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Biomedical subjects

P Shaw

Publications and source records attributed to P Shaw.

At least 37 records · Page 2Linked to original sources

Schizophrenia-like psychosis arising de novo following a temporal lobectomy: timing and risk factors.

OBJECTIVES: To clarify risk factors for the development of schizophrenia-like psychotic disorders following temporal lobectomy, and to explore the possibility that the early postoperative period is a time of high risk for the onset of such chronic psychotic disorders. METHODS: Patients who developed schizophrenia-like psychosis were identified from a series of 320 patients who had a temporal lobectomy for medically intractable epilepsy. The relationship of their disorders to both the operation and subsequent seizure activity was examined. Using a retrospective case-control design, risk factors for the development of schizophrenia-like psychosis were established. RESULTS: Eleven patients who developed schizophrenia-like psychosis postoperatively were identified and compared with 33 control subjects who remained free of psychosis postoperatively. The onset of de novo psychotic symptoms was typically in the first year following the operation. No clear relationship between postoperative seizure activity and fluctuations in psychotic symptoms emerged. Compared with the controls, patients who become psychotic had more preoperative bilateral electroencephalogram (EEG) abnormalities, pathologies other than mesial temporal sclerosis in the excised lobe and a smaller amygdala on the unoperated side. CONCLUSIONS: Temporal lobectomy for medically intractable epilepsy may precipitate a schizophrenia-like psychosis. Patients with bilateral functional and structural abnormalities, particularly of the amygdala, may be at particular risk for the development of such psychoses.

Adolescent↗

How important is removal of the parametrium at surgery for carcinoma of the cervix?

OBJECTIVES: The aims of this study were (1) to determine the incidence and factors predictive for pathologic parametrial involvement in clinical stage IA1/2 and IB1 cervical cancer after radical surgery and (2) to identify a population at low risk for pathologic parametrial involvement. METHODS: All patient information was collected prospectively and extracted from a cervical cancer radical surgery database. Selection criteria for surgery were generally based upon tumor size, with the cutoff for surgery between 3 and 4 cm. Parametrial involvement (PI) was defined as either positive parametrial lymph nodes (PMLN) or malignant cells in the parametrial tissue (PT) (including lymphovascular channels) by either contiguous or discontiguous spread. Statistical analysis included the chi2 test, the Wilcoxon rank test, and the Mantel-Haentzel test. RESULTS: Between July 1984 and January 2000, 842 patients underwent radical surgery for clinical stage IA1/2 and IB1 cervical cancer at our center. Forty-nine patients (6%) had positive pelvic lymph nodes. Thirty-three patients (4%) had pathologic PI, 8 in the PMLN and 25 in the PT (none had both). PI was associated with older age (42 vs 40 years, P < 0.04), larger tumor size (2.2 vs 1.8 cm, P < 0.04), higher incidence of capillary-lymphatic space invasion (85% vs 45%, P = 0.0004), tumor grades 2 and 3 (95% vs 65%, P = 0.001), greater depth of invasion (18.0 vs 5.0 mm, P < 0.001), and pelvic lymph node metastases (44% vs 5%, P < 0.0001). The incidence of PI in patients with tumor size < or =2 cm, negative pelvic lymph nodes, and depth of invasion < or =10 mm was 0.6%. CONCLUSION: Pathologic parametrial involvement in clinical stage IA1/2 and /IB1 cervical cancer is uncommon. Acknowledging that almost all patients with pelvic lymph node metastases and a high proportion of patients with tumor invasion >10 mm will receive adjuvant radiation regardless of the radicality of surgery, a population at low risk for pathologic parametrial involvement can be identified. These patients are worthy of consideration for studies of less radical surgery performed in conjunction with pelvic lymphadenectomy.

Adult↗

The human amygdala: a systematic review and meta-analysis of volumetric magnetic resonance imaging.

The structure and function of the human amygdala is attracting increasing attention in the scientific literature, particularly since the advent of high resolution magnetic resonance imaging (MRI). We carried out a systematic review of the published literature reporting left and right amygdala volumes from MRI in non-clinical subjects. Our aim was to estimate the normal range of the volume of the amygdala and to account for heterogeneity of the measures. The factors we considered included the detail given regarding various subject factors, the plane of scan acquisition, slice thickness and contiguity, magnet strength, positional and volume correction, and the reliability of measurement. Thirty-nine studies with 51 data sets fulfilled selection criteria. The mean+/-95% confidence interval for the left amygdala volume was 1726.7 mm(3)+/-35.1, and right was 1691.7 mm(3)+/-37.2. The left-right difference did not reach statistical significance. The overall range of reported volumes was 1050 mm(3) to 3880 mm(3). The amygdala is significantly larger in men and shows an inverse correlation with age. The main methodological factor found to influence amygdala measurement was anatomical definition. Studies using 'Watson's criteria' (Neurology 42 (1992) 1743) produced significantly larger volumes than the remainder. An index of study quality revealed an inverse relationship with volume-the higher the quality the smaller the volume. This reflected such factors as slice thickness, correction for brain volume, positional correction and number of subjects. We conclude by putting forward a detailed operationalized anatomical delineation of the amygdala, based on Watson's criteria. This work should guide future research in obtaining accurate and reliable amygdala volume measures which in turn will aid comparisons with clinical groups and the specification of structural-functional relationships.

Amygdala↗

Acetylcholinesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine.

Acetylcholinesterase is one of the most prominent constituents of central cholinergic pathways. It terminates the synaptic action of acetylcholine through hydrolysis and yields the choline moiety that is necessary for transmitter recycling. Despite these pivotal relationships, mice nullizygous for acetylcholinesterase established all principal anatomical components of central cholinergic pathways. No compensatory increase in the distribution of butyrylcholinesterase was detected. However, both the wild-type and nullizygous mice showed that butyrylcholinesterase enzyme activity extended to all parts of the brain receiving cholinergic innervation and that it could hydrolyze the acetylcholine surrogate acetylthiocholine. As opposed to acetylcholinesterase which was mostly of neuronal origin, butyrylcholinesterase appeared to be mostly of glial origin. These experiments lead to the unexpected conclusion that acetylcholinesterase is not necessary for the establishment of cholinergic pathways. They also show that butyrylcholinesterase can potentially substitute for acetylcholinesterase and that this enzyme is likely to play a constitutive (rather than just back-up) role in the hydrolysis of acetylcholine in the normal brain. The inhibition of butyrylcholinesterase may therefore provide a desirable feature of cholinergic therapies, including those aimed at treating Alzheimer's disease.

Acetylcholine↗

Molecular evidence for putative tumour suppressor genes on chromosome 13q specific to BRCA1 related ovarian and fallopian tube cancer.

BACKGROUND/AIMS: Loss of heterozygosity (LOH) on chromosome 13q has been reported to occur frequently in human ovarian cancer, and indications have been found that chromosome 13 may also play a specific role in the inherited form of ovarian cancer. The aim of this study was to define regions on chromosome 13 that may harbour additional tumour suppressor genes involved in the tumorigenesis of BRCA1 related ovarian and fallopian tube cancer. MATERIALS/METHODS: DNA extracted from paraffin wax blocks of 36 BRCA1 associated ovarian and fallopian tube carcinomas was analysed by LOH polymerase chain reaction using seven highly polymorphic microsatellite markers spanning chromosome 13q. RESULTS: High LOH frequencies were found on loci 13q11, 13q14, 13q21, 13q22-31, 13q32, and 13q32-4, suggesting the presence of putative tumour suppressor genes on the long arm of chromosome 13 that may play a role in the pathogenesis of BRCA1 related ovarian and fallopian tube cancer. LOH patterns appeared to be independent of the type of BRCA1 mutation, stage, and grade. Although in some cases there were indications for loss of larger parts of chromosome 13, in most cases losses were fairly randomly distributed over chromosome 13 with retained parts in between lost parts. Microsatellite instability was found in six cases. CONCLUSION: Several loci on chromosome 13q show high frequencies of LOH in BRCA1 related ovarian and fallopian tube cancer, and may therefore harbour putative tumour suppressor genes involved in the carcinogenesis of this particular type of hereditary cancer.

Chromosomes, Human, Pair 13↗

Diagnostic imaging of lung cancer.

Carcinoma of the bronchus is the most common malignancy in the Western world. It is also the leading cause of cancer-related death accounting for 32% of all cancer deaths in males and 25% in females. In the USA it causes more deaths than cancers of the colon, breast and prostate combined. Disappointingly, in a recent UK survey of improvements in cancer survival, carcinoma of the bronchus showed the smallest percentage reduction in the number of deaths avoided between 1981-1990 (0.2%). This compares badly with breast (11% reduction) and melanoma (32%). The overall 5-yr survival for lung cancer diagnosed between 1986-1990 was only 5.3% (against 66% for breast and 76% for melanoma). It is on this background that the radiologist remains actively employed in the detection, diagnosis, staging and review of this common malignancy.

Biopsy, Needle↗

Crystallization and preliminary x-ray crystallographic studies of trichosanthin delta C7.

Trichosanthin (TCS) is a type I ribosome-inactivating protein (RIP) which possesses rRNA N-glycosidase activity. TCS has various pharmacological properties. It is possible to reduce the antigenicity of TCS by deleting up to seven C-terminal residues of TCS (TCS-C7) with minimal effect on its activity. TCS-C7 has been crystallized and the crystal diffracted to 1.8 A. It belongs to space group P2(1), with unit-cell parameters a=71.6A, b=74.4A, c=87.6A, beta=97.0 degrees. It is given that there are four molecules per asymmetric unit.

Antineoplastic Agents, Phytogenic↗

Does histology influence prognosis in patients with early-stage cervical carcinoma?

BACKGROUND: The objective of this study was to examine the influence of histology on the outcome of patients with surgically treated, Stage IA-IB carcinoma of the uterine cervix. METHODS: All patient information was collected prospectively and was extracted subsequently from the University of Toronto cervical carcinoma surgery data base. Selection criteria for surgery were based on tumor size and were independent of histology. Patients with adenocarcinoma were separated into two groups: those with mucinous/endometrioid adenocarcinoma (M/E AC) and those with adenosquamous/clear cell adenocarcinoma (AS/CC AC). Statistical analysis used Wilcoxon rank tests, Mantel-Hanzel tests, chi-square tests, and Cox regression analyses. RESULTS: Between July 1984 and January 2000, 880 patients with Stage IA-IB cervical carcinoma underwent radical surgery, including pelvic lymphadenectomy, as the primary treatment. Two hundred fifty-five patients had M/E AC (29%), 81 patients had AS/CC AC (9%), and 544 patients had squamous cell carcinoma (SCC; 62%). Compared with patients who had SCC, patients with M/E AC had significantly more favorable prognostic characteristics: age (median, 39 years vs. 41 years; P < 0.03), depth of invasion (3.7 mm vs. 5.5 mm; P < 0.001), vascular space involvement (24% vs. 57%; P < 0.0001), Grade 2-3 tumor (40% vs. 78%; P < 0.0001), and pelvic lymph node metastases (4% vs. 8%; P < 0.04), respectively. Characteristics among patients with AS/CC AC tended have values similar to the median values for patients with SCC (or intermediate between the values for patients with M/E AC and the values for patients with SCC): age (38 years), depth of invasion (6 mm), vascular space involvement (40%), Grades 2-3 (70%), and pelvic lymph node metastases (6%). The 2-year and 5-year recurrence free survival rate was similar between patients with M/E AC and patients with SCC (95% vs. 94% and 90% vs. 90%, respectively); however, both were significantly superior to the rates for patients with AS/CC AC (2-year recurrence free survival rate: 86%, P < 0.03; 5-year recurrence free survival rate: 81%, P % 0.03). There were no differences in the pattern of first recurrence by histology. CONCLUSIONS: Patients with surgically treated Stage IA-IB cervical carcinoma with M/E AC and SCC histology have a similar prognosis. For patients with disease with AS/CC AC histology, the current results and the literature indicate that patients with uncommon histologies have an inferior recurrence free survival rate. Although the optimal therapy for these patients remains undefined, there is no obvious rationale for altering the treatment strategies from those currently employed for patients with M/E AC and SCC.

Adenocarcinoma↗

The Ph1 locus is needed to ensure specific somatic and meiotic centromere association.

The correct pairing and segregation of chromosomes during meiosis is essential for genetic stability and subsequent fertility. This is more difficult to achieve in polyploid species, such as wheat, because they possess more than one diploid set of similar chromosomes. In wheat, the Ph1 locus ensures correct homologue pairing and recombination. Although clustering of telomeres into a bouquet early in meiosis has been suggested to facilitate homologue pairing, centromeres associate in pairs in polyploid cereals early during floral development. We can now extend this observation to root development. Here we show that the Ph1 locus acts both meiotically and somatically by reducing non-homologous centromere associations. This has the effect of promoting true homologous association when centromeres are induced to associate. In fact, non-homologously associated centromeres separate at the beginning of meiosis in the presence, but not the absence, of Ph1. This permits the correction of homologue association during the telomere-bouquet stage in meiosis. We conclude that the Ph1 locus is not responsible for the induction of centromere association, but rather for its specificity.

Binding Sites↗

KOJAK encodes a cellulose synthase-like protein required for root hair cell morphogenesis in Arabidopsis.

The cell wall is an important determinant of plant cell form. Here we define a class of Arabidopsis root hair mutants with defective cell walls. Plants homozygous for kojak (kjk) mutations initiate root hairs that rupture at their tip soon after initiation. The KJK gene was isolated by positional cloning, and its identity was confirmed by the molecular complementation of the Kjk(-) phenotype and the sequence of three kjk mutant alleles. KOJAK encodes a cellulose synthase-like protein, AtCSLD3. KOJAK/AtCSLD3 is the first member of this subfamily of proteins to be shown to have a function in cell growth. Subcellular localization of the KOJAK/AtCSLD3 protein using a GFP fusion shows that KOJAK/AtCSLD3 is located on the endoplasmic reticulum, indicating that KOJAK/AtCSLD3 is required for the synthesis of a noncellulosic wall polysaccharide. Consistent with the cell specific defect in the roots of kjk mutants, KOJAK/AtCSDL3 is preferentially expressed in hair cells of the epidermis. The Kjk(-) phenotype and the pattern of KOJAK/AtCSLD3 expression suggest that this gene acts early in the process of root hair outgrowth. These results suggest that KOJAK/AtCSLD3 is involved in the biosynthesis of beta-glucan-containing polysaccharides that are required during root hair elongation.

Amino Acid Sequence↗

Changes in the demographics and perioperative care of stage IA(2)/IB(1) cervical cancer over the past 16 years.

OBJECTIVES: The aim of this study was to determine whether there have been any significant changes in the demographics and perioperative care of FIGO stage IA(2)/IB(1) cervical cancer over the past 16 years and, if so, to quantify them. METHODS: Since July 1984, all patients with FIGO stage IA(2)/IB(1) cervical cancer undergoing radical surgery by members of our division have been entered into a prospective database. Selection for surgery has been unchanged over the past 16 years. Since March 1994 and November 1996, one surgeon has performed radical vaginal trachelectomy and laparoscopic assisted radical vaginal hysterectomy, respectively. Statistical analysis used Spearman's correlation analysis, the proportional hazards regression model of Cox, and the Mantel-Hanzel test was performed. Due to the number of statistical analyses, statistical significance was defined as P < 0.01. RESULTS: Eight hundred sixty-four patients have undergone radical surgery (784 radical hysterectomy, 42 radical vaginal trachelectomy, 32 radical vaginal hysterectomy, 6 radical abdominal trachelectomy) for FIGO stage IA(2)/IB(1) carcinoma of the cervix by members of our division since 1984. There have been no changes in the median age (40 years), tumor size (2.0 cm), incidence of capillary lymphatic space involvement (47%), or positive pelvic lymph nodes (6%) over the past 16 years. The median Quetelet index (24.6), depth of tumor invasion (squamous cell carcinomas only) (6.0 mm), and proportion of patients with comorbid conditions (17%) have increased over time (P = 0.001, P = 0.003, and P < 0.001, respectively). Pathologically, there has been an increase in the proportion of adenocarcinomas (28%) and a decrease in the proportion of grade 3 tumors (28%) (P < 0.001 and P < 0.001, respectively). The median operating time (2.8 h), hospital stay (7.0 days), blood loss (600 cc), allogeneic blood transfusion (23%), postoperative infections (13%), and noninfectious complications (6%) have all decreased (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively). There has been no change in the incidence of positive surgical margins (3%), adjuvant radiation (13%), or recurrence-free survival (2 and 5 years, 94 and 90%, respectively) after a median follow-up of 45 months. CONCLUSION: Despite no substantive changes in the selection criteria for surgery and the small time interval studied (16 years), almost all indices of operative and postoperative morbidity analyzed have decreased significantly. These changes have occurred without an increase in the use of adjuvant radiation or decrease in recurrence-free survival. Although little progress has been made in the cure rates associated with surgical management of FIGO stage IA(2)/IB(1) cervical cancer during this time interval, it appears that the morbidity of surgery has decreased.

Adenocarcinoma↗

A novel highly informative polyA microsatellite on the telomeric side of the INK4a/ARF locus.

The INK4a/ARF locus encodes two cell cycle-regulatory proteins, p16(INK4a)and p14(ARF). Inactivation of the p16(INK4a)(MTS1) tumor suppressor gene by mutations, promoter methylation or gene deletions is a common event in the development of many different human tumors. The present report describes a novel polyA mononucleotide repeat situated 7.2 kb on the telomeric side of the INK4a/ARF locus. This highly polymorphic microsatellite marker (heterozygote frequency: 0.78) proved to be efficient for p16 allele loss and microsatellite instability analyses in human colon cancer.

Adenocarcinoma↗

Complex variant t(4;11) characterized by fluorescence in situ hybridization in infant acute lymphoblastic leukemia.

A 6-month-old girl was diagnosed with acute lymphoblastic leukemia (ALL). Chromosome analysis of bone marrow aspirate showed 46,XX,t(4;11)(q21;q23) with an atypical appearance of the 11p on the der(11) chromosome. FISH studies to fully characterize the translocation utilised 8 probes: whole chromosome painting probes for chromosome 11 and chromosome 4; separate chromosome 11 short arm and long arm paints; specific subtelomere probes from 11p, 11q, and 4q; MLL gene probe. Taken together, the results indicated a two-step abnormality: an initial standard t(4;11)(q21;q23), followed by another t(4;11)--this time, between the two derivative chromosomes. The MLL gene was split by the first translocation and its position altered by the second.

Antineoplastic Combined Chemotherapy Protocols↗

Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer.

The INK4a-ARF locus encodes two tumor suppressor proteins involved in cell-cycle regulation, p16INK4a and p14ARF, whose functions are inactivated in many human cancers. The aim of this study was to evaluate p14ARF and p16INK4a gene inactivation and its association with some clinocopathological parameters in colon cancer. The mutational and methylation status of the p14ARF and p16INK4a genes was analyzed in 60 primary colon carcinomas and 8 colon cancer cell lines. We have identified the first two reported mutations affecting exon 1beta of p14ARF in the HCT116 cell line and in one of the primary colon carcinomas. Both mutations occur within the N-terminal region of p14ARF, documented as important for nucleolar localization and interaction with Mdm2. Tumor-specific methylation of the p14ARF and p16INK4a genes was found in 33% and 32% of primary colon carcinomas, respectively. Methylation of the p14ARF was inversely correlated with p53 overexpression (p = 0.02). p14ARF and p16INK4a gene methylation was significantly more frequent in right-sided than in left-sided tumors (p = 0.02). Methylation of the p14ARF gene occurred more frequently in well-differentiated adenocarcinomas (p = 0.005), whereas the p16INK4a gene was more often methylated in poorly differentiated adenocarcinomas (p = 0.002). The present results underline the role of p14ARF and p16INK4a gene inactivation in the development of colon carcinoma. They suggest that the methylation profile of specific genes, in particular p14ARF and p16INK4a, might be related to biologically distinct subsets of colon carcinomas and possibly to different tumorigenic pathways.

Adaptor Proteins, Signal Transducing↗

River basin-related genetic structuring in an endangered fish species, Chondrostoma lusitanicum, based on mtDNA sequencing and RFLP analysis.

Chondrostoma lusitanicum is a Portuguese endemic cyprinid with a restricted distribution and reduced numbers in some basins, justifying its status as a threatened species. We examined genetic population structure using samples from throughout its geographical range in Portugal, using sequencing of b cytochrome and restriction fragment length polymorphism analysis of the NADH subunits 5 and 6. There was reduced within-population genetic variability but considerable among-population differentiation, particularly marked between both the Mira and Arade basins in the extreme south and other populations. These results confirm phylogeographic relationships suggested by previous fragmentary allozyme studies for C. lusitanicum, and are in accordance with allozyme and mitochondrial DNA data on phylogeography of coexisting cyprinid species of the genus Leuciscus. The levels of genetic divergence revealed by sequence and RFLP data showed strongly concordant patterns: geographical genetic structuring, with the definition of three distinct groups, was observed. The high values of nucleotide divergence and pairwise sequence divergence of the Mira and Arade groups, when compared with all other samples, support a distinct taxonomic status probably at the species level. Results are also discussed in relation to conservation of this highly fragmented species, in terms of Evolutionary Significant Units and Management Units.

Analysis of Variance↗

Increasing incidence of midterm and long-term complications after endovascular graft repair of abdominal aortic aneurysms: a note of caution based on a 9-year experience.

OBJECTIVE: To analyze the late complications after endovascular graft repair of elective abdominal aortic aneurysms (AAAs) at the authors' institution since November 1992. SUMMARY BACKGROUND DATA: Recently, the use of endovascular grafts for the treatment of AAAs has increased dramatically. However, there is little midterm or long-term proof of their efficacy. METHODS: During the past 9 years, 239 endovascular graft repairs were performed for nonruptured AAAs, many (86%) in high-risk patients or in those with complex anatomy. The grafts used were Montefiore (n = 97), Ancure/EVT (n = 14), Vanguard (n = 16), Talent (n = 47), Excluder (n = 20), AneuRx (n = 29), and Zenith (n = 16). All but the AneuRx and Ancure repairs were performed as part of a U.S. phase 1 or phase 2 clinical trial under a Food and Drug Administration investigational device exemption. Procedural outcomes and follow-up results were prospectively recorded. RESULTS: The major complication and death rates within 30 days of endovascular graft repair were 17.6% and 8.5%, respectively. The technical success rate with complete AAA exclusion was 88.7%. During follow-up to 75 months (mean +/- standard deviation, 15.7 +/- 6.3 months), 53 patients (22%) died of unrelated causes. Two AAAs treated with endovascular grafts ruptured and were surgically repaired, with one death. Other late complications included type 1 endoleak (n = 7), aortoduodenal fistula (n = 2), graft thrombosis/stenosis (n = 7), limb separation or fabric tear with a subsequent type 3 endoleak (n = 1), and a persistent type 2 endoleak (n = 13). Secondary intervention or surgery was required in 23 patients (10%). These included deployment of a second graft (n = 4), open AAA repair (n = 5), coil embolization (n = 6), extraanatomic bypass (n = 4), and stent placement (n = 3). CONCLUSION: With longer follow-up, complications occurred with increasing frequency. Although most could be managed with some form of endovascular reintervention, some complications resulted in a high death rate. Although endovascular graft repair is less invasive and sometimes effective in the long term, it is often not a definitive procedure. These findings mandate long-term surveillance and prospective studies to prove the effectiveness of endovascular graft repair.

Aged↗