Epidemiological characteristics of uveitis in Switzerland

Since January 1990, data from uveitis patients have been systematically stored in a computer data bank. During the period from January 1990 to March 1993, 435 new patients (185 female and 250 male, mean age 43 years; range 6–92) were seen at the Uveitis Clinic of the Hopital Jules Gonin. These 435 patients (630 eyes) were subdivided into anterior uveitis (268 patients — 62%), intermediate uveitis (47 patients — 11%), posterior uveitis (89 patients — 20%) and panuveitis (31 patients — 7%). The incidence of uveitis for the referral area considered was calculated to be 17 per 100,000 inhabitants per year. A specifie diagnosis was found in 312 cases (72%). The most frequently diagnosed entities were HLA-B27-associated acute anterior uveitis (67 cases — 15.4%), uveitis associated with acute herpes zoster ophthalmicus (40 cases — 9.2%), toxoplasmosis (39 cases — 9%), typical pars planitis (29 cases — 6.7%), sarcoidosis (29 cases — 6.7%), Fuchs' heterochromic cyclitis (27 cases — 6.2%), herpetic anterior uveitis (21 cases — 4.8%) and acute retinal necrosis (11 cases — 2.5%). Incidence and distribution of most disease entities correspond to those of other European series.     

Evaluation of a novel bis-naphthalimide anticancer agent,DMP 840, against human xenografts derived from adult,juvenile, and pediatric cancers

The new bis-naphthalimide antitumor agent (R,R)2,2-[1,2-ethanediylbis[imino(1-methyl-2.1-ethanediyl)]-bis {5-nitro-1H-benz[de]-isoquinoline-1,3-2H) dione} dimethanesulfonate (DMP 840) was evaluated against parental and multidrug-resistant human KB cell lines in vitro and against these lines growing as xenografts in immunedeprived mice. In vitro, KB8-5 cells were 50-fold resistant to vincristine but only 16-fold resistant to DMP 840 as measured by clonogenic survival. For in vivo evaluation, DMP 840 was given by i. v. injection daily for 9 days or for 5 days/week for 2 consecutive weeks [(dx5)2]. In contrast to the cross-resistance of KB cell lines in vitro, both KB3-1 and KB8-5 tumors were highly and equally sensitive to DMP 840; only KB3-1 xenografts demonstrated sensitivity to vincristine, which was consistent with the in vitro results. DMP 840 was also evaluated against a panel of human tumors comprising colon adenocarcinoma and rhabdomyosarcoma xenografts. Against eight lines of colon adenocarcinoma, DMP 840 caused a high frequency of partial and complete regressions in two lines and significant inhibition of growth in two lines. DMP 840 caused complete regressions in five of six lines of advanced rhabomyosarcomas, demonstrating a broad range of effective dose levels. The pattern of activity against this tumor panel was similar but not identical to that of two inhibitors of topoisomerase I. There was no cross-resistance to DMP 840 in xenografts selected for resistance to vincristine or in a rhabdomyosarcoma selected for resistance to the topoisomerase I inhibitor topotecan. In contrast, a colon tumor selected for topotecan resistance was completely resistant to DMP 840. Slight cross-resistance to DMP 840 was demonstrated in a rhabdomyosarcoma xenograft that was selected for primary resistance to melphalan and was cross-resistant to topoisomerase I inhibitors. The pattern of activity and cross-resistance in these tumors was compared with that shown by two agents that inhibit topoisomerase I: topotecan and CPT-11.This work was supported in part by CA23099, Cancer Center Support (CORE) grant CA21675, The Du Pont Merck Pharmaceutical Company, and by American Lebanese Syrian Associated Charities (ALSAC)     

Characterization of the epitope recognized by a mAb that reacts differentially with murine suppressor T cells

Although reliable antibodies are available that distinguishhuman suppressor T (T_s) cells from CTL and other T cells, feware available for murine T_s cells. We have developed a mAb (984D4.6.5)that, in the presence of complement, depletes alloantigen-specificT_s cells but not CTL. This antibody recognizes activated TT_scells but not their precursors. In these studies, flow cytometricanalysis demonstrates that 984D4.6.5 reacts with several T_scell hybridomas, cloned T_h cell lines and WEHI-3 (a myelomonocytictumor cell line). Reactivity was not detected with BW5147, T_hcell hybridomas, cloned T_h cells, CTL lines and hybridomas,B cell lines, thymocytes, splenocytes, bone marrow cells nora variety of tumor cells. Among 984D4.6.5 positive lines, expressionis heterogeneous and the number of cells expressing high levelsof the epitope is increased when the hybridomas are maintainedat a relatively high cell density. Neuriminidase and pronasedeplete the epitope recognized by mAb 984D4.6.5. Protein synthesisand glycosylation inhibitors also reduce expression of thisepitope. These observations suggest that the epitope recognizedby 984D4.6.5 is a carbohydrate linked to a polypeptide. Thisantibody was tested by ELISA for binding to a large panel ofcarbohydrates and glycollpids coupled to BSA. The only one thatbound 984D4.6.5 was LS tetrasaccharide c (NeuNAc2-6Galpß1-4GIcNAcß1-3GaIß1-4Glc),an O-linked carbohydrate. Comparative analysis shows that boththe sequence and the linkage of these sugars are essential tothe reactivity with the 984D4.6.5 antibody. This epitope isexpressed by a glycoprotein of-200 kDa, as shown by Westernblots. The identity of this glycoprotein remains to be determined,but indirect evidence suggests that it is not CD45.     

Hypertension two years after renal transplantation: causes and consequences

The incidence of hypertension 2 years after renal transplantation and the possible causes of hypertension were studied retrospectively. A group of 93 patients treated with cyclosporin (CyA), azathioprine (Aza), and/or prednisolone (Pred) were compared to a group of 31 patients treated with Aza and Pred. There were more patients with hypertension in the CyA group (73%) than in the Aza group (58%). Hypertension before transplantation predisposed to hypertension after transplantation. After transplantation, hypertension was most common among patients with polycystic kidney disease (46%), chronic glomerulonephritis (67%), and diabetes (71%). The accumulated immunosuppressive medication (CyA/Pred) did not affect the occurrence of hypertension. Hypertensive patients had significantly poorer graft function than did normotensive patients (serum creatinine level 229 mol/l vs 162 mol/l, P<0.01). The 10-year graft survival was markedly impaired in the group with hypertension (42% vs 65% for normotensives, P<0.05). The 10-year patient survival was 59% vs 79% (P=NS). The study further confirms the frequent finding that hypertension has a negative effect on graft and patient survival rates.     

Treatment of Vitamin B12 Deficiency after Gastric Surgery for Severe Obesity

Background: Vitamin B₁₂ deficiency after gastric surgery for obesity is due to a failure of separation of vitamin B₁₂ from protein foodstuffs and to a failure of absorption of crystalline vitamin B₁₂ in the presence of intrinsic factor. The purpose of this study was to determine which of four oral doses of crystalline vitamin B₁₂ was most effective in treating vitamin B₁₂ deficiency in 102 patients. Methods and Results: At time of entry into the study, the patients had a serum vitamin B₁₂ < 100 pmol L ⁻¹, were 29.9 ± 21.7 months post-op, were 37 ± 8 years old and had a body mass index of 30 ± 6 kg m⁻². Eight (8%) had had a vertical banded gastroplasty and 94 (92%) a gastric bypass. For the first 3 months all patients received 350 μg per day of crystalline vitamin B₁₂ and all increased their serum vitamin B₁₂ levels to over 100 pmol L⁻¹. The patients were then assigned to receive for a further 3 month period one of four oral doses of crystalline vitamin B₁₂-100 μg, 250 μg, 350 μg and 600 μg. Serum vitamin B₁₂ levels were greater than 150 pmol L⁻¹ after 6 months in 83.3% of patients who received 100 μg; 92.3% of patients who received 250 μg; 94.7% after 350 μg and 95.2% after 600 μg (p%0.525). Conclusion: At least 350 μg per day is the appropriate oral dose of crystalline vitamin B₁₂ after gastric surgery for obesity to correct low serum vitamin B₁₂ levels in 95% of patients.     

Systematic Differences in Validity of Self-Reported Mammography Behavior: A Problem for Intergroup Comparisons?

Background. Prior studies of recall accuracy for screening mammogram behavior have examined relatively homogeneous groups. Data are limited on possible systematic group differences, so we evaluated women's recall accuracy in two separate care systems in one city.Methods. Women 50 to 70 years old with and without screening mammograms 10 to 14 months prior were identified from fiscal, clinic, and radiology records at a military care system (MCS) and a county-funded system (CFS) for indigents. Mammogram status was verified through radiology records. Women were excluded if mammograms were diagnostic, done for other than annual screening, or had abnormal results. Interview ers blinded to mammogram status surveyed randomly selected eligible women.Results. For 62 screened/31 unscreened MCS women and 78 screened/61 unscreened CFS women, specificity was similar, at 65 and 62%, respectively. In contrast, sensitivity varied significantly: 95% versus 79% (P = 0.011). Primary ethonocultural groups were Euro-American (MCS—60%) and Mexican American (CFS—85%). Although not different in specificity of recall (67% versus 61%), these major subgroups significantly differed in sensitivity (97% versus 80%, P = 0.017), proportion of true negatives due to never having a mammogram (35% versus 57%, P = 0.003), and proportion with ≥high school education (78% versus 19%, P < 0.00001).Conclusion. Systematic differences in recall validity may exist and compromise the accuracy of intergroup comparisons.     

Laparoscopy and Peripancreatic Neoplasia

Since its inception laparoscopy has been a valuable tool for diagnosis, and more recently it has become widely accepted as a medium for surgical intervention. In this light, the addition of minimally invasive techniques to the management of peripancreatic cancer has gained notable attention. Although most practitioners agree that there is some role for minimally invasive therapy, opinions vary as to the extent and significance these applications carry to the overall management of peripancreatic malignancies.