosa, urothelial cells, and peripheric blood lymphocyte samples obtained from 15 healthy male smokers (>5 pack-years) and 15 healthy male nonsmoker controls who had not been exposed to any known genotoxic agent. STATISTICAL ANALYSIS USED: The statistical differences between smoker and nonsmoker groups were calculated by using student t test. The differences between smoker-group tissues were compared by ANOVA. RESULTS: It was found that MN frequency (mean value ± standard deviation) in oral mucosa cells from smokers and controls were 1.20 ± 0.22% and 0.26 ± 0.10%; in urothelial exfoliative cells, 1.29 ± 0.28% and 0.12 ± 0.08%; in peripheric blood lymphocytes, 1.53 ± 0.23% and 0.38 ± 0.12%, respectively. The mean MN frequencies in buccal mucosa, urothelial exfoliative cells, and peripheric blood lymphocytes were significantly higher in smokers than in those of controls (P<0.05). All tissues were affected from smoking, but the most destructive effect was seen in urothelial cells of smokers (P<0.05). CONCLUSIONS: Our data showed that cigarette smoke is a DNA damage causitive agent on exfoliative buccal mucosa and urothelial cells and peripheric blood lymphocytes of young smokers, but it has most destructive effect on urothelial cells.

Relation of adrenergic receptors, which have roles in gastroprotective and anti-inflammatory effect of adrenal gland hormones, with cyclooxygenase enzyme levels in rats.

BACKGROUND AND AIMS: COX-2 enzyme inhibition is responsible for the anti-inflammatory effects of NSAIDs, COX-1 for their effects upon the gastrointestinal system (GIS), along with other side effects. We investigated the relationship between COX levels and those adrenergic receptors known to play a role in gastroprotection and anti-inflammatory activity. METHOD: The effects of adrenaline and prednisolone on gastric COX-1 and COX-2 levels in both intact and adrenalectomized rats treated with doxazosin, yohimbine, propranolol, and metoprolol were determined. RESULTS: We found that adrenaline increases COX-1 levels in the gastric tissue of both intact and adrenalectomized rats by stimulating alpha-2 receptors. Adrenaline decreases COX-2 levels by stimulating beta-2 adrenergic receptors. Prednisolone inhibits both COX-1 and COX-2 in the gastric tissue of intact rats. In adrenalectomized rats, prednisolone increases gastric COX-1 by stimulating alpha-2 receptors, and decreases COX-2 levels by stimulating beta-2 receptors. CONCLUSION: Prednisolone cannot bind to a adrenergic receptors in the presence of adrenaline (intact rats) but, in its absence (adrenalectomy), binds to alpha-2 receptors, and stimulates them more effectively than adrenaline, suggesting a direct relationship between alpha-2 adrenergic receptors and COX-1 levels, whereas beta-2 receptors are directly related to COX-2 levels.

Papillon-lefevre syndrome with congenital hepatic fibrosis.

Papillon Lefevre syndrome (PLS) is a rare autosomal recessive disorder, which is characterized by palmar-plantar hyperkeratosis, periodontitis, and premature loss of dentition. We report a 16 years old girl with PLS. The patient presented at 08 years of age with complaints of corn on the feet and hands, and failure to thrive. On examination, her upper primarily canines were loose, she had severe periodontitis, eruption of permanent teeth, diffuse eritematous and hyperkeratotic palms and soles that suggested the syndrome. During the follow-up, the patient was diagnosed to have congenital hepatic fibrosis (CHF) when she was 16 years old, while she was being investigated for the etiology of her splenomegaly and pancytopenia. We report a patient with PLS associated with CHF, an association that has not been previously described. Abbreviations-HbsAg: Hepatitis B virus surface antigen, Anti Hbs: Antibody against Hepatitis B surface antigen, Anti Hbc IgM: Antibody against Hepatitis B cor antigen immunglobulin M, Anti dsDNA: Antibody against double stranded deoksiribonucleic acid, Anti HCV: Antibody against Hepatit C virus, Anti HIV: Antibody against human immun deficiency virus, AST: Aspartat amino transferase, ALT: Alanin amino transferase, Gamma-GT: Gamma glutamyl transferase, LDH: Lactate dehydrogenase & MRI: Magnetic resonance imaging.

A new heritable fragile site at 15q13 in a three-generation family.

Here, we describe a family ascertained through recurrent spontaneous abortions in which a new heritable fragile site located at 15q13 is segregating. The fragile site was present in nine members of a three-generation family and expressed spontaneously in a high proportion of the metaphases varying from 88 to 95% under standard culture conditions in all the carriers. This didn't change under folate deficiency.

Serum levels of sL-selectin and tumour necrosis factor-alpha in children with type 1 diabetes mellitus.

Type 1 diabetes mellitus (DM) is a result of inflammation and destruction of alpha-cells in the pancreatic islet cells. The aim of this study is to evaluate the associations of diabetes with soluble L-selectin (sL-selectin) and tumour necrosis factor-alpha (TNF-alpha) in children with type 1 DM; and also to evaluate the associations of these parameters with the disease period, glycaemic control state and puberty stage. Serum sL-selectin and TNF-alpha levels were measured in 44 children with type 1 DM and 44 healthy children. Neither the patients nor the control group showed significant difference between the levels of sL-selectin and TNF-alpha (sequence mean 12.17+/-1.62 ng/ml vs. 12.62+/-1.56 ng/ml and 7.27+/-3.1 pg/ml vs. 7.88+/-2.7 pg/ml). There was no statistically significant difference between children with duration of diabetes longer than 5 years and children with duration of diabetes shorter than 1 year. There was also no statistically significant difference between poor glycaemic control and good-acceptable glycaemic control patients. The present results indicate that sL-selectin and TNF-alpha serum levels are not increased and cannot be used as prognostic predictors in type 1 DM; and also sL-selectin and TNF-alpha do not change with the disease period, glycaemic control state and puberty stage.

Antioxidant enzyme activities and lipid peroxidation levels in erythrocytes of patients with oesophageal and gastric cancer.

In this study, levels of lipid peroxidation and antioxidant enzyme activities were investigated in the erythrocytes of patients with oesophageal and gastric cancers. Erythrocytes were obtained from 17 patients with oesophageal cancer, 37 patients with gastric cancer and 20 healthy controls. Levels of malondialdehyde (MDA), a lipid peroxidation marker, and activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GPx) were determined using spectrophotometric methods. MDA levels and CuZn-SOD activity were significantly higher and GPx and CAT activities significantly lower in patients with oesophageal and gastric cancer than in controls. There were no statistically significant differences in the parameters measured in relation to disease stage in either patient group. These results indicate significant changes in the antioxidant defence system in patients with oesophageal and gastric cancer. It is postulated that this may lead to enhanced action of oxygen radicals, resulting in lipid peroxidation.

Intravenous pulse cyclophosphamide therapy in focal segmental glomerulosclerosis.

AIMS: We herein report the results of intravenous pulse cyclophosphamide (IVCP) therapy of 5 patients with steroid-resistant focal segmental glomerulosclerosis (FSGS). All patients had been treated with oral and intravenous pulse methylprednisolone and failed to respond to steroids from onset and were considered as primary steroid-resistant. Before starting IVCP, all patients were also treated with other immunosuppressive drugs with or without steroids, but none of them responded to such therapies and no patient had any NPSH2 gene mutations. METHODS: IVCP was given monthly at a dose of 500 mg/m2 for 6 months. At the end of 6 months, IVCP was discontinued in case there was no response. Otherwise, IVCP was continued for every 2 months. Oral prednisone was given concurrently at 60 mg/m2 daily for 6 weeks and then 40 mg/m2 on alternate days for 4 weeks. Prednisone was then tapered to 10 mg/m2 alternate days and continued during the therapy period. RESULTS: Only 1 of these patients achieved remission after IVCP while 4 patients showed no response to IVCP. 2 patients who did not achieve remission progressed to end-stage renal disease (ESRD) and 2 others who had not been treated with cyclosporine before underwent cyclosporine therapy. None of our patients has suffered from adverse effects of IVCP. CONCLUSION: We found that IVCP had a limited beneficial effect in treatment of steroid-resistant FSGS and it may be suggested that IVCP can be tried to treat steroid-resistant patients, also for patients with primary steroid resistance and those who do not respond to other immunosuppressive therapies.

Effects of type 2 diabetes mellitus on plasma fatty acid composition and cholesterol content of erythrocyte and leukocyte membranes.

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes mellitus (T2DM) and is related to the fatty acid profile of the plasma membranes. The purpose of the present study was to investigate fatty acid composition and cholesterol content of cell membranes in patients with type 2 diabetes and, thus, to evaluate the possible factors leading to the alteration of plasma membrane fluidity. The study was performed in 20 healthy control subjects and 32 patients with type 2 diabetes. The fatty acid profiles and cholesterol content of the erythrocyte (RBC) and leukocyte (WBC) membranes were determined by a gas chromatographic method. When one considers the membrane constituents increasing fluidity and the ones decreasing it, the diabetics had a membrane composition decreasing fluidity compared to controls. On the other hand, when compared to control subjects, type 2 diabetic patients showed a significantly higher proportion of C16:0 components in erythrocyte and leukocyte membranes and plasma samples (25.4+/-3.1% vs. 31.1+/-4%; 23.3+/-2.4% vs. 29.3+/-5.2%; 27.6+/-3.9% vs. 34.5+/-5.7%; p<0.005, p<0.01 and p<0.005, respectively). Our results suggest that the ratio of saturated:unsaturated fatty acids changes in plasma and cell membranes of patients with type 2 diabetes. This situation may cause, at least in part, RBC-WBC function abnormalities and insulin resistance because of inconvenient membrane fluidity.

A child with Beckwith-Wiedemann syndrome and posterior urethral valves.

Beckwith-Wiedemann syndrome is a somatic overgrowth syndrome characterized by a variable incidence of congenital anomalies, including hemihypertrophy, omphalocele, macroglossia and renal malformations. We report a child with Beckwith-Wiedemann syndrome and posterior urethral valves. Urethral valve resection was successfully performed under general anesthesia after voiding cystourethrography. This is the first report of Beckwith-Wiedemann syndrome associated with posterior urethral valves.

Effectiveness of hyperbaric oxygen therapy in the treatment of complex regional pain syndrome.

In this double-blind, randomized, placebo-controlled study we aimed to assess the effectiveness of hyperbaric oxygen (HBO) therapy for treating patients with complex regional pain syndrome (CRPS). Of the 71 patients, 37 were allocated to the HBO group and 34 to the control (normal air) group. Both groups received 15 therapy sessions in a hyperbaric chamber. Pain, oedema and range of motion (ROM) of the wrist were evaluated before treatment, after the 15th treatment session and on day 45. In the HBO group there was a significant decrease in pain and oedema and a significant increase in the ROM of the wrist. When we compared the two groups, the HBO group had significantly better results with the exception of wrist extension. In conclusion, HBO is an effective and well-tolerated method for decreasing pain and oedema and increasing the ROM in patients with CRPS.

A new treatment modality for fibromyalgia syndrome: hyperbaric oxygen therapy.

Fibromyalgia syndrome (FMS) is characterized by longstanding multifocal pain with generalized allodynia/hyperalgesia. There are several treatment methods but none has been specifically approved for this application. We conducted a randomized controlled study to evaluate the effect of hyperbaric oxygen (HBO) therapy in FMS (HBO group: n = 26; control group: n = 24). Tender points and pain threshold were assessed before, and after the first and fifteenth sessions of therapy. Pain was also scored on a visual analogue scale (VAS). There was a significant reduction in tender points and VAS scores and a significant increase in pain threshold of the HBO group after the first and fifteenth therapy sessions. There was also a significant difference between the HBO and control groups for all parameters except the VAS scores after the first session. We conclude that HBO therapy has an important role in managing FMS.

Traumatic spinal cord injuries in Turkey: a nation-wide epidemiological study.

STUDY DESIGN: An epidemiological study conducted all over the country. OBJECTIVE: The present retrospective study was conducted to survey the new traumatic spinal cord injury (SCI) cases during 1992 in Turkey. SETTING: Intensive care units, emergency services and departments of orthopaedic surgery, neurosurgery and rehabilitation of state hospitals, rehabilitation centers, military and university hospitals. METHODS: Postal questionnaires were used for data collection and the records from medical institutes nation-wide were reviewed for the analysis of the epidemiological factors. RESULTS: Five hundred and eighty-one new traumatic SCI cases were reported in 1992. The annual incidence was found to be 12.7 per million population. Male to female ratio was 2.5:1 and the average age at injury was 35.5+/-15.1 (35.4+/-14.8 for males and 35.9+/-16.0 for females). The most common cause of injury was motor vehicle accidents (48.8%) followed by falls (36.5%), stab wounds (3.3%), gunshot injuries (1.9%) and injuries from diving (1.2%). One hundred and eighty-seven patients (32.18%) were tetraplegic and 394 patients (67.8%) were paraplegic. The most common level of injury was C5 among tetraplegics and T12 among paraplegics. The most prevalent associated injury was head trauma followed by extremity fractures. Severe head trauma resulting in death may obscure the real incidence of SCI and may cause underreporting of cases in epidemiological studies. CONCLUSION: Considering that motor vehicle accidents and falls were found to be the leading causes of traumatic SCI, it was concluded that the prevention measures should be focused mainly on these in order to reduce the frequency of SCI in Turkey.

Peripheral nerve block with phenol to treat spasticity in spinal cord injured patients.

In this study an attempt was made to treat spinal cord injured patients with severe spasticity by peripheral nerve blocks. Thirty-six patients (5 female, 31 male) ranging in age from 20 to 71 years (mean: 29 +/- 8.2) were treated by phenol injections. A specially designed electrostimulation needle was used for the injections. The results showed that peripheral nerve blocks with phenol solution could be a remedy on a temporary basis, but are not as effective as has been described previously.