Treatment of esophageal perforation in octogenarians: a multicenter study.

Esophageal perforation is associated with significant mortality, and this may markedly increase with advanced age. This multicenter study investigates this issue in patients older than 80 years. Data on 33 patients >80 years old who underwent conservative (10 patients), endoclip (one patient), stent grafting (11 patients), or surgical treatment (11 patients) for esophageal perforation were collected from nine centers. Surgical repair consisted of repair on drain in one patient, primary repair in seven patients, and esophagectomy in two patients. Among patients who underwent stent grafting, one required repeat stenting and another stent graft repositioning. One patient was converted to surgical repair after stent grafting. Thirteen patients (39.4%) died during the 30-day and/or in-hospital stay. Their mortality was significantly higher than in a series of patients<80 years old (13.0%, 21/161 patients, P=0.001). Three patients (30.0%) died after conservative treatment, one (100%) after treatment with endoclips, five (45.5%) after stent grafting, and four (36.4%) after surgical repair (P=0.548). Early survival with salvaged esophagus was 42.4% (conservative treatment: 70.0% endoclips 0%, stent grafting: 54.5%, and surgical repair: 54.5%, respectively, P=0.558). Estimated glomerular filtration rate<60 mL/minute/1.73 m2 (70.0% vs. 25.0%, P=0.043) and sepsis (100% vs. 32.1%, P=0.049) at presentation were associated with increased risk of early mortality in univariate analysis. Esophageal perforation in octogenarians is associated with very high early and intermediate high mortality irrespective of the treatment method used.

Aarskog-Scott syndrome: clinical update and report of nine novel mutations of the FGD1 gene.

Mutations in the FGD1 gene have been shown to cause Aarskog-Scott syndrome (AAS), or facio-digito-genital dysplasia (OMIM#305400), an X-linked disorder characterized by distinctive genital and skeletal developmental abnormalities with a broad spectrum of clinical phenotypes. To date, 20 distinct mutations have been reported, but little phenotypic data are available on patients with molecularly confirmed AAS. In the present study, we report on our experience of screening for mutations in the FGD1 gene in a cohort of 60 European patients with a clinically suspected diagnosis of AAS. We identified nine novel mutations in 11 patients (detection rate of 18.33%), including three missense mutations (p.R402Q; p.S558W; p.K748E), four truncating mutations (p.Y530X; p.R656X; c.806delC; c.1620delC), one in-frame deletion (c.2020_2022delGAG) and the first reported splice site mutation (c.1935+3A>C). A recurrent mutation (p.R656X) was detected in three independent families. We did not find any evidence for phenotype-genotype correlations between type and position of mutations and clinical features. In addition to the well-established phenotypic features of AAS, other clinical features are also reported and discussed.

Further delineation of Pitt-Hopkins syndrome: phenotypic and genotypic description of 16 novel patients.

BACKGROUND: Haploinsufficiency of the gene encoding for transcription factor 4 (TCF4) was recently identified as the underlying cause of Pitt-Hopkins syndrome (PTHS), an underdiagnosed mental-retardation syndrome characterised by a distinct facial gestalt, breathing anomalies and severe mental retardation. METHODS: TCF4 mutational analysis was performed in 117 patients with PTHS-like features. RESULTS: In total, 16 novel mutations were identified. All of these proven patients were severely mentally retarded and showed a distinct facial gestalt. In addition, 56% had breathing anomalies, 56% had microcephaly, 38% had seizures and 44% had MRI anomalies. CONCLUSION: This study provides further evidence of the mutational and clinical spectrum of PTHS and confirms its important role in the differential diagnosis of severe mental retardation.

Clinical score of 62 Italian patients with Cornelia de Lange syndrome and correlations with the presence and type of NIPBL mutation.

Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder characterized by facial dysmorphisms, upper limb abnormalities, growth and cognitive retardation. About half of all patients with CdLS carry mutations in the NIPBL gene. The first Italian CdLS cohort involving 62 patients (including 4 related members) was screened for NIPBL mutations after a clinical evaluation using a quantitative score that integrates auxological, malformation and neurodevelopmental parameters. The patients were classified as having an overall 'severe', 'moderate' or 'mild' phenotype. NIPBL screening showed 26 mutations so classified: truncating (13), splice-site (8), missense (3), in-frame deletion (1) and regulatory (1). The truncating mutations were most frequently found in the patients with a high clinical score, whereas most of the splice-site and all missense mutations clustered in the low-medium score groups. The NIPBL-negative group included patients covering the entire clinical spectrum. The prevalence of a severe phenotype in the mutated group and a mild phenotype in the non-mutated group was statistically significant. In terms of the isolated clinical signs, the statistically significant differences between the mutation-positive and mutation-negative individuals were pre- and post-natal growth deficits, limb reduction, and delayed speech development. The proposed score seems to be a valuable means of prioritizing the patients with CdLS to undergo an NIPBL mutation test.

Gastrointestinal surgical emergencies in patients treated for hemathological malignancies.

BACKGROUND: Upper and lower gastrointestinal symptoms are major and serious complications in patients who undergo chemotherapy for hematological malignancies. Their most frequent causes are acute intestinal graft-versus-host disease (GVHD) after bone marrow transplant, infections, toxicity or preexisting gastrointestinal diseases. Mortality can reach 30-60% of cases. PATIENTS AND METHODS: We report 15 cases operated on for abdominal emergencies: 3 severe gastrointestinal bleeding and 12 acute abdomen. RESULTS: We performed 10 bowel resections, one cholecystectomy, one splenectomy, two laparotomy with pancreatic debridement and peritoneal lavage, and one suture of perforated peptic ulcer. Operative mortality was 33.3% (5/15). Deaths have been reported only in the group of patients with acute abdomen. In all cases death was correlated to generalized sepsis related to immunosuppression. CONCLUSIONS: We believe that an aggressive approach, consisting of close monitoring and early laparotomy combined with vigorous supportive therapy, should be used when dealing with suspected gastrointestinal complications in patients with hematological malignancies.

Systematic radical gastrectomy and D2 lymphadenectomy in primary gastric B cell lymphoma: impact on diagnosis, classification and long term results. A prospective study.

The role of surgery in the treatment of primary gastric lymphoma has been recently re-evaluated. We report the results of a series of 37 operated patients for primary gastric lymphoma (PGL). All patients underwent gastrectomy with D2 lymphadenectony and bilateral liver biopsies. Postoperative histopathological classification was compared to preoperative staging data. No mortality and low morbidity were observed in this series of patients. We found a high incidence of mixed grading of tumors and a relatively high incidence of lymph node metastases in low grade lymphoma. Relying on preoperative biopsies and imaging techniques could lead to preoperative staging inaccuracy and therefore to inappropriate treatment planning. For these reasons we advocate systematic primary surgery in PGL. Surgery could be useful for staging purposes and seems to be curative in stage IE.

Mutation and transcription analysis of transthyretin gene in Italian families with hereditary amyloidosis: a putative novel hot spot' in codon 47.

Transthyretin gene mutations are associated with autosomal dominant familial amyloidosis. The commonest phenotype in the patients is peripheral neuropathy, but restrictive cardiomyopathy is also a frequent sign. More than 70 different mutations in the gene have been described. Although these mutations are randomly distributed, some hot spots have also been reported notably at position 6, 30, 33, 58, 109, 119 and 122. A few of these codons contain a CpG dinucleotide. We describe an additional 'hot spot' occurring at codon 47, in which we report one novel and two previously described mutations. This codon, however, does not contain a CpG dinucleotide, suggesting that other mechanisms might be responsible for the allelic heterogeneity. All the reported mutations in codon 47 are located in the exon 2 consensus sequence and are potentially involved in splicing. We performed transcription analysis on two livers obtained from transplanted patients carrying the Ala47 mutation. These livers showed a normally spliced message, indicating that this mutation does not affect splicing.

[Gardner syndrome]. / La sindrome di Gardner.

The observation of Gardner's syndrome case, in a six year old girl, referred to the hospital for seizures, provides the Authors with the opportunity of reviewing that important subject of the medical and surgical clinical pathology. The diagnostic features and differential diagnosis are described. The current criteria for diagnosis and surveillance of the affected or at risk subjects are outlined. Today the molecular, and, thereafter, the prenatal, neonatal and preclinical diagnosis of the disease, is possible.

[Peutz-Jeghers syndrome]. / La sindrome di Peutz-Jeghers.

An observation of Peutz-Jeghers syndrome, in a 13 year old girl, provides the Authors with the opportunity of reviewing the clinical features, the natural history and the complications of the disease, mainly the malignancies. In recent reviews the occurrence of cancer was further on investigated: gastrointestinal and non gastrointestinal tumors occurred in 22-48% of the patients examined. The surveillance protocols of the subjects at risk and genetic counseling are discussed.

Radiological findings in a case of Menkes' disease.

Menkes' disease, a neurodegenerative progressive X-linked disorder, was diagnosed in a 4-month-old child. The diagnosis was made on the combination of clinical features with laboratory and radiological findings. The pathogenesis of the skeletal findings in Menkes' disease is as yet unclear. Because of the severity of the prognosis and in order to plan treatment, the correct diagnosis has to be reached quickly. Typical manifestations of the syndrome are likely to develop after 3 months of age, with a pleiotropic appearance. In the present case, on the basis of the clinical investigation the patient underwent retrograde cystourethrography, roentgenographic examination of the skeleton, and magnetic resonance imaging of the brain. On analysis of the magnetic resonance imaging, we detected one-sided involvement of both subcortical and cortical parenchyma resembling a unilateral ischemic lesion such as, to our knowledge, has not yet been reported.

C5b-9 generation and cytokine production in hemodialyzed patients.

The role of the complement system in the induction of cytokine release is controversial. Plasma terminal C complex C5b-9 along with Bb and C4d fragments were evaluated in 22 patients during routine acetate or bicarbonate hemodialysis using cuprophane membranes and hemodiafiltration (HDF) or acetate-free-biofiltration (AFB) using polyacrylonitrile (PAN) membranes. In a subgroup of six uremic patients we also evaluated the release of tumor necrosis factor (TNF alpha) and interleukin-6 (IL-6) from monocytes before and after six subsequent sessions with bicarbonate-cuprophane, HDF and AFB-PAN. At beginning of the dialysis increased plasma C5b-9 levels were found in patients treated by acetate or bicarbonate-cuprophane. Moreover, a rapid significant (P < 0.001) increase of C5b-9 levels occurred in both groups 15 minutes after the onset of the hemodialysis procedure with a plateau at 180 minutes. In contrast, only a slight increase in the plasma C5b-9 levels was observed in patients dialysed with HDF or AFB using PAN membranes. This increase was more pronounced with HDF at 0 minutes compared with controls. A positive linear correlation was found in all patients between C5b-9 generation and plasma Bb levels at different times in the dialysis session. The production of C4d fragment remained unchanged in all groups, indicating that C5b-9 complex generation is due to the prevalent alternative complement pathway activation. The pattern of cytokine production strictly resembled the complement system activation and C5b-9 generation.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and electrophysiological reports in a case of early onset myotonia congenita (Thomsen's disease) successfully treated with mexiletine.

A sporadic event of myotonia congenita in a infant admitted to the Paediatric Clinic for frequent crises of apnoea, cyanosis, vomiting and difficult feeding is reported. EMG analysis was consistent with the dominant variety of myotonia congenita. Mexiletine therapy showed excellent results in reducing myotonic activity. It is worthwhile stressing that early symptoms may go unnoticed or may be misinterpreted and that information on the genetic form of the disease can be obtained also from the EMG analysis through a repetitive stimulation test.

Involvement of peripheral blood monocytes in haemodialysis: in vivo induction of tumour necrosis factor alpha, interleukin 6 and beta 2-microglobulin.

Our aim was to evaluate the role of three different variables in the activation of the monocyte system: dialysis membrane (cuprophane or polyacrylonitrile), dialysate (acetate or bicarbonate), and procedure (standard or high-flux haemodialysis). By ELISA test we measured the 'in vivo' intracellular (monocyte-associated) production and extracellular release of tumour necrosis factor alpha (TNF alpha), interleukin-6 (Il-6) and beta 2-microglobulin (beta 2-M) by monocytes from 20 uraemic patients before and after the dialysis session. At the beginning of the dialysis session, uraemic patients' cultured monocytes spontaneously released a greater amount of TNF alpha, Il-6 and beta 2-M compared to normal controls. However, no differences in cytokine and beta 2-M were observed in monocyte lysate between the two groups. At the end of the dialysis session, cultured monocytes from patients treated with cellulosic membranes and acetate dialysate showed greater TNF alpha values than normal controls (P less than 0.001 and P less than 0.05 respectively). Moreover, TNF alpha and Il-6 values were strictly correlated (P less than 0.05). These results clearly show an activation of the monocyte system in uraemic patients undergoing periodic haemodialysis. The implicated factors may be multiple, such as complement activating cellulosic membranes or acetate dialysate. The production of TNF alpha, Il-6 and beta 2-M may explain some of the pathological findings observed in long-term haemodialysis patients.

[A case of partial 6q trisomy diagnosed at birth]. / Un caso di trisomia 6q parziale diagnosticato alla nascita.

This report concerns a male newborn investigated with chromosomal analysis due to dysmorphic and malformative signs. His caryotype was 46,XY but the short arm of one 3 was not normal: parental chromosomes showed a maternal balanced translocation (3;6)(p25;q23) which had led to 6q23----6qter duplication in the patient. The phenotype was like the twenty-one cases found in the literature: it is characterized by facial dysmorphism (bow shaped mouth, high prominent forehead, protruding ocular bulbs, anteverted nostrils), short neck with pterigium, flexion contractures especially at extremities and neurological problems as well as internal malformations. Moreover, it seems not affected, or very little, by monosomies accompanying unbalanced translocations.

Interleukin-1-like activity produced by hybrids constructed with Epstein-Barr-virus-transformed human B lymphocytes and mouse myeloma cells.

Peripheral blood B lymphocytes from a donor with positive tuberculin skin test reaction were transformed into lymphoblastoid cell lines by Epstein-Barr virus and then fused by polyethylene glycol with mouse myeloma cells. Human-mouse hybrid cells producing human IgM monoclonal antibody to purified protein derivative of tuberculin were isolated, and the concentrated supernatant of one of these cell hybrids was tested for the capacity of interfering with DNA synthesis of human and mouse lymphocytes. The hybrid cell supernatant was found to contain soluble factors that increased DNA synthesis in unstimulated human and mouse lymphocytes and that, conversely, decreased DNA synthesis in concanavalin-A-stimulated cells. Gel filtration experiments showed that these antagonistic activities were due to at least two different factors, one of which resembled human interleukin-1 in biochemical and biological properties.

Recessive cancer genes in meningiomas? An analysis of 31 cases.

Cytogenetic studies on 31 human meningiomas revealed clonal abnormalities in 14 of them. Monosomy 22 was present in three cases as the only abnormality, and in five it was associated with monosomy 18, monosomy 14, loss of X, loss of Y, and trisomy 20, respectively. We found a number of rearrangements involving chromosome #22: an i psu dic(22)(pter----q11::q11----pter) in two cases and a t(18;22)(q12;q11) in another case. Two cases showed a complex translocation involving #7 and #14: t(2;7;14)(q23;q36;q22) and t(1;7;14)(q25;q32;q22), respectively. Other clonal chromosome abnormalities were del(1p) (present in two cases); der(9)t(9;?)(q34;?); der(7)t(7;?)(q31;?); der(22)t(22;?)(q11;?); and a 9p+ chromosome. The relevance for the pathogenesis of human meningiomas of these chromosome anomalies is also discussed with reference to the previous literature. The possible involvement of recessive cancer genes present on the long arm of chromosome #22 is also discussed.