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P Richman

Publications and source records attributed to P Richman.

18 recordsLinked to original sources
PubMed2006

Dynamic contrast-enhanced magnetic resonance imaging is a poor measure of rectal cancer angiogenesis.

BACKGROUND: The aim of this study was to investigate the use of magnetic resonance imaging (MRI) for non-invasive measurement of rectal cancer angiogenesis and hypoxia. METHODS: Fifteen patients with rectal adenocarcinoma underwent preoperative dynamic contrast-enhanced (DCE) and blood oxygenation level-dependent (BOLD) MRI. Microvessel density (CD31 level), and expression of vascular endothelial growth factor (VEGF) and carbonic anhydrase (CA) 9 were measured immunohistochemically in histological tumour sections from 12 patients. Serum VEGF levels were also measured in 14 patients. Correlations between quantitative imaging indices and immunohistochemical variables were examined. RESULTS: There was good correlation between circulating VEGF and CD31 expression (r(S) = 0.88, P < 0.001). CD31 expression did not correlate with any dynamic MRI parameter, except transfer constant, with which it correlated inversely (r(S) = -0.65, P = 0.022). Tissue and circulating VEGF levels did not correlate, and neither correlated with any tumour DCE MRI parameter. No relationship was seen between BOLD MRI and CA-9 expression. CONCLUSION: The negative correlation between transfer constant (reflecting tumour blood flow and microvessel permeability) with CD31 expression is paradoxical. DCE MRI methods for assessing tissue vascularity correlate poorly with histological markers of angiogenesis and hypoxia, suggesting that DCE MRI does not simply reflect static histological vascular properties in patients with rectal cancer.

Adenocarcinoma↗
PubMed2005

Can pathological complete response in the primary tumour following pre-operative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for sterilisation of pelvic lymph nodes, a low risk of local recurrence and the appropriateness of local excision?

INTRODUCTION: Local excision is considered inappropriate treatment for T3-T4 rectal adenocarcinomas, as it cannot provide prognostic information regarding lymph node involvement and has a high risk of pelvic recurrence. Preoperative chemoradiation (CRT) studies in rectal cancer suggest that a pathological complete response (pCR) in the primary tumour provides an excellent long-term outcome. If downstaging to stage pT0 predicts a tumour response within the perirectal and pelvic lymph nodes, this may allow local excision to be performed without increased risk of pelvic recurrence. This retrospective study aimed to determine the incidence of involved lymph nodes following pCR (ypT0) after preoperative CRT and total mesorectal excision. METHOD: The outcome and treatment details of 211 patients undergoing preoperative CRT for clinically staged T3-T4 unresectable rectal adenocarcinomas between 1993 and 2003 at Mount Vernon Hospital were reviewed. RESULTS: Data were recorded from the 143 patients who completed treatment with a median follow-up of 25 months. Twenty-three patients (18%) were found to have had a pCR. Four out of 23 patients (17%) had involved lymph nodes. No pelvic recurrences developed after a ypCR. Overall survival was similar for patients with ypT0 or residual tumour. CONCLUSION: Pathological complete response in the primary tumour failed to predict a response in the perirectal lymph nodes (p=0.08). The degree of response predicted a lymph node response (p=0.02). The detection of ypCR identified patients with a low rate of pelvic recurrence. This may in the future allow selection of patients for whom local excision can be performed without a higher risk of local relapse.

Adenocarcinoma↗
PubMed2005

The reliability of lymph-node staging in rectal cancer after preoperative chemoradiotherapy.

AIMS: To determine the prognostic significance of the nodal stage and number of nodes recovered in the surgical specimen after preoperative synchronous chemoradiation (SCRT) and surgery for locally advanced or unresectable rectal cancer. MATERIALS AND METHODS: One hundred and eighty-two consecutive patients with locally advanced or unresectable (T3/T4) rectal carcinomas were entered on a prospective database and treated in this department with preoperative chemoradiation, followed 6-12 weeks later by surgical resection. Most patients received chemotherapy in the form of low-dose folinic acid and 5-fluorouracil (5-FU) 350 mg/m2 via a 60-min infusion on days 1-5 and 29-33 of a course of pelvic radiotherapy delivered at a dose of 45 Gy in 25 fractions over 33 days to a planned volume. After resection, patients with a positive circumferential margin (< or = 1 mm), extranodal deposits or Dukes' C histology received adjuvant 5-FU-based-chemotherapy (n = 40). RESULTS: After SCRT, 161 patients underwent resection. Twenty-one patients remained unresectable or refused an exenterative operation. Median follow-up is 36 months. Down-staging was achieved in most patients, with 19 having a complete pathological response (pT0). The median number of lymph nodes recovered for all patients was five (range 0-21). The 3-year survival rate for node-positive patients is 47%, for node-negative patients with less than three lymph nodes recovered is 62% and for node-negative patients with three or more lymph nodes recovered is 70%. Compared with node-positive patients, simple regression models revealed a reduced hazard ratio (HR) of 0.72 (0.36-1.43) for node-negative patients with less than three nodes recovered and 0.48 (0.26-0.89) for node-negative patients with three or more lymph nodes recovered. In a multivariate model, including nodal status, excision status, age and sex only positive excision margins significantly predicted a poor outcome: HR = 3.05 (1.55-5.97). CONCLUSIONS: The number of nodes found after preoperative chemoradiation is a significant prognostic factor by univariate analysis. In this study, patients with node-negative histology, and at least three nodes recovered, had better long-term survival than patients in whom two or less nodes were recovered or with positive nodes. This effect was attenuated by the inclusion of excision status in multivariate models.

Adenocarcinoma↗
PubMed2001

Primary pulmonary hypertension in Israel: a national survey.

OBJECTIVES: To characterize the incidence of patients with primary pulmonary hypertension (PPH) in Israel and their outcomes. METHODS: We have evaluated retrospectively all the patients in Israel in whom PPH was diagnosed between the years 1988 and 1997. We looked at medical history, hemodynamic data, pulmonary function and gas exchange, and demographic variables. Patients were followed up for survival until November 1997. Life table analysis and Kaplan-Meier statistics were used to estimate the overall survival distribution. Regression analysis was used to examine the relations between survival and selected variables. RESULTS: Overall, we found 44 patients with PPH. The estimated incidence of PPH in Israel is 1.4 new cases per year per million population. The mean (+/- SD) age at diagnosis was 43 +/- 13 years. In the Jewish population, PPH was more frequent among immigrants from Europe and the United States. The mean interval from the onset of symptoms to diagnosis was 3 years (median, 2 years). The median survival time was 4 years. The 1-year, 3-year, and 5-year survival rates were 82%, 57%, and 43%, respectively. The major variables influencing the survival rate were the following: interval from symptom onset to diagnosis; and hemodynamic measurements (ie, mean pulmonary artery pressure, mean right atrial pressure, and cardiac index). In comparison to rates discerned from the National Institutes of Health registry data, the survival rate in Israel is somewhat better and prognosis is influenced by similar hemodynamic variables. CONCLUSION: PPH is a rare and fatal disease in Israel. New therapeutic modalities such as prostacyclin therapy and lung transplantation may improve survival among patients with this malignant disease.

Adolescent↗
PubMed1998

Review of current preclinical testing strategies for bacterial vaccines.

A wide variety of bacterial vaccines is in various stages of preclinical and clinical development. These products range from whole killed or live attenuated bacterial organisms to purified proteins, peptides and plasmid DNA. Although preclinical strategies may be directed by a set of common guidelines focused on demonstrating safety and biological activity, the exact developmental scheme will depend on product-specific characteristics. In general, preclinical data should support the proposed clinical formulation and include detailed information on the source and quality of starting materials, manufacturing processes, characterization of bacterial seed stocks, potency, general safety, purity, and identity. Data describing product validation and testing may be appropriate depending on the type of product, e.g., genetic stability for recombinant constructs, details on inactivation or attenuation methods for organisms or toxins, demonstration of potency of combination products, and safety and toxicology studies of plasmid DNA vaccines or vaccines with novel adjuvants. The choice of dose, route, and formulation to be used clinically may be greatly affected by rigorous preclinical developmental strategies.

Adjuvants, Immunologic↗
PubMed1994

Acute effects of a single dose of porcine surfactant on patients with the adult respiratory distress syndrome.

In an attempt to restore functional surfactant to the lungs of patients with the adult respiratory distress syndrome (ARDS), we have treated six patients within the first 2 days of the onset of ARDS with a single dose of hydrophobic components of porcine surfactant. Surfactant (4 g in 50 ml) delivered via a bronchoscope in aliquots to each of the lobar bronchi was well tolerated and caused a modest transient improvement in gas exchange. No significant changes in chest radiograph or lung compliance were detected. Analysis of bronchoalveolar lavage (BAL) fluid showed no change in albumin, alpha-1-proteinase inhibitor specific activity, or cell count. Bronchoalveolar lavage phospholipid concentrations were elevated 3 h after surfactant administration relative to preadministration levels and fell by 24 h. In addition, in two patients we found reduced inhibition of surfactant function in BAL after surfactant replacement. These observations suggest a role for surfactant replacement in the treatment of patients with ARDS and support the need for continuing investigation.

Adult↗
PubMed1992

An inter-observer and intra-observer variability study on the diagnosis of lymph node biopsy specimens.

One hundred lymph node biopsy specimens were examined on two separate occasions by seven pathologists differing in experience in lymphoreticular pathology. Neither history nor immunohistochemistry was provided and the study, therefore, focused on morphological interpretation alone. The participants evaluated each case using a constructed response form in which the confidence with which they entered each response was also entered. Agreement on various points, between pathologists, between the two rounds, and with the referring centre was assessed. Whilst there was a high level of agreement over a diagnosis of benign vs. malignant and non-Hodgkin lymphoma vs. Hodgkin's disease, there was considerably less agreement over both T vs. B cell phenotype and high vs. low grade. The lack of agreement over grade, an evaluation which is usually made independent of immunohistochemistry, is particularly important, because of the relevance to selection of treatment. Proliferation markers may be more appropriate determinants of treatment choice.

Biopsy↗
PubMed1990

Culture and comparison of human bronchial and nasal epithelial cells in vitro.

Human nasal and bronchial epithelial cells were cultured in vitro and compared morphologically and functionally. Morphologic assessment by both light and electron microscope and indirect immunoperoxidase staining techniques confirmed the identity of the two cell types as being epithelial. Light microscopy of confluent cultures revealed tightly packed cell monolayers, whilst electron microscopy showed that cells were linked by tight junctions. Estimation of cell size by planimetry found these cells to have a mean width of 10.6 +/- 1.1 microns for nasal cells and a mean width of 10.2 +/- 1.0 microns for bronchial cells. A high proportion of both the nasal and the bronchial cells exhibited features of the mature ciliated cell types, and constituted between 50 and 76% of the total cells at the earlier stages of culture although this decreased to between 16 and 23% of the total by 4 weeks in culture. The ciliary beat frequencies of the nasal and bronchial cells were found to be similar at 10.8 +/- 0.7 Hz and 11.8 +/- 2.3 Hz, respectively. The cilial beat on adjacent cells was synchronous, suggesting the presence of intercellular communication between the neighbouring cells. These studies demonstrated that there was little difference between the cultured nasal and bronchial epithelial cells with respect to either their morphology or ciliary activity.

Bronchi↗
PubMed1990

Morphological integrity of the bronchial epithelium in mild asthma.

In severe asthma bronchial epithelial cells are damaged and detached, and it has been proposed that such damage might lead to the bronchial hyperresponsiveness that characterises asthma. To investigate the relation between airway hyperresponsiveness and epithelial damage, biopsy specimens of the bronchial mucus membrane were obtained at fibreoptic bronchoscopy from 11 patients with mild atopic asthma and airway hyperresponsiveness (provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) less than 1.0 mg/ml), and from 17 healthy non-atopic subjects who did not have airway hyperresponsiveness (PC20 methacholine greater than 8.0 mg/ml). Observers who were blind to the presence or absence of asthma examined the biopsy specimens by light and electron microscopy. Epithelial cells, intercellular spaces, and goblet cells were counted. Intercellular junctional complexes were examined, and a semiquantitative assessment was made of ciliary loss, non-parallel central ciliary filaments, and vacuoles in ciliated cells. There were no differences between the asthmatic and healthy groups in any of these measurements. These findings indicate that airway hyperresponsiveness may be present when there is no apparent change in the structure of the bronchial epithelium.

Adult↗
PubMed1990

99mTc radioimmunoscintigraphy of colorectal cancer.

The monoclonal antibody PR1A3 against a normal colonic columnar cell surface antigen has been labelled with 99mTc and used for imaging colorectal cancer. High uptake in undifferentiated cancer is seen. The tumour to mucosa ratio was up to 63:1 and the percentage of the injected activity in the tumour up to 1.7 X 10(-2%)g-1. As 99mTc is continuously available in a Nuclear Medicine Department, on receipt of a request the study may be completed within 24 h enabling radioimmunoscintigraphy to be used routinely in the management of patients with colorectal cancer.

Adenocarcinoma↗
PubMed1988

Immunomodulation by pulmonary surfactant.

Canine pulmonary surfactant is recognized to modulate both T and B cell response in vitro. Because both responses involve cell proliferation, it has been suggested that surfactant interferes with the proliferation of lymphocytes. We herein report studies using human surfactant collected from amniotic fluid (HAFS). HAFS inhibited the proliferative response of human lymphocytes to antigen (PPD) and to allogeneic lymphocytes. Inhibition was linear within the dose range examined. Inhibition of the response to phytohemagglutinin was only evident when suboptimal doses of phytohemagglutinin were used. The effect of HAFS on the lysis of K562 human myeloid target cells by natural killer (NK) cells was also studied. Lysis in this system does not require proliferation. HAFS inhibited NK cell-induced lysis by 70% (250 micrograms HAFS per milliliter) to 95% (500 micrograms HAFS per milliliter). Inhibition was evident whether the cells were incubated with HAFS for 4 hours or for 18 hours. The NK suppressor activity was contained in the lipid fraction of HAFS, whereas the protein fraction revealed little activity. The washout experiments demonstrated that the action of HAFS was on NK cells and not on target cells. The immunomodulatory properties of surfactant affect NK cell activity and the proliferative response. Surfactant may protect the lungs from inappropriate immune reactions. Abnormalities of the lipid fraction of surfactant should be considered in studies of the mechanism of pulmonary diseases characterized by local pulmonary immune responses.

Amniotic Fluid↗
PubMed1981

Alterations in chromatin structure during early sea urchin embryogenesis.

Sea urchin sperm before fertilization possess the longest nucleosome repeat length yet determined for any chromatin. By the time the fertilized egg gives rise to a blastula or gastrula embryo, the chromatin has a considerably shorter repeat length and, in addition, a sequence of different histone variants of H1, H2A, and H2B has appeared. We have investigated the relationship between these variations in histone composition and concomitant alterations in chromatin structure during the earliest stages of embryogenesis in two species of sea urchin. In contrast to the long repeat distance in sperm, chromatin loaded with cleavage stage histones has a much smaller repeat. Later stages containing predominantly alpha histones display an intermediate spacing. More detailed analysis of the events in the first cell cycle was carried out with polyspermically fertilized eggs. During the first 30 min after fertilization, in which sperm-specific H1 is completely replaced by cleavage-stage H1, the male pronuclear repeat remains unchanged. The decrease toward the repeat length of cleavage stages begins at about the time of DNA synthesis. Higher degrees of polyspermy extend the length of the cell cycle, including the duration of S phase and the length of time to reach the first chromosome condensation. At these higher degrees of polyspermy, the decrease in repeat length is also slowed. We conclude that the adjustment of the arrangement of nucleosomes in embryonic chromatin from that found in sperm can occur within the first cell cycle and that its timing is cell-cycle dependent. The adjustment is separable from a corresponding change in H1 composition.

Animals↗
PubMedDate not supplied

Polycythemia: a review article and case report of erythrocytosis secondary to Wilms' tumor.

We describe a child with Wilms' tumor whose only finding at presentation was polycythemia. A review of the mechanism of erythropoiesis regulation as well as the differential diagnosis, work-up, and management of polycythemia in children is presented. Our report emphasizes the need for a thorough evaluation of children who present with polycythemia.

Child, Preschool↗