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Biomedical subjects

P Shaw

Publications and source records attributed to P Shaw.

At least 127 records · Page 7Linked to original sources

Differences in the morbidity of radical hysterectomy between gynecological oncologists.

A multivariate analysis was performed on 405 patients who underwent radical hysterectomy and pelvic lymphadenectomy by eight surgeons for stage IB cervical carcinoma, to determine the influence of primary surgeon on morbidity. Patient characteristics analyzed (mean/proportion) were age (41 years), quetelet index (25.4), American Society of Anesthesiologists classification of physical status (0.5% > 2), previous laparotomies (23%), previous radiation (0.7%), prophylactic antibiotics (95%), prophylactic heparin (67%), tumor size (1.0 cm), histology (68% SCC), grade (68% grades 2 or 3), vascular space involvement (45%), pelvic lymph node metastases (6%), and depth of invasion (6.6 mm). Morbidity characteristics analyzed (mean/proportion) were blood loss (910 ml), operative time (3.0 hr), intra-op complications (5%), post-op infectious (21%) and non-infectious complications (7%), transfusions (35%), post-op hospital stay (9.9 days), time to normal urine residual (9.0 days), and bladder dysfunction at 3 months post-op (21%). Mean tumor size was the only preoperative characteristic that was significantly different among surgeons (P < 0.001). Of the factors evaluated for morbidity, mean blood loss (P < 0.0001), operative time (P < 0.001), and postoperative hospital stay (P < 0.001) varied among physicians as did the incidence of blood transfusion (P < 0.0001) and bladder dysfunction at 3 months postoperatively (P < 0.0001). On multivariate analysis, surgeon was independently significant for blood loss (P < 0.0001), operative time (P < 0.0001), postoperative hospital stay (P < 0.001), incidence of blood transfusion (P < 0.0001), and bladder dysfunction at 3 months postoperatively (P < 0.0001). Despite differences in tumor size, patients appeared similar among the surgeons. Differences in patient morbidity among surgeons do exist and are of significant magnitude. Since the design of surgical trials to assess the therapeutic ratio should include not only measures of efficacy, but also measures of morbidity to be meaningful, intersurgical morbidity between centers/surgeons must continue to be quantified.

Adult↗

The neuropeptide VIP regulates the expression of the tyrosine hydroxylase gene in cultured avian sympathetic neurons.

The neuropeptide vasoactive intestinal polypeptide (VIP) increases the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of catecholamines, in cultured chicken sympathetic neurons. We report here that VIP acts by increasing TH mRNA levels in these cells. Induction of TH mRNA is transient and reaches maximal values 6-8 h after the addition of the peptide to the cultures. TH mRNA levels return to control values after 1-2 days. The quail cDNA probe detects a single mRNA species of approximately 9 kb in RNA extracted both from embryonic chicken sympathetic neurons and adult quail adrenal medulla.

Animals↗

Parvalbumin and calbindin D-28k in the human motor system and in motor neuron disease.

Calbindin D-28k and parvalbumin are neuronal calcium binding proteins of interest in relation to neurodegenerative diseases. Expression of calbindin and parvalbumin may be one of the determinants of selective vulnerability in these disorders. The distribution of these proteins was surveyed in the normal human motor system and in motor neuron disease (MND) using immunocytochemistry in formalin fixed post-mortem tissues. CNS tissues from 14 MND patients (mean age 61.2 years, mean post-mortem delay 24.6 h) and seven controls (mean age 62.6 years, mean post-mortem delay 25.3 h) were studied. Preliminary studies on the effects of fixation were performed. In normal cases upper and lower motor neurons showed absent expression of both proteins. Several neuronal groups characteristically spared in MND showed varying patterns of immunoreactivity: oculomotor neurons showed parvalbumin staining of the perikaryon; the thoracic preganglionic sympathetic neurons showed calbindin staining in perikarya. Onuf's nucleus showed calbindin staining in the neuropil only. In motor neuron disease a loss of ventral horn interneurons and calbindin immunoreactive processes was observed with no other disease related changes in the spinal cord, brain-stem, or motor cortex. These findings are consistent with the hypothesis that the distribution of these proteins is one determinant of selective vulnerability to the neurodegenerative processes in MND acting via disturbance of neuronal calcium homeostasis.

Amyotrophic Lateral Sclerosis↗

A role for culture in diagnosis of Helicobacter pylori-related gastric disease.

UNLABELLED: In this study, our objective was to determine the presence of Helicobacter pylori and other rapid urease-positive (RUP) organisms in gastric biopsies in 70 patients, 30 of whom had ulcers or erosions. A retrospective chart review was undertaken to correlate diagnostic tests (culture and direct urease) with results of endoscopic examination and the patient's clinical information. Eleven of 70 (15.7%) patients' biopsies were positive by both culture and direct urease for H. pylori, seven (10%) patients' biopsies were positive by culture only, and eight (11.4%) biopsies by direct urease only. Of 30 patients with ulcers (esophageal, antral, stomach, or duodenal), 15 had evidence of H. pylori infection by culture and/or direct urease test. In addition, patients with a positive direct urease test but a negative culture for H. pylori were more likely to have other rapid urease-positive organisms (RUP) isolated from their gastric biopsy cultures than patients with negative results from both tests. CONCLUSIONS: As a result of problems associated with commonly used diagnostic tests, a combination of tests performed on multiple biopsies is more sensitive and specific for the diagnosis of H. pylori infection than any single test. The common occurrence of RUP streptococcal and staphylococcal species in gastric biopsy tissue is demonstrated and proposed as a cause of false-positive direct urease tests.

Adult↗

Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line.

A wild-type p53 gene under control of the metallothionein MT-1 promoter was stably transfected into human colon tumor-derived cell line EB. Repeated inductions of the metallothionein wild-type p53 gene with zinc chloride results in progressive detachment of wild-type p53 cells grown on culture dishes. Examination at both the light and electron microscopic level revealed that cells expressing wild-type p53 developed morphological features of apoptosis. DNA from both attached and detached cells was degraded into a ladder of nucleosomal-sized fragments. Expression of wild-type p53 inhibited colony formation in soft agar and tumor formation in nude mice. Furthermore, established tumors in nude mice underwent regression if wild-type p53 expression was subsequently induced. Regressing tumors showed histological features of apoptosis. Thus, regression of these tumors was the result of apoptosis occurring in vivo. Apoptosis may be a normal part of the terminal differentiation program of colonic epithelial cells. Our results suggest that wild-type p53 could play a critical role in this process.

Base Sequence↗

Intraperitoneal therapy of malignant ascites associated with carcinoma of ovary and breast using radioiodinated monoclonal antibody 2G3.

A phase I/II study of intraperitoneal (ip) radioimmunotherapy was conducted in ovarian or breast cancer patients with symptomatic chemotherapy-resistant ascites using a novel anti-mucin monoclonal antibody (mAb) 2G3 labeled with 131I. Tracer doses of 2 mCi [131I]2G3 were given by ip injection to 11 patients, followed by increasing therapeutic doses up to 150 mCi (cumulative) in 9 patients. There was no serious toxicity. Temporary palliation of ascites was observed in 3 of 4 patients who received doses greater than 50 mCi. Total body elimination half-life of the radiolabeled antibody assessed by gamma scintigraphy ranged from 95 to 250 hr, longer than data previously reported in patients without ascites treated with ip administered radiolabeled antibodies. However, uptake of radiolabel by tumor nodules was small and variable (2 x 10(-4) - 2 x 10(-2) % ID/g), and preferential uptake by tumor compared to normal peritoneum was observed in only 2 of 5 patients in whom biopsies were obtained. These results suggest that the observed palliation of ascites is due to prolonged retention of radiolabeled antibody in the peritoneal cavity even in the absence of specific targeting.

Adult↗

The value of CT scanning and percutaneous fine needle aspiration of adrenal masses in biopsy-proven lung cancer.

Pre-operative CT scans of 546 patients with biopsy-proven primary bronchial carcinoma were reviewed. Twenty-two patients had a solid adrenal tumour (2 bilateral). Sixteen underwent percutaneous fine needle aspiration (FNA). Malignant cells were aspirated in five, eight revealed benign cells and in three cases there was insufficient material for diagnostic purposes. Six patients did not undergo FNA, four of these were considered to have benign adenomas on CT. This was confirmed by the unchanged CT image at more than 21 months follow-up. The five subjects with FNA-proven metastases died at a median of 14 months (range 3-24 months). All five would have been regarded as operable on their staging chest CT scan. Five patients with a negative biopsy underwent surgery, two died of metastases at 6 and 11 months respectively and one died of post-operative complications. The other two have unchanged adrenal lesions on CT at 9 months and 25 months. The CT appearances of these lesions were analysed. Well defined, low attenuation lesions which had a smooth attenuation rim or only involved part of the gland were benign and the survivors had unchanged CT appearances at follow-up (six lesions in five patients). Of these four lesions were less than or equal to 2 cm in diameter. Low attenuation lesions without a rim were malignant (n = 2). These latter both measured more than 2 cm in diameter. The CT appearances of many adrenal lesions were insufficiently distinctive to exclude malignancy and biopsy was necessary to establish a diagnosis.

Adrenal Gland Neoplasms↗

Self-reported sleep quality in college students: a repeated measures approach.

A longitudinal assessment of sleep quality is presented. Undergraduates provided two levels of repeated measures data. Sleep log information was gathered across the 7 days of the week, in three replications, over a semester. There were several new findings. Across the week, students spent significantly more time in bed on weekend days as compared with weekdays. Further, a new measure for quality of sleep covaried with the amount of time spent in bed during the week. The students enjoyed their sleep more on the weekends. Finally, both the amount of time in bed and the number of awakenings reported dropped significantly as the semester progressed.

Adolescent↗

Occurrence of Ki-ras and p53 mutations in primary colorectal tumors.

Twenty-four colorectal tumors and their paired mucosa were examined for allele loss on chromosomes 5 and 17, using polymerase chain reaction-amplified DNA, and for mutations in the Ki-ras and p53 genes. In addition, 19 benign polyps were analysed for mutations in the p53 gene. RFLP analysis of the long arm of chromosome 5 indicated an allele loss frequency of 47% for malignant tumors, a value somewhat higher than previously observed. Examination of the short arm of chromosome 17 indicated an allele loss of 60%. Sequence analysis of the p53 gene in colorectal tumors indicated that 64% contained a mutation. All tumors showing allele loss on chromosome 17 were mutant for p53, suggesting that mutation of one p53 allele precedes the hemizygotic loss of the wild-type allele. Sequence analysis of the p53 gene in 19 benign polyps, devoid of severe dysplasia, did not reveal any mutants, suggesting that the mutation of one p53 allele is an event that takes place after polyp formation. Ki-ras mutations were observed in 48% of the tumors examined. All tumors which were mutant for Ki-ras, except for one, were also mutant for p53.

Blotting, Northern↗

Detection of Epstein-Barr virus DNA by polymerase chain reaction in lymph node biopsies from patients with angioimmunoblastic lymphadenopathy.

Epstein-Barr virus DNA was detected by the polymerase chain reaction (PCR) in five lymph node biopsies from eight patients with diagnosis of angioimmunoblastic lymphadenopathy (AILD). Three pairs of specific primers detected EBV DNA sequences near the 5' end (Bam W region), the middle (BMRF 1 region) and the 3' end (Eco RI D region) of the viral genome with equal accuracy when 1 microgram of DNA and 30 amplification cycles were used. When only 100 ng of DNA were screened with the BMRF 1 set of primers, a specific amplification product was still identifiable. The 593 base pair amplification product obtained using the Eco RI D set of primers was shown to contain an expected Sma I site at position 215, confirming the viral origin of the amplified sequence [corrected]. Our findings indicate that lymph nodes of AILD patients frequently harbour the entire EBV genome at a high percentage of at least 1 viral copy per 15,000 human cells.

Base Sequence↗

Ascitic fluid from human ovarian cancer patients contains growth factors necessary for intraperitoneal growth of human ovarian adenocarcinoma cells.

Human ovarian cancer, the leading cause of death from gynecologic malignancy, tends to remain localized to the peritoneal cavity until late in the disease. In established disease, ascitic fluid accumulates in the peritoneal cavity. We have previously demonstrated that this ascitic fluid is a potent source of in vitro mitogenic activity including at least one unique growth factor. We now report that the human ovarian adenocarcinoma line, HEY, can be induced to grow intraperitoneally in immunodeficient nude mice in the presence (23/28 mice), but not absence (0/21 mice) of ascitic fluid from ovarian cancer patients. Ascitic fluid from patients with benign disease did not have similar effects on intraperitoneal growth of HEY cells (1/15 mice). Once tumors were established by injections of exogenous ascitic fluid, they could progress in the absence of additional injections of ascitic fluid. The mice eventually developed ascitic fluid which contained potent growth factor activity, suggesting that the tumors eventually produced autologous growth factors. This nude mouse model provides a system to study the action of ovarian cancer growth factors on tumor growth in vivo and to evaluate preclinically, therapeutic approaches designed to counteract the activity of these growth factors.

Animals↗

Comparison of 99Tcm dimercaptosuccinic acid scans and intravenous urography in children.

A retrospective comparison of 99Tcm dimercaptosuccinic acid (DMSA) scans and intravenous urograms (IVUs) was performed on a large, unselected paediatric population to assess critically the relative merits of these two techniques. A total of 205 children were studied, providing 388 kidneys for comparison. The studies agreed in 81%, both being normal in 39%, and both abnormal in 42%. In 28 kidneys (7%), the IVU was abnormal when the 99Tcm DMSA was normal. There was a collecting system abnormality in 27 kidneys, but 10 kidneys also showed a parenchymal abnormality. In all these the parenchymal abnormality was global thinning on the IVU, and the contralateral kidney was small. In 40 kidneys (10%) the 99Tcm DMSA was abnormal when the IVU was normal: the abnormalities demonstrated were predominantly focal defects. After excluding IVUs of poor diagnostic quality, only 14 kidneys (3.6%) showed this disparity. The important clinical subgroups are infection, with or without reflux (27 kidneys), hypertension (4) and neonates with poor renal function (2). The one false positive 99Tcm DMSA was a result of an anatomical variant. Global thinning in a "normal" kidney on a 99Tcm DMSA scan may be overlooked when the contralateral kidney is poorly functioning and small.

Adolescent↗

Laser angioplasty with a pulsed NdYAG laser: early clinical experience.

Since December 1986, 40 laser angioplasty procedures have been performed using the energy from a pulsed NdYAG laser, delivering near infrared light (1064 nm) in 100-microseconds pulses of approximately 300 mJ per pulse, directly through a transparent sapphire tipped device. All patients had total occlusion of the superficial femoral artery and symptoms severe enough to warrant surgery, with ulceration or gangrene in eight, rest pain in 14 and severe claudication interfering with life-style in the others. The device was introduced through an antegrade puncture of the superficial or common femoral artery and laser recanalization was followed by attempted balloon angioplasty in all cases. Occlusions were a median length of 15 cm (range 2-35 cm); ten patients had previously undergone failed attempts at conventional balloon angioplasty and four had occluded femoropopliteal grafts. Thirty-seven legs of 34 patients were treated with an average of 60 J (range 10-235 J) with successful recanalization in 27 and immediate reocclusion in seven. The 20 successful recanalizations have been followed up for up to 24 months (median 7 months) with only one late occlusion at 5 months. Failed recanalization was due to poor transmission by the delivery device in the early part of the series (five cases), repeated passage of the device down a collateral branch (four cases), dissection at the site of previous surgery (two cases) or no apparent reason (two cases). Immediate reocclusion was due to very poor run off in patients with severely ischaemic limbs (three cases) or technical difficulties with balloon dilatation (two cases). Complete symptomatic relief was obtained in all the cases of radiologically successful laser angioplasty. Early surgery was required in one case following reocclusion of the artery when an angioplasty balloon failed to deflate, and one patient suffered a skin reaction thought to be due to inadequate removal of the sterilizing solution. A different sterilizing procedure is now followed. Laser angioplasty can reduce the number of patients requiring bypass surgery and improvements in the device and access methods may reduce the number of untreatable cases.

Adult↗

Diagnostic fine needle core biopsy of deep lymph nodes for the diagnosis of lymphoma in patients unfit for surgery.

The use of a technique for safe percutaneous fine needle biopsy of inaccessible lymph nodes is described. In a prospective study of 24 patients, including five cases positive for the human immunodeficiency virus (HIV), this technique was used to provide diagnostic material. A firm diagnosis was made in 21 cases; four cases of Hodgkin's disease, 14 non-Hodgkin's lymphomas, one case of Kaposi's sarcoma, one case of mycobacterial infection, and one which showed the features of persistent generalized lymphadenopathy (PGL). In the cases of lymphoma, available serial sections allowed characterization of the tumour with immunocytochemistry. In three cases, no diagnosis could be made, with one of these requiring a subsequent open biopsy. Percutaneous fine needle biospy is ideal for patients unfit or unsuitable for general anaesthesia or surgery. The biopsy obtained gives the pathologist sufficient tissue for an accurate diagnosis in the majority of cases. The preservation of architecture and multiple sections available are advantages over fine needle aspiration.

Adult↗