Apolipoprotein A-I (Glu 198----Lys): a mutant of the major apolipoprotein of high-density lipoproteins occurring in a family with dyslipoproteinemia

To detect genetic mutants of apo A-I, the major structural protein of human HDL, we screened 530 unrelated Austrian probands (168 children, 362 adults). An apo A-I mutant characterized by an exchange of the acidic amino acid Glu in position 198 with the basic amino acid Lys was identified in the serum of the mother of a hyperlipoproteinemic girl. So far only two patients with this mutant, referred to as apo A-I (Glu 198----Lys) have been described. We detected six new patients (two children and four adults) with apo A-I (Glu 198----Lys) among 20 members in three generations of the affected family. An autosomal codominant inheritance of the apolipoprotein variant could be established. All affected individuals were heterozygous for the mutant. Among the six new subjects with apo A-I (Glu 198----Lys) two children and one adult presented with high-density lipoprotein (HDL) cholesterol concentrations below the fifth percentile for age and sex and with low serum apo A-I and A-II. Although there was no consistent relationship of the mutant with low serum HDL in this family, a moderate effect of apo A-I (Glu 198----Lys) on HDL levels cannot be ruled out. Hyperlipoproteinemia of types IIa, IIb, and IV was observed in eight of the 20 family members studied, but did not cosegregate with the mutant apo A-I. There was no association of apo A-I (Glu 198----Lys) with premature clinical manifestations of atherosclerosis. The mutation occurred in a part of the apo A-I molecule, which is thought to be involved in lipid binding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myeloablative radiochemotherapy followed by reinfusion of purged autologous stem cells for Waldenström's macroglobulinaemia

Waldenström's macroglobulinaemia (WM) is an incurable lymphoproliferative disorder. The purpose of this study was to investigate the role of autologous peripheral blood stem cell transplantation (ASCT) for the treatment of WM. Seven patients (untreated or after first-line therapy) with symptomatic WM underwent two or three cycles of Dexa-BEAM chemotherapy + G-CSF with stem cell harvesting and proceeded to total body irradiation and high-dose cyclophosphamide followed by reinfusion of ex-vivo B-cell-depleted stem cells. Engraftment was prompt, and procedure-related deaths did not occur. A strong reduction or normalization of BM infiltration and serum IgM levels occurred in all evaluable patients, but immunofixation electrophoresis revealed persistent paraproteinaemia in five of them. With 3–30 months of follow-up, all patients are alive without clinical or serological signs of disease progression. This pilot trial shows for the first time that high-dose radiochemotherapy with purged stem cells is effective and may improve the course of patients with WM. In the majority of cases, however, complete eradication of the disease does not appear to be possible with ASCT alone.     

The use of wax and self-curing acrylic resin in border molding.

A procedure for border molding of impression trays with border wax and cold-curing acrylic resin has been described. The use of modeling compound, the water bath, and the alcohol torch has been eliminated.     

Stellenwert der SPECT/CT zur Abkl?rung von Kiefererkrankungen

CLINICAL/METHODICAL ISSUE: Diseases of the jaw, such as osteomyelitis, condylar hyperactivity and tumors need adequate imaging to evaluate the extension and activity for therapy planning. STANDARD RADIOLOGICAL METHODS: Conventional planar scintigraphy, orthopantomography, computed tomography (CT) and magnetic resonance imaging (MRI) can be used for the evaluation of jaw diseases. METHODICAL INNOVATIONS: Single photon emission computed tomography/computed tomography (SPECT/CT) provides metabolic and morphologic information in one imaging step and is becoming increasingly more available in larger hospitals. PERFORMANCE: The SPECT/CT is superior to planar scintigraphy alone, CT and orthopantomography in the evaluation of the extension and activity of osteomyelitis and jaw tumors. ACHIEVEMENTS: In our hospital SPECT/CT has replaced the other imaging modalities in the evaluation of osteomyelitis and condylar hyperactivity. PRACTICAL RECOMMENDATIONS: If available SPECT/CT should be performed for the evaluation of osteomyelitis of the jaw.     

Using the existing complete denture as a surgical template

This technique uses the patient's denture as a combination surgical splint and transitional prosthesis. Wire ligation or other methods of support used for surgical templates are unnecessary. Modifications of the existing complete denture can be accomplished in one setting, and the need for special equipment is eliminated. This method is applicable to the mandible as well as the maxilla.     

Performance of orthopantomography, planar scintigraphy, CT alone and SPECT/CT in patients with suspected osteomyelitis of the jaw

Purpose

The aim of this study was to evaluate the performance of a novel flat-panel single photon emission computed tomography (SPECT)/CT in patients with suspicion of osteomyelitis (OM) of the jaw in comparison with conventional orthopantomography (OPT), planar bone scintigraphy (PS) and CT alone.

Methods

Forty-two patients (21 female, 21 male, mean age 52, range 10–84 years) with suspected OM (n?=?38) or exacerbation of a known OM (n?=?4) were investigated with OPT, CT alone, PS and combined SPECT/CT. Images were separately reviewed by a nuclear physician/radiologist and jaw surgeon regarding presence of OM. Additionally, the different methods were rated regarding their usefulness for diagnosis (5-point scale: from 1 = diagnostic to 5 = useless). Biopsy served as the standard of reference in 30 patients and clinical/imaging follow-up of at least 6 months in 12 patients.

Results

In 35 of 42 patients the final diagnosis of OM was established according to the reference standard. Sensitivity, specificity and accuracy for OPT was 59, 100 and 66 %, for CT alone 77, 86 and 79 %, for PS 100, 71 and 95 % and for SPECT/CT 100, 86 and 98 %. SPECT/CT was significantly more accurate compared with CT alone (p?=?0.0078) and OPT (p?=?0.001). SPECT/CT was rated as the most useful imaging modality (mean value 1.2) compared with PS (2.2), CT (2.5) and OPT (3.2).

Conclusion

SPECT/CT is an accurate method to assess the presence of OM of the jaw and superior to CT alone and OPT. SPECT/CT slightly improved the specificity of PS. However, SPECT/CT in this study was not significantly more accurate compared with PS and whether the advantages to the patient of a one-stop study as opposed to doing separate CT and PS justifies its routine use in terms of cost requires further study.     

Carbohydrate intake modulates the effect of the ABCA1-R230C variant on HDL cholesterol concentrations in premenopausal women

The R230C variant of the ATP-binding cassette transporter A1 (ABCA1) gene has been consistently associated with decreased HDL-cholesterol (HDL-C) concentrations in several studies in the Mexican mestizo population. However, information on how diet composition modifies the effect of the ABCA1-R230C variant on HDL-C concentrations is very scarce. The aim of the present study was to analyze whether the effect of ABCA1-R230C on HDL-C concentrations is modulated by dietary factors in a nationwide population sample of 3591 adults from the National Health and Nutrition Survey conducted by the State's Employees' Social Security and Social Services Institute. All participants answered a validated questionnaire to assess health status and weekly food consumption. Fasting blood samples were drawn for biochemical analysis and DNA extraction, and the ABCA1-R230C variant was genotyped using TaqMan assays. Statistical analyses consisted of simple linear and multiple regression modeling adjusting for age, BMI, smoking, and alcohol consumption. The overall C risk allele frequency was 9.3% and the variant was significantly associated with low HDL-C concentrations in both sexes. A significant negative correlation between carbohydrate consumption and HDL-C concentrations was observed in women bearing the R230C variant (P = 0.021) and a significant gene-diet interaction was found only in premenopausal women (P = 0.037). In conclusion, the effect of the ABCA1-R230C gene variant on HDL-C concentrations is modulated by carbohydrate intake in premenopausal women. This finding may help design optimized dietary interventions according to sex and ABCA1-R230C genotype.     

An Object‐Oriented Regression for Building Disease Predictive Models with Multiallelic HLA Genes

Recent genome‐wide association studies confirm that human leukocyte antigen (HLA) genes have the strongest associations with several autoimmune diseases, including type 1 diabetes (T1D), providing an impetus to reduce this genetic association to practice through an HLA‐based disease predictive model. However, conventional model‐building methods tend to be suboptimal when predictors are highly polymorphic with many rare alleles combined with complex patterns of sequence homology within and between genes. To circumvent this challenge, we describe an alternative methodology; treating complex genotypes of HLA genes as “objects” or “exemplars,” one focuses on systemic associations of disease phenotype with “objects” via similarity measurements. Conceptually, this approach assigns disease risks base on complex genotype profiles instead of specific disease‐associated genotypes or alleles. Effectively, it transforms large, discrete, and sparse HLA genotypes into a matrix of similarity‐based covariates. By the Kernel representative theorem and machine learning techniques, it uses a penalized likelihood method to select disease‐associated exemplars in building predictive models. To illustrate this methodology, we apply it to a T1D study with eight HLA genes (HLA‐DRB1, HLA‐DRB3, HLA‐DRB4, HLA‐DRB5, HLA‐DQA1, HLA‐DQB1, HLA‐DPA1, and HLA‐DPB1) to build a predictive model. The resulted predictive model has an area under curve of 0.92 in the training set, and 0.89 in the validating set, indicating that this methodology is useful to build predictive models with complex HLA genotypes.