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Biomedical subjects

W Gray

Publications and source records attributed to W Gray.

At least 37 records · Page 2Linked to original sources
PubMed1995

HIV associated cytomegalovirus colitis as a mimic of inflammatory bowel disease.

Cytomegalovirus (CMV) colitis may cause symptoms and signs identical to those of idiopathic inflammatory bowel disease. Although difficult to diagnose with certainty, the histological finding of cytomegalovirus inclusions in tissue from a case of suspected inflammatory bowel disease is strongly suggestive. CMV colitis is an entity almost entirely confined to cases of severe immunosuppression. The case of a 79 year old widower who was admitted to hospital with symptoms suggestive of inflammatory bowel disease is presented. Despite medical treatment his condition worsened and he developed toxic dilatation of the colon requiring colectomy. Histological examination showed a mild superficial pancolitis, with focal severe inflammation, deep fissuring ulceration, and pseudopolyposis. Abundant CMV inclusions were seen in cells associated with the ulcerating inflammatory tissue. A diagnosis of indeterminate colitis with CMV was made. The patient's condition worsened after surgery and he died a few days later despite intensive treatment, including antiviral chemotherapy directed against CMV. After death HIV serology was found to be positive. Regardless of the age and perceived lifestyle of the patient, a diagnosis of CMV colitis in someone not known to be immunosuppressed raises the possibility of HIV infection.

Aged↗
PubMed1995

Combined modalities in the treatment of head and neck cancers.

The higher the T and N stages at diagnosis of head and neck cancer, the lower the proportion of patients who achieve complete, durable local control and the lower the survival. These cancers and their treatments often produce considerable anatomic distortion, affecting function, nutritional status, and appearance. New treatment approaches for locally and regionally advanced head and neck cancers are thus needed to improve survival, quality of life, or both. Combined-modality approaches show promise. Induction chemotherapy and subsequent radiotherapy produce results equivalent to aggressive surgery but allow for better organ function and speech. Induction chemotherapy and radiotherapy are superior to radiotherapy alone. Concurrent chemotherapy and radiotherapy may produce additive or synergistic interactions but increase toxicities. Some studies suggest that concurrent chemotherapy and radiotherapy significantly improves survival over radiotherapy alone in regionally advanced disease. Drug selection criteria have included enhancement of radiation cytotoxicity, effect on cellular kinetics, and, possibly, single-agent antitumor activity. The platinum compounds are of interest, especially in combination with other chemotherapy agents, like 5-fluorouracil and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ). Concurrent carboplatin and radiotherapy produced a 77-week duration of survival in responders in a University of Maryland Cancer Center study. A study of concurrent carboplatin/bleomycin/radiotherapy had to be halted because of severe bleomycin-induced mucositis. The results in this small group suggest that attenuating mucositis would be desirable. In a subsequent trial, paclitaxel, which shows considerable activity against head and neck cancers, was substituted for bleomycin. Data from the seven patients accrued thus far are too immature to define response. The study continues to accrue patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Pulmonary sarcoidosis presenting as a granulomatous tattoo reaction.

A 29-year-old man presented with nodular skin lesions localized to areas of navy-blue pigmentation within a tattoo. Light microscopy demonstrated well-defined epithelioid granulomata in close relation to blue and black pigment. Although the patient was asymptomatic, a chest X-ray showed bilateral pulmonary shadowing, and histology of a transbronchial biopsy specimen showed features compatible with a diagnosis of sarcoidosis. X-ray energy dispersive spectroscopy identified copper and titanium in the tattoo pigment. These elements were not found in tissue from the lung biopsy. The cutaneous eruption resolved with oral steroid therapy. Our observations suggest that the granulomatous reaction in the tattoo was a manifestation of sarcoidosis, rather than a specific reaction to pigment.

Adult↗
PubMed1994

Adaptive responses of coronary circulation and myocardium to chronic reduction in perfusion pressure and flow.

We tested the hypothesis that chronic reduction in perfusion pressure and flow in the coronary circulation induces a state of myocardial "hibernation" characterized not only by a steady-state reduction in myocardial O2 consumption (MVO2) but also by evidence of persistent dilator reserve of the distal vasculature. Biochemical and morphological changes in the coronary vasculature were also assessed. Experiments were conducted in swine with an extraluminal coronary stenosis placed 4-32 wk before study. Stenosis reduced lumen diameter by approximately 80% at the time of final experimentation. Baseline, regional myocardial blood flow distal to the stenosis in both endocardial and epicardial layers was reduced vs. that of the normal zone. Vasodilator reserve persisted in both endocardial and epicardial layers of the stenosis zone. Flow increased in each layer in response to adenosine plus phenylephrine and failed to decline despite a marked reduction in perfusion pressure in response to adenosine alone. Regional MVO2 at baseline was reduced vs. historical controls without coronary stenosis. Protein synthesis rate in coronary vessels of the stenosis zone was reduced vs. that of the normal zone. Morphological responses of stenosis zone vessel walls were heterogeneous. Smaller microvessels exhibited mild hypertrophy of their walls, whereas walls of larger microvessels tended to atrophy. Thus chronic reduction in perfusion pressure and flow induces a state of myocardial hibernation characterized by a steady-state reduction in MVO2 in association with persistent dilator capacity. Biochemical and morphological changes occur in microvessel walls and may contribute to observed physiological responses.

Acclimatization↗
PubMed1994

Chemoradiotherapy for the treatment of regionally advanced head and neck cancers.

Despite the use of aggressive surgery and radiotherapy, patients with locoregionally advanced squamous cell carcinoma of the head and neck continue to suffer poor local control and poor survival. Chemotherapy produces excellent regressions of locoregional disease when given as part of initial induction therapy. The use of chemoradiotherapy for regionally advanced disease offers the possibility of organ preservation and retention of organ function for many of these patients. Randomized studies have suggested that chemoradiotherapy also offers better local control and survival than radiotherapy alone. Many chemotherapy regimens used in modern chemoradiotherapy include cisplatin. Because of its ease of outpatient administration, lesser degree of nausea and vomiting, reduced nephrotoxicity, improved nutritional status during therapy, and predictable myelotoxicity, carboplatin has important advantages over cisplatin. Carboplatin possesses well-defined single-agent activity against head and neck cancers, and produces excellent responses in combination with 5-fluorouracil in previously untreated patients. Sequential studies at the University of Maryland Cancer Center showed that weekly carboplatin could be safely and easily combined with standard doses and fractions of radiotherapy. With this regimen, 57% of the patients achieved a complete response and 21% achieved a partial response. Although the addition of bleomycin to this regimen proved somewhat toxic, concurrent carboplatin and radiotherapy allows for the further testing of new agents in developing a combination chemotherapy/concurrent radiotherapy program. Such regimens may improve local control and survival, and may be developed further for organ preservation studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Purification and characterization of a yeast DNA polymerase alpha complex with associated primase, 5'-->3' exonuclease, and DNA-dependent ATPase activities.

We have purified a multimeric form of yeast DNA polymerase alpha with DNA polymerase, primase, 5'-->3' exonuclease, and single-stranded (ss) DNA-dependent ATPase activities to near-homogeneity. The molecular mass of complex was 650 kDa with subunits ranging in sizes from 30 to 180 kDa. The alpha-subunit of the complex could be detected by DNA polymerase alpha antibody. No cross-reactivity of polypeptides within the complex was observed with antibodies directed against polymerase delta or epsilon. The multimeric polymerase alpha could be selectively inhibited by p-n-butylphenyl-dGTP (I50 of approximately 0.2 microM), p-n-butylanilino-dATP (I50 of 1.3 microM), and aphidicolin (I50 of 2.5 micrograms/mL). The complex synthesized RNA primers on various ssDNA templates and rapidly elongated these primers into nascent DNA fragments in the presence of required deoxynucleotides. It has a strong 5'-->3' exonuclease activity. In addition, the complex hydrolyzed both ATP and dATP in a ssDNA-dependent manner. Thus, the multiprotein complex of DNA polymerase alpha had multiple activities (primase, polymerase, and ATPase) which could act concertedly to synthesize primers and elongate the primers to nascent DNA fragments in the lagging strand of the fork.

Adenosine Triphosphatases↗
PubMed1992

The effects of carbocisplatin and radiation on skin flap survival.

Carbocisplatin is used as an inductive chemotherapeutic agent prior to irradiation in the treatment of head and neck cancers. Controversy exists whether carbocisplatin sensitizes normal epithelial tissues, including skin, to radiation. The combined effect of radiation and carbocisplatin on the survival of skin flaps was studied in an experimental model using dorsal flaps in Sprague-Dawley rats. Skin flaps were created 6 weeks after exposure to irradiation and carbocisplatin. Flap survival was assessed 7, 14, and 21 days after the flaps were initially created. Exposure of the flaps to irradiation alone, carbocisplatin alone, combined irradiation and carbocisplatin, or combined irradiation and fractionated carbocisplatin did not result in any significant decrease in flap survival when compared with untreated animals.

Animals↗
PubMed1992

Phase II trial of 5 day continuous intravenous infusion of 6-thioguanine in patients with recurrent and metastatic squamous cell carcinoma of the head and neck.

Fifteen patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck received a 5 day continuous I.V. infusion of 6-thioguanine repeated every five weeks. Dose limiting toxicity was primarily hematological with grade III/IV leucopenia and thrombocytopenia seen in seven patients. Nausea and vomiting was moderate and well controlled with antiemetics. No complete or partial responses were observed, with a median time to progression of 58 days and a median survival of 227+ days for the entire group. Based on these results we do not recommend I.V. 6-thioguanine for the treatment of this disease.

Adult↗
PubMed1992

Immunocytochemical staining of serous effusions with the monoclonal antibody Ber-EP4.

Cytospin preparations were made from 102 serous effusions for immunocytochemical staining using a panel of monoclonal antibodies including a new monoclonal antibody Ber-EP4. On cytological examination, 32 fluids were reported to contain tumour cells consistent with metastatic adenocarcinoma; 66 contained benign cells only and three were reported to contain cells suspicious of malignancy. One effusion contained tumour cells consistent with malignant mesothelioma. Positive staining of the tumour cells with Ber-EP4 was observed in the 32 effusions (100%) which contained adenocarcinoma cells. No staining of the mesothelial cells in these 32 specimens was observed. Carcinoembryonic antigen, epithelial membrane antigen Ca2 and CD15 staining of tumour cells was noted in 53%, 50%, 50% and 9% of these cases, respectively. None of the mesothelial cells in the benign effusions stained with Ber-EP4. Nor did the malignant mesothelial cells in the only case of malignant mesothelioma. These findings suggest that Ber-EP4 is a valuable addition to antibodies available for the differential diagnosis of mesothelial cells and adenocarcinoma cells in serous effusions.

Antibodies, Monoclonal↗
PubMed1991

The Saccharomyces cerevisiae SPT14 gene is essential for normal expression of the yeast transposon, Ty, as well as for expression of the HIS4 gene and several genes in the mating pathway.

To investigate the role of the trans-acting transcription factor encoded by the essential SPT14 (SPT = Suppressor of Ty insertion mutations) gene, we have cloned, mapped and sequenced the gene. From the analysis of the effect of spt14 mutations on expression of various genes, we conclude that the SPT14 product has an important role in activation of Ty transcription as well as in the regulation of other genes including HIS4 and several of the a- and alpha-specific mating type genes. Similarities in the phenotypes of spt14 and spt13 mutants (suppression of Ty insertion mutations but not delta insertion mutations), lead to the suggestion that the SPT14 gene and the previously characterized SPT13/GAL11 gene might encode transcriptional regulators with related functions. Our current findings show that in contrast to SPT13/GAL11, which appears negatively to regulate Ty transcription, SPT14 plays a role in the activation of Ty transcription. Thus, despite the similarities in the suppression phenotype exhibited by spt13 and spt14 mutants, SPT13/GAL11 and SPT14 probably differ in their transcriptional roles.

Amino Acid Sequence↗
PubMed1991

Conversion of a cyclooxygenase (CO) inhibitor into a 5-lipoxygenase (LO) inhibitor: a general route to novel orally active anti-inflammatory and anti-allergy drugs.

Previously, the conversion of a CO inhibitor, naproxen, into an orally active 5-LO inhibitor, Wy-50,295, by covalent attachment of a quinoline group was reported. The authors now report the extension of this transformation to other CO inhibitors. Replacement of an existing substituent or a hydrogen in sulindac, etodolac, carprofen, diclofenac, oxaprozin, des-alpha-methyl-ketoprofen, or des-alpha-methyl-flurbiprofen by a methoxyquinoline group afforded new hybrid structures which were orally active 5-LO inhibitors in the rat RPAR (reverse passive Arthus reaction) assay. In contrast to Wy-50,295 which is a selective 5-LO inhibitor, some of these new hybrids were dual inhibitors of 5-LO and CO. For example, the quinoline-etodolac hybrid WAY-120,739, (1,8-diethyl-1,3,4,9-tetrahydro-6-(2-quinolinylmethoxy)pyrano [3,4-b]indole-1-acetic acid) was a dual inhibitor of 5-LO and CO (91% and 47% inhibition, respectively at 10 microM, rat PMN). In contrast, the quinoline-flurbiprofen hybrid WAY-121,006, (3-fluoro-4'-(2-quinolinylmethoxy)-[1,1'-biphenyl]-4-acetic acid), the quinoline-oxaprozin hybrid, WAY-120,460, (5-phenyl-4-[4-(2- quinolinylmethoxy)phenyl]-2-oxazolepropanoic acid) and the quinoline-carprofen hybrid WAY-120,429 (alpha-methyl-6-(2-quinolinylmethoxy)-9-(2-quinolinylmethoxy)-9H- carbazole-2-acetic acid) were purely 5-LO inhibitors (100%, 96% and 92% inhibition of 5-LO at 10 microM, rat PMN, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Non-neurosurgical operative intervention in head-injured patients.

Guidelines relating to non neurosurgical operative intervention in head-injured patients are not available for the British Isles. We present a series of seven patients with extradural haematoma operated upon in the referring hospital prior to transfer to our unit. The cases were analysed in an attempt to elucidate the efficacy of the emergency procedures and the associated problems. Recommendations are made in order to generate discussion on this aspect of head injury management.

Adolescent↗
PubMed1989

Carboplatin (CBDCA) and radiotherapy for stage IV carcinoma of the head and neck: a phase I-II study.

The prognosis of patients with squamous cell carcinoma (SQC) of the head and neck (H&N) depends on the primary site and anatomical extent of the disease. Recurrence rates after conventional surgery (S) and/or radiotherapy (RT) remain low for localized tumors, whereas in advanced loco-regional disease they occur in over 60% of all cases. Several combinations of treatment modalities have been attempted in order to improve local control in Stages III and IV. Unfortunately, the recurrence rate remains high with added morbidity when conventional surgery is combined with pre or post-operative radiotherapy. Induction chemotherapy (CT) with Cisplatinum and Bleomycin has resulted in severe toxicities when combined with radiotherapy. To evaluate the toxicity of Carboplatin (CBDCA), a second generation platinum analog, when given simultaneously with conventional doses of radiotherapy, 26 patients with Stage IV SQC of the head and neck were treated at the University of Maryland Medical Systems. There were 23 males and 3 females; median age was 59 years and median Karnofski performance status was 60. Twenty patients had received no prior therapy; six had surgical exploration and excision with measurable residual disease. Anatomically, six patients had tumors of the oral cavity, twelve in the pharynx, one in the nasopharynx, four in the larynx, one in the hypopharynx, one in the maxillary antrum, and one was an unknown primary. These patients were treated as out-patients with weekly injections of Carboplatin. The dose was escalated: two patients received 60 mg/M2, seven received 75 mg/M2, thirteen were treated with 100 mg/M2, and four with 400 mg/M2. The radiotherapy was given daily with conventional fractions of 180 cGy and total tumor doses of 60-75 Gy. Toxicities were mainly hematological with median nadirs decreasing with increasing doses of Carboplatin. Mucositis was seen in over 80% of the patients, but interestingly enough, it has never been more severe than that observed with radiotherapy alone. So far, there has not been any kidney, ear, or neurotoxicities. Of 25 evaluable patients, 19 (76%) responded with 13 (52%) showing complete response. The overall median survival time is 266+ days (324+ for responders and 179+ for non-responders). The follow-up is still short, 10-14 months, but 9 of 13 patients with complete response have not yet progressed.

Antineoplastic Agents↗