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Biomedical subjects

P Carroll

Publications and source records attributed to P Carroll.

At least 109 records · Page 6Linked to original sources
PubMed1994

Epidermal-growth-factor-receptor expression is associated with rapid tumor proliferation in bladder cancer.

Epidermal-growth-factor-receptor (EGF-r) expression has been proposed as a prognostic marker in bladder cancer and is associated with rapid proliferation in cell lines. Ninety-three fresh and 74 formalin-fixed bladder tumors were examined by fluorescence in situ hybridization (FISH) and immunohistochemistry to assess the relationship between EGF-r expression and proliferation as well as the prevalence of epidermal-growth-factor-receptor (EGF-r) gene amplification. EGF-r expression was strongly associated with BUdr labeling index, grade and stage. EGF-r expression emerged as a stronger predictor of tumor proliferation than grade or stage in analysis of variance. Rapid tumor proliferation might be responsible for bad prognosis reported in EGF-r positive bladder tumors. Also chromosome 7 copy number was associated with grade and stage. EGF-r gene amplification was uncommon (5 of 107 tumors). However, FISH analysis allowed characterization of the pattern of amplification, with clustering of signals suggestive of intrachromosomal amplification more common than diffuse distribution consistent with extrachromosomal amplification.

Bromodeoxyuridine↗
PubMed1994

Ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) was first identified and partially purified from embryonic chick eye tissues. Subsequently, it was shown that CNTF is also present in large amounts in sciatic nerves of adult rats and rabbits, which led to its final purification and cloning. CNTF is not secreted by the classical secretory pathway involving the endoplasmatic reticulum and Golgi complex, but can be detected in high quantities within the cytoplasm of myelinating Schwann cells and astrocytes using immunohistochemistry. CNTF supports survival and/or differentiation of a variety of neuronal cell types including sensory, sympathetic, and motoneurons. Also, nonneuronal cells, such as oligodendrocytes, microglial cells, liver cells, and skeletal muscle cells, respond to exogenously administered CNTF, both in vitro and in vivo. During development, expression of CNTF is very low, if indeed it is expressed at all, and the phenotype of mice lacking endogenous CNTF after inactivation of the CNTF gene by homologous recombination suggests that CNTF does not play a crucial role for responsive cells during embryonic development. However, motoneurons are lost postnatally in mice lacking endogenous CNTF, suggesting that CNTF acts physiologically on the maintenance of these cells. The ability of exogenous CNTF to protect against motoneuron loss following lesion or in other animal models indicates that CNTF might be useful in the treatment of human motoneuron disorders, provided appropriate means of administration can be found.

Amino Acid Sequence↗
PubMed1994

Primary osteogenic sarcoma of the urinary bladder successfully treated with combination therapy.

A 54-year-old woman presented with a large bladder mass and left hydroureteronephrosis. At radical cystectomy (with ileal loop urinary diversion), an unresectable left obturator mass was found. Combination chemotherapy postoperatively resulted in significant shrinkage, and she underwent excision of the residual mass. No residual cancer was seen. The patient remains free of disease 56 months after cystectomy and 51 months after resection of the residual mass. Primary osteogenic sarcoma of the urinary bladder may respond to combination chemotherapy and surgery. All patients found to have advanced disease should be considered for this approach.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity.

Escherichia coli can ameliorate the toxic effects of alkylating agents either by preventing DNA alkylation or by repairing DNA alkylation damage. The alkylation-sensitive phenotype of E. coli alkB mutants marks the alkB pathway as an extremely effective defense mechanism against the cytotoxic effects of the SN2, but not the SN1, alkylating agents. Although it is clear that AlkB helps cells to better handle alkylated DNA, no DNA alkylation repair function could be assigned to the purified AlkB protein, suggesting that AlkB either acts as part of a complex or acts to regulate the expression of other genes whose products are directly responsible for alkylation resistance. However, here we present evidence that the provision of alkylation resistance is an intrinsic function of the AlkB protein per se. We expressed the E. coli AlkB protein in two human cell lines and found that it confers the same characteristic alkylation-resistant phenotype in this foreign environment as it does in E. coli. AlkB expression rendered human cells extremely resistant to cell killing by the SN2 but not the SN1 alkylating agents but did not affect the ability of dimethyl sulfate (an SN2 agent) to alkylate the genome. We infer that SN2 agents produce a class of DNA damage that is not efficiently produced by SN1 agents and that AlkB somehow prevents this damage from killing the cell.

AlkB Homolog 1, Histone H2a Dioxygenase↗
PubMed1994

Staging accuracy of magnetic resonance imaging versus transrectal ultrasound in stages A and B prostatic cancer.

The present study was undertaken to compare the ability of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) to identify the presence or absence of extracapsular tumor extension and seminal vesicle involvement in patients with clinically localized (stages A and B, T1-T2) prostatic cancer. Sixty-four patients (ages 44-77 years) underwent radical retropubic prostatectomy and pelvic lymphadenectomy after staging with both MRI and TRUS. Surgical specimens were step-sectioned and examined at multiple levels. Radiographic staging was correlated with pathological staging. Both MRI and TRUS demonstrated better staging accuracy than conventional digital rectal examination [42% for digital rectal examination (DRE), 63% by TRUS, and 67% by MRI], although they suffered from understaging (31% by TRUS and 22% by MRI). The positive predictive value (PPV) for stage B disease was disappointingly low (42% for DRE, 53% for TRUS and 59% for MRI). However, the PPV for stage C disease was higher (81% for TRUS and 77% for MRI). In the evaluation of extracapsular invasion, the PPV of TRUS (81%) was higher than that of MRI (77%). The negative predictive value (NPV), however, for both TRUS and MRI was low (58 and 56%, respectively). In the evaluation of seminal vesicle invasion, both TRUS and MRI demonstrated poor PPV (50 and 40%, respectively), but the NPV was excellent (90% for TRUS and 96% for MRI). MRI failed to detect metastatic lymph nodes in 4 of 6 patients while falsely predicting their presence in 4 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A lupus anticoagulant neutralization procedure using the patient's own platelets.

An auto platelet neutralization procedure (APNP) which assists identification of lupus anticoagulants (LA) is described. Patient platelet-rich plasma is frozen then thawed (PRPF) and an activated partial thromboplastin time (aPTT) is performed on both platelet-poor plasma and PRPF. The degree of correction between the two plasmas is calculated and the percentage APNP is obtained. A lupus anticoagulant was suspected if a sample had a prolonged aPTT and at least two out of three of the following characteristics: (1) aPTT resistant to correction with equal parts normal plasma, (2) prolonged kaolin clotting time mixing test (delta KCT), (3) prolonged dilute Russell's Viper Venom Time that did not correct with normal plasma (DRVVR). Ten normal volunteers had mean (+/- SD) APNP of 7.7 +/- 4.3%. Fifty LA negative patients with normal aPTT, delta KCT and DRVVR, had a mean APNP of 10.0 +/- 6.3%. Twenty-eight patients suspected as LA positive had APNP > 25% with a mean of 39.0 +/- 7.5%. Twenty-one patients with prolonged aPTT attributed to factor deficiency had APNP < 25% with a mean of 6.3 +/- 12.0%. LA was also suspected in two other patients with prolonged aPTT that did not meet the above criterion but had APNP > 25%. In three patients with normal aPTT, LA was suspected and APNP ranged from 21 to 28%. An intermediate APNP range of 20-25% may be suggestive of LA in patients with normal aPTT. The APNP did not appear to be effected by platelet count in the samples tested unless the platelet count in PRP was less than 175 x 10(9)/1.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1994

Physical deletion of the p53 gene in bladder cancer. Detection by fluorescence in situ hybridization.

To understand better the role of physical p53 deletion in bladder cancer, 106 formalin-fixed and 45 unfixed bladder tumors were examined using fluorescence in situ hybridization. Probes for centromere 17 and the p53 locus were hybridized simultaneously to interphase tumor cells to analyze p53 and chromosome 17 copy number on a cell by cell basis. 17p deletion was found in four of 43 pTa tumors, 18 of 43 pT1 tumors and 29 of 58 pT2-4 tumors (P = 0.0001). 17p deletion was also highly correlated with grade (P = 0.0001) and with p53 immunostaining (P = 0.0005). Chromosome 17 polysomy was associated with stage, grade, 17p deletions, and p53 immunostaining (P = 0.0001). The strong difference in centromere 17 copy number and 17p deletions between pTa and pT1 tumors supports a relevant biological distinction between pTa and pT1 tumors.

Alleles↗
PubMed1993

Heterogeneity of erbB-2 gene amplification in bladder cancer.

erbB-2 amplification and overexpression have been suggested as potentially useful prognostic markers in bladder cancer. We examined 141 bladder tumor specimens (45 fresh tissue samples and 96 formalin fixed tissue blocks) for erbB-2 amplification using fluorescence in situ hybridization. A dual labeling hybridization using a repetitive pericentromeric probe specific for chromosome 17 and a cosmid probe for the erbB-2 locus was performed to analyze the erbB-2 copy number in relation to chromosome 17 copy number on a cell by cell basis. Amplification (more than twice as many erbB-2 signals as centromere 17 signals per tumor) was found in 10 of 141 tumors. There was considerable heterogeneity in erbB-2 amplification. In a given tumor there was a wide range of erbB-2 copy number in amplified cells. The arrangement of erbB-2 signals in clusters in all amplified cases suggests that erbB-2 amplification occurs intrachromosomally in bladder cancer. Amplification was found only in tumors with aneusomy of chromosome 17 and was more frequent in pT2-T4 tumors than in pTa/T1 tumors. Overexpression was present without amplification in 51 tumors. All tumors with erbB-2 amplification showed erbB-2 overexpression. However, in 5 samples the proportion of cells with amplification was significantly lower than the fraction of cells with overexpression, indicating coexistence of two different mechanisms leading to overexpression in these tumors.

Bromodeoxyuridine↗
PubMed1993

Rat ciliary neurotrophic factor (CNTF): gene structure and regulation of mRNA levels in glial cell cultures.

The structure of the rat ciliary neurotrophic factor (CNTF) gene and the regulation of CNTF mRNA levels in cultured glial cells were investigated. The rat mRNA is encoded by a simple two-exon transcription unit. Sequence analysis of the region upstream of the transcription start-site did not reveal a typical TATA-box consensus sequence. Low levels of CNTF mRNA were detected in cultured Schwann cells, and CNTF mRNA was not increased by a variety of treatments. Three-week-old astrocyte-enriched cell cultures from new-born rat brain contained easily detectable CNTF mRNA. In astrocyte-enriched cultures, upregulation of CNTF mRNA levels was observed after treatment with IFN-gamma. CNTF mRNA levels were down-regulated in these cells by treatments that elevate intracellular cyclic AMP and by members of the fibroblast growth factor (FGF) family. The implications of these results for potential in vivo functions of CNTF are discussed.

Amino Acid Sequence↗
PubMed1993

The value of prostate specific antigen and transrectal ultrasound guided biopsy in detecting prostatic fossa recurrences following radical prostatectomy.

The combination of prostate specific antigen (PSA) and transrectal ultrasonography was used to detect recurrent cancer in the prostatic fossa after radical prostatectomy. A total of 43 patients with persistently elevated PSA levels and negative bone scintigraphy following radical prostatectomy underwent digital rectal examination and transrectal ultrasonography. Ultrasound findings were considered suspicious if the scan showed any unusual hypoechoic tissue adjacent to the bladder neck, retro-trigone or peri-anastomotic site. Of 22 patients (51%) with biopsy proved cancer 21 (95%) had positive transrectal ultrasonography, while digital rectal examination was able to detect cancer in only 10 (45%). Among transrectal ultrasonography detected recurrences 15 (68%) were detected at the initial biopsy and 7 (32%) at repeat biopsies. Our study shows that the combination of PSA and transrectal ultrasonography provides a more effective method than digital rectal examination and PSA to detect biopsy proved cancer following radical prostatectomy.

Adenocarcinoma↗
PubMed1993

Insulin requirements after liver transplantation and FK-506 immunosuppression.

Hyperglycemia and new-onset diabetes mellitus is a well-recognized complication of solid organ transplantation. With the advent of FK-506 as a new immunosuppressive drug used in orthotopic liver transplantation (OLT), much attention has been paid to its diabetogenic effects. Currently, there are no data on the long term effects of FK-506 in glucose metabolism after OLT. In the present study, we determined the need for outpatient insulin in 52 American veterans who received 58 liver transplants using primary immunosuppression with FK-506 and PRED, with a mean follow-up of 467 days (range 17-952 days). We also analyzed their plasma glucose and FK-506 levels as well as the doses of PRED and FK-506 that they received at various intervals post-OLT. There were 7/52 (13.6%) patients who required insulin for the first time after OLT. Of these, the number of patients on insulin at 3, 6, and 12 months post-OLT was 5/47 (10.6%), 6/44 (13.6%), and 1/26 (3.8%), with none requiring insulin de novo at 18, 24, and 30 months post-OLT. Three patients required insulin temporarily but subsequently became normoglycemic without additional therapy. The need for insulin was not related to the dose of FK-506 administered nor the plasma level. Patients who required outpatient insulin were receiving higher doses of PRED than those not requiring insulin. The need for insulin did not affect the long-term graft or patient survival. In conclusion, the need for insulin with FK-506 compares favorably to that of previous immunosuppressive regimens, and FK-506 may have a reversible diabetogenic effect that is not dose dependent.

Actuarial Analysis↗
PubMed1993

Pressure ulcers and materiel management: cost-effective prevention and care.

In summary, it's important for the materiel manager to have an understanding of the clinical aspects of pressure ulcers. By understanding how ulcers are staged, treated, and prevented, the materiel manager will have a better idea why certain products are needed and how they are used to reduce overall patient costs. Specialty beds, replacement mattresses, and high-end overlays represent a significant cost--approximately $500,000 to $1 million based on studies cited in this article. Further proven by research is the fact that these costs can be reduced by carrying out utilization plans with specific criteria for patient selection. Finally, materiel managers can be key coordinators in the entire process since they are often on the front lines in any institution's cost containment efforts.

Beds↗