Retinopathy of prematurity in infants less than 29 weeks' gestation at birth

From January 1986 to December 1991 we examined the eyes of 206 infants born at Westmead Hospital, Neonatal Intensive Care Unit who were less than 29 weeks' gestation at birth to determine the incidence of retinopathy of prematurity. Eighty-five infants (41.3%) had no retinopathy of prematurity (ROP) in either eye, 82 infants had stages 1 or 2 ROP (39.8%), 29 had stage 3 ROP (14.1%) and 11 had stage 4 ROP (5.3%). Of these, cryotherapy was performed in 18; six now have bilateral retinal detachment and are blind The more severe stages of ROP were significantly associated with an increase in the number of days of oxygen supplementation, an increase in the number of days of mechanical ventilation and the presence of patent ductus arteriosus. Infants receiving steroids for mechanical ventilator dependence had a significantly greater chance of requiring cryotherapy (11 or 22 receiving steroids versus seven of 43 without steroids; P < 0.01).     

Induction of collagenase synthesis in chondrocytes by a factor synthesized by inflamed synovial tissue

Rabbit inflamed synovial tissue grown in culture synthesizes a factor that induces collagenase synthesis in chondrocytes and in cartilage. Synthesis of this factor by the synovial tissue is inhibited by cycloheximide but not by indomethacin. The factor has an apparent molecular weight of 30,000, is stable to heat and to trypsin treatment but is inactivated by acid. Induction of collagenase synthesis in chondrocytes occurs after a lag period of 6 hours.     

Flow cytometry analysis of platelet antibodies

We have devised assays to detect both circulating alloantibodies to platelets (indirect assay) and platelet-association IgG and IgM (direct assay) using a flow cytometric technique. A variety of patients with immune thrombocytopenia were studied. Employment of a confocal lens in the flow cytometer increased the discrimination power of the instrument. Patients with autoimmune thrombocytopenia (idiopathic thrombocytic purpura [ITP], systemic lupus erythematosus (SLE), lymphoma, leukemia, and drug-induced thrombocytopenia showed a significant increase in platelet-associated antibody. Circulating antibodies to platelets (alloantibodies) were demonstrated in cases of platelet refractoriness and neonatal isoimmune purpura. Day-today precision of the assays ranged from 3% to 6% (coefficient of variation). No interference was shown in the presence of hemoglobin (5 g/L), triglycerides (10 g/L), or polyclonal and monoclonal immunoglobulinemia (50 g/L: IgG, IgA, IgM). The sensitivity of the direct assay was 500 attograms of IgG or IgM platelet.     

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): past medical history in children with cancer.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) collected interview and medical information relating to the child's past medical experiences from parents of 555 children diagnosed with cancer and parents of 1110 unaffected matched controls. No significant associations emerged overall for ante-natal care, place and mode of delivery, length of gestation, birth weight, condition at birth, special care, neonatal procedures or breast-feeding. Few risk factors relating to previous illnesses and medication were found, although increasing numbers of illnesses appeared to be associated with an increased risk of childhood cancer, particularly acute lymphoblastic leukaemia. A highly significant excess of case children had not been immunised (p = 0.005). In general, these results indicate that past medical experiences have little influence on the development of cancer in children.     

A cluster of bacterial genes for anaerobic benzene ring biodegradation

A reductive benzoate pathway is the central conduit for the anaerobic biodegradation of aromatic pollutants and lignin monomers. Benzene ring reduction requires a large input of energy and this metabolic capability has, so far, been reported only in bacteria. To determine the molecular basis for this environmentally important process, we cloned and analyzed genes required for the anaerobic degradation of benzoate and related compounds from the phototrophic bacterium, Rhodopseudomonas palustris. A cluster of 24 genes was identified that includes twelve genes likely to be involved in anaerobic benzoate degradation and additional genes that convert the related compounds 4-hydroxybenzoate and cyclohexanecarboxylate to benzoyl-CoA. Genes encoding benzoyl-CoA reductase, a novel enzyme able to overcome the resonance stability of the aromatic ring, were identified by directed mutagenesis. The gene encoding the ring-cleavage enzyme, 2-ketocyclohexanecarboxyl-CoA hydrolase, was identified by assaying the enzymatic activity of the protein expressed in Escherichia coli. Physiological data and DNA sequence analyses indicate that the benzoate pathway consists of unusual enzymes for ring reduction and cleavage interposed among enzymes homologous to those catalyzing fatty acid degradation. The cloned genes should be useful as probes to identify benzoate degradation genes from other metabolically distinct groups of anaerobic bacteria, such as denitrifying bacteria and sulfate-reducing bacteria.     

Canadian Association of General Surgeons Evidence Based Reviews in Surgery. 10. Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomized trial.

Question: Is there a difference in cancer-related survival between laparoscopic assisted colectomy (LAC) and open colectomy (OC)? Design: Randomized controlled trial. Setting: Single-centre trial, Barcelona, Spain. Patients: Two hundred and nineteen of 442 eligible patients with adenocarcinoma of the colon were included. Patients were excluded if the tumour was below 15 cm from the anal verge or was in the transverse colon; if there were distant metastases, adjacent organ involvement or obstruction; or the patient had previous colonic surgery. One hundred and eleven were randomized to the LAC group and 108 to the OC. Interventions: Randomization was done the day before surgery. Patients were stratified into 2 groups according to tumour location (right or left side with respect to the splenic flexure) and assigned to the LAC or OC group by means of sealed opaque envelopes containing computer-generated random numbers. Patients in both groups had surgery by a single gastrointestinal surgical team. Pre- and postoperative care was standardized for bowel prep and perioperative antibiotics. Patients received either LAC or OC using a no-touch technique and initial vascular ligation. Main outcome measure: Overall survival. Results: The Cox model showed that LAC was independently associated with reduced risk of tumour relapse (hazard ratio 0.39, 95% CI 0.19 – 0.82), death from any cause (0.48, 0.23 –1.01) and death from a cancer-related cause (0.38, 0.16– 0.91) compared with OC. This superiority of LAC was due to differences in patients with stage III tumours (freedom from recurrence p = 0.04, overall survival p = 0.02, and cancer- related survival p = 0.006). Conclusion: LAC is more effective than OC for treatment in terms of morbidity, hospital stay, tumour recurrence and cancer-related survival.     

Ocular findings in the chromosome 22q11.2 deletion syndrome.

PURPOSE: To identify the ocular features of the chromosome 22q11.2 deletion syndrome and to provide ophthalmologic examination recommendations for affected patients. METHODS: Ocular abnormalities were evaluated prospectively in patients with 22q11.2 deletion at the Children's Hospital of Philadelphia between 1997 and 1999. RESULTS: Ninety patients with confirmed 22q11.2 deletion were examined. Posterior embryotoxon was found in 49%, tortuous retinal vessels in 34%, eyelid hooding in 20%, strabismus in 18%, ptosis in 4%, amblyopia in 4%, and tilted optic nerves in 1%. CONCLUSIONS: The high incidence of ocular conditions that can potentially affect visual development suggest that children with 22q11.2 deletion should undergo a comprehensive eye examination upon diagnosis of the condition with follow-up as indicated by the findings in each case. In addition, knowledge of the ocular findings, in conjunction with certain cardiac, otolaryngologic, immunologic, and other systemic findings, may alert physicians to the possibility of a chromosome 22q11.2 deletion.     

Phospholipase A2-catalyzed conversion of hepatic cytochrome P450 to P420 in microsomal membranes prepared from young and old rats

Previous studies from this Laboratory have revealed few significant age-related changes in either hepatic microsomal cytochrome P₄₅₀ content or NADPH-cytochrome P₄₅₀ reductase activity, prompting the suggestion that the nearly ubiquitous age-associated decline in the hepatic metabolism of xenobiotics by the mixed-function oxidases is a result of alterations in the lipid matrix in which the macromolecular components are organized. In order to examine this postulate, the membrane microenvironment surrounding hepatic microsomal cytochrome P₄₅₀ was enzymatically digested with snake venom phospholipase A₂, and the kinetics of conversion of cytochrome P₄₅₀ to cytochrome P₄₂₀ determined for preparations obtained from rats of varying age. There were no significant differences in the kinetics of conversion of cytochrome P₄₅₀ to cytochrome P₄₂₀, suggesting that there are no significant age-related changes in the lipid microenvironment immediately adjacent to cytochrome P₄₅₀. However, there was a slight difference, independent of age, in the rate of conversion of cytochrome P₄₅₀ to cytochrome P₄₂₀ between smooth and rough microsomes. The results are discussed in terms of general experimental approaches toward understanding drug metabolism in senescent organisms.