Proliferative responses to allogeneic HLA class I peptides.
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Ten patients with Parkinson's disease and urinary symptoms underwent urodynamic assessments before and after subcutaneous administration of the dopamine receptor agonist apomorphine. Voiding efficiency improved after apomorphine injection, with an increase in mean and maximum flow rates in nine patients and reduction in post-micturition residual volume in six. Although the effect on detrusor behaviour was variable, subcutaneous apomorphine may be of use in both the assessment and treatment of voiding dysfunction in patients with Parkinson's disease.
The usual osteoblastic phenotype of metastatic prostate cancer is unexplained. Here we show that tissue and serum concentrations of prostate-specific antigen (PSA)-vary inversely with a substrate protein that binds a growth factor known to activate osteoblasts. These findings suggest that PSA may contribute to the osteoblastic phenotype, and could thus represent a new drug target devoid of antiandrogenic toxicity.
PURPOSE: The standard treatment for retinal breaks is thermal adhesion. Breaks in the posterior pole (i.e., macular holes) recently have been treated using vitrectomy and the recombinant cytokine transforming growth factor-beta. This has been shown to achieve closure of the retinal breaks by stimulating localized fibrocellular proliferation. Serum has been shown to contain chemoattractants and mitogens for many types of cells. The authors studied the clinical and histologic effect of autologous serum application to retinal breaks in an experimental model. METHOD: Twenty-four rabbits underwent pars plana lensectomy, vitrectomy, retinectomy, fluid-air exchange, application of test solution (12 with Hank's buffered salt solution and 12 with autologous serum), and air-gas exchange. Clinical examination with indirect ophthalmoscopy was performed, and animals were killed 5, 14, and 28 days after treatment. Tissue sections through the retinectomy were studied by light microscopy, electron microscopy, and immunocytochemistry. RESULTS: None of the serum-treated eyes showed retinal detachment at the site of the retinectomy by evaluation with indirect ophthalmoscopy at each of the time points. In contrast, in control eyes retinal detachment developed at the retinectomy site from 0% at day 5 to 50% at day 14 and 75% at day 28. By light microscopy, serum-treated eyes contained multilayers of fibroblast-like cells adhering the retinectomy edges to the underlying retinal pigment epithelium and choroid. The control eyes had nonadherent retinal edges at the retinectomy site with little sign of fibrocellular response. Results were confirmed by electron microscopy. The fibroblast-like cells by immunocytochemistry contained vimentin, cytokeratin 18, and/or glial fibrillary acidic protein. CONCLUSION: This study suggests that serum induces a localized fibrocellular response at the retinectomy edges compared with control eyes. This response, characterized by light microscopy, electron microscopy, and immunocytochemistry, appears to involve a mixed population of glial, retinal pigment epithelial, and/or fibroblastic cells. These cells seem to enhance adhesion and subsequent reattachment of the edges of the retinectomies at the time points studied when compared with controls.
OBJECTIVE: To evaluate the frequency and prognosis of reopening of a macular hole after initially successful repair in a defined patient cohort. DESIGN: Retrospective consecutive noncomparative case series. PARTICIPANTS: Seventeen cases of reopened macular holes among 390 cases of idiopathic macular holes that previously had undergone macular hole surgery were studied. MAIN OUTCOME MEASURES: Assessment of demographics, visual acuity, preoperatively, postoperatively, after reopening of macular hole and after reoperation, if applicable, and precipitating factors. RESULTS: There were 17 (4.8%) of 353 cases in which the macular hole reopened after initial successful surgical closure. The mean visual acuity before reopening was 20/48 and was 20/133 after reopening. Twelve eyes underwent reoperation with improvement to a mean visual acuity of 20/54. The five eyes that were not reoperated on maintained a mean visual acuity of 20/200. Ten of the eyes had undergone cataract surgery between macular hole surgeries, but in only one did the reopening appear to occur in association with this procedure. CONCLUSIONS: Reopening of a previously successfully operated macular hole is uncommon and seems to be a spontaneous event. Reoperation generally yields results similar to those present before the reopening. Reopening of a macular hole associated with cataract surgery is rare.
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AIMS: Complete excision of nodal masses during post-chemotherapy retroperitoneal lymph-node dissection (RPLND) for metastatic non-seminomatous germ-cell tumours (NSGCT) of the testis often requires vascular surgical intervention. We report our experience of vascular interventions and complications in a large series of men undergoing postchemotherapy RPLND. METHODS: A retrospective review of vascular interventions during post-chemotherapy RPLND in 98 patients was undertaken (103 procedures). RESULTS: Macroscopic tumour clearance was complete in 95/98 men (97%). Vascular intervention was required in all cases. Major complications included acute tubular necrosis in one patient who had undergone left nephrectomy and extensive dissection around the right renal artery, progressive atrophy of the ipsilateral kidney in three men and a colonic stricture and associated colocutaneous fistula in one patient after division of the inferior mesenteric artery. Iliac and femoral venous thrombosis developed in both patients in whom the inferior vena cava (IVC) was excised and in one patient after partial IVC excision. Eight of the 98 patients have died. No late vascular complications have occurred to date. CONCLUSION: Complete tumour clearance can be achieved in most post-chemotherapy RPLNDs but invariably involves vascular intervention. Metastatic NSGCT should be treated by surgeons with the ability to undertake the vascular procedures required.
Interleukin-8 (IL-8) is a member of the chemokine family of pro-inflammatory chemotactic cytokines and is secreted by some human colorectal carcinoma cell lines. We have used in situ hybridisation and immunohistochemistry to determine whether IL-8 mRNA and protein, respectively, are produced by human colorectal carcinoma cells in vivo. IL-8 mRNA was detected within the cytoplasm of tumour cells in all nine samples tested, including that of a tumour which had metastasised to a lymph node. Non-involved colonic mucosa within the same tissue blocks showed much weaker labelling. IL-8 protein was detected in 74% (23/31) of tumour samples and was mainly localised to the tumour cell cytoplasm. In 30% of cases, staining was heterogeneous, with between 1 and 30% of cells being positive. In some tumour cells, IL-8 showed a perinuclear distribution resembling that found by in situ hybridisation. Some infiltrating leucocytes, endothelial cells and fibroblast-like cells within the tumour sections were also positive for IL-8 mRNA and protein. The possibilities that colorectal tumours produce IL-8 to aid invasion and/or metastasis or as a tumour growth factor are discussed.
Chemokines are important mediators of leucocyte chemoattraction to inflammatory sites. Previous work has shown that the expression of some chemokines is upregulated during renal transplant rejection. The objectives of the present study were to determine whether chemokine expression is increased during renal transplant rejection. Immunohistochemistry was used to localize the C-X-C (alpha) chemokine interleukin-8 (IL-8) and the C-C (beta) chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta) in 30 needle biopsies of human kidney transplants taken for diagnosis of renal dysfunction. Urine samples from transplant patients taken immediately prior to biopsy were assayed for chemokine content using enzyme-linked immunosorbent assays (ELISAs). Results from groups of patients having different clinicopathological diagnoses were then compared. All three chemokines were detected in most renal transplant biopsies showing acute cellular rejection but, although infiltrating leucocytes were often positive, staining was predominantly localized to renal tubular epithelium. Staining for MCP-1 was generally weaker than for the other chemokines, and collecting tubules were usually stained more strongly than proximal convoluted tubules. Tubular epithelial staining was also found in biopsies from patients without signs of acute cellular rejection. There were significantly higher amounts of IL-8 in the urine of patients with acute cellular rejection, even when patients with urinary tract infections were excluded, but mean titres of urinary MIP-1beta did not differ between patient groups. This was also found when titres were normalized for urine volume and creatinine levels. Production of IL-8, MCP-1 and MIP-1beta is not confined to kidney transplants showing acute cellular rejection, and may be a relatively nonspecific response of tubular epithelial cells to renal damage.
This case demonstrates actinomycosis in a previously unreported site, and outlines some of the difficulties encountered in diagnosing and treating this rare but unimportant condition.