Chemokine expression and leucocyte infiltration in Sjogren's syndrome

OBJECTIVE: To investigate the expression and source of chemokines in minor salivary gland biopsies (MSGs) in patients with Sjogren's syndrome (SS). METHODS: Immunohistochemical analysis was used to determine the pattern of chemokine expression in MSGs from patients with (n=6) and without (n=5) SS, as well as to examine the phenotype of both resident and infiltrating cells expressing chemokines. RESULTS: Significant differences in the number of infiltrating mononuclear (MN) cells in patients with and without SS were noted. Ductal epithelial cells of SS biopsies expressed significantly increased levels of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, interleukin-8 (IL-8) and RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted). Biopsies from patients with SS showed that MIP-1beta was expressed by 51% of infiltrating cells, while 41% expressed MIP-1alpha, whereas 22 and 7% expressed RANTES and IL-8, respectively. CONCLUSION: Chemokines expressed by ductal epithelial cells may attract circulating leucocytes, in particular CD4+ T cells, towards the site of inflammation, thereby orchestrating the influx of MN cells characteristically seen in MSGs in SS. Chemokines may be induced directly by a putative triggering agent for SS, or secondary to the release of pro-inflammatory cytokines produced by epithelial cells. These findings further implicate epithelial cells as playing a major role in the pathogenesis of SS and implicate chemokines in the leucocyte recruitment in this setting.      

Long-term engraftment of normal and post-5-fluorouracil murine marrow into normal nonmyeloablated mice [see comments]

We report the successful long-term engraftment of normal male donor bone marrow (BM) transfused into noncytoablated female mice, challenging the assumption that "niches" need to be created for marrow to engraft. We have used chromosomal banding and Southern blot analysis to identify transplanted male marrow cells, and shown the long-term stability of the chimeric marrows. Balb/C, BDF1, or CBA-J female hosts (no irradiation) received for 5 consecutive days 40 x 10(6) male cells (per day) of the same strain, and repopulation patterns were observed. Parallel studies were performed using tibia/femur equivalents of normal marrow or marrow from Balb/C mice pretreated 6 days previously with 150 mg/kg 5-fluorouracil (5-FU). Chromosome banding techniques showed that 5% to 46% of marrow cells were male 3 to 9 months posttransplant with normal donor marrow. Southern blot analysis, using the pY2 probe, showed continued engraftment at 21 to 25 months posttransplant, ranging from 15% to 42% male engrafted cells in marrow. Normal donor male marrow engrafted significantly better than 5-FU-pretreated male marrow as shown 1 to 12 months posttransplant in non-cytoablated female recipients. Percentages of male engrafted cells in BM ranged from 23% to 78% for recipients of normal donor marrow and from 0.1% to 39% for recipients of 5-FU marrow. Mean engraftment for 6 mice receiving normal marrow was 38%, whereas that for 6 mice receiving post-5-FU marrow was 8%, as assayed 1 to 3 months posttransplant. At 10 to 12 months, mean engraftment for the normal donor group was 46%, compared with 16% for the 5-FU group. The patterns of engraftment with normal and 5-FU marrow were similar for spleen and thymus. These results show that long-term chimerism can be established after transplantation of normal donor marrow to normal nonirradiated host mice and indicate that marrow spaces do not have to be created for successful engraftment. They suggest that transplanted marrow competes equally with host marrow for marrow space. Finally, these data show that post-5-FU Balb/C male marrow is markedly inferior in the repopulation of Balb/C female host marrow, spleen, and thymus, and suggest that this population of cells may not be the ideal population for gene transfer studies.     

Mycobacterial Infections After Renal Transplantation

Mycobacterial infections occurred in 11 of 633 (1.7 per cent)recipients of successful renal transplants. There were no casesof tuberculosis in patients receiving chemoprophylaxis, butamongst those who did not receive prophylaxis disease occurredin six of the 27 (22 per cent) high-risk patients. The majorcause of morbidity during treatment was renal allograft rejection,largely due to reduction in immunosuppressive drug therapy.     

PATIENT ACCIDENTS IN HOSPITAL: INCIDENCE,DOCUMENTATION AND SIGNIFICANCE

SUMMARY Many previous studies of reported patient accidents in hospital used the accident report forms as the only data source, without questioning their reliability and despite 80% of the accidents being unwitnessed. This paper reports on three studies using data from patient interviews, staff questionnaires, medical and nursing notes and the accident report forms. The studies confirm that falls amongst elderly patients are the most common type of patient accident. However, patients' and staff's versions of the event often differed widely. Accident reports are stated to be required for legal purposes, but they were often incomplete and unreliable. Patient accidents and safety are too important to remain marginalised to mere compliance with out-of-date regulations. A new, ‘slim-line‘, more accurate but less time-consuming patient accident reporting system should be developed, for which improvement in patient safety is the main aim and legal considerations the secondary aim.     

Trabecular bone architecture in female renal allograft recipients-- assessed by computed tomography

BACKGROUND: Osteopenia with decreased bone mineral density (BMD) is a frequent finding in renal allograft recipients. Data concerning the bone architecture in these patients do not exist, however. METHODS: We compared the bone architecture of 33 randomly assigned women (age 49 +/- 12 years), who had received renal allografts 5.6 +/- 5.3 years before the investigation, with 74 women (age 50 +/- 14 years) who were admitted for osteodensitometry. All patients underwent single-energy computed tomography (SEQCT) and a midvertebral high-resolution tomography with computer-assisted analysis of the trabecular vertebral body architecture. RESULTS: Progressive alteration of bone architecture was associated with increasing vertebral height loss of the vertebral body. Height reduction of a vertebral body of more than 15% was associated with a significantly lower BMD (-2.3 +/- 0.8 versus -1.1 +/- 1.1 standard deviations below normal BMD), a lower trabecular bone area (13 +/- 8% versus 42 +/- 22%) and a lower trabecular diameter (1.4 +/- 0.5 mm versus 2.2 +/- 0.8 mm) compared to recipients without height reduction. In comparison to a matched group of patients with similarly reduced BMD (1.1 +/- 1.2 versus 1.2 +/- 1.1 SD below normal BMD), renal allograft recipients showed a lower number of trabecular plates (5.6 +/- 3.1 versus 7.0 +/- 3.7) and a smaller intertrabecular surface (54 +/- 116 mm versus 75 +/- 138 mm). CONCLUSIONS: Alterations of bone architecture in renal allograft recipients were associated with progressive vertebral height loss. Despite similar bone mineral density, differences of bone architecture could be observed between renal allograft recipients and patients with osteoporosis.      

Gene Probe Analysis in an Informative Family with Multiple Endocrine Neoplasia Syndrome Type 2A (MEN 2A). Improvement in Carrier Risk Estimation

Gene probe analysis of the MEN 2A locus on chromosome 10 hasbeen undertaken using the markers TB10.163, RBP 3 and TB14.34in a large kindred with familial medullary thyroid carcinomas,with or without phaeochromocytomas or primary hyperparathyroidism.A maximum LOD score of 2.97 gave strong evidence of close linkagewith zero recombination. For 12 members of the family so far not known to be affectedby any form of the disease the estimated risk of carrying thegene has been considerably decreased in all but one, whose riskhas been greatly increased.