F. De Stefano

Allogeneic hemopoietic SCT for patients with primary myelofibrosis: a predictive transplant score based on transfusion requirement, spleen size and donor type

A total of 46 patients with primary myelofibrosis (PMF) (median age 51 years), underwent an allogeneic hemopoietic SCT (HSCT) after a thiotepa-based reduced-intensity conditioning regimen. The median follow-up for surviving patients is 3.8 years. In multivariate analysis, independent unfavorable factors for survival were RBC transfusions >20, a spleen size >22 cm and an alternative donor—24 patients had 0–1 unfavorable predictors (low risk) and 22 patients had 2 or more negative predictors (high risk). The overall actuarial 5-year survival of the 46 patients is 45%. The actuarial survival of low-risk and high-risk patients is, respectively, 77 and 8% (P<0.0001); this is because of a higher TRM for high-risk patients (RR, 6.0, P=0.006) and a higher relapse-related death (RR, 7.69; P=0.001). In multivariate Cox analysis, the score maintained its predictive value (P=0.0003), even after correcting for donor–patient age and gender, Dupriez score, IPSS (International Prognostic Scoring System) score pre-transplant and splenectomy. In conclusion, PMF patients undergoing an allogeneic HSCT may be scored according to the spleen size, transfusion history and donor type; this scoring system may be useful to discuss transplant strategies.

Long-term follow-up of two children with a variant of mild autosomal recessive osteopetrosis undergoing bone marrow transplantation

Malignant autosomal recessive (AR) osteopetrosis represents an absolute indication for bone marrow transplantation (BMT). Over the last 15 years, almost 100 BMTs for osteopetrosis have been reported. The median age at transplant of most patients is 4 months. Very few cases of mild AR osteopetrosis have been described. Here, we report the good outcome of two cases of mild AR osteopetrosis with a follow-up of 5 and 6 years, respectively, after an HLA-identical sibling transplant undergone at 5 and 12 years of age, respectively. At the time of BMT, severe visual impairment was present in both children. Bone biopsy demonstrated hypermineralization with virtual obliteration of the medullary spaces, rare microfoci of hematopoiesis and marked deficiency in osteoclastic activity. Successful engraftment was complicated by hypercalcemia, controlled by a combination of bisphosphonate, phosphate infusions, vigorous hydration and calcitonin. Following BMT, radiological and histological findings showed extensive bone resorption with marked augmentation of the osteoclasts in normalized marrow. No improvement was observed in visual acuity, despite complete remodeling of skeletal abnormalities. We conclude that allogeneic BMT is the only chance of curing mild AR osteopetrosis. Bone Marrow Transplantation (2000) 26, 219–224.

A ‘de novo’ point mutation of the low‐density lipoprotein receptor gene in an Italian subject with primary hypercholesterolemia

Severe hypercholesterolemia was found in an 11‐year‐old boy with no family history of familial hypercholesterolemia. The reduced LDL‐receptor activity in cultured skin fibroblasts (40%125I‐LDL degradation as compared with a control cell line) indicated the presence of an LDL‐receptor defect. The analysis of the promoter region and the exons of LDL‐receptor gene by single strand conformation polymorphism revealed an abnormal migration pattern in exon 1, which was due to a T A transversion at nucleotide 28 of the cDNA. This novel mutation causes an arginine for tryptophane substitution at position‐12 of the signal peptide (W‐12R) and introduces an AviII restriction site in exon 1. Screening of the mutation by polymerase chain reaction (PCR) amplification of exon 1 and AviII digestion revealed that none of the probands family members carried the mutation. Non‐paternity was excluded after the analysis of a battery of 14 short tandem repeats located in 13 different chromosomes. These results are consistent with the hypothesis that the proband is heterozygous for a ‘de novo’ mutation of the LDL‐receptor gene producing a non‐conservative amino acid substitution. We suggest that the change in the net charge of the signal peptide, caused by the addition of a positively charged amino acid, impairs the co‐translational translocation of the nascent receptor protein across the endoplasmic reticulum membrane.

The legal implications of error in radiology

Evaluation of the legal implications of error in radiology and therefore the assessment of criminal and civil liability in the practice of the profession requires an analysis of how the public perception of the right to health has radically changed. This change has initiated a defensive approach to medicine and radiology that tends to be oriented towards precautionary measures, with a proliferation of often unnecessary imaging studies. In radiology, errors of omission or commission are frequent. A critical appraisal of the different types of error in radiology will help practitioners undertake the essential corrective measures. Through analysis of several cases derived from legal or insurance proceedings brought against radiologists, the most common forms of error are described, and their implications for criminal and civil liability are illustrated, although it is emphasised that the existence of an error does not always translate into the presence of malpractice.Evaluation of the legal implications of error in radiology and therefore the assessment of criminal and civil liability in the practice of the profession requires an analysis of how the public perception of the right to health has radically changed. This change has initiated a defensive approach to medicine and radiology that tends to be oriented towards precautionary measures, with a proliferation of often unnecessary imaging studies. In radiology, errors of omission or commission are frequent. A critical appraisal of the different types of error in radiology will help practitioners undertake the essential corrective measures. Through analysis of several cases derived from legal or insurance proceedings brought against radiologists, the most common forms of error are described, and their implications for criminal and civil liability are illustrated, although it is emphasised that the existence of an error does not always translate into the presence of malpractice.RiassuntoLa valutazione della rilevanza medico-legale dell’errore in radiologia e, quindi, della responsabilità penale e civile nell’esercizio della professione impone l’analisi di come radicalmente sia modificata nell’opinione pubblica la percezione del diritto alla tutela della salute e, da questo, siano nate una medicina e, quindi, anche una radiologia sempre più facilmente orientate a principi cautelativi o difensivi, con proliferare di accertamenti e procedure spesso inutili. In radiologia l’errore omissivo o commissivo è frequente. Un’analisi critica delle diverse tipologie di errore più facilmente porta ad assumere gli indispensabili comportamenti correttivi. Tramite casi esemplificativi tratti da procedimenti giudiziari o assicurativi ormai risolti contro radiologi, l’articolo descrive le più comuni forme di errore e ne illustra le ricadute in sede penale e civile, evidenziando comunque che l’errore non sempre configura l’esistenza di una responsabilità ovvero di una colpa, in particolare in ambito penalistico.

Regulating the communication of genetic risk information: the Italian legal approach to questions of confidentiality and disclosure

Battistuzzi L, Ciliberti R, Forzano F, De Stefano F. Regulating the communication of genetic risk information: the Italian legal approach to questions of confidentiality and disclosure.

An unusual observation of tetragametic chimerism: forensic aspects

A 41-year-old healthy Caucasian male showed an unidentifiable direct AB0 group and a B group by an indirect method revealing the presence of natural antibodies anti-A1 and anti-A2. Mixed fields with anti-B and anti-A+B antisera led to the conclusion that blood group B and 0 cell populations were present in a 1:1 ratio. A negative anamnesis for both transplantation and transfusion suggested a chimerism. DNA analysis of tissues revealed a tetragametic chimerism due to an apparent double parental contribution of nuclei in a phenotypically normal man.

Forensic evaluation of HUMCD4: An Italian database

The YTTTC pentanucleotide short tandem repeat polymorphism HumCD4 was studied in an Italian population sample. PCR products were compared to an allelic ladder by manual PAGE and silver staining. A total of 6 alleles ranging from 5 to 12 repeats were represented in the analysed sample, of which 3 alleles (10, 6 and 5 repeats) were predominant and displayed a combined frequency of 0.91. Successful amplification was obtained from different sources such as blood and urine stains, teeth and paraffin embedded tissues. Results were also determined in cases of severely degraded DNA. We consider that the HUMCD4 polymorphism may be a useful tool for individual identification, paternity testing, population studies and have also employed this locus to monitor engraftment of bone marrow transplantation.

Analysis of a short tandem repeat locus on chromosome 19 (D19S253)

A tetranucleotide tandem repeat locus on chromosome 19 (D19S253) was analysed. PCR products were detected by denaturing polyacrylamide gels with fluorescent-based technology. This study has confirmed a polymorphism with 9 alleles ranging from 209 to 241 by with a simple repeat structure arranged from 7 to 15 repeats. Family studies confirmed mendelian inheritance of alleles. The efficiency on DNA extracted from bloodstains and cigarette butts has been evaluated. The protocol has shown sensitivity and reproducibility.

HLA-DQA1 and Amelogenin Coamplification: A Handy Tool for Identification

A protocol for HLA-DQA1 and gender identification by single amplification is described. The use of the commercial HLA-DQA1 amplification kit (Perkin Elmer) permits a positive response for sex determination by adding primers for a short sequence on the first intron of Amelogenin gene. The suggested amplification protocol results in PCR products easily and clearly detectable on ethidium bromide stained agarose gel or silver stained polyacrylamide gel. In both gels the HLA-DQA1 observations at 242-239 bp are accomplished with a single band at 106 bp in females and a doublet 112-106 bp in males. HLA-DQA1 reverse dot-blot hybridization is unaffected by the presence of X and Y amplified fragments.

La rilevanza medico-legale dell'errore in radiologia

Evaluation of the legal implications of error in radiology and therefore the assessment of criminal and civil liability in the practice of the profession requires an analysis of how the public perception of the right to health has radically changed. This change has initiated a defensive approach to medicine and radiology that tends to be oriented towards precautionary measures, with a proliferation of often unnecessary imaging studies. In radiology, errors of omission or commission are frequent. A critical appraisal of the different types of error in radiology will help practitioners undertake the essential corrective measures. Through analysis of several cases derived from legal or insurance proceedings brought against radiologists, the most common forms of error are described, and their implications for criminal and civil liability are illustrated, although it is emphasised that the existence of an error does not always translate into the presence of malpractice.Evaluation of the legal implications of error in radiology and therefore the assessment of criminal and civil liability in the practice of the profession requires an analysis of how the public perception of the right to health has radically changed. This change has initiated a defensive approach to medicine and radiology that tends to be oriented towards precautionary measures, with a proliferation of often unnecessary imaging studies. In radiology, errors of omission or commission are frequent. A critical appraisal of the different types of error in radiology will help practitioners undertake the essential corrective measures. Through analysis of several cases derived from legal or insurance proceedings brought against radiologists, the most common forms of error are described, and their implications for criminal and civil liability are illustrated, although it is emphasised that the existence of an error does not always translate into the presence of malpractice.RiassuntoLa valutazione della rilevanza medico-legale dell’errore in radiologia e, quindi, della responsabilità penale e civile nell’esercizio della professione impone l’analisi di come radicalmente sia modificata nell’opinione pubblica la percezione del diritto alla tutela della salute e, da questo, siano nate una medicina e, quindi, anche una radiologia sempre più facilmente orientate a principi cautelativi o difensivi, con proliferare di accertamenti e procedure spesso inutili. In radiologia l’errore omissivo o commissivo è frequente. Un’analisi critica delle diverse tipologie di errore più facilmente porta ad assumere gli indispensabili comportamenti correttivi. Tramite casi esemplificativi tratti da procedimenti giudiziari o assicurativi ormai risolti contro radiologi, l’articolo descrive le più comuni forme di errore e ne illustra le ricadute in sede penale e civile, evidenziando comunque che l’errore non sempre configura l’esistenza di una responsabilità ovvero di una colpa, in particolare in ambito penalistico.