Systematic review of central pancreatectomy and meta-analysis of central versus distal pancreatectomy.

BACKGROUND: Central pancreatectomy (CP) is a parenchyma-sparing surgical procedure that enables the removal of benign and/or low-grade malignant lesions from the neck and proximal body of the pancreas. The aim of this review was to evaluate the short- and long-term surgical results of CP from all published studies, and the results of comparative studies of CP versus distal pancreatectomy (DP). METHODS: Eligible studies published between 1988 and 2010 were reviewed systematically. Comparisons between CP and DP were pooled and analysed by meta-analytical techniques using random- or fixed-effects models, as appropriate. RESULTS: Ninety-four studies, involving 963 patients undergoing CP, were identified. Postoperative morbidity and pancreatic fistula rates were 45·3 and 40·9 per cent respectively. Endocrine and exocrine pancreatic insufficiency was reported in 5·0 and 9·9 per cent of patients. The overall mortality rate was 0·8 per cent. Compared with DP, CP had a higher postoperative morbidity rate and a higher incidence of pancreatic fistula, but a lower risk of endocrine insufficiency (relative risk (RR) 0·22, 95 per cent confidence interval 0·14 to 0·35; P < 0·001). The risk of exocrine failure was also lower after CP, although this was not significant (RR 0·59, 0·32 to 1·07; P = 0·082). CONCLUSION: CP is a safe procedure with good long-term functional reserve. In situations where DP represents an alternative, CP is associated with a slightly higher risk of early complications.

Translational mini-review series on immunodeficiency: molecular defects in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a primary immunodeficiency that typically affects adults and is characterized by abnormalities of quantative and qualitative humoral function that are heterogeneous in their immunological profile and clinical manifestations. The recent identification of four monogenic defects that result in the CVID phenotype also demonstrates that the genetic basis of CVID is highly variable. Mutations in the genes encoding the tumour necrosis factor (TNF) superfamily receptors transmembrane activator and calcium-modulating ligand interactor (TACI) and B cell activation factor of the TNF family receptor (BAFF-R), CD19 and the co-stimulatory molecule inducible co-stimulator molecule (ICOS) all lead to CVID and illustrate the complex interplay required to co-ordinate an effective humoral immune response. The molecular mechanisms leading to the immune defect are still not understood clearly and particularly in the case of TACI, where a number of heterozygous mutations have been found in affected individuals, the molecular pathogenesis of disease requires further elucidation. Together these defects account for perhaps 10-15% of all cases of CVID and it is highly likely that further genetic defects will be identified.

A locus for asphyxiating thoracic dystrophy, ATD, maps to chromosome 15q13.

Asphyxiating thoracic dystrophy (ATD), or Jeune syndrome, is a multisystem autosomal recessive disorder associated with a characteristic skeletal dysplasia and variable renal, hepatic, pancreatic, and retinal abnormalities. We have performed a genome wide linkage search using autozygosity mapping in a cohort of four consanguineous families with ATD, three of which originate from Pakistan, and one from southern Italy. In these families, as well as in a fifth consanguineous family from France, we localised a novel ATD locus (ATD) to chromosome 15q13, with a maximum cumulative two point lod score at D15S1031 (Zmax=3.77 at theta=0.00). Five consanguineous families shared a 1.2 cM region of homozygosity between D15S165 and D15S1010. Investigation of a further four European kindreds, with no known parental consanguinity, showed evidence of marker homozygosity across a similar interval. Families with both mild and severe forms of ATD mapped to 15q13, but mutation analysis of two candidate genes, GREMLIN and FORMIN, did not show pathogenic mutations.

Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome.

Hand-foot-genital syndrome (HFGS) is a rare, dominantly inherited condition affecting the distal limbs and genitourinary tract. A nonsense mutation in the homeobox of HOXA13 has been identified in one affected family, making HFGS the second human syndrome shown to be caused by a HOX gene mutation. We have therefore examined HOXA13 in two new and four previously reported families with features of HFGS. In families 1, 2, and 3, nonsense mutations truncating the encoded protein N-terminal to or within the homeodomain produce typical limb and genitourinary abnormalities; in family 4, an expansion of an N-terminal polyalanine tract produces a similar phenotype; in family 5, a missense mutation, which alters an invariant domain, produces an exceptionally severe limb phenotype; and in family 6, in which limb abnormalities were atypical, no HOXA13 mutation could be detected. Mutations in HOXA13 can therefore cause more-severe limb abnormalities than previously suspected and may act by more than one mechanism.

Synthesis and biological activities of new carbaacyclonucleosides and 1'-oxaacyclonucleosides related to clitocine.

We describe the synthesis of two series of acyclonucleosides:carbaacyclonucleosides and 1'-oxaacyclonucleosides which possess the same aglycone as clitocine 3 which is a natural nucleoside exhibiting interesting biological properties. These compounds have been obtained by condensation of 4-aminobutanol or 3-silyloxypropoxyamine with 4,6-dichloro-5-nitropyrimidine. Structural modifications have been made on the heterocyclic base and the side chain to enhance their potential activity. All these compounds have been tested against different viruses: HIV-1, HSV-1, HSV-2, CMV, VZV, EBV. The carbaacyclonucleoside 10 was associated with an anti-EBV activity (EC50 = 0.86 microg/mL).