Preimplantation genetic diagnosis for early-onset torsion dystonia

Early-onset primary torsion dystonia (DYT1) is the most severe and common form of hereditary movement disorders, characterized by sustained twisting contractures that begin in childhood, which is caused in majority of cases by a 3-bp deletion of the DYT1 gene on chromosome 9q34 at the heterozygote state. As there is no effective treatment of this disease, preimplantation genetic diagnosis (PGD) may be a useful option for at-risk couples to establish an DYT1 mutation-free pregnancy. PGD was performed for two obligate carriers of the DYT1 3-bp deletion, using blastomere testing to preselect the mutation-free embryos, based on mutation analysis with simultaneous testing of the three closely linked markers, D9S62, D9S63 and ASS. Of 19 tested blastomeres in three cycles, 17 had conclusive information about the mutation and linked markers, of which eight were predicted to be free of 3-bp deletion. Six of these embryos were transferred back to patients, two in each cycle, yielding singleton DYT1 3-bp deletion-free clinical pregnancies in two. One of these pregnancies was terminated due to severe anencephaly and the other resulted in birth of a mutation-free child. This is the first PGD for primary torsion dystonia, providing an alternative for those at-risk couples who cannot accept prenatal diagnosis and termination of pregnancy as an option for avoiding early onset torsion dystonia.     

Juvenile polyarteritis: results of a multicenter survey of 110 children

OBJECTIVE: To characterize pediatric patients who had been diagnosed with polyarteritis nodosa (PAN) through necrotizing vasculitis of the small and mid-size arteries or those with characteristic findings on angiograms data were collected. STUDY DESIGN: Pediatricians were asked to classify their patients into one of the four suggested groups for juvenile PAN. Twenty-one pediatric centers worldwide participated with 110 patients. RESULTS: The girl:boy ratio was 56:54, with a mean age of 9.05 +/- 3.57 years. The cases were classified as: 33 (30%) cutaneous PAN; 5 (4.6%) classic PAN associated with hepatitis B surface antigen (HBs Ag); 9 (8.1%) microscopic polyarteritis of adults associated with antineutrophil cytoplasmic antibodies (ANCA); and 63 (57.2%) systemic PAN. Cutaneous PAN was disease confined to the skin and musculoskeletal system. All patients with HBs Ag-associated classic PAN were diagnosed with renal angiograms. Antiviral treatment was administered in most cases. Microscopic PAN patients had pulmonary-renal disease, in combination or separately. ANCA was present in 87%, and 2 patients progressed to end-stage renal failure. Patients classified with systemic PAN had multiple system involvement, almost all had constitutional symptoms, and all had elevated acute phase reactants. Corticosteroids and cyclophosphamide were the first choices of immunosuppressive treatment. The overall mortality was 1.1%. CONCLUSIONS: There were remarkable differences among pediatric patients with PAN, with different clinical manifestations and overall better survival and lower relapse rates when compared with adults.     

Acute neck infections in children

A retrospective review was conducted on 132 patients aged between two and 15 years with cervical lymphadenitis and/or with abscess formation to determine the epidemiologic and clinical presentation of these infections. The most common locations were the upper anterior cervical space (43.2%) and the submandibular space (27.3%). The duration of symptoms ranged from 12 hours to 20 days. Results of the pus cultures were available in 31 patients (23.5%). Of these, 16 cultures (51.6%) were positive. The isolated organisms were Staphylococcus aureus (50%), Staphylococcus epidermidis (31.3%), group A beta-hemolytic streptococcus (12.5%), Streptococcus pneumoniae (6.3%) and Escherichia coli (6.3%). One of the specimens yielded mixed organisms (Staphylococcus epidermidis and Streptococcus pneumoniae). Penicillin resistance was documented in six (37.5%) of the 16 gram-positive bacteria isolated from the pus culture. Both throat and blood cultures were available in all 132 patients. Seven throat cultures (5.3%) were positive for group A beta hemolytic streptococci, whereas five blood cultures (3.8%) were reported to have bacterial growth. Sixty-seven patients (50.8%) were treated with ampicillin-sulbactam, 53 patients (40.1%) with ampicillin-sulbactam and ornidazole and 12 patients (9.1%) with ceftriaxone parenterally. The mean duration of hospital stay related to the infection was 7.30 +/- 3.89 days (range, 2-28 days). The mean period for downsizing of the cervical mass by half was 4.05 +/- 2.05 days, and the recovery period (total antibiotic usage period) was 13.72 +/- 5.33 days. All of the patients had an uneventful recovery without complications. Results of both throat and blood cultures were not predictive for etiologic agents in our study group. Since ultrasonographic evaluation of each patient has limited additional benefits in clinical management, it must be reserved for selected cases to document abscess formation.     

Preimplantation genetic diagnosis for polycystic kidney disease

OBJECTIVE: To use preimplantation genetic diagnosis for achieving a polycystic kidney disease (PKD)-free pregnancy for a couple in which the female partner was affected by PKD but whose PKD1 or PKD2 carrier status was not established. DESIGN: Case report. SETTING: The IVF program of Reproductive Genetics Institute, Chicago, Illinois. PATIENT(S): An at-risk couple with the female partner affected by PKD, whose PKD1 or PKD2 carrier status was not established. INTERVENTION(S): Removal of PB1 and PB2 and testing for three closely linked markers to PKD1 (Kg8, D16S664, and SM7) and four closely linked markers to PKD2 (D4S2922, D4S2458, D4S423, and D4S1557) after standard IVF. MAIN OUTCOME MEASURE(S): Deoxyribonucleic acid analysis of PB1 and PB2 indicating whether corresponding oocytes were PKD1 or PKD2 allele free, for the purpose of transferring only embryos resulting from mutation-free oocytes. RESULT(S): Of 11 oocytes tested by PB1 and PB2 DNA analysis, 7 were predicted to contain PKD1 or PKD2, with the remaining 4 free of both mutations. Three embryos resulting from these oocytes were transferred, yielding a twin pregnancy and the birth of two unaffected children. CONCLUSION(S): This is the first preimplantation genetic diagnosis for PKD, which resulted in the birth of healthy twins confirmed to be free of PKD1 and PKD2. Preimplantation genetic diagnosis based on linked marker analysis provides an alternative for avoiding the pregnancy and birth of children with PKD, even in at-risk couples without exact PKD1 or PKD2 carrier information.     

Relationship between some reproductive parameters and biochemical properties of blood serum in rams

The objective of the present study was to describe the relationship between some reproductive parameters, hormonal levels, and some biochemical properties of blood serum in rams under the Afyon province conditions. The total protein and globulin were positively (P < 0.01) correlated with sperm motility and sperm concentration in all of rams. Total lipid was negatively (P < 0.05) correlated with sperm motility and concentration in Daglic, and it was positively (P < 0.01) correlated with percentage of abnormal spermatozoa in Chios rams. Total lipid and cholesterol was positively (P < 0.01) correlated with triiodothyronine in all of rams and was negatively (P < 0.05) correlated with testosterone in Daglic rams. Percentage of abnormal spermatozoa were negatively (P < 0.01) correlated with alanine amino transaminase (ALT) level, but were positively (P < 0.01) associated with aspartate amino transaminase (AST) level and AST/ALT ratio in all of rams.     

Erdosteine prevents bleomycin-induced pulmonary fibrosis in rats

Oxidative stress plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. Therefore, erdosteine, an antioxidant, is expected to have an inhibitor potential against the disease. Rats were given one dose of bleomycin in pulmonary fibrosis groups and saline in controls. The first dose of oral erdosteine (10 mg/kg/day) was given 2 days before the bleomycin injection to achieve the plateau level in blood and continued until killing. At day 14, fibrotic changes were evaluated, using Aschoft's criteria and lung hydroxyproline content. Bleomycin produced a fivefold increase in fibrosis score that was decreased by 87% by erdosteine (P>0.001) and almost twofold increases in hydroxyproline content which were completely prevented by erdosteine. Myeloperoxidase activities and MDA levels, which were significantly higher in the bleomycin group, were then significantly attenuated by erdosteine. These results revealed that oral erdosteine may prevent the development of acute pulmonary inflammation caused by bleomycin injection via the repression of neutrophil accumulation and lipid peroxidation, resulting in the inhibition of subsequent lung fibrosis.     

Gynecomastia following chemotherapy for testicular cancer

A 22-year-old man received 4 cycles of bleomycin, etoposide and cisplatin combination chemotherapy for clinical stage IIA embryonal cell carcinoma of the right testis. The treatment resulted in complete remission. Five months following cessation of the chemotherapy first on the left and then 2 weeks later on the right side painful gynecomastia developed. His hormonal values are all normal with no evidence of recurrence of the cancer. Gynecomastia on both sides resolved in 8 months spontaneously without any treatment. He is still in clinical remission 14 months after completion of the chemotherapy. We should be aware that gynecomastia following cytotoxic chemotherapy in a young man does not necessarily mean the return of the cancer.     

MR fluoroscopy-guided transthoracic fine-needle aspiration biopsy: feasibility

The purpose of this study was to evaluate the feasibility of using an open-configuration magnetic resonance (MR) imaging system with MR fluoroscopic guidance to perform percutaneous transthoracic fine-needle aspiration biopsy in patients with lung masses. Percutaneous transthoracic aspiration biopsies were performed with MR fluoroscopic guidance in 14 patients. The masses were 2-7 cm in diameter (mean, 4.1 cm). The needle was positioned by using a free-hand technique with MR fluoroscopic guidance. The needle tip reached the target lesion, and biopsy was performed. Analysis of the biopsy specimens facilitated a specific diagnosis in all patients. Pneumothorax was noted in two patients (14%) with chronic obstructive pulmonary disease. Study results showed that the described MR fluoroscopy-guided transthoracic biopsy technique can be used safely and successfully for lung masses. MR fluoroscopy can be used to reach the target lesion easily and accurately.     

A comparison of the therapeutic efficacy and tolerability of etoricoxib and diclofenac in patients with osteoarthritis

OBJECTIVE: To evaluate and compare the efficacy and tolerability of etoricoxib and diclofenac in patients with osteoarthritis of the knee or hip. METHODS: In this 6-week double-blind, active comparator controlled, parallel-group study eligible osteoarthritis patients were randomised to receive either etoricoxib 60 mg once daily (n = 256) or diclofenac 50 mg three times daily (n = 260). The primary study endpoint was the Western Ontario McMaster osteoarthritis index (WOMAC) pain subscale. Other endpoints included were the WOMAC stiffness and physical function subscales, and the Patient's Global Assessment of Response to Therapy (PGART) questionnaire. Early efficacy was evaluated using WOMAC first question (pain walking on a flat surface) and PGART 4 h after the morning dose of each drug on days 1 and 2. Rescue medication (paracetamol) used was also recorded. The study was designed to show comparable efficacy between etoricoxib 60 mg once daily and diclofenac 50 mg three times daily with respect to the primary endpoint and was conducted outside the United States at 67 centres in 29 countries. RESULTS: Etoricoxib (60 mg once daily) was comparable in efficacy to diclofenac (150 mg daily) on all the above parameters. The one exception was in the assessment of early efficacy where etoricoxib demonstrated significantly greater benefit within 4 h of taking the first dose on the first day of therapy (p = 0.007) as evaluated by the percentage of patients with good or excellent (PGART) responses. The treatment effects of both drugs were similar by the time day 2 was reached and were sustained throughout the 6 weeks of therapy. Both treatments were generally well tolerated. CONCLUSIONS: Etoricoxib is clinically effective in the therapy of osteoarthritis providing a magnitude of effect comparable to that of the maximum recommended daily dose of diclofenac. The onset of clinical benefit with etoricoxib on day one is more rapid than that of diclofenac. Both drugs were generally well tolerated.