Role of electrohydraulic extracorporeal shockwave lithotripsy (Dornier HM 4) in the treatment of caliceal diverticulum lithiasis

Caliceal diverticula may be congenital or acquired malformations of the collecting system, normally asymptomatic and discovered during an IVP. Indications for treatment included chronic vague flank pain, acute renal colic, urinary tract infection and hematuria. We present the results of 29 patients with symptomatic calculi in caliceal diverticula who were managed by ESWL monotherapy. All treatments were performed with electrohydraulic machine (Dornier HM 4) in ambulatory form. RESULTS: The average followup was 42 months. 12 patients (40%) had passed successfully all of the stone fragments, while 2 patients (7%) had passed more than half and 4 (13.5%) had passed less than half of the fragments. 66 per cent of patients had been rendered free of symptoms. The possibility of producing a satisfactory result (66% free of symptoms and 40% stone free by X ray) and the low morbidity of ESWL suggest that this treatment may be appropriate for majority of calculi in calicea diverticula.     

Mitotic inhibition of corneal endothelium in neonatal rats

PURPOSE: Corneal endothelium in humans does not divide to any significant extent after birth; therefore, with age there is a gradual loss of cells. When cell density is reduced to a critical level, the endothelium cannot function to maintain corneal clarity, and the cornea becomes permanently cloudy. Currently, the blindness that results can be treated only by corneal transplantation. The long-term goal is to find methods to stimulate corneal endothelial proliferation in a clinically relevant manner. The first step toward achieving this goal is to identify mechanisms responsible for the induction and maintenance of mitotic inhibition of the corneal endothelium in vivo. During corneal development, the endothelium is formed by migration and proliferation of mesenchymal cells from the ocular periphery. Soon after the monolayer is formed, proliferation ceases. In tissue culture, many cell types cease proliferating upon formation of stable cell-cell and cell-substrate attachments. The goal of the present studies was to determine whether establishment of stable contacts correlates with cessation of endothelial proliferation during corneal development in vivo. METHODS: Corneas from neonatal (days 1, 3, 7, 10, 13, 14, 17, 21, 28, and 42) and adult rats were used for immunolocalization of the following: bromodeoxyuridine (BrdU), an S-phase marker; p27kip1 and p21cip1, G1-phase inhibitors; connexin-43 and ZO-1, proteins associated with gap and tight junctions, respectively; Na+/K+-ATPase and beta3-integrin, markers of plasma membrane polarity; and fibronectin and collagen type IV, constituents of Descemet's membrane. Nuclei staining positively for BrdU were counted to determine the relative number of S-phase cells at various times after birth. Marker protein expression and localization were determined by conventional fluorescence microscopy and by confocal microscopy. RESULTS: The number of endothelial cells staining positively for BrdU gradually decreased between postnatal days 1 and 13. After postnatal day 13, positive BrdU staining was no longer detectable. During the first postnatal week, cells stained positively for the G1-phase inhibitor p27kip1 but not for p21cip1. Connexin-43 achieved its mature location by postnatal day 1. ZO-1, Na+/K+-ATPase, beta3-integrin, fibronectin, and collagen type IV achieved their mature localization patterns between postnatal days 14 and 21. CONCLUSIONS: In neonatal rat, corneal endothelial cells are still entering the cell cycle at birth, but cell cycle entry gradually decreases, so that by postnatal day 13 cells are no longer entering the S-phase. The G1-phase inhibitor p27kip1, but not p21cip1, may help mediate this inhibition. Stable cell-cell and cell-substrate contacts gradually form, and monolayer maturation is complete between postnatal days 14 and 21. The results lead to the hypothesis that, in developing rat cornea in vivo, the establishment of stable cell-cell and cell-substrate contacts initiates a cascade of events, mediated by p27kip1, which induces mitotic inhibition in the endothelial monolayer.     

Comparison of pneumatic retinopexy and scleral buckling in the management of primary rhegmatogenous retinal detachment. Southern Wisconsin Pneumatic Retinopexy Study Group

PURPOSE: To compare pneumatic retinopexy and scleral buckling for repair of primary rhegmatogenous retinal detachment with respect to visual outcome, single-procedure reattachment rate, and development of proliferative vitreoretinopathy. METHODS: A consecutive series of eyes initially treated with pneumatic retinopexy (n = 56) between March 1986 and February 1996 were compared with a selected group of eyes treated with scleral buckling (n = 86) with similar location and distribution of retinal breaks and absence of proliferative vitreoretinopathy. A regression model was developed to adjust for underlying differences between treatment groups, resulting in a cohort of 50 eyes in each group for final comparison. A minimum follow-up of 6 months was obtained. RESULTS: Single-procedure reattachment rate was significantly higher for scleral buckle eyes (42 of 50 eyes, 84%) than for pneumatic retinopexy eyes (31 of 50 eyes, 62%; P < or = .01). Correspondingly, reoperation rate was significantly higher for pneumatic retinopexy eyes (19 of 50 eyes, 38%) than for scleral buckle eyes (7 of 50 eyes, 14%; P < or = .01). Multiple regression analysis evaluating perioperative factors demonstrated that the use of pneumatic retinopexy was the sole factor predictive of retinal detachment after a single procedure (relative odds = 2.20, P = .02). Final reattachment rate, after reoperations, was 98% (49 of 50 eyes) in each group. Except for nonphakic eyes, final visual outcome and rate of postoperative proliferative vitreoretinopathy development did not differ significantly between the two procedures. CONCLUSIONS: In phakic eyes, pneumatic retinopexy was associated with a significantly higher reoperation rate than scleral buckling, but resulted in equivalent final visual outcome and reattachment rate after reoperations. If used, it must be incorporated into a strategy in which patient and physician are prepared for a greater chance of reoperation compared to initial management with scleral buckling.     

Prenatal diagnosis and perinatal management of fetal sacrococcygeal teratoma

OBJECTIVE: To perform an exploratory analysis of the relative contribution of single MHC genes to the pathogenesis of systemic lupus erythematosus (SLE) in a homogenous white population. METHODS: MHC class II alleles and C4 allotypes were determined in 64 SLE patients and in ethnically matched controls. HLA-DR and DQ typing was performed by polymerase chain reaction amplification with sequence specific primers. C4 allotypes were determined by agarose gel electrophoresis. RESULTS: The frequency of C4A*Q0 was significantly higher in patients than in controls (46.9% v 25.3%, p = 0.002). HLA-DRB1, DQA1, and DQB1 alleles in the whole group of SLE patients were not significantly different from those of controls. On the other hand increase in DRB1*03 was observed in the group of patients with C4A*Q0, as compared with patients with other C4A allotypes (p = 0.047). There was no significant correlation between severe and mild disease, as judged by the SLEDAI, and HLADR, DQ alleles and comparing the patients with C4A*Q0 with those with other C4A allotypes there was no significant difference regarding clinical manifestations. CONCLUSION: The results are consistent with the argument that C4A deficiency contributes independently to susceptibility and the pathogenesis of SLE. C4A*Q0 in SLE patients in Iceland shows weaker linkage disequilibrium with DR3 genes than reported in most other white populations and emphasises the role of ethnicity.     

Drug metabolism biosensors: electrochemical reactivities of cytochrome P450cam immobilised in synthetic vesicular systems

Biosensors containing cytochrome P450cam in a didodecyldimethylammonium bromide vesicular system were prepared by cross-linking onto a glassy carbon electrode (GCE) with glutaraldehyde in the presence of bovine serum albumin. Cyclic voltammetric responses of the sensor in air-free buffer solution showed that the sensor exhibited reversible electrochemistry due to direct electron exchange between the haem Fe(3+/2+) redox system and the GCE surface. In air-saturated solution containing camphor, the biosensor gave an irreversible electrocatalytic current which is compatible with the monooxygenation of the substrate. Steady state amperometric experiments with camphor, adamantanone and fenchone were performed with a biosensor prepared by cross-linking P450cam with glutaraldehyde onto a Pt disc electrode. The sensor was characterised by fast amperometric responses, attaining steady-state in about 20 s in a cobalt sepulchrate mediated electrochemical system. The kinetic parameters of the biosensor were analysed using the electrochemical Michaelis Menten equation. The estimated apparent Michaelis-Menten constant, Km, values for the biosensors were in the range of 1.41-3.9 mM.     

Autologous stem-cell transplantation for non-Hodgkin's lymphomas: the role of graft purging and radiotherapy posttransplantation--results of a retrospective analysis on 120 patients autografted in a single institution

PURPOSE: To analyze retrospectively survival and prognostic factors of patients with non-Hodgkin's lymphoma (NHL) autografted from 1979 to 1995 in a single institution. PATIENTS AND METHODS: A total of 120 patients, 64 with aggressive and 56 with low-grade NHL, were autografted. The carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) regimen was used in 104. The autograft was marrow in 101 patients. Marrow was purged in vitro by mafosfamide for 63 patients (adjusted dose [AD] in 32; unique dose [UD] in 31); 27 patients received a CD34+-selected graft. Following intensification, 45 patients received additional radiotherapy on previous sites of involvement. RESULTS: Outcome at 5 years for patients transplanted with low-grade NHL in first complete remission (CR1), in first partial remission (PR1), and in second complete remission (CR2) or beyond showed an event-free survival (EFS) of 75% +/- 12%, 46% +/- 18%, and 57% +/- 24%, a relapse incidence (RI) of 21% +/- 12%, 49% +/- 19%, and 43% +/- 25%, and a transplant-related mortality (TRM) of 5% +/- 5%, 10% +/- 7%, and 0%, respectively. For patients with aggressive NHL transplanted in CR1, in PR1, in CR2 or beyond, and in resistant relapse or in primary refractory disease, the EFS was of 73% +/- 9%, 58% +/- 19%, 29% +/- 16%, and 10% +/- 9%, the RI 22% +/- 9%, 14% +/- 9%, 77% +/- 18%, and 66% +/- 20%, and the TRM 6% +/- 6%, 32% +/- 21%, 11% +/- 10%, and 71% +/- 22%, respectively. In patients autografted upfront in first remission, additional radiotherapy was associated with a higher EFS, in univariate (P = .03) and multivariate analysis (P = .02, relative risk [RR] = .021). The role of graft purging with mafosfamide on the outcome reflected by the dose of colony-forming unit-granulocyte-macrophage (CFU-GM) per kilogram infused postpurging was assessed by univariate analysis: patients in first remission who received lower doses of CFU-GM had a lower RI and a higher EFS. CONCLUSION: This retrospective analysis suggests that marrow purging and posttransplant radiotherapy improve the outcome of patients with NHL autografted in first remission.     

Randomised, dose-ranging, placebo-controlled study of chimeric antibody to CD4 (keliximab) in chronic severe asthma

BACKGROUND: There is substantial circumstantial evidence that CD4 lymphocytes have a role in the pathogenesis of chronic asthma. We investigated the efficacy and safety in severe corticosteroid-dependent asthma of a single intravenous infusion of keliximab (IDEC CE9.1), a chimeric monoclonal antibody to CD4. METHODS: 22 patients were recruited from two asthma clinics. In an ascending-dose design, the first eight patients were assigned 0.5 mg/kg keliximab (six) or placebo (two); the next seven were assigned 1.5 mg/kg (five) or placebo (two); and the last seven were assigned 3.0 mg/kg (five) or placebo (two). Masked data on safety for each dose group were assessed before progression to the next dose. Patients kept a daily symptom diary and measured morning and evening peak expiratory flow (PEF) at home. PEF and forced expiratory volume in 1 s (FEV1) were measured at follow-up clinic visits. FINDINGS: Patients given 0.5 mg/kg or 1.5 mg/kg keliximab and placebo recipients did not differ in change from baseline of PEF, FEV1, or symptom score. Those given 3.0 mg/kg keliximab differed significantly from placebo recipients in change in morning PEF (median area under curve [AUC] 445 vs -82.5, p=0.005) and evening PEF (median AUC 548 vs -85, p=0.014). Symptom score showed the same pattern (though differences did not achieve significance), but there was no difference in clinic FEV1. There were no serious adverse effects related to treatment. Two patients had mild exacerbations of eczema and one developed a transient maculopapular rash. All doses of keliximab were associated with a reduction from baseline in CD4 count. INTERPRETATION: Our findings raise the possibility that T-cell-directed treatment may be an alternative approach to the treatment of severe asthma.