Polymerase chain reaction analysis of allele frequency and loss at the Harvey ras locus in myeloid malignancies

The hypothesis that 'rare' variable number tandem repeat (VNTR) alleles of the Harvey ras (Ha-ras) locus are an inherited predisposing factor in myeloid malignancies has been evaluated. We describe an application of the polymerase chain reaction (PCR) which amplifies the VNTR region at the Ha-ras locus and offers a number of advantages over conventional Southern analysis. Ha-ras VNTR genotypes were assigned to 57 normal subjects, 46 patients with acute myeloid leukaemia (AML), 26 with myelodysplastic syndrome (MDS) and 49 with chronic granulocytic leukaemia (CGL). By comparison with previous reports we found significantly higher frequencies of rare alleles (20.2%) in our normal subjects of whom more than 35% had at least one 'rare' allele. The frequencies of rare alleles in the patient groups was not significantly different from the normal group (chi 2 = 0.54, p = 0.91). In studies of constitutional and leukaemic DNA from patients with AML, we found that allelic loss at the Ha-ras locus was not a common phenomenon. The improved resolution achievable with PCR compared with Southern analysis was demonstrated by the inability of Southern analysis to resolve six out of 34 PCR heterozygotes. We therefore suggest that previous studies showing linkage between rare Ha-ras alleles and susceptibility to malignancy should be reevaluated using our sensitive PCR technique.     

The clinical spectrum of mid-dermal elastolysis and the role of UV light in its pathogenesis

BACKGROUND: We observed four patients with mid-dermal elastolysis (MDE) that was either precipitated or aggravated by UV light (UVL) exposure or was primarily confined to areas of UVL exposure. OBJECTIVE: Our purpose was to report four cases of MDE occurring after significant UVL exposure and to demonstrate why we suspect that MDE in some instances may be photoinduced or photoaggravated. We also wish to demonstrate the varied clinical presentation of this disorder. METHODS: Because all our patients had MDE involving skin exposed to UVL, biopsies were performed on clinically uninvolved sun-exposed and sun-protected skin in one patient to elucidate further the role of UVL in this process. RESULTS: On routine histopathologic examination we found that uninvolved sun-exposed skin but not sun-protected skin demonstrated early MDE. Ultrastructural examination revealed a spectrum of elastic fiber changes in involved and clinically uninvolved sun-exposed skin. Phagocytosis of elastic fibers was not present. CONCLUSION: We conclude that UVL exposure was a major causative or aggravating factor of MDE in our patients and that the clinical appearance of this disorder is variable.     

Yersinia enterocolitica infection in a 4-month-old infant associated with infection in household dogs

Colon atresia is a rare cause of intestinal obstruction in the neonate and requires early diagnosis and prompt surgical treatment. It is impossible in the neonate to differentiate colon atresia from other forms of obstruction at the time of initial presentation. The diagnosis is confirmed roentgenographically, including views of the abdomen and contrast barium enema series. Lesions proximal to the splenic flexure are treated with initial resection of the atretic segment and a primary anastomosis. Those lesions distal to the splentic flexure are managed initally with a diverting loop colostomy with subsequent staged resection and anastomosis.     

Cytokines in vitreous humor: interleukin-6 is elevated in proliferative vitreoretinopathy

PURPOSE: To measure the levels of interleukins (IL) 1 beta, 6, and 8, and tumor necrosis factor-alpha (TNF alpha) in the vitreous of patients with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), vitreous hemorrhage, and macular pucker. METHODS: Vitreous samples were collected, undiluted, from patients with PVR, PDR of varying severity, and miscellaneous lesions (vitreous hemorrhage from trauma, macular degeneration, vein occlusion, and non-PVR patients with giant tear, retinal detachment, and macular pucker). Immunoreactive levels of the cytokines, IL-1 beta, IL-6, IL-8, and TNF alpha were determined by enzyme-linked immunoadsorbent assays, and samples were analyzed for protein and hyaluronic acid content using standard assays. RESULTS: The levels of TNF alpha were below detection limits of the assay (< 3 pg/ml). In 45 of the 47 samples tested, IL-1 beta levels also were below detection limits of the assay (< 3 pg/ml). IL-6 levels ranged from < 30 to 5487 pg/ml, with the highest values observed in the PVR patients. IL-8 levels ranged from < 20 to 1900 pg/ml, and were consistently high in the miscellaneous group. Some of the PVR patients with C2 and C3 level severity also exhibited IL-8 levels exceeding 100 pg/ml. In a second study, IL-6 content of vitreous from miscellaneous and PVR patients was compared. In this study, significantly elevated levels of IL-6 were observed in the PVR patients (91.5 +/- 18 pg/ml) compared to the miscellaneous group (10.3 +/- 3.7 pg/ml) CONCLUSIONS: Elevated levels of IL-6 in the vitreous occur in PVR, implicating a role for this cytokine in the pathogenesis of this ocular disorder.     

Disease caused by Mycobacterium kansasii in patients with HIV infection

BACKGROUND: To describe the clinical features and response to therapy in Mycobacterium kansasii disease among HIV infected patients, an increasing problem in our setting. METHODS: A retrospective survey of all charts from patients with HIV infection with Mycobacterium kansasii infection recorded between April 1985 and December 1991. RESULTS: A total of 13 patients were identified. All of them had clinically significant respiratory tract samples with a definite M. kansasii isolation. Only three had disseminated disease. In all but two cases, CD4 cell count at diagnosis time was lower than 200/mm3. Chest X-ray films showed interstitial pattern (8 cases) or alveolar condensation (3 cases) and lung cavities were seen in 4 patients. All patients with lung disease and one with disseminated disease responded well to anti-tuberculous therapy. CONCLUSION: Mycobacterium kansasii produces disease in advances stages of HIV-induced immunosuppression. The most common primary location is pulmonary, but disseminated forms can also be seen. The infection can be controlled with standard anti-tuberculous therapy.     

Surgical repair of type A aortic dissection by the circulatory arrest-graft inclusion technique in sixty-six patients

During an 8-year period (1984 to 1991) 66 patients (mean age 59 years, range 26 to 84 years) with type A aortic dissection (60 ascending aorta tears, 6 arch tears; 35 acute, 31 chronic) had surgical repair by a continuous suture-graft inclusion technique. Hypothermic circulatory arrest (16 degrees C) was used in 58 patients (35/35 acute, 23/31 chronic; mean arrest time 26 minutes, range 10 to 55 minutes). Fifty-two patients had hemiarch repair and 6 had total arch replacement. Aortic valve disease necessitated treatment in 38 patients (1 valved conduit, 20 valve replacements, 17 valve repairs). Recently 11 patients had valve repair by reconstruction of the native aortic root, by means of techniques similar to those used for homograft valve insertion. Operative mortality was 9% (14% acute, 3% chronic). Stroke occurred in 2 patients (3%) and was fatal in both. Variables suggestive of increased operative risk by univariate analysis were acuteness (p = 0.12), visceral ischemia (p = 0.12), and preoperative shock (p = 0.13). No variable was significant by multivariate analysis. Overall actuarial survival at 48 months was 77%, with 3 late deaths from a ruptured distal aneurysm. Late computed tomography or magnetic resonance imaging scan was done in 28 patients at a mean interval of 33 months. These studies identified 1 patient with a pseudoaneurysm requiring reoperation and 3 patients with contained flow between the graft and the wrap. Three patients required late operation: 1 for pseudoaneurysm, 1 for arch dissection, and 1 for repair of a distal aneurysm.     

Investigations of antisense oligonucleotides targeted against bcl-2 RNAs

The purpose of this article is to describe how nurse instructors understand nursing and the necessary conditions for high quality nursing care. The approach of the study was inductive and based on phenomenology and a sociological field research method, i.e. grounded theory. It emerged that the core of nursing is a process, termed here caring, with three stages. Three types of caring emerged. Understanding the client, the art of nursing, co-operation between the nurse and other health care professionals were found to be necessary conditions for a high quality nursing care and it was also found that it is not possible to separate caring from the society and its history.     

Spontaneous mutagenesis of a plant potyvirus genome after insertion of a foreign gene

The RNA genome of tobacco etch potyvirus (TEV) was engineered to express bacterial beta-glucuronidase (GUS) fused to the virus helper component proteinase (HC-Pro). It was shown previously that prolonged periods (approximately 1 month) of TEV-GUS propagation in plants resulted in the appearance of spontaneous deletion variants. Nine deletion mutants were identified by nucleotide sequence analysis of 40 cDNA clones obtained after polymerase chain reaction amplification. The mutants were missing between 1,741 and 2,074 nucleotides from TEV-GUS, including the sequences coding for most of GUS and the N-terminal region of HC-Pro. This region of HC-Pro contains determinants involved in helper component activity during aphid transmission, as well as a highly conserved series of cysteine residues. The deletion variants were shown to replicate and move systemically without the aid of a helper virus. Infectious viruses harboring the two largest HC-Pro deletions (termed TEV-2del and TEV-7del) were reconstructed by subcloning the corresponding mutated regions into full-length DNA copies of the TEV genome. Characterization of these and additional variants derived by site-directed mutagenesis demonstrated that deletion of sequences coding for the HC-Pro N-terminal domain had a negative effect on accumulation of viral RNA and coat protein. The TEV-2del variant possessed an aphid-nontransmissible phenotype that could be rescued partially by prefeeding of aphids on active HC-Pro from another potyvirus. These data suggest that the N-terminal domain of HC-Pro or its coding sequence enhances virus replication or genome expression but does not provide an activity essential for these processes. The function of this domain, as well as a proposed deletion mechanism involving nonhomologous recombination, is discussed.     

Endoscopic ultrasonography in the local staging of primary gastric lymphoma

Endoscopic ultrasonography (EUS) and endoscopy were prospectively performed and compared to the histopathologic findings of the resection specimens in 24 patients with primary gastric lymphoma (PGL). On EUS, three types of PGL could be differentiated, a superficial type (n = 10), an infiltrating type (n = 12) and a tumorous type (n = 2). In the correct assessment of surface extension of the tumors, endoscopy and EUS agreed in 37.5% of cases and EUS showed more extensive disease than endoscopy in 58% of cases. However, in comparison to the resection specimens, EUS still underestimated the tumor surface extension in 37.5% of cases; this was mainly in low grade malignant PGL. The depth of tumor infiltration was correctly determined on EUS compared to the resection specimens in 91.5% of cases. Sensitivity, specificity and accuracy of diagnosing lymph node metastases were 100%, 80% and 83%, respectively. We conclude that EUS is a useful pre-therapeutic staging tool for primary gastric lymphoma but there remain some problems in determining the longitudinal and circular tumor spread in order to accurately guide the extent of gastric resection.