Refining the phenotype of alpha-1a Tubulin (TUBA1A) mutation in patients with classical lissencephaly.

Mutations in the alpha-1a Tubulin (TUBA1A) gene have recently been found to cause cortical malformations resemblant of classical lissencephaly but with a specific combination of features. To date, TUBA1A mutations have been described in five patients and three foetuses. Our aims were to establish how common TUBA1A mutations are in patients with lissencephaly and to contribute to defining the phenotype associated with TUBA1A mutation. We performed mutation analysis in the TUBA1A gene in 46 patients with classical lissencephaly. In 44 of the patients, mutations in the LIS1 and/or DCX genes had previously been excluded; in 2 patients, mutation analysis was only performed in TUBA1A based on magnetic resonance imaging (MRI) findings. We identified three new mutations and one recurrent mutation in five patients with variable patterns of lissencephaly on brain MRI. Four of the five patients had congenital microcephaly, and all had dysgenesis of the corpus callosum and cerebellar hypoplasia, and variable cortical malformations, including subtle subcortical band heterotopia and absence or hypoplasia of the anterior limb of the internal capsule. We estimate the frequency of mutation in TUBA1A gene in patients with classical lissencephaly to be approximately 4%, and although not as common as mutations in the LIS1 or DCX genes, mutation analysis in TUBA1A should be included in the molecular genetic diagnosis of classical lissencephaly, particularly in patients with the combination of features highlighted in this paper.

Randomized trial comparing early postoperative irradiation vs. the use of nonsteroidal antiinflammatory drugs for prevention of heterotopic ossification following prosthetic total hip replacement.

PURPOSE: A randomized trial was undertaken to assess the comparative efficacy of early postoperative irradiation with either 5 or 7 Gy vs. the use of nonsteroidal antiinflammatory drug (NSAID) for prevention of heterotopic ossification (HO) following prosthetic total hip replacement (THP). METHODS AND MATERIALS: Between 1993 and 1994, 301 patients were randomized to receive postoperative irradiation (5 or 7 Gy) or NSAID. One hundred and thirteen patients were treated with NSAID (indomethacin 2 x 50 mg/day for 1 week), 93 patients were irradiated with a single 7 Gy fraction, 95 patients with a single 5 Gy fraction. The treatment volume included the soft tissues between the periacetabular region of pelvis and the intertrochanteric portion of the femur. X-rays of treated hips were obtained immediately and 6 months after surgery. Heterotopic ossification was scored according to the Brooker Grading system. One hundred patients receiving no prophylactic therapy after total hip arthroplasty between 1988 and 1992, were analyzed and defined as historical control group. RESULTS: Incidence of heterotopic ossification was 16.0% in NSAID-group (Brooker Score I: 8.0%; II: 6.2%; III: 1.8%; IV: 0%), 30.1% in 5 Gy group (Brooker Score I: 24.7%; II: 4.3%; III: 1.1%; IV: 0%), and 11.1% in 7 Gy group (Brooker Score I: 11.6%; II: 0%; III: 0%; IV: 0%). Regarding overall heterotopic ossification there was a significant difference between the NSAID group and the 5 Gy group (p < .015), respectively, between the 7 Gy group and the 5 Gy group (p < .0001). No significant difference was noted in the influence of overall HO between the NSAID and the 7 Gy group (p > 0.3). Analyzing the clinically significant HO (Brooker Score III and IV) patients irradiated with 7 Gy developed less HO than those treated with NSAID (p = 0.003). Incidence of HO was greater in the untreated historical control group (Brooker Score I: 26%; II: 15%; III: 19%; IV: 5%) than in all three prophylacticly treated groups. CONCLUSION: Prophylactic irradiation of the operative site after hip replacement with single a 7 Gy fraction is the most effective postoperative treatment schedule in prevention of clinically significant heterotopic ossification. This therapy modality is more effective than irradiation with a single 5 Gy fraction or use of NSAID.

Prevention of heterotopic ossification after total hip replacement. A prospective, randomised study using acetylsalicylic acid, indomethacin and fractional or single-dose irradiation.

We have carried out a prospective, randomised study of prophylaxis for heterotopic ossification (HO) comparing indomethacin for 7 and 14 days, acetylsalicylic acid, and fractional (4 x 3 Gy) or single exposure of 5 or 7 Gy irradiation after operation. We initially had 723 patients (733 hip replacements), but after withdrawals there were 685 hips of which 18.4% developed HO; 14% were grade I, 2.9% grade II and 1.5% grade III of the Brooker classification. We compared the results between these groups with those of a matched control series and found that indomethacin, 2 x 50 mg for 7 and 14 days, and postoperative irradiation of 4 x 3 Gy or 1 x 7 Gy, significantly reduced the development of HO compared with the control group. Patients in the acetylsalicylic acid group and those with a single irradiation of 5 Gy after operation developed significantly more ossification than those in the indomethacin and other irradiation groups. We suggest the use of 2 x 50 mg of indomethacin with mucoprotection for seven days as prophylaxis against HO after total hip replacement for all patients. A single irradiation of 7 Gy is recommended for patients who have developed HO after previous operations or to whom administration of indomethacin is contraindicated.

[Prospective study on the prevention of heterotopic ossification after total hip replacement. Non-steroidal anti-inflammatory agents versus radiation therapy]. / Prospektive Studie zur Vermeidung heterotoper Ossifikationen nach Hüftgelenksersatz. Nichtsteroidales Antirheumatikum versus Strahlentherapie.

PURPOSE: Two prospective trials were undertaken to assess the comparative efficacy of early postoperative irradiation with different radiation doses versus the postoperative use of nonsteroidal antiinflammatory drugs (NSAID) for prevention of heterotopic ossification (HO) following prothetic total hip replacement (THP). PATIENTS AND METHOD: Between 1992 and 1994 585 patients received THP. These patients were randomed in two longitudinal studies each with 3 treatment arms comparing postoperative irradiation with 4 x 3 Gy (101 patients), 1 x 5 Gy (93 patients), 1 x 7 Gy (95 patients) and the postoperative use of the NSAID indometacin for 7 days (113 patients) respectively for 14 days (90 patients) und acetyl salicyl acid (ASS) for 14 days (93 patients). Heterotopic ossification was scored according to the Brooker grading system. One hundred patients receiving no prophylactic therapy after total hip arthroplasty between 1988 and 1992 were analysed and defined as historical control group. RESULTS: Incidence of heterotopic ossification was 5% in the 4 x 3 Gy group (Brooker grade I 5%, grade II 0%, grade III 0%), 30.5% in the 1 x 5 Gy group (Brooker grade I 24.7%, grade II 4.1%, grade III 1.0%) and 10.5% in the 1 x 7 Gy group (Brooker grade I 10.5%, grade II 0%, grade III 0%). 15.9% of the indometacin-7 days-group developed heterotopic ossification (Brooker grade I 8%, grade II 6.2%, grade III 1.7%, grade IV 0%), 12.2% of the indometacin-14 days-group (Brooker grade I 8.9%, grade II 2.2%, grade III 1.1%) and 37.5% of the ASS-group (Brooker grade I 27.9%, grade II 4.3%, grade III 5.3%). The lowest incidence of heterotopic ossification was found for the 4 xx 3 Gy and the 1 x 7 Gy group, but no significant difference between these two different treatments was observed. CONCLUSION: Prophylactic irradiation of the operative site after hip replacement is more effective than the use of NSAID. Because no significant difference between the fractionated ingle dose irradiation was found and the latter is more comfortable for patients and more economical, irradiation with single 7 Gy fraction should be preferred.

Analysis of type-restricted and cross-reactive epitopes on virus-like particles of human papillomavirus type 33 and in infected tissues using monoclonal antibodies to the major capsid protein.

A panel of six monoclonal antibodies recognizing at least three different antigenic regions has been raised against the L1 major capsid protein of human papillomavirus type 33 (HPV-33), which is associated with cervical carcinoma. The antigenic sites defined by these antibodies have been mapped and classified as type-restricted or broadly cross-reactive using bacterially expressed L1 fusion proteins of a variety of HPV types. Conformational and linear epitopes have been distinguished using native and denatured virus-like particles. HPV infection of genital lesions has been analysed using both monoclonal antibodies and DNA amplification by PCR. The antibodies obtained should be useful to probe the structure of HPV capsids and to develop a general assay for the detection and classification of productive HPV infections.

[Histocompatibility of porous ceramics in the jaw bones of Cavia cobaya]. / Histokompatibilität poröser Keramik im Kieferknochen von Cavia cobaya.

Porous ceramic basically fuses hard in osseous connective tissue of the jaw if closed implantation has been successful. The date were derived from ground serial sections in different postoperative intervals. Light, fluorescence (after intravital staining), and scanning electron microscopy were used for the evaluation. The positive results obtained with this test series do not imply that porous ceramic material used as root replacements persists under normal masticatory stress and in the same type of tissue.