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Biomedical subjects

J F Madden

Publications and source records attributed to J F Madden.

At least 19 recordsLinked to original sources

Apical soft tissue biopsies predict biochemical failure in radical perineal prostatectomy patients with apical cancer involvement.

The aim of the study was to prospectively assess the role of apical soft tissue biopsies in radical perineal prostatectomy (RPP) patients with documented apical prostate cancer (PCA) involvement. Between June 1998 and May 1999, 77 consecutive men with localized PCA and documented invasion of the prostatic apex underwent RPP by a single surgeon. Soft tissue biopsies were systematically obtained from the prostatic fossa overlying the apex at the time of surgery. Time to biochemical failure was calculated using the Kaplan-Meier method. The rates of positive apical margins and positive apical soft tissue biopsies were 23.4% (18/77) and 15.6% (12/77). The sensitivity, specificity and positive predictive value of positive apical margins for residual apical disease as determined by apical soft tissue biopsy were 41.7, 80, and 28%, respectively. The overall biochemical failure rate was 28.6% (22/77) with a median follow-up of 51 months (range 3-73 months). The 36-month biochemical recurrence-free survival rate was 55.9+/-14.9% for patients with positive apical biopsies and 78.7+/-5.3% for those with negative biopsies (P=0.023). In conclusion, positive apical soft tissue biopsy is an independent predictor of biochemical failure in patients with apical PCA who undergo RPP. Positive apical surgical margins poorly predict residual apical disease that is frequently identifiable by apical soft tissue biopsy. Apical soft tissue biopsies should therefore be obtained in patients with known extensive apical cancer involvement at the time of RPP.

Adult↗

Zinc alpha-2-glycoprotein is expressed by malignant prostatic epithelium and may serve as a potential serum marker for prostate cancer.

Zinc alpha-2-glycoprotein (ZAG) is a M(r) 41,000 glycoprotein secreted by a variety of normal epithelia. ZAG was recently shown to stimulate lipolysis in adipocytes, leading to the development of cachexia in animals with ZAG-producing tumors. To understand the possible contribution of ZAG to the development of cachexia in men with prostate cancer, ZAG production by normal and malignant prostate tissue was investigated using immunohistochemical assays. Anti-ZAG monoclonal antibodies reacted strongly with normal prostate epithelium but not with other components of prostate or seminal vesicles. The majority of prostate cancers tested (35 of 48; 73%) also reacted with anti-ZAG antibodies. High-grade tumors expressed significantly less ZAG than moderate-grade tumors (mean ZAG score 1.1 versus 1.9; P < 0.01). Men with ZAG-producing prostate carcinomas had elevated levels of serum ZAG relative to their normal age- and race-matched controls (P < 0.02). Furthermore, s.c. growth of human ZAG-producing murine tumors in syngeneic mice and orthotopic growth of ZAG-producing human prostate carcinomas in nude rats resulted in readily detectable levels of human ZAG in the serum. Taken together, these studies show that ZAG production by prostate cancer can lead to systemically elevated serum ZAG levels that may be useful diagnostically. The effects of elevated systemic ZAG on cachexia-associated complications in patients with advanced prostate cancer deserves additional investigation.

Aged↗

Parasitic lesion of the insula suggesting cerebral sparganosis: case report.

Cerebral sparganosis, a parasitic disease, rarely produces a chronic active inflammatory response in the brain. Clinically and radiographically the process may mimic a neoplasm. We report a 30-year-old man who underwent surgical exploration for a mass in the insular cortex. Histology revealed a densely fibrotic mass heavily infiltrated with plasma cells and lymphocytes, in which were embedded parasitic forms consistent with sparganosis. We describe the MRI appearances and pathologic features. Intracranial mass lesions secondary to sparganosis must be considered in patients with a history of travel to endemic areas, especially Asia.

Adult↗

Paramedic success rate for blind nasotracheal intubation is improved with the use of an endotracheal tube with directional tip control.

STUDY OBJECTIVES: Blind nasotracheal intubation (BNTI) is used to secure the airway in patients who are spontaneously breathing. The success rate for BNTI is often lower than for orotracheal intubation. We conducted this study to determine whether the use of an endotracheal tube (ETT) capable of directional tip control can improve the BNTI success rate. METHODS: This prospective, experimental study was conducted by a state emergency medical services agency during 1997, 1998, and 1999. Consecutive patients undergoing attempted BNTI or orotracheal intubation were included. Five paramedic units were trained to use an ETT with triggeractivated distal tip directional control for BNTIs (intervention group). Ten units used conventional ETTs for BNTIs and served as concurrent controls (control group). Subjects in the 2 groups were enrolled concurrently with nonrandomized allocation based on the agency providing service. An intubation attempt was defined by tube passage, and success was defined as confirmed endotracheal placement. RESULTS: A total of 219 BNTIs were studied (141 in the control group and 78 in the intervention group). BNTI was successful in 82 (58%) of 141 cases using conventional ETTs, and in 56 (72%) of 78 cases using directional tip control (P =.04). The overall success rate was 63%. CONCLUSION: Use of ETTs with distal directional control is associated with a higher success rate for BNTI than conventional ETTs. Use of ETTs with directional tip control significantly improves the success rates for BNTIs.

Allied Health Personnel↗

Calpain inhibition prevents sinusoidal endothelial cell apoptosis in the cold ischemic rat liver.

BACKGROUND: Cold preservation of the liver followed by reperfusion results in sinusoidal endothelial cell (SEC) apoptosis. Calpain-like activity is dramatically increased during reperfusion and inhibition of calpains results in lower graft injury and longer survival. Recently, calpains have been implicated in inducing apoptosis. Our aim was to determine the effect of calpain inhibition on SEC apoptosis. METHODS: Livers were stored in the University of Wisconsin solution for 24 hr (survival conditions) and 40 hr (nonsurvival conditions) and ex vivo reperfused for 1 hr at 37 degrees C. Calpain-like activity was inhibited in some experiments using an i.p. injection of a selective inhibitor 2 hr before explantation. Apoptosis was quantified using the terminal deoxynucleotidyl trans. ferase-mediated dUTP nick end-labeling assay. Cross-inhibition by the inhibitor was determined for caspases 1 and 3. RESULTS: Apoptosis of exclusively the SEC was a key feature of reperfusion injury after both storage periods in University of Wisconsin solution after 1 hr normothermic reperfusion. Inhibition of calpain activity with Cbz-Val-Phe methyl ester resulted in a 50% reduction of apoptotic SEC in the 40-hr preserved liver, and an almost complete abrogation of SEC apoptosis after 24 hr preservation. Only minimal cross-inhibition of caspases was determined at high concentrations in vitro by the calpain inhibitor. CONCLUSION: Apoptosis of exclusively SEC is a key feature of reperfusion injury partially mediated through calpain-dependent processes. Calpain inhibition reduces the number of apoptotic SEC. Based on these data and our previous work, calpain inhibition may prove to be useful in clinical transplantation.

Animals↗

Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver.

BACKGROUND: Ischemic injury of the liver is generally considered to result in necrosis, but it has recently been recognized that mediators of apoptosis are activated during ischemia/reperfusion. This study was designed to characterize the extent and the type of cells within the liver that undergo apoptosis at different periods of ischemia and reperfusion. METHODS: Male Wistar rats were subjected to 30 or 60 min of normothermic ischemia. Liver sections were evaluated at the end of ischemia and at 1, 6, 24, and 72 hr after reperfusion. Apoptosis was determined by DNA fragmentation as evaluated by laddering on gel electrophoresis, in situ staining for apoptotic cells using TdT-mediated dUTP-digoxigenin nick-end labeling (TUNEL), and morphology on electron microscopy. RESULTS: In situ staining of liver biopsy specimens using TUNEL showed significant apoptosis after reperfusion. Sinusoidal endothelial cells (SEC) showed evidence of apoptosis earlier than hepatocytes. For example, at 1 hr of reperfusion after 60 min of ischemia, 22+/-4% of the SEC stained TUNEL positive compared with 2+/-1% of the hepatocytes (P<0.001). With a longer duration of ischemia, a greater number of SEC and hepatocytes became TUNEL positive. An increase in TUNEL-positive cells was also noted with an increasing duration of reperfusion. The presence of apoptotic SEC and hepatocytes was supported by DNA laddering on gel electrophoresis and cell morphology on electron microscopy. Several Kupffer cells were seen containing apoptotic bodies but did not show evidence of apoptosis. Only rare hepatocytes showed features of necrosis after 60 min of ischemia and 6 hr of reperfusion. CONCLUSION: These results suggest that apoptosis of endothelial cells followed by hepatocytes is an important mechanism of cell death after ischemia/reperfusion injury in the liver.

Animals↗

Diagnosis of anaplastic large-cell lymphoma, including multifocal osseous KI-1 lymphoma, by fine-needle aspiration biopsy.

We present the fine-needle aspiration (FNA) findings of 4 cases of anaplastic (Ki-1) large-cell lymphoma (ALCL). A primary diagnosis of ALCL was made on FNA material in 2 cases, of which one was a multifocal osseous Ki-1 lymphoma. In the other 2 patients who had a known history of ALCL, FNA was used to detect recurrent disease. In all cases, large discohesive pleomorphic cells in the absence of lymphoglandular bodies in the background raised the possibility of a nonhematopoietic neoplasm. Immunochemical staining for CD30 was positive in all cases. The cytomorphologic and immunochemical features are discussed, along with the differential diagnosis of Ki-1 lymphoma. Diagn. Cytopathol. 1999;21:174-179.

Adolescent↗

Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis.

BACKGROUND & AIMS: Calpain proteases have been implicated in cell death by necrosis and more recently by apoptosis. Experiments were designed to determine the role of calpain proteases in ischemic rat liver injury by measurement of cytosolic calpain activity after different periods of ischemia-reperfusion and by evaluation of the effects of calpain inhibition on tissue injury and animal survival. METHODS: Calpain activity was measured in the cytosol using Suc-Leu-Leu-Val-Try-7 amino-4 methyl coumarin, a specific fluorogenic substrate, and Cbz-Leu-Leu-Tyr-CHN2, a specific inhibitor. RESULTS: Calpain activity increased significantly with the duration of ischemia-reperfusion and was inhibited more than 80% by the inhibitor. Calpain inhibition resulted in a significant decrease in transaminase release and tissue necrosis and converted nonsurvival ischemic conditions to survival conditions. When the in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling assay for apoptosis was used, 35% +/- 6% of nonparenchymal cells and 16% +/- 3% of hepatocytes stained positively after 60 minutes of ischemia and 6 hours of reperfusion. In contrast, animals pretreated with the calpain inhibitor showed minimal evidence of apoptosis. This was further substantiated by gel electrophoresis assay for DNA fragmentation and by electron-microscopic evaluation. CONCLUSIONS: These data suggest that calpain proteases play a pivotal role in warm ischemia-reperfusion injury of the rat liver through modulation of apoptosis and necrosis.

Alanine Transaminase↗

Cryptosporidium, enterocytozoon, and cyclospora infections in pediatric and adult patients with diarrhea in Tanzania.

Cryptosporidiosis, microsporidiosis, and cyclosporiasis were studied in four groups of Tanzanian inpatients: adults with AIDS-associated diarrhea, children with chronic diarrhea (of whom 23 of 59 were positive [+] for human immunodeficiency virus [HIV]), children with acute diarrhea (of whom 15 of 55 were HIV+), and HIV control children without diarrhea. Cryptosporidium was identified in specimens from 6/86 adults, 5/59 children with chronic diarrhea (3/5, HIV+), 7/55 children with acute diarrhea (0/7, HIV+), and 0/20 control children. Among children with acute diarrhea, 7/7 with cryptosporidiosis were malnourished, compared with 10/48 without cryptosporidiosis (P < .01). Enterocytozoon was identified in specimens from 3/86 adults, 2/59 children with chronic diarrhea (1 HIV+), 0/55 children with acute diarrhea, and 4/20 control children. All four controls were underweight (P < .01). Cyclospora was identified in specimens from one adult and one child with acute diarrhea (HIV-). Thus, Cryptosporidium was the most frequent and Cyclospora the least frequent pathogen identified. Cryptosporidium and Enterocytozoon were associated with malnutrition. Asymptomatic fecal shedding of Enterocytozoon in otherwise healthy, HIV children has not been described previously.

Acute Disease↗

Species and genotypic diversities and similarities of pathogenic yeasts colonizing women.

We examined the patterns of strain relatedness among pathogenic yeasts from within and among groups of women to determine whether there were significant associations between genotype and host condition or body site. A total of 80 yeast strains were isolated, identified, and genotyped from 49 female volunteers, who were placed in three groups: (i) 19 women with AIDS, (ii) 11 pregnant women without human immunodeficiency virus (HIV) infection, and (iii) 19 women who were neither pregnant nor infected with HIV. Seven yeast species were recovered, including 59 isolates of Candida albicans, 9 isolates of Candida parapsilosis, 5 isolates of Candida krusei, 3 isolates of Candida glabrata, 2 isolates of Saccharomyces cerevisiae, and 1 isolate each of Candida tropicalis and Candida lusitaniae. Seventy unique genotypes were identified by PCR fingerprinting with the M13 core sequence and by random amplified polymorphic DNA analysis. Of the nine shared genotypes, isolates from three different hosts were of one genotype and pairs of strains from different body sites of the same host shared each of the other eight genotypes. Genetic similarities among groups of strains were calculated and compared. We found no significant difference in the patterns of relatedness of strains from the three body sites (oral cavity, vagina, and rectum), regardless of host conditions. The yeast microflora of all three host groups had similar species and genotypic diversities. Furthermore, a single host can be colonized with multiple species or multiple genotypes of the same species at the same or different body sites, indicating dynamic processes of yeast colonization on women.

AIDS-Related Opportunistic Infections↗

Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation injury in rat liver transplantation.

In livers excised for transplantation, sinusoidal endothelium appears especially vulnerable to injury during organ preservation in the cold and subsequent reperfusion. The degree of endothelial cell injury correlates with functional impairment of the graft following transplantation. The mechanism of injury remains obscure, but endothelial cell damage has been described as coagulative necrosis secondary to irreversible physico-chemical damage. We investigated whether endothelial cell death is caused by apoptosis rather than by necrosis. Tissue from rat livers stored for varying periods in cold (1 degree C) Euro-Collins solution and then reperfused for 1 hour at 37 degrees C were studied for evidence of apoptosis by detection of DNA fragmentation using the in situ terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling (TUNEL) assay, DNA gel electrophoresis, and by transmission electron microscopy (EM). DNA fragmentation of the type characteristic of apoptosis was identified in 49.7% +/- 2.2% of sinusoidal lining cells after 8 hours of ischemia + reperfusion (viable graft) vs. 70.7% +/- 4.3% after 16 hours + reperfusion (nonviable graft) (P < .001). No such fragmentation was observed after cold preservation without reperfusion or in unpreserved, reperfused livers. EM demonstrated changes characteristic of apoptosis exclusively in endothelial cells. The study suggests that the apoptosis of sinusoidal endothelial cells is a pivotal mechanism of preservation injury in liver transplantation.

Animals↗

Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent.

Interleukin-6 (IL-6) is an acute reactant cytokine with anti-inflammatory properties, which has been found to prevent injury in a model of acute hepatitis in mice through downregulation of tumor necrosis factor alpha (TNF-alpha); to correlate inversely with markers of hepatocellular injury in patients with liver ischemia; and to initiate liver regeneration in mice. In this study, we investigated the role of IL-6 in rodent models of hepatic warm ischemia/reperfusion (WI/Rp) injury. IL-6-deficient mice (-/-) were subjected to hepatic WI and compared with C57BL/6 mice, as well as IL-6 -/- mice pretreated with recombinant IL-6 (rIL-6). The effects of rIL-6 following various periods of ischemia were further studied in models of hepatic ischemia in rats. IL-6 -/- mice had increased reperfusion injury as assessed by transaminase levels and a tissue necrosis scoring system when compared with controls, an effect prevented by pretreatment with rIL-6. Similarly, rats pretreated with rIL-6 had reduced reperfusion injury and better survival than controls in each respective WI group. Tissue TNF-alpha expression measured by Northern blot analysis and serum C-reactive protein (CRP) levels, a marker of inflammation, were significantly reduced in animals pretreated with rIL-6. Administration of antibodies to TNF-alpha reproduced the beneficial effect of rIL-6. Hepatocyte proliferation, as assessed by a scoring method for mitotic index and proliferating nuclear cell antigen staining, was markedly increased in rIL-6-treated rats when compared with controls. In conclusion, this study suggests that IL-6 could play an important role in limiting hepatic warm ischemia/reperfusion (WI/Rp) injury, probably through its anti-inflammatory properties, modulation of TNF-alpha, and/or promotion of liver regeneration. rIL-6 might become an important cytokine in clinical situations associated with WI/Rp injury.

Acute-Phase Reaction↗

Duration of incubation of fungal cultures.

To determine the optimum duration of incubation for recovery of fungi, the results of 2,173 consecutive clinical cultures were reviewed. Overall, 94% of fungal isolates were detected by day 7 and 98% were detected by day 14. Yeasts were usually (98%) detected within the first week of incubation. Recovery of molds required more time, but 81% were detected by day 7 and more than 96% were detected by day 14.

Cross Infection↗