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Biomedical subjects

K M Kerr

Publications and source records attributed to K M Kerr.

At least 19 recordsLinked to original sources
PubMed2006

Idiopathic pulmonary fibrosis: an update.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition of uncertain aetiology that should be considered in the differential diagnosis of patients who experience breathlessness, cough and reduced exercise tolerance. IPF is characterized histologically by the presence of usual interstitial pneumonia, and often has typical radiological appearances. Long-term successful management options are limited and frequently unsuccessful; as the disease progresses, palliation of symptoms becomes the mainstay of treatment. In a minority of patients, lung transplantation provides the only hope of long-term survival. The median survival of patients with IPF is approximately 3 years, which in turn emphasizes the need for further investigation into its pathogenesis and potential disease-modifying pharmacological therapies.

Acute Disease↗
PubMed2006

Timing phases of the sit-to-walk movement: validity of a clinical test.

The sit-to-walk (STW) movement is a functional task that challenges balance and co-ordination. There is a paucity of literature investigating the phases of this movement and its significance in a clinical rehabilitation context. Measuring phases of this movement may provide clinically applicable data for screening subjects for mobility problems and evaluating interventions. Fifty-six subjects from three groups; young (<65 years old), elderly (>65 years old) and elderly at risk of falling (EARF), performed the STW movement freely from a chair. Switches placed on the backrest, chair seat and two on the floor identified the times of movement events: onset, seat-off, swing-off and stance-off. These events defined three phases: flexion, extension and stance. Timing of events and phase duration data derived from this switch system were correlated with those taken from a three-dimensional motion analysis system. All switch events closely matched the motion analysis events with ICC (model 2.1) scores ranging from 0.93 to 1.00. Duration of all STW phases were statistically longer in the EARF group compared to both unimpaired groups (p<0.05). Data from the four switch configuration demonstrated excellent concurrent validity when associated with data from a three-dimensional motion analysis system in identifying the phases of STW. Measurement of the phases of the STW task has potential in screening those at risk of falling and informing care strategies to prevent falls.

Adult↗
PubMed2006

EU-USA pathology panel for uniform diagnosis in randomised controlled trials for HRCT screening in lung cancer.

Randomised controlled trials for lung cancer screening using high-resolution computed tomography are now underway. In order to allow effective future comparison of the different trials, as well as strengthening conclusions based upon the analysis of larger data sets, uniformity and consistency of pathology diagnosis are essential. The aim of the present study was to determine the effectiveness of the learning process in this difficult area of diagnostic pathology. Eight pathologists received two CD-ROMs, each with digital images of 30 cases. After diagnosing the first series, selected background reading was provided. Kappa (kappa) scores were calculated for each pathologist and category, and were compared to the consensus score. The readings of the first series showed a moderate agreement kappa score: mean+/-sd for category numbers 8 (all eight categories) and 2 were 0.53+/-0.05 and 0.65+/-0.04, respectively. The kappa 2 score distinguished between categories denoting benign and malignant lesions. The second series resulted in a good agreement kappa score: 0.65+/-0.06 for category number 8 and 0.81+/-0.02 for category number 2. In conclusion, this study demonstrates that screen-detected cases pose particular problems for pathologists and that a trained pathology panel serving randomised controlled trials is likely to lead to more consistent and accurate tissue diagnosis.

Adenocarcinoma↗
PubMed2005

Predicting the sorption of fatty alcohols and alcohol ethoxylates to effluent and receiving water solids.

Alcohol ethoxylates (AEs) are an important group of nonionic surfactants. Commercial AEs consist of a mixture of several homologues of varying carbon chain length (Cx) and degree of ethoxylation (EOy). The major disposal route of AE is down the drain to municipal wastewater treatment plants that discharge into receiving surface waters. Sorption of AE homologues onto activated sludge and river water solids is an important factor in assessing exposure of AE in the environment. This study presents the experimental determination of sorption coefficients for a wide array of AE homologues including five alcohols under environmentally relevant conditions and combines these data with literature data to generate a predictive model for the sorption of AEs in the environment. These results demonstrate that sorption can be effectively modeled using a log Kd vs. Cx and EOy predictive equation having the form log Kd = 0.331C - 0.00897EO - 1.126(R2 = 0.64).

Adsorption↗
PubMed2004

Defining phases for the sit-to-walk movement.

OBJECTIVE: To define phases of the sit-to-walk movement and test their consistency in a normal population. DESIGN: An observational study of thirteen healthy volunteers. BACKGROUND: Moving from sitting to walking is a daily activity that may present difficulty for some populations in terms of control and stability. METHODS: The movement was partitioned into phases according to changes in ground reaction forces and peak velocity of the total body centre of mass. Consistency of each phase duration was assessed. RESULTS: Four phases of sit-to-walk were defined; flexion momentum, extension, unloading and stance. ICC scores for phase duration ranged from 0.54 (extension) to 0.81 (stance). CONCLUSIONS: This is the first study to define distinct phases of the sit-to-walk movement. There was moderate to good consistency for phase duration. RELEVANCE: By defining and testing phases of the sit-to-walk movement this study enhances understanding of this everyday movement and provide a model for future research.

Activities of Daily Living↗
PubMed2004

Thyroid transcription factor 1 in pulmonary adenocarcinoma.

AIMS: To discover whether variations in thyroid transcription factor 1 (TTF-1) staining in different subtypes and patterns of pulmonary adenocarcinoma are related to the putative origin of the tumour. In addition, to confirm the specificity of TTF-1 for pulmonary (as opposed to other sites) adenocarcinoma, to examine the possible prognostic relevance of TTF-1 positivity in lung cancer, and to review this laboratory's experience of TTF-1 in diagnostic practice. MATERIALS/METHODS: In total, 128 primary lung adenocarcinomas, 106 primary non-pulmonary adenocarcinomas, and 37 pulmonary non-adenocarcinoma tumours were studied. In addition, 100 cases where TTF-1 was used in routine surgical pathology practice were investigated. Immunoperoxidase staining was performed on formalin fixed, paraffin wax embedded sections using anti-TTF-1 antibody. Staining was evaluated semiquantitatively using the frequency and intensity of nuclear positivity. RESULTS: None of the 106 non-pulmonary adenocarcinomas expressed TTF-1 and only three of the 37 non-adenocarcinoma lung cancers, all neuroendocrine carcinomas, were positive. Of the pulmonary adenocarcinomas, 75% were strongly positive for TTF-1. Mucinous (two of six) and poorly differentiated adenocarcinomas (four of 10) were less likely to stain. Of the peripheral adenocarcinomas, 33 of 37 were positive, whereas only seven of 14 of those of bronchial origin stained strongly. Atypical adenomatous hyperplasia strongly expressed TTF-1. No "false positives" were encountered in the 100 routine diagnostic cases. CONCLUSION: Positive TTF-1 staining is useful in the differential diagnosis of pulmonary adenocarcinomas. TTF-1 may be a lineage marker for tumours arising from the peripheral airway or alveolar epithelium and has no prognostic relevance.

Adenocarcinoma↗
PubMed2004

Inter-observer variation between pathologists in diffuse parenchymal lung disease.

BACKGROUND: There have been few inter-observer studies of diffuse parenchymal lung disease (DPLD), but the recent ATS/ERS consensus classification provides a basis for such a study. METHODS: A method for categorising numerically the percentage likelihood of these differential diagnoses was developed, and the diagnostic confidence of pathologists using this classification and the reproducibility of their diagnoses were assessed. RESULTS: The overall kappa coefficient of agreement for the first choice diagnosis was 0.38 (n = 133 biopsies), increasing to 0.43 for patients (n = 83) with multiple biopsies. Weighted kappa coefficients of agreement, quantifying the level of probability of individual diagnoses, were moderate to good (mean 0.58, range 0.40-0.75). However, in 18% of biopsy specimens the diagnosis was given with low confidence. Over 50% of inter-observer variation related to the diagnosis of non-specific interstitial pneumonia and, in particular, its distinction from usual interstitial pneumonia. CONCLUSION: These results show that the ATS/ERS classification can be applied reproducibly by pathologists who evaluate DPLD routinely, and support the practice of taking multiple biopsy specimens.

Biopsy↗
PubMed2004

Continuous intravenous epoprostenol for chronic thromboembolic pulmonary hypertension.

Pathophysiological findings in chronic thromboembolic pulmonary hypertension (CTEPH) have suggested that a secondary small vessel arteriopathy may contribute to the haemodynamic impairment observed in these patients. It was hypothesised that this element of the elevated vascular resistance may be responsive to continuous intravenous epoprostenol therapy. Retrospectively, the clinical and haemodynamic responses to continuous intravenous epoprostenol were evaluated in nine CTEPH patients who subsequently underwent pulmonary thromboendarterectomy (PTE). Cardiopulmonary haemodynamics were determined prior to the initiation of epoprostenol, while on epoprostenol, prior to PTE, and after PTE. Six patients, treated for 2-26 months prior to PTE, experienced either clinical stability or improvement that was associated with a mean reduction in pulmonary vascular resistance (PVR) of 28% (median 33%, range 0-46%). Three patients, treated for 3-9 months, experienced clinical deterioration during epoprostenol administration, with a significant increase in PVR in two patients. Subsequent PTE resulted in a highly significant improvement of cardiac index, mean pulmonary artery pressure and total pulmonary resistance. To conclude, selected patients with chronic thromboembolic pulmonary hypertension may benefit clinically and haemodynamically from continuous intravenous epoprostenol treatment prior to pulmonary thromboendarterectomy. Factors predictive of a beneficial response, and whether this intervention influences either morbidity or mortality associated with pulmonary thromboendarterectomy, remain to be established.

Adult↗
PubMed2003

Metastatic pulmonary ameloblastoma. An unusual case.

We present a patient who had a large metastatic pulmonary ameloblastoma resected 25 years after removal of an apparently benign primary ameloblastoma of the jaw. It highlights three areas: problems with the histopathological diagnosis of pulmonary metastases using fine needle aspiration; a noted radiological improvement after a 5-year course of oral cyclophosphamide, in keeping with occasional patients who have responded to chemotherapy; and the technical difficulties of resection of a large pulmonary metastasis, particularly when it is adherent to the mediastinum.

Ameloblastoma↗
PubMed2002

Integration of aquatic fate and ecological responses to linear alkyl benzene sulfonate (LAS) in model stream ecosystems.

An integrated model stream ecosystem fate and effect study of dodecyl linear alkylbenzene sulfonate (C(12)LAS) was performed in the summer and fall of 1996. The study addressed responses of periphytic microbes, immature benthic fauna including abundance, drift, and emergence of adult insects in a 56-day exposure. Exposures ranged from 126 to 2978 microg/L and were continuously presented in a single-pass, flow-through test system. Microbial heterotrophs acclimated to C(12)LAS exposure quickly (14 days) and biodegraded C(12)LAS at all concentrations. Blue-green algae responded by increasing in abundance with increasing C(12)LAS concentration. Invertebrates responded by increased drift and reduced benthic abundances at concentrations exceeding 293 microg/L. Emergence at 927 microg/L also declined relative to the control. Adverse responses for mayflies and chironomids were indicated using univariate statistical techniques. Multivariate techniques indicated these taxa plus mollusks, aquatic worms, caddisflies, and stoneflies were impaired at some concentrations. Bioavailability of C(12)LAS was investigated in streams as a function of the total suspended solid load in the water column driven by local weather and watershed patterns. A continuous bioavailability model indicated exposure was reduced by an average of 8.5+/-8.9%. A model ecosystem no-observed-effect concentration (NOEC) was concluded to be 293 microg/L based on measured water column exposure and adjusted to 268 microg/L by the bioavailability model. A literature review of 13 available model ecosystem studies was conducted and NOEC conclusions were adjusted by a structure-activity relationship to a dodecyl chain length (sulfophenyl position and distribution being ignored due to lack of information in the reviewed studies). Lentic studies (n=7) were found to have higher NOECs than lotic studies (n=6) and were more variable. Mean NOECs+/-SD for all studies, lentic studies only, and lotic studies only were 3320+/-6040, 5720+/-7640, and 530+/-430 microg/L, respectively. Interpretation of results for anomalies from specific studies suggests the importance of experimental design, use of laboratory versus natural surface water, biological complexity of the test system, and physical test system design as relevant factors for consideration. The specific results of the new model ecosystem study presented in this article can be well defended on the basis of a robust experimental and physical design and because the system contained a diverse and sensitive aquatic community. A low or no uncertainty factor could be applied to the result.

Adsorption↗
PubMed2001

The impact of follow-up telephone calls to patients after hospitalization.

We studied whether pharmacists involved in discharge planning can improve patient satisfaction and outcomes by providing telephone follow-up after hospital discharge. We conducted a randomized trial at the General Medical Service of an academic teaching hospital. We enrolled General Medical Service patients who received pharmacy-facilitated discharge from the hospital to home. The intervention consisted of a follow-up phone call by a pharmacist 2 days after discharge. During the phone call, pharmacists asked patients about their medications, including whether they obtained and understood how to take them. Two weeks after discharge, we mailed all patients a questionnaire to assess satisfaction with hospitalization and reviewed hospital records. Of the 1,958 patients discharged from the General Medical Service from August 1, 1998 to March 31, 1999, 221 patients consented to participate. We randomized 110 to the intervention group (phone call) and 111 to the control group (no phone call). Patients returned 145 (66%) surveys. More patients in the phone call than the no phone call group were satisfied with discharge medication instructions (86% vs. 61%, P = 0.007). The phone call allowed pharmacists to identify and resolve medication-related problems for 15 patients (19%). Twelve patients (15%) contacted by telephone reported new medical problems requiring referral to their inpatient team. Fewer patients from the phone call group returned to the emergency department within 30 days (10% phone call vs. 24% no phone call, P = 0.005). A follow-up phone call by a pharmacist involved in the hospital care of patients was associated with increased patient satisfaction, resolution of medication-related problems, and fewer return visits to the emergency department.

Academic Medical Centers↗
PubMed2001

Parathyroid hormone-related protein and lung injury after pulmonary thromboendarterectomy.

Parathyroid hormone-related protein (PTHrP) is an autocrine growth and differentiation factor for alveolar type II epithelial cells. Type II cells secrete pulmonary surfactant and are pluripotent cells with a role in alveolar epithelial repair after lung injury. The goals of this study were to investigate whether the levels of PTHrP in bronchoalveolar lavage liquid (BAL) varied between patients who did and did not develop lung injury after pulmonary thromboendarterectomy (PTE). BAL was performed in 48 patients undergoing PTE for unresolved pulmonary emboli. Samples were obtained following induction of anesthesia, following separation from cardiopulmonary bypass, and 48 h postoperatively. PTHrP was measured by radioimmunoassay. Lung injury was diagnosed in 23 patients on the basis of hypoxemia (PaO(2)/FIO(2) < 300) and the presence of lung infiltrates in the absence of infection or atelectasis. Patients with lung injury had significantly lower preoperative BAL levels of PTHrP, 21 (21-30) pg/ml (median, interquartile gap), compared to patients without lung injury, 34 (21-41) pg/ml (P < 0.05). Preoperative BAL PTHrP levels < 32 pg/ml predicted lung injury with a positive predictive value of 60% and negative predictive value of 82%. The odds of developing lung injury for patients with preoperative PTHrP levels below this cutpoint were 6 times the odds for patients with higher levels.

Acute Disease↗
PubMed2001

Primary pulmonary osteosarcoma: case report and molecular analysis.

BACKGROUND: Primary pulmonary osteosarcoma is an extremely rare malignancy. To date, only 12 cases have been reported, with a high mortality rate. The authors report on a newly diagnosed patient and describe investigations that were performed using immunohistochemistry and comparative genomic hybridization (CGH). METHODS: The clinical course of a woman age 37 years is presented. Along with routine histologic examination, immunohistochemistry was used to demonstrate differentiation-associated proteins, oncoproteins, and other markers; CGH analysis for genomic alterations; and histochemistry to demonstrate alkaline phosphatase activity. RESULTS: Immunohistochemical analysis showed varying expression patterns using antibodies against a panel of tumor markers. Most notable was high overexpression of BCL-2 and cyclin D. CGH analysis showed that this neoplasm contained a much higher level of genetic aberrations compared with skeletal osteosarcoma. CONCLUSIONS: This tumor exhibited features common to skeletal osteosarcomas but also had some unique features. Genome analysis suggests that this tumor has several genetic aberrations in common with extraskeletal osteosarcoma. The novel regions of instability identified within the tumor genome may contribute toward the unique tumor phenotype and relative chemoresistance.

Adult↗
PubMed2001

Chronic thromboembolic pulmonary hypertension.

Remarkable advances have occurred over the past 2 decades in the diagnostic approach, surgical management, and postoperative care of patients afflicted with chronic thromboembolic pulmonary hypertension. Despite these advances, a great deal needs to be achieved if the morbidity and mortality of the disease process are to be reduced further. First, the preliminary insights that have been achieved into the natural history of the disease must be defined further. The level of pulmonary hypertension encountered in most patients with chronic thromboembolic pulmonary hypertension at the time of initial clinical recognition cannot be reached on an acute basis. Gradual hemodynamic progression, therefore, must occur over time. The basis for this progression, why it occurs in certain patients and not others, following an acute thromboembolic event and why it seems to occur over months in certain patients and over decades in others, remain entirely speculative. It is possible that the overall extent of central pulmonary vascular obstruction represents the primary pathophysiologic determinant of disease progression. Given the lack of correlation between the degree of central thromboembolic obstruction and hemodynamic impairment in certain patients, however, it is also possible that other factors, such as the circulating vasoconstrictors, the development of a hypertensive pulmonary arteriopathy, an individual genetic predisposition to pulmonary hypertension, or the compensatory adaptations of the right ventricle, contribute to the extent and rate of disease progression. By identifying and sequentially evaluating patients with persistent pulmonary vascular obstruction or pulmonary hypertension following an acute thromboembolic event, valuable insights into the natural history of thromboembolic pulmonary hypertension and other variants of pulmonary hypertension might be achieved. It is also important to recognize that the development of chronic thromboembolic pulmonary hypertension represents a failure in the long-term management or follow-up surveillance of those with documented acute thromboembolic disease. Recent insights into the recurrent nature of acute thromboembolic disease and its potential for only partial resolution in a number of afflicted individuals suggest that a repeat perfusion scan and, if abnormal, an echocardiogram be performed at the time of anticipated discontinuation of anticoagulation in patients with documented pulmonary embolic disease. Although the cost-effectiveness of this approach has been questioned in the past, recent data suggest that doing so would help identify that subset of patients with unresolved embolism, provide additional information regarding the optimal duration of anticoagulation, and provide a new baseline study for patients in whom anticoagulation is discontinued and who subsequently present with suspected embolic recurrence. Improved diagnostic techniques are also necessary if the mortal risk of thromboendarterectomy is to be reduced. Even in the setting of a broad experiential base, prognostic uncertainty exists in approximately 10% of patients before operative intervention. Because many of these patients will benefit from the procedure, and because many are ineligible for transplantation for reason of age or other restriction, it has been the authors' practice to offer surgery to these patients, although at an assumed higher risk. To not do so would be to deny a potentially lifesaving procedure to many who would benefit and who might be left without an effective therapeutic alternative. The ability to better define the group of patients who will not benefit from surgery, however, would spare those patients the morbid and mortal risks of the procedure and provide a basis for the investigation of other therapeutic alternatives such as pulmonary vasodilating agents. Finally, this patient population offers a unique opportunity to enhance understanding of the pathophysiologic mechanisms involved in acute lung injury. The population involved is uniform, the predisposing event is consistent, the time of onset is predictable, and, compared with other populations at risk for acute lung injury, the presence of confounding variables is negligible. It also provides a unique opportunity to evaluate pharmacologic interventions designed to prevent or diminish the occurrence of acute lung injury and postoperative management strategies designed to minimize its impact.

Angiography, Digital Subtraction↗
PubMed2001

The mechanism of action of multidrug-resistance-linked P-glycoprotein.

P-glycoprotein (Pgp), the ATP-binding cassette (ABC) transporter, confers multidrug resistance to cancer cells by extruding cytotoxic natural product amphipathic drugs using the energy of ATP hydrolysis. Our studies are directed toward understanding the mechanism of action of Pgp and recent work deals with the assessment of interaction between substrate and ATP sites and elucidation of the catalytic cycle of ATP hydrolysis. The kinetic analyses of ATP hydrolysis by reconstituted purified Pgp suggest that ADP release is the rate-limiting step in the catalytic cycle and the substrates exert their effect by modulating ADP release. In addition, we provide evidence for two distinct roles for ATP hydrolysis in a single turnover of Pgp, one in the transport of drug and the other in effecting conformational changes so as to reset the transporter for the next catalytic cycle. Detailed kinetic measurements determined that both nucleotide-binding domains behave symmetrically and during individual hydrolysis events the ATP sites are recruited in a random manner. Furthermore, only one nucleotide site hydrolyzes ATP at any given time, causing (in this site) a conformational change that drastically decreases (>30-fold) the affinity of the second site for ATP-binding. Thus, the blocking of ATP-binding to the second site while the first one is in catalytic conformation appears to be the basis for the alternate catalytic cycle of ATP hydrolysis by Pgp, and this may be applicable as well to other ABC transporters linked with the development of multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Pulmonary preinvasive neoplasia.

Advances in molecular biology have increased our knowledge of the biology of preneoplastic lesions in the human lung. The recently published WHO lung tumour classification defines three separate lesions that are regarded as preinvasive neoplasia. These are (1) squamous dysplasia and carcinoma in situ (SD/CIS), (2) atypical adenomatous hyperplasia (AAH), and (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIP-NECH). SD/CIS is graded in four stages (mild, moderate, severe, and CIS), based upon the distribution of atypical cells and mitotic figures. Most airways showing SD/CIS demonstrate a range of grades; many epithelia are hard to assess and the reproducibility of this complex system remains to be established. Detailed criteria are, however, welcome and provide an objective framework on which to compare various molecular changes. Alterations in gene expression and chromosome structure known to be associated with malignant transformation can be demonstrated in CIS, less so in dysplasias, but also in morphologically normal epithelium. The changes might be sequential, and their frequency and number increase with atypia. Less is known of the "risk of progression" of SD/CIS to invasive "central" bronchial carcinoma. It may take between one and 10 years for invasion to occur, yet the lesion(s) may be reversible if carcinogen exposure ceases. AAH may be an important precursor lesion for peripheral "parenchymal" adenocarcinoma of the lung: the "adenoma" in an adenoma-carcinoma sequence. There is good morphological evidence that AAH may progress from low to high grade to bronchioloalveolar carcinoma (BAC; a non-invasive lesion by definition). Invasion then develops within BAC and peripheral lung adenocarcinoma evolves. The molecular events associated with this progression are not well understood and studies are hampered by a lack of clear criteria to distinguish high grade AAH from BAC. Nonetheless, as with SD/CIS, the patterns of expression of tumour associated genes are consistent with neoplastic progression. We have little idea of the incidence of AAH in the normal or "smoking" populations. It is found more frequently in cancer bearing lungs, especially in those with adenocarcinoma, and is more common in women. No data are available on the risk of progression of AAH. DIPNECH is an exceptionally rare lesion associated with the development of multiple carcinoid tumours. Almost nothing is known of its biology. Knowledge of these lesions will be crucial in the design and understanding of lung cancer screening programmes, where it is likely that the morphological and, more importantly perhaps, the molecular characteristics of these lesions will provide useful targets for detection and possibly even treatment.

Adenocarcinoma↗