Germline mutations in the neurofibromatosis type 2 tumour suppressor gene

The recent identification of the NF2 tumour suppressor genehas enabled large scale screening for pathological mutationsin the gene. We have sought germline mutations In the NF2 geneby SSCP and heteroduplex analysis of cDNA and genomic DNA samplesfollowed by cloning and sequencing of mutant alleles. In thepresent report we describe 11 putative pathological mutations,including five nonsense mutations, three short insertions ordeletions cauing frameshifts and three missense mutations. Moststop mutations and frameshift mutations were found In Individualsexpressing a severe phenotype while one of the three missensemutations was associated with a mild phenotype. Four unrelatedNF2 patients of the 93 tested were found to have identical nonsensemutations caused by a C to T transition (C169) in a CpG dinucleotide,which is a potential mutational hotspot in the NF2 tumour suppressorgene.     

Serum erythropoietin quantitation in pregnancy using an enzyme-linked immunoassay.

During normal pregnancy there is a decrease in the hematocrit due to a disproportionate increase in the blood volume compared with the red cell mass. Using a new enzyme-linked immunoassay (Amgen Diagnostics), serum erythropoietin was quantified in normal nonanemic pregnancies throughout gestation and in third trimester anemic patients. We found that the mean hematocrit in normal pregnancy reached a nadir late in the second trimester and the serum erythropoietin plateaued at a 50% increase. Those pregnancies complicated by anemia defined by a hematocrit less than 30 vol% demonstrated a statistically significant increase in serum erythropoietin above those not anemic.     

Biochemical evidence that cytokeratins are present in smooth muscle

Recent immunocytochemical studies have revealed that cytokeratin intermediate filaments, previously thought to be restricted to epithelial tissues, are present in muscle. In view of the implications of these reports for diagnostic pathology it is important to investigate by biochemical means whether these findings represent the presence of true cytokeratin proteins or an unexpected antigenic cross-reaction. In the present study intermediate filament proteins have been extracted from samples of human myometrium and identified by immunoblotting techniques using well characterized monoclonal antibodies, two against cytokeratins and two against desmin. The results show that the proteins of the appropriate molecular weight for cytokeratin were labelled by anti-cytokeratin antibodies and were quite distinct from those recognized by anti-desmin antibodies. This study therefore confirms previous immunocytochemical findings and emphasizes the need for caution when using anti-intermediate filament antibodies for diagnostic purposes.     

Who is providing ambulatory care to Medicaid beneficiaries with acquired immunodeficiency syndrome in New York State?

This study examined the number of ambulatory care providers treating individuals with the acquired immunodeficiency syndrome who were Medicaid beneficiaries in New York State in 1988 and examined the distribution of this care across various practice settings. The study population was identified retrospectively in the New York State Medical HIV/AIDS Research Data Base and included a cohort of 5535 individuals with the acquired immunodeficiency syndrome who were enrolled in Medicaid in 1988 for at least 6 months after being diagnosed as having the disease and who had at least one ambulatory care encounter during the year. Ambulatory care for the study group was provided by more than 700 hospital or freestanding clinics and more than 3000 private physicians in 1988. Many sites had low caseloads; 47% of the clinics and 68% of the physicians treating this population saw only one or two patients with the acquired immunodeficiency syndrome who were enrolled in Medicaid. More than half the patients in the study group were seen most frequently in clinics for their ambulatory care during 1988. These data provide reassurance that a wide network of providers is involved in the care of patients with the acquired immunodeficiency syndrome who are Medicaid beneficiaries in New York.     

Assessment of quadriceps/hamstring strength, knee ligament stability, functional and sports activity levels five years after anterior cruciate ligament reconstruction

The purpose of this study was to examine individuals 5 years after ACL reconstruction and analyze changes involving strength, stability, function, and sports activities. Nineteen males and six females, mean age = 31.4 +/- 7.31 years, participated in this study. Fifteen subjects had received extraarticular and ten subjects had received intraarticular ACL reconstructions. Subjects completed a 100 point subjective functional activity questionnaire and a sports participation survey. Knee ligament stability was assessed during an objective knee examination. Isokinetic quadriceps and hamstring muscle strength were tested at 240 and 120 deg/sec using the Cybex II dynamometer. Anterolateral rotatory instability and positive Lachman were elicited on the operated leg for 80% of the subjects. No significant relationship was found between objective instability and the functional activity score. For the intraarticular group, a significant correlation (P less than 0.05) was found between increased quadriceps and hamstring strength on the operated leg and return to functional activities. Subjects' functional activity score was positively correlated (P less than 0.001) with their ability to participate in sports. Subjects participating in sports involving cutting and twisting motions were less successful in returning to their preinjury participation levels and reported more subjective complaints of pain, swelling, and/or instability. These results indicate that long-term progressive rehabilitation emphasizing increased quadriceps and hamstring strength to approximate the nonoperated leg may enhance successful return to functional and sports activities after ACL reconstruction.     

Postprandial acid reflux is reduced by delayed gastric emptying.

The aim of this study was to investigate influence of delayed gastric emptying on postprandial reflux in esophageal pH. Sixty-nine consecutive patients underwent 24 hour (h) esophageal pH monitoring and gastric emptying. In 24 h esophageal pH monitoring, % postprandial reflux pH<4 for 2 h after each meal (% PRT) was extracted from the 24 h pH profile. After solid test meal (1 mCi, Tc99m) was given, gastric emptying was measured with a gamma detector placed transnasally 5 cm below lower esophageal sphincter. % PRT was similar among the 34 normal, 26 delayed and 9 rapid gastric emptying rate patients. Thirty-five with a positive pH study and 34 with a negative had a similar prevalence of gastric emptying disorder. In the positive pH study group, patients with normal gastric emptying had significantly higher % PRT than those with delayed gastric emptying (22.0 vs 12.1%, P<0.05). In the same population, patients with a normal %PRT had a significantly higher prevalence of delayed gastric emptying compared with those with a positive % PRT (6/8 vs 9/27, P<0.05). In patient with abnormal acid exposure but normal % PRT on 24 h esophageal pH monitoring, gastric emptying may be delayed.     

Indium-111 labelled pooled human immunoglobulin imaging to monitor the efficacy of specific therapy for Pneumocystis carinii pneumonia

Functional imaging is ideally suited to monitoring the effect of specific therapy on disease processes. In this pilot study five patients with AIDS and Pneumocystis carinii pneumonia (PCP) were imaged with Indium-111 labelled pooled human immunoglobulin (111In-HIG) during infection and after therapy for PCP. The lung activity of t t tln-HIG, measured as a lung/heart ratio, was calculated in a study performed during infection with PCP and after therapy. In all five patients the lung/heart ratio of t t 1ln-HIG was reduced after treatment. The mean reduction in heart/lung ratio was 27% (range 12%-53%). If these results are confirmed by a larger study, ¹¹In-HIG will be useful in monitoring the response of PCP to therapy in patients with AIDS.