A study of beta 2-microglobulin skin deposits in dialyzed patients and healthy controls

This study reports on beta 2-microglobulin (beta 2M) deposits in the skin of 12 uremic patients and three kidney transplant recipients compared with eight healthy controls. Uremic patients were treated by hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), or continuous ambulatory peritoneal dialysis (CAPD) for a period lasting from 1 to 19 years. Congo red staining of the skin was negative in patients and controls. However, immunofluorescent staining with an anti-beta 2-microglobulin monoclonal antibody was positive in the skin of all patients and of six of the eight controls. Beta 2M skin deposition is more intense in patients than in controls and increases with patient age and the duration of dialysis. A stron correlation is observed between the extent of skin beta 2M deposits and clinical manifestations due to beta 2M deposits in internal organs. However, no correlation is found between beta 2M skin deposits and sex or beta 2M serum levels.     

Veinous thrombectomy. Six case reports]

The aim of this study is to raise up the effect of surgical thrombectomy among other alternative therapies. This retrospective study reports 6 patients (mean age 63 years) admitted with phlegmasia cerulea dolens. All patients underwent surgical venous thrombectomy associated with infracava filter insertion in 2 cases. One patient died in the early postoperative course. In all other cases we noticed good early and late outcome both on clinical examination and duplex scanning assessment. In conclusion, surgical venous thrombectomy can be considered as a good and efficient procedure in the presence of phlegmasia cerulea dolens in order to relieve ischemia and to prevent whenever possible severe chronic venous disorders. However, fibrinolytic therapy might achieve as good results as surgery. Thus, the latter is to be reserved to very severe veinous ischemia with limb loss threatening where fibrinolytic therapy fails or is contre-indicated.     

CYP3A5 and ABCB1 Polymorphisms and Tacrolimus Pharmacokinetics in Renal Transplant Candidates: Guidelines from an Experimental Study

Genetic polymorphisms in biotransformation enzyme CYP3A5 (6986G > A, CYP3A5*3; 14690A > G, CYP3A5*6) and drug transporter ABCB1 (1236C > T; 2677G > T/A; 3435C > T) are known to influence tacrolimus (Tac) dose requirements and trough blood levels in stable transplant patients. In a group of 19 volunteers selected with relevant genotypes among a list of 221 adult renal transplant candidates, we evaluated whether consideration of CYP3A5 and ABCB1 genetic polymorphisms could explain the interindividual variability in Tac pharmacokinetics after the first administration of a standard dose (0.1 mg/kg body weight twice a day). Lower area under the time versus blood concentration curves (AUC) or lower trough concentrations were observed among CYP3A5 expressors (n = 9) than among nonexpressors (n = 10) using two different analytical methods for Tac determination (liquid chromatography with tandem mass spectrometry (LC-MS/MS) and immunoassay). The median AUC(0-infinity) was 2.6- and 2.1-fold higher in nonexpressors for LC-MS/MS and immunologic methods, respectively. No difference was observed in Tac pharmacokinetic parameters in relation to ABCB1 polymorphisms. In conclusion, our study confirms the very significant effect of CYP3A5 polymorphism early after the first administration of Tac. It also provides a strong argument for a doubling of the loading dose in patients early identified a priori on the transplantation list as possessing at least one CYP3A5*1 allele.     

Decreased serum levels of nutritional biochemical indices in healthy children with marginally delayed physical growth

Biochemical markers of nutritional status (albumin, transthyretin, insulin-like growth factor-I and zinc) were measured in slowly growing two- to five-year-old, low-income Parisian children whose weight-for-height or height-for-age z scores (WHZ or HAZ) were between — 1 and — 2 SD of the NCHS median. The results were compared to controls who were matched for age, sex, and ethnic origin with WHZ and HAZ between — 1 and + 2 SD. Mean serum levels of transthyretin, albumin and insulin-like growth factor-I and mean plasma zinc concentrations were significantly lower in the growth-impaired children than in the controls ( p = 0.002, p = 0.006, p = 0.015, and p = 0.035, respectively). While the height-retarded children had low mean serum insulin-like growth factor-I values, the weight-retarded subjects had decreased levels of albumin, transthyretin and zinc when compared to controls. Lower mean levels of nutritional markers in healthy, slowly growing children suggest that inadequate dietary intakes of zinc, protein and/or energy may result in marginal delays in weight and height gains.     

Murine intranasal challenge model for the study of Campylobacter pathogenesis and immunity.

Campylobacter jejuni infection of mice initiated by intranasal administration was investigated as a potential model for studies of pathogenesis and immunity. By using a standard challenge (5 x 10(9) CFU), C. jejuni 81-176 was more virulent for BALB/c (72% mortality) than for C3H/Hej (50%), CBA/CAJ (30%), or C58/J (0%). Intranasal challenge of BALB/c was used to compare the relative virulence of three reference strains; C.jejuni 81-176 was more virulent (killing 83% of challenged mice) than C. jejuni HC (0%) or C. coli VC-167 (0%). The course of intranasally initiated C. jejuni 81-176 infection in BALB/c was determined. C. jejuni was recovered from the lungs, intestinal tract, liver, and spleen at 4 h after challenge, the first interval evaluated. After this initial interval, three distinct patterns of infection were recognized: (i) a progressive decline in number of C. jejuni CFU (stomach, blood, lungs), (ii) decline followed by a second peak in the number of organisms recovered at 2 or 3 days postchallenge (intestine, liver, mesenteric lymph nodes), and (iii) persistence of approximately the same number of C.jejuni CFU during the course of the experiment (spleen). Intranasally induced infection initiated with a sublethal number of bacteria or intranasal immunization with killed Campylobacter preparations resulted in both the generation of Campylobacter antigen-specific immune responses and an acquired resistance to homologous rechallenge. The model was used to evaluate the relative virulence of nine low-in vitro-passage (no more than five passages) isolates of C. jejuni species from patients with diarrhea. The patient isolates were differentially virulent for mice; one killed all exposed mice, three were avirulent (no deaths) and the remainder showed an intermediate virulence, killing 17 to 33%. Mouse virulence of Campylobacter strains showed a trend toward isolates originating from individuals with watery diarrhea; however, no association was found between mouse virulence and other signs or symptoms. There were no observed relationships between mouse virulence and bacterial Lior serotype or Fla polymorphic group. Intranasal challenge of BALB/c with C. jejuni is a useful model for the study of infection and vaccination-acquired immunity to this agent.     

Fine-needle aspiration cytology of recurrent and metastatic mixed mesodermal tumors

We report the cytological and clinical findings of 16 fine-needle aspirates (FNAs) performed on recurrent (n = 6) and metastatic (n = 10) mixed mesodermal tumors (MMMTs). The median interval between the primary diagnosis and FNA was 16 mo. Primary sites were the endometrium (n = 11), the ovary (n = 3), the cervix (n = 1), and pelvic soft tissue (n = 1). Primary tumors showed carcinoma with homologous mesenchymal components in 13 cases and focal heterologous elements in three (two chondrosarcomas and one rhabdomyosarcoma). The FNAs showed carcinoma in all 16 cases, with adenocarcinoma differentiation in three, Mesenchymal elements were identified in aspirates of three recurrent and two metastatic lesions. They were all homologous. No heterologous mesenchymal elements were identified in the aspirates. We conclude that mesenchymal components in FNAs of MMMTs are less likely to be seen in metastatic lesions, and that heterologous mesenchymal components are rarely seen in these aspirates even in recurrent disease. These findings confirm that the epithelial component is responsible for the malignant behavior of MMMTs, and suggest that these lesions may need to be classified as sarcomatoid carcinomas rather than true carcinosarcomas. Diagn Cytopathol 1994;11:328–332. © 1994 Wiley-Liss, Inc.