Familial acquired thrombotic thrombocytopenic purpura: ADAMTS13 inhibitory autoantibodies in identical twins

Thrombotic thrombocytopenic purpura (TTP) either occurs in a congenital form caused by ADAMTS13 gene mutations or it is acquired and most often due to ADAMTS13 inhibitory autoantibodies. In congenital TTP siblings are often affected, while acquired TTP occurs sporadically and familial clustering has not been described so far. We report identical twin sisters suffering from acquired TTP due to immunoglobulin G (IgG) autoantibodies inactivating ADAMTS13, suggesting an important role of hitherto unidentified genetic determinants of ADAMTS13 inhibitor formation. These cases also demonstrate that familial clustering is not sufficient for unambiguously diagnosing hereditary ADAMTS13 deficiency and congenital TTP.     

Ultrastructure of regenerated bone mineral surrounding hydroxyapatite-alginate composite and sintered hydroxyapatite

We report the ultrastructure of regenerated bone surrounding two types of biomaterials: hydroxyapatite-alginate composite and sintered hydroxyapatite. Critical defects in the calvaria of Wistar rats were filled with micrometer-sized spherical biomaterials and analyzed after 90 and 120 days of implantation by high-resolution transmission electron microscopy and Fourier transform infrared attenuated total reflectance microscopy, respectively. Infrared spectroscopy showed that hydroxyapatite of both biomaterials became more disordered after implantation in the rat calvaria, indicating that the biological environment induced modifications in biomaterials structure. We observed that the regenerated bone surrounding both biomaterials had a lamellar structure with type I collagen fibers alternating in adjacent lamella with angles of approximately 90°. In each lamella, plate-like apatite crystals were aligned in the c-axis direction, although a rotation around the c-axis could be present. Bone plate-like crystal dimensions were similar in regenerated bone around biomaterials and pre-existing bone in the rat calvaria. No epitaxial growth was observed around any of the biomaterials. A distinct mineralized layer was observed between new bone and hydroxyapatite-alginate biomaterial. This region presented a particular ultrastructure with crystallites smaller than those of the bulk of the biomaterial, and was possibly formed during the synthesis of alginate-containing composite or in the biological environment after implantation. Round nanoparticles were observed in regions of newly formed bone. The findings of this work contribute to a better understanding of the role of hydroxyapatite based biomaterials in bone regeneration processes at the nanoscale.     

Renal involvement in primary Sjogren syndrome of childhood: case report and literature review

Renal tubular acidosis (RTA) is common in adults with primary Sjogren syndrome (pSS) but to date this condition has only been identified in 12 pediatric cases of pSS. Here we present the case of a 13-year-old, otherwise asymptomatic girl in whom the search for the etiology of incidentally found nephrocalcinosis led to diagnosis of distal RTA and nephrogenic diabetes insipidus secondary to SS-associated tubulointerstitial nephritis. Immunosupressive treatment and alkali/electrolyte supplementation resulted in stable renal function over the 6-year follow-up. A review of the literature focuses on two aspects of pSS: (1) the difficulties in diagnosing pSS in childhood and (2) clinical–pathological features, treatment and outcome of renal tubulointerstitial disease in childhood pSS. SS should be considered in older children, particularly females with otherwise unexplained RTA. A careful search for other renal dysfunctions is necessary, and renal biopsy may be of value in assessing the extent of renal damage and the need for immunomodulatory therapy.     

Re-use of the original infusional induction chemotherapy as salvage therapy in myeloma patients relapsing after one autograft

If standard infusional therapy (IC) has been used to treat myeloma at presentation, it is a matter of debate whether patients should receive the original induction therapy or a different drug combination in first relapse. Instinctively, most clinicians may switch treatment, particularly since the advent of new drugs for the treatment of myeloma. Hitherto, there has been no data on the efficacy of repeating standard IC in the salvage setting.

We studied 62 myeloma patients whose initial treatment consisted of C-VAMP and a single high dose melphalan procedure and who were retreated with C-VAMP at the time of first relapse. Response to salvage C-VAMP was seen in 50% (95% confidence interval = 0.37–0.62) but we were unable to identify any predictors for response to salvage C-VAMP. Only patients resistant to salvage C-VAMP benefited from a second autograft. The survival of patients who responded to salvage C-VAMP was not prolonged by a second transplant.

In conclusion, our data supports the use of C-VAMP for patients with myeloma in first relapse and suggest that only patients resistant to salvage C-VAMP should be offered a second autograft.     

Measurement of inorganic fibrous particulates in ambient air and indoors with the scanning electron microscope

In the Federal Republic of Germany, the concentration of inorganic fibrous particles in the ambient air is measured by scanning electron microscopy (SEM) in accordance with draft guideline VDI 3492. Fibres of length greater than or equal to 2.5 microns are counted at a magnification of X2000. The concentrations and fibre dimensions of asbestos fibres and other mineral fibres were determined for 231 ambient air samples, 219 indoor air samples taken during asbestos removal and 21 taken at workplaces. In the ambient air measurements in rural and urban areas, the average concentration of other inorganic fibres was greater than 1000 fibres of length greater than or equal to 5 microns per m3. On the average, only about 100 or fewer asbestos fibres of length greater than or equal to 5 microns per m3 were observed. These 'asbestos fibres' from ambient air had low aspect ratios. They differed substantially from asbestos fibres measured in the ambient air close to sources of asbestos emissions, indoors during asbestos removal or at workplaces. Furthermore, the size distribution of these 'asbestos fibres' was similar to that of 'other inorganic fibres'. We suggest, therefore, that a substantial portion of the 'asbestos fibres' observed by SEM analysis in ambient air samples from rural and urban areas should be classified instead as 'other mineral fibres'.     

Malignant Tumors in Families of Thyroid Cancer Patients

A case-control study comprised 177 patients with various types of thyroid cancer and the same number of hospital controls individually matched by age, sex and place of residence. Malignant tumors were more frequent among first and second degree relatives of cases as compared to controls. The odds ratio (95% confidence interval) was 2.43 (1.33-4.44) and 5.33 (1.77-16.01) respectively. The most frequent were cancers of uterus and stomach with odds ratio of 6.00 (1.61-22.36) and 9.00 (1.64-49.35). Thyroid cancer was present only in first-degree relatives of two cases and none of controls.