Long-term results on VK partial and total temporomandibular joint systems

This article reviews the results obtained on 262 VK partial and total temporomandibular joint (TMJ) procedures followed up to 10 years. VK I total joint (placed 1982 to 1986) cumulative success rate was 44% at 6 years and 20% at 10 years, while VK II (placed 1986 to 1990) cumulative success rate was 80% at 6 years. Material wear of the Teflon FEP surface of the VK I fossa was the most common reason for failure. There were no VK II material failures. A significant improvement in clinical success parameters for both prostheses was found if no previous surgeries were done before VK I or VK II total joint placement. Rib grafts were not helpful after removal of total joint prostheses if patients had a history of multiple procedures. Total TMJ prostheses must be reserved for patients with alternative surgical failures or when these procedures are no longer indicated. Close monitoring by clinical examination and imaging is necessary.     

The future ain't what it used to be

Base salaries for all health care managers will rise an average of 4.0 to 4.5 percent from 1993 to 1994--less than in previous years. Why the slowdown?     

Molecular genetic studies of early breast cancer evolution

Summary In the past few years there has been an explosion in the number of patients diagnosed with hyperplastic breast disease andin situ breast cancer. Based on epidemiological data, these morphologically defined lesions may be categorized as those with little malignant potential (e.g. typical hyperplasia or proliferative disease without atypia [PDWA]), those with significant malignant potential which may already be initiated (e.g. atypical ductal hyperplasia [ADH]), and early transformed lesions which are malignant but not yet invasive (e.g. ductal carcinomain situ [DCIS]). They may represent sequential evolutionary stages in the ontogeny of invasive breast cancer, with each morphologically defined stage resulting from accumulating genetic changes culminating in a transformed clonal lineage capable of invasion and metastasis. Using loss-of-heterozygosity (LOH) analysis, we are studying the genetic changes associated with these lesions in archival tissue samples. 50% (6/12) of the proliferative lesions (PDWA and ADH) and 80% of the DCIS shared their LOH patterns with more advanced lesions from the same breast, strongly supporting a precursor/product relationship between these lesions and the cancers they accompany.     

Comorbidity of autistic spectrum disorders in children with Down syndrome

The aim of the study was to identify the comorbidity of autistic spectrum disorders in a population of children with Down syndrome (DS). All children with DS within a defined population of South Birmingham were identified. The Asperger Syndrome Screening Questionnaire and the Child Autism Rating Scale were completed and diagnosis made according to ICD-10 criteria following interview and observation. Thirty-three of 58 identified children completed the measures, four of whom received a diagnosis of an autistic spectrum disorder. This is equivalent to a minimum comorbid rate of 7%. The questionnaire items concerning social withdrawal, restricted or repetitive interests, clumsiness, and unusual eye contact were associated with an autistic disorder. Of the remaining 29 participating children, 11 also displayed marked obsessional and ritualistic behaviours. The comorbid occurrence of autism and DS is at least 7%. It is important that these children are identified and receive appropriate education and support. A full assessment of social, language, and communication skills and behaviour is crucial, particularly in children with DS who appear different from other children with DS. Potential mechanisms accounting for this comorbidity are discussed.     

Identification of amino-terminal sequences contributing to tryptophan hydroxylase tetramer formation

Tryptophan hydroxylase (TPH) catalyzes the rate-limiting step in the biosynthesis of serotonin. In the rabbit, TPH exists as a tetramer of four identical 51-kDa subunits comprised of 444 amino acids each. The enzyme consists of an amino-terminal regulatory domain and a carboxyl-terminal catalytic domain. Previous studies demonstrated that within the carboxyl-terminus of TPH, there resides an intersubunit binding domain (a leucine zipper) that is essential for tetramer formation. However, it is hypothesized that a 4,3-hydrophobic repeat identified within the regulatory domain of TPH (residues 21–41) may also be involved in macromolecular assembly. To test this hypothesis, a series of amino-terminal deletions (NΔ15, 30, 41, and 90) were created and assessed for macromolecular structure using size-exclusion chromatography. The amino-terminal deletion NΔ15, upstream from the 4,3-hydrophobic repeat, was capable of forming tetramers. However, when a portion of the 4,3-hydrophobic repeat was deleted (NΔ30), a heterogeneous elution pattern of tetramers, dimers, and monomers was observed. Complete removal of the 4,3-hydrophobic repeat (NΔ41) rendered the enzyme incapable of forming tetramers; a monomeric form predominated. In addition, a double-point mutation (V28R-L31R) was created in the hydrophobic region of the enzyme. The introduction of two arginines (R) at positions 28 and 31 respectively, in the helix disrupted the native tetrameric state of TPH. According to size-exclusion chromatography analysis, the double-point mutant (V28R-L31R) formed dimers of 127 kDa. Thus, it is concluded that there is information within the amino-terminus that is necessary for tetramer formation of TPH. This additional intersubunit binding domain in the amino-terminus is similar to that found in the carboxyl-terminus.     

Modulation of retinal pigment epithelial cell behavior by Agaricus bisporus lectin.

PURPOSE: To determine whether Agaricus bisporus lectin (ABL) binds retinal pigment epithelial cells (RPEs), to conduct a preliminary viability study of RPEs exposed to ABL, and to evaluate the effects of ABL on RPE proliferation and RPE-mediated matrix contraction in vitro. METHODS: Using cultured bovine RPEs, immunohistochemistry was used to study ABL binding. Morphologic and trypan blue exclusion techniques were used for toxicity studies. The effect of ABL on RPE proliferation was investigated by [methyl-3H]-thymidine incorporation. The effect of ABL on RPE-mediated matrix contraction was evaluated with RPE-populated three-dimensional collagen matrices. RESULTS: ABL bound to RPE cells. This binding was inhibited by asialomucin. No change in RPE morphology or trypan blue exclusion compared with controls was observed in RPEs incubated with 5 to 60 microg/ml ABL for 3 days. Twenty-four-hour incubations of RPEs with ABL significantly inhibited RPE proliferation in a dose-dependent way, 40 microg/ml ABL inhibited proliferation by 83% (SE 14, P<0.05). ABL showed a dose-dependent significant inhibition of RPE-mediated collagen matrix contraction over 3 days, with 93% inhibition compared with controls by 40 microg/ml lectin (P<0.05). The inhibitory effect of ABL on proliferation and gel contraction was partly reversible after eliminating ABL from the culture medium. CONCLUSIONS: Bovine RPE cells bind ABL, and preliminary evaluations suggest that levels of ABL that are nontoxic to the cells potently inhibit RPE proliferation and RPE-mediated matrix contraction. ABL deserves further investigation as a potential inhibitor of RPE proliferation and cell-mediated matrix contraction in anomalous reparative processes such as proliferative vitreoretinopathy and as a laboratory tool for RPE behavioral studies.