Effect of MHC class-I transfection on local tumor growth and metastasis in an H-2-negative clone derived from a chemically induced fibrosarcoma.

GR9 is a chemically induced fibrosarcoma composed of clones with different H-2 class-I expression. These clones differ with respect to local growth and spontaneous metastasis. The B9 clone (H-2 negative) is highly tumorigenic (local growth) but of low metastatic potential (spontaneous metastasis assay). We have analyzed the effect that transfection of H-2Dd and H-2Kd genes on this clone have upon local growth, lung colonization after i.v. injection and ability to form spontaneous metastases. The results showed that the effect on local growth of transfection of the Kd-gene was stronger than that of the Dd gene. In addition, B9 co-transfected with H-2Kd and Dd genes showed the highest immunogenic properties in syngeneic BALB/c mice. Interestingly, the pSV2-neo transfected clone gave almost the same result as that obtained with Dd transfection. Lung colonization after i.v. injection of the different clones (experimental metastasis), paralleled the results obtained for local growth: the number of lung nodules followed the cadence KdDd less than Kd less than Dd less than pSV2. Survival of mice was always inversely correlated with local growth, e.g., all mice injected with 5 x 10(5) B9 H-2KdDd transfected cells survived. In contrast, no mice injected with the B9 control did. These differences were abrogated in irradiated and nude BALB/c mice. Finally, all transfected clones remained non-metastatic in a spontaneous metastasis assay, behaving as the control, non-transfected B9 cells.     

Acute and chronic ethanol alter somatosensory-evoked potentials in conscious rats.

This study examined the effects of acute and chronic ethanol on cortical somatosensory-evoked potentials (SEPs) of laboratory rats. Evoked potentials were recorded following stimulation of the left hindpaw before and after injection of either saline or ethanol. Animals were then chronically exposed to ethanol in vapor inhalation chambers for five weeks. Recordings of SEPs before and after acute ethanol injection were then obtained 24 h and again seven days after withdrawal from ethanol exposure. The results indicate that acute ethanol produced a dose-dependent reduction in SEP amplitude, but did not alter peak latencies. Chronic ethanol exposure and withdrawal resulted in a significant increase in preinjection baseline response amplitudes when measured at 24 h after withdrawal, but not at seven days, and this treatment did not alter response latency or the effects of acute ethanol administration.     

The emergency physician and patient confidentiality: A review

Confidentiality is a promise rooted in tradition, law andmedical ethics. Emergency physicians treat a variety of patients to whom confidentiality is of vital importance: employees, celebrities, victims of violence or disaster, minors, students, criminals, drug abusers, and patients with STDs. EDs should develop methods of ensuring confidentiality for all patients.³⁴Although confidentiality is an important principle thatshould be respected and guarded, it is not absolute. Various laws mandate disclosure of certain patient information; in addition, an overriding moral duty may occasionally require, a breach of confidentiality. As Beauchamp and Childress noted, “the therapeutic role may sometimes have to yield to ones role as citizen and as protector of the interests of others”.¹⁹ In general, however, circumstances requiring a breach of confidentiality are rare.     

Anastomotic stenosis after Roux-en-Y gastric bypass: A rational approach to treatment.

BACKGROUND: Anastomotic stenosis, a common sequela to Roux-en-Y gastric bypass, has a reported incidence of 1.6-27% and recurs in 17-33%. No universal guidelines for optimal treatment exist. The aim of this study was to develop guidelines to treat stenosis that achieve the lowest rate of recurrence while avoiding the complications of excessive dilation. METHODS: This prospective 2-part study enlisted consecutive patients undergoing Roux-en-Y gastric bypass who developed an anastomotic stenosis. In the first part, all patients, regardless of the grade of stenosis, underwent dilation to 12 mm and were followed up for recurrence. In the second part, patients underwent dilation according to the grade of stenosis (12 mm for low, 13.5 mm for medium, 15 mm for high) and were followed up for recurrence. RESULTS: Among 1345 consecutive Roux-en-Y gastric bypass patients, 204 developed an anastomotic stenosis (15.2%). No differences were found in gender, mean age, preoperative body mass index, or weight loss at 1 year. In part 1, the recurrence rate for low-, medium-, and high-grade stenosis was 2.6%, 34.4%, and 35.9%. In part 2, the corresponding rates were 9.7%, 26.3%, and 43.6%. The corresponding mean number of additional dilations per patient with recurrence in part 1 was 1.0, 1.5, and 2.1 and, in part 2, were 1.0, 1.0 and 1.2. CONCLUSION: The results of this study have shown that the stenosis grade can predict the risk of recurrence and determine the optimal balloon size. Definitive treatment was achieved in >90% of patients with low-grade stenosis dilated to 12 mm. Medium- and high-grade stenosis predicted > or =25% recurrence, but increasing the balloon size reduced the number of additional dilations required for patients with recurrence.     

Nephrogenic adenoma of the bladder: report of 10 cases

Nephrogenic adenoma is an uncommon metaplastic lesion of the lower urinary tract that usually is associated with antecedent inflammation or surgical procedures. We report 10 new cases, 8 of which followed renal transplantation and 1 of which followed partial cystectomy for squamous cell carcinoma of the bladder. No predisposing factors could be identified in 1 patient. The nephrogenic adenomas, all of which were located in the bladder, were treated by either biopsy with fulguration or transurethral resection. The lesion recurred locally in 1 patient.     

IL-1-like production in adriamycin-induced nephrotic syndrome in the rat.

Rats receiving a single dose of adriamycin (7.5 mg/kg) develop heavy proteinuria and morphological abnormalities similar to those observed in minimal change nephrotic syndrome in humans. A concomitance between enhanced I-a display by resident glomerular macrophages, IL-1-like cytokine secreted by whole isolated rat glomeruli and proteinuria was observed in adriamycin-injected rats during the experimental protocol. In addition, in vitro studies have shown that after stimulation with adriamycin or lipopolysaccharide (LPS) this cytokine is mainly produced by resident glomerular macrophages in culture. Although the precise mechanism of proteinuria in this model needs to be further studied, our results indicate that IL-1-like cytokine could be an important mediator implicated in the structural and functional disturbances occurring at the glomerular capillary wall level in adriamycin nephrosis.     

Blue nevus of the prostate: report of two new cases with immunohistochemical and electron-microscopic studies.

Two new cases of prostatic blue nevus are studied with routine histological, immunohistochemical and ultrastructural methods. Both cases showed a chronic lower urinary tract obstruction due to a benign prostatic hyperplasia with spindle-shaped stromal cells loaded with melanin pigment. These cells were positive for S-100 and negative for HMB-45 antibodies, being, to the best of our knowledge, the first time that this antibody has been tested in prostatic pigmented lesions. The electron-microscopy study was performed in the first case, confirming the nature of these pigmented cells as melanocytes derived from the neural crest showing melanosomes in all the stages of differentiation and without complete basal cell membrane. The histogenesis of pigmented lesions of the prostate and the differences between blue nevus and melanosis are discussed, and the literature is reviewed.     

Astrocytic induction of matrix metalloproteinase-9 and edema in brain hemorrhage.

We tested the hypothesis that astrocytic matrix metalloproteinase-9 (MMP-9) mediates hemorrhagic brain edema. In a clinical case of hemorrhagic stroke, MMP-9 co-localized with astrocytes and neurons in peri-hematoma areas. In a mouse model where blood was injected into striatum, MMP-9 was colocalized with astrocytes surrounding the hemorrhagic lesion. Because MMP-9 is present in blood as well as brain, we compared four groups of wild type (WT) and MMP-9 knockout (KO) mice: WT blood injected into WT brain, KO blood into KO brain, WT blood into KO brain, and KO blood into WT brain. Gel zymography showed that MMP-9 was elevated in WT hemorrhagic brain tissue but absent from KO hemorrhagic brain tissue. Edematous water content was elevated when WT blood was injected into WT brain. However, edema was ameliorated when MMP-9 was absent in either blood or brain or both. To further assess the mechanisms involved in astrocytic induction of MMP-9, we next examined primary mouse astrocyte cultures. Exposure to hemoglobin rapidly upregulated MMP-9 in conditioned media within 1 to 24 h. Hemoglobin-induced MMP-9 was reduced by the free radical scavenger U83836E. Taken together, these data suggest that although there are large amounts of MMP-9 in blood, hemoglobin-induced oxidative stress can trigger MMP-9 in astrocytes and these parenchymal sources of matrix degradation may also be an important factor in the pathogenesis of hemorrhagic brain edema.