Paediatric dacryocystorhinostomy

Of 258 cases of dacryocystorhinostomy performed on children in the period September 1981 to September 1991, 130 were for simple, unresolved congenital nasolacrimal duct obstruction. Other indications for surgery included punctal agenesis, lacrimal fistula, post-traumatic and post-inflammatory canalicular obstruction. Of 177 children without canalicular pathology, 171 (96%) were relieved of symptoms with one operation, without canalicular intubation. Of 81 cases with canalicular disease, 55 of 70 (79%) who underwent DCR plus canalicular intubation, and 10 of 11 who underwent DCR plus Lester-Jones tube, were substantially improved with one operation. No child required peroperative or postoperative blood transfusion. Dacryocystorhinostomy in childhood, in experienced surgical hands, is a safe procedure, achieving relief of symptoms in most cases, particularly in the absence of canalicular disease.     

New developments in flow cytometric analyses of lymphocyte markers.

This article addresses several fundamental features of clinical flow cytometry. A practical overview of the technical and methodologic aspects of this fast-growing and increasingly important new clinical and investigative field is provided. The use of flow cytometry for the diagnosis and monitoring of various chronic lymphoproliferative diseases also is discussed. This article may serve as a useful guide to those seeking to set up or maintain a clinical flow cytometry laboratory.     

Increased expression of CD152 (CTLA-4) by normal T lymphocytes in untreated patients with B-cell chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) have defects in both cellular and humoral immunity. Since CD152 (CTLA-4) plays a critical role in downregulating T-cell responses, we studied the expression of surface and cytoplasmic CD152 (sCD152 and cCD152, respectively) in freshly isolated T cells from treatment-na?ve patients with CLL. CD4+ and CD8+ T cells from these patients demonstrated significantly increased sCD152 and cCD152 compared to normal donors. Furthermore, these patients had an increased proportion of the regulatory CD4(+)/CD25(+)/CD152+ subset that correlated with advanced Rai stage, unfavorable cytogenetics and low serum IgG and IgA levels. The expression of sCD152 by T cells also correlated with ZAP-70 expression by CLL B cells. The proportion of CD4(+)/CD25+ cells was also correlated with unmutated immunoglobulin heavy chain variable gene status. Blockade of CD152 with monoclonal antibody (mAb) in proliferation assays was associated with potent T-cell proliferation in response to autologous and allogeneic CD40-activated CLL B cells. In summary, T cells from patients with CLL may be primed for anergy by expressing increased amounts of CD152; anti-CD152 mAb may represent a therapeutic opportunity to enhance an immune response against autologous leukemia cells.     

Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.