Polyploidization and centrosome hyperamplification in inflammatory bronchi

OBJECTIVE AND DESIGN: Inflammatory and tumorous bronchi were screened in order to obtain new tumor relevant cytogenetic parameters. MATERIAL OR SUBJECTS: Bronchial cells of 32 patients were cultivated by standard cell culture procedures. METHODS: Tetraploidy and aneuploidy was determined by enumeration of chromosome 7 and 8 versus the number of centrosomes. The resulting data were correlated with histopathological data. RESULTS: Tetra- and aneuploidy of epithelial cells were detectable in 76% of tumor cell cultures, 75% of high grade inflammatory tissues and 40% of non- and low grade-inflammatory tissues. Additionally, we observed centrosome hyper-amplification and multipolar mitoses not only in the tumor but also in the early stages of inflammation. CONCLUSION: Inflammatory bronchi already show tumor-specific features and may consequently represent the preliminary genetic stage of cancer development in bronchi.     

Experimental axonopathy induced by immunization with campylobacter jejuni lipopolysaccharide from a patient with guillain‐barré syndrome

Campylobacter jejuni (C. jejunj) infection is the most common antecedent in the axonal variant of Guillain‐Barré syndrome (GBS). Antibodies against nerve gangliosides found in GBS patients recognize cross‐reactive epitopes in the lipopolysaccharide (LPS) of C. jejuni. This led to the molecular mimicry hypothesis of GBS. We immunized eleven rabbits with a LPS extracted from HS:19 C. jejuni strain isolated from a patient with GBS and complete Freund's adjuvant (CFA)(group I). In a second experiment we immunized seven rabbits with LPS, CFA and keyhole limpet hemocyanin (KLH)(group II). All group I rabbits developed high titers of anti‐LPS, anti‐GM1, anti‐GD1b antibodies and lower titers of anti‐GD1a. One rabbit, 50 days after initial inoculation, showed tremor and weakness. All rabbits of group II developed high titres of antiganglioside antibodies and six animals showed weakness 59–113 days after initial inoculation. Two rabbits died. Pathology showed mild to moderate, tendentially grouped, axonal degeneration in sciatic nerves of four out of five animals. Control rabbits of group I (immunized with CFA only) did not develop antibodies, controls of group II (immunized with CFA + KLH) developed low titers of IgG anti‐GM1. None developed neurological signs or showed axonal degeneration. C. jejuni LPS is a potent B‐cell stimulator capable to induce a strong antiganglioside response in rabbits. However, to induce the neuropathy is crucial to employ KLH, a glycoprotein known to stimulate both humoral and cellular responses. This animal model reproduces the pathogenetic process hypothesized in axonal GBS with antiganglioside antibodies post C. jejuni infection.     

FIRST DIAGNOSIS OF SEVERE HANDICAP: A STUDY OF PARENTAL REACTIONS

This paper reports the results of interviews with 190 parents of severely mentally handicapped children. Questions were asked about parents' satisfaction with the way they were first informed of the child's impairment. Most parents were informed by a doctor, and almost two-thirds were dissatisfied with the first information given. Satisfaction was associated with being told early in the child's life. There was a significant association between the time of telling and the diagnostic condition of the child: parents of children with handicap of no known pathology were more likely to be told during or after the second year of the child's life, while parents of children with Down's syndrome were most likely to be told at birth. The authors discuss ways in which parents can be helped through this difficult time and suggest procedures for breaking the news to parents in a sensitive way.     

Postoperative radiation therapy in the management of lung cancer

Postoperative radiation therapy for lung cancer is still controversial. In a 9-year period, 69 patients with non-oat-cell carcinoma of the lung (16% stage I, 26% stage II, and 58% stage III) received such therapy. The radiation dose was less than 5,000 cGy in 42 patients, 5,000-5,900 cGy in 16, and 6,000 cGy or more in 11; follow-up ranged from 24 to 64 months. Actuarial survival at 2 and 4 years was 50% and 16%, respectively, for squamous cell carcinoma, and 40% and 26% for adenocarcinoma. The 5-year survival for stages I, II, and III cancer was 29%, 17%, and 19%, respectively. Histologic findings and type of surgery did not affect survival, but the radiation dose apparently did. The 3-year survival for patients who received less than 6,000 cGy was 35%, compared with 73% for patients who received higher doses. In eight patients, treatment failed within the irradiated volume: all had received doses of less than 6,000 cGy, and the volume in three was judged to be inadequate.     

Pathology of digestive organs in renal transplant recipients

A necropsy study of the pathological findings in the digestive system of 19 renal transplant recipients revealed that gastrointestinal (GI), hepatobiliary, and pancreatic pathologies are common in renal transplant recipients. Fifteen of the 19 patients studied had GI pathology. Hepatobiliary pathology was the most common finding with all but one of the 19 cases exhibiting one or more abnormalities. Pancreatic abnormalities were less frequent with 11 patients demonstrating normal findings.     

Long-stay hospital closure. Managing the staff

The gradual closure of a long-stay hospital is stressful for staff. Some may have doubts about the case for community care, and almost all are affected by uncertainty and by the provisional step-by-step changes as patients gradually move out. The maintenance of staff morale during the transition is therefore important and difficult. This article examines some of the stresses and misunderstandings, and suggests how they could be managed.     

The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice [published erratum appears in Blood 1995 Apr 1;85(7):1983]

CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type- specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells.     

Timing of Return to Dialysis in Patients with Failing Kidney Transplants

In the last decade, the number of patients starting dialysis after a failed kidney transplant has increased substantially. These patients appear to be different from their transplant‐naïve counterparts, and so may be the timing of dialysis therapy initiation. An increasing number of studies suggest that in transplant‐naïve patients, later dialysis initiation is associated with better outcomes. Very few data are available on timing of dialysis reinitiation in failed transplant recipients, and they suggest that an earlier return to dialysis therapy tended to be associated with worse survival, especially among healthier and younger patients and women. Failed transplant patients may also have unique issues such as continuation of immunosuppression versus withdrawal or the need for remnant allograft nephrectomy with regard to dialysis reinitiation. These patients may have a different predialysis preparation work‐up, worse blood pressure control, higher or lower serum phosphorus levels, lower serum bicarbonate concentration, and worse anemia management. The choice of dialysis modality may also represent an important question for these patients, even though there appears to be no difference in mortality between patients starting peritoneal versus hemodialysis. Finally, failed transplant patients returning to dialysis appear to have a higher mortality rate compared with transplant‐naïve incident dialysis patients, especially in the first several months of dialysis therapy. In this review, we will summarize the available data related to the timing of dialysis initiation and outcomes in failed kidney transplant patients after returning to dialysis.