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Biomedical subjects

D Kendall

Publications and source records attributed to D Kendall.

At least 19 recordsLinked to original sources

Binge eating and other psychopathology in patients with type II diabetes mellitus.

OBJECTIVE: Type II diabetes mellitus (DM), a common disease with many potential complications, is strongly associated with obesity. Alterations in food consumption can dramatically alter glucose control in individuals with Type II DM. Binge eating disorder (BED) is also closely associated with obesity. The nature of the relationship, if any, between Type II DM and BED is unclear. METHODS: Forty-three individuals (23 females, 20 males) with Type II DM were assessed using the Structured Clinical Interview for DSM-IV (SCID-I), the Three-Factor Eating Questionnaire (TFEQ), and the Impact of Weight Scale. The most recent hemoglobin A1c level was recorded. Height and weight were also measured. RESULTS: Eleven subjects (25.6%) were diagnosed with BED. Individuals with BED had higher body mass index (BMI) scores, higher TFEQ Disinhibition and Hunger scores, and higher scores on all Impact of Weight subscales (except eating) compared with those without BED. Glycosylated hemoglobin levels did not differ between the two groups (8.1% vs. 8.4%; p = 0.553). DISCUSSION: Rates of BED in subjects with Type II DM were substantial. Other types of psychopathology were also common. Although glycosylated hemoglobin levels were similar in patients with and without BED, the presence of BED was associated with greater obesity. Assessment for BED is an important aspect of the management of patients with Type II DM.

Adolescent↗

A comprehensive set of coded chief complaints for the emergency department.

OBJECTIVE: To develop a generally applicable set of coded chief complaints for the computerized patient records of emergency departments (EDs). METHODS: At an urban teaching ED the chief complaints of more than 50,000 patients were analyzed retrospectively during a 29-month period (June 1995-October 1997). Applying continuous quality improvement methods, a multidisciplinary team examined the current process documenting the patient's chief complaint. During two prospective periods (November 1997-December 1998; January 1999-June 1999), more than 34,000 chief complaints were analyzed. To reduce free-text charting practices, a variety of interventions on individual and team level were applied. Quantitative analysis was performed with statistical process control charts, and a qualitative evaluation was performed with a questionnaire. RESULTS: The charting of chief complaint in free-text format decreased from 23% to 1%. The range among individual ED staff members narrowed from 45% to 9%. During the refinement of the set of coded chief complaints, six infrequently charted items were removed. Five new chief complaints identified by analysis of free-text entries during the second study period were added. The current set of chief complaints consists of 54 codable and the three original free-text items. The ED staff members perceived all the interventions beneficial. A poster displaying all available terms as a visual aid, however, had the largest impact on charting the patient's chief complaint in coded format. CONCLUSIONS: Applying continuous quality improvement methods, the authors created a clinically developed and applicable set of codable chief complaints that can be easily integrated into a computerized patient record of an ED.

Emergency Service, Hospital↗

Diabetes complication screening in general practice: a two pass audit with benchmarking.

AIM: To determine whether a two pass audit cycle of diabetes complication screening improves screening rates. METHODS: General practitioners in North Canterbury were invited to participate in a diabetes complications screening audit. Key complication screening tasks and maximum screening intervals were agreed. Patients with diabetes were identified in the primary care setting. General practitioners were given the option of participating in group feedback sessions between the first and second passes of the audit cycle. RESULTS: 106 general practitioners and 2234 patients participated in the first pass. Ninety-three of these 106 general practitioners and 2169 patients participated in the second pass. Screening rates either improved or remained unchanged and a small improvement was seen in the study population's risk factor profile (i.e. total cholesterol and glycated haemoglobin). The group feedback sessions facilitated discussion on interpretation of results from the benchmarking exercise, the optimal time interval between screening procedures and the development of general practice diabetes data sets. CONCLUSION: This two pass primary care audit of diabetes complications screening resulted in improved screening rates for diabetes complications and a small improvement in the study population's risk factor profile.

Aged↗

The use of the hypoglycaemic clamp in the assessment of pituitary function.

OBJECTIVE: The standard dynamic test used to diagnose hypopituitarism is the insulin tolerance test (ITT), in which insulin-induced secretion of ACTH, GH and cortisol is measured. However, because of differences in insulin sensitivity some patients fail achieve sufficient hypoglycaemia to assess pituitary function and colleagues experience severe hypoglycaemia and are at risk for cardiac dysrhythmia, seizure or coma. This risk may be particularly pertinent in the evaluation of older adults. We hypothesized that the hypoglycaemic clamp may be useful in assessing pituitary function in some patients. PATIENTS AND MEASUREMENTS: Twenty-one normal subjects (14 old [50-76 years] and 7 young [18-36 years]) and 7 hypopituitary subjects were studied. A clamp study was performed in which insulin infusion was given at 2 mU/kg/min and increased to 4 mU/kg/min if the target glucose concentration was not reached after 40 min. Dextrose was infused as needed to clamp the plasma glucose concentration at 2.2 mmol/l for 30 min. On a separate day, 7 young controls also underwent an ITT in which 0.15 U/kg insulin was administered as a bolus intravenous injection at time 0. In both studies, baseline values were taken at - 10, - 5 and 0 min. Samples were then collected every 5 min for plasma glucose and every 10 min for insulin, ACTH, cortisol and GH. RESULTS: ACTH and GH secretion during each test were similar in younger controls (P = NS) but cortisol secretion was lower during ITT (P < 0.01 vs. clamp). Hypopituitary subjects had significantly less ACTH, cortisol and GH secretion than controls of all ages (P < 0.001 for all). Peak GH secretion was significantly lower in the old controls than in young controls (22 +/- 12 vs. 48 +/- 26 mU/l, respectively; P < 0.01) but significantly higher than the hypopituitary subjects (2 +/- 2 mu/l; P < 0.001). CONCLUSION: These data demonstrate that the hypoglycaemic clamp can be used in the assessment of pituitary function and suggest that this technique may be particularly beneficial in the evaluation of GH deficiency in older adults who may not tolerate the ITT.

Adrenocorticotropic Hormone↗

Cerebrovascular disease as a general medicine discharge diagnosis: assessment of diagnostic agreement on case note review.

BACKGROUND: Accurate clerical coding of discharge diagnoses is important partly because results may be used to derive a recommended costing for hospital length of stays (LOS). Some authors think that discharge coding undertaken by clinicians will result in less diagnostic misclassification than clerical coding. This presupposes a high degree of between-observer diagnostic agreement between clinicians. AIMS: To compare discharge coding undertaken by two general physicians, for patients receiving a clerical discharge code of cerebrovascular disease. The recommended LOS was then calculated from each observer's discharge codes using the Physicians Diagnosis Related Group Working Guidebook. RESULTS: Eighty-two cases were coded as stroke by the clerical coder. Both medical coders agreed with this diagnosis in 68 (83%) of these cases. The corresponding figure for cases coded by the clerical coder as transient cerebral ischaemia was 47% (32/68) agreement between all three observers. Correcting for chance agreement between medical observers using the kappa statistic, a value of 0.64 was obtained for the combined stroke and transient cerebral ischaemia discharges, suggesting moderate diagnostic agreement. Using the clerical coder's results, the mean recommended LOS for all cases of cerebrovascular disease over the study period was calculated at 6.68 days. The corresponding values for the two medical coders were 6.68 days and 6.75 days. CONCLUSIONS: Diagnostic agreement between clinicians was moderate. Consideration of alternative diagnostic possibilities and the difficulty in determining the duration of neurological deficit were the main reasons for diagnostic disagreement. The mean recommended LOS was similar, however, when comparing results from all three observers.

Adult↗

A population-based study of bone mineral density in women with longstanding type 1 (insulin dependent) diabetes.

This study aimed to explore multiple determinants of BMD (bone mineral density) in 99 women with long-standing type 1 diabetes, recruited from a population based register of insulin users. BMD was measured using DEXA (dual energy X-ray absorptiometry) at the femoral neck and lumbar spine, age adjusted Z scores were calculated and results compared to those of healthy volunteers. The median age of diabetic subjects was 42 years and the median duration of diabetes was 27 years. BMD was positively associated with body mass index and height at both the lumbar spine and femoral neck. There was a positive association with oral contraceptive pill use and lumbar spine BMD, and peripheral vascular disease was negatively associated with femoral neck BMD. No correlation was seen with either age or duration of diabetes and absolute BMD values. Mean Z score at the femoral neck was -0.12 (95% confidence interval -0.37 to +0.12). At the lumbar spine, the corresponding value was -0.21 (-0.44 to +0.02). Pre- and post-menopausal values for the diabetic subjects and healthy volunteers were found to be similar. In summary, axial BMD values in subjects with long-standing diabetes were similar to those observed in healthy non diabetic populations.

Adult↗

Distribution of monoclonal antibodies in intestinal and urogenital secretions of mice bearing hybridoma 'backpack' tumours.

Mice bearing IgA hybridoma 'backpack' tumours have been used to demonstrate that secretion of a single monoclonal IgA can protect against mucosal infection, but the relevance of this model to normal IgA protection is not clear. The authors analysed the distribution of specific monoclonal and total antibodies in bile, local intestinal secretions, cervical-vaginal secretions, urine and serum of mice bearing anti-cholera toxin (CT) IgA and IgG backpack tumours, with and without bile duct ligation. Backpack tumours resulted in high levels of both anti-CT and total IgA or IgG in serum, and IgA (but not IgG) in bile. Secretions recovered by absorbent filter 'wicks' from mucosal surfaces throughout the intestines of backpack tumour mice contained significant concentrations of monoclonal anti-CT IgA, but total IgA levels were as in normal mice. Neither monoclonal nor total IgA levels on mucosal surfaces were altered by bile duct ligation. Furthermore, anti-CT monoclonal IgA levels in local intestinal secretions of backpack tumour mice were comparable to specific polyclonal IgA levels previously elicited by mucosal immunization with CT. Thus, IgA-mediated protection against enteric challenge in the backpack tumour model may be a valid predictor of protection provided by natural mucosal immunization in vivo. High monoclonal IgA levels in bile, urine and the female genital tract, however, may not reflect the situation in normal immunized mice.

Animals↗

Lack of association of secretory component with IgA in J chain-deficient mice.

J chain has been proposed to play a role in the mucosal transport of polymeric Igs (pIg) by the polymeric Ig receptor (pIgR). We have previously reported the generation of J chain-deficient mice. These mice exhibited elevated serum IgA and depleted biliary and fecal IgA levels compared with wild-type mice. We report here that, unlike the IgA levels in bile and feces, IgA levels in local mucosal and glandular secretions were not depressed in J chain-deficient mice. Breast milk, intestinal mucosal surface, and nasal wash IgA levels in the mutant mice were similar to wild-type mice while bronchoalveolar lavage IgA levels were higher in the J chain-deficient animals. Western blot analysis with an Ab to secretory component (SC), the portion of the pIgR that remains bound to pig in secretions, and immunoprecipitation with Abs directed against IgA showed that secreted IgA was associated with SC in wild-type but not J chain-deficient mice. The IgA in wild-type secretions was polymeric while the secretions of J chain-deficient mice contained IgA monomers and other nonpolymeric IgA forms. Thus, J chain is not essential for IgA transport by intestinal, mammary, or respiratory epithelia but is necessary for the stable association of pIgA with SC. Further, we suggest that J chain-deficient IgA is transported into secretions by a different mechanism than wild-type IgA.

Animals↗

Altered hepatic transport of immunoglobulin A in mice lacking the J chain.

We have created J chain knockout mice to define the physiologic role of the J chain in immunoglobulin synthesis and transport. The J chain is covalently associated with pentameric immunoglobulin (Ig) M and dimeric IgA and is also expressed in most IgG-secreting cells. J chain-deficient mice have normal serum IgM and IgG levels but markedly elevated serum IgA. Although polymeric IgA was present in the mutant mice, a larger proportion of their serum IgA was monomeric than was found in wild-type mouse serum. Bile and fecal IgA levels were decreased in J chain-deficient mice compared with wild-type mice, suggesting inefficient transport of J chain-deficient IgA by hepatic polymeric immunoglobulin receptors (pIgR). The pIgR-mediated transport of serum-derived IgA from wild-type and mutant mice was assessed in Madin-Darby canine kidney (MDCK) cells transfected with the pIgR. These studies revealed selective transport by pIgR-expressing MDCK cells of wild-type IgA but not J chain-deficient IgA. We conclude that although the J chain is not required for IgA dimerization, it does affect the efficiency of polymerization or have a role in maintaining IgA dimer stability. Furthermore, the J chain is essential for efficient hepatic pIgR transport of IgA.

Animals↗

The relationship between the adrenoceptor and nonadrenoceptor-mediated effects of imidazoline- and imidazole-containing compounds.

This article brings together work on imidazoline or imidazole-containing compounds concerned with the pharmacology of alpha-adrenoceptors, principally on smooth muscle, to illustrate how imidazolines have contributed to the subclassification of alpha-adrenoceptors and how, against this background, attempts have been made to use this knowledge to uncover "nonadrenoceptor"-mediated biological effects of previously uncharacterized compounds, notably imidazole-containing dipeptides and "clonidine displacing substance" (CDS). Recent data are included on (1) the pharmacology of UK-14304, (2) nonadrenoceptor actions of phentolamine, (3) the pharmacology of tissue extracts containing imidazole-containing dipeptides and CDS activity, and (4) ligand binding data at I1 and I2 sites.

Animals↗

Affinity, conservation, and surface exposure of hemopexin-binding proteins in Haemophilus influenzae.

Haemophilus influenzae can acquire heme from hemopexin for use as a source of both essential porphyrin and iron. In classical ligand-binding studies, we observed time-dependent, saturable, and displaceable binding of human 125I-labelled hemopexin to intact cells of H. influenzae type b (Hib) strain 760705 grown in an iron-restricted medium. From these experiments, which demonstrate that hemopexin associates with a single class of binding site, the affinities (Kds) and receptor numbers were calculated for heme-hemopexin (Kd, 205 nM; 3,200 receptors per cell) and apohemopexin (Kd, 392 nM; 4,400 receptors per cell). Thus, Hib expresses a specific hemopexin receptor which shows some preference for the heme-protein complex. Affinity chromatography on hemopexin-Sepharose 4B of detergent-solubilized membranes from Hib strain 760705 results in the copurification of three proteins with molecular masses of 57, 38, and 29 kDa. Trypsinization of whole cells of Hib 760705 abolishes hemopexin binding and correlates with the disappearance of the 57-kDa hemopexin-binding protein and appearance of a 52-kDa species which does not bind either hemopexin in ligand blot assays or a monoclonal antibody (MAbT11-30) raised against the 57-kDa protein. From immunoblotting assays and NH2-terminal amino acid sequence analysis, the 38-kDa protein isolated following hemopexin affinity chromatography was identified as the porin protein P2. These data, taken together with the receptor-binding studies which support a single class of hemopexin-binding site, suggest that P2 and the 29-kDa protein function as accessory proteins to the 57-kDa hemopexin-binding protein to facilitate the uptake of heme from receptor-bound hemopexin. To determine whether hemopexin binding and the 57-kDa protein are conserved in Haemophilus strains, whole-cell dot blots and immunoblots of the outer membrane proteins prepared from strains belonging to each of 21 different Hib outer membrane protein subtypes, six nontypeable strains, and five Haemophilus parainfluenzae strains were probed with either hemopexin or MAbT11-30. Only the H. parainfluenzae strains which lack the 57-kDa protein do not bind hemopexin. Since H. influenzae has also been shown to produce a soluble 100-kDa hemopexin-binding protein, cell-free culture supernatants were also examined for the presence of this protein. Apart from Hib 760705 and H. parainfluenzae, the 100-kDa hemopexin-binding protein was detected in all the other Haemophilus strains. The abilities of Hib 760705 to both bind and acquire heme from hemopexin without expressing a 100-kDa soluble hemopexin-binding protein show that in strain 760705, this 100-kDa protein is not essential for the utilization of heme from hemopexin.

Amino Acid Sequence↗

Induction of specific immunoglobulin A in the small intestine, colon-rectum, and vagina measured by a new method for collection of secretions from local mucosal surfaces.

In order study patterns of local antibody responses following mucosal immunization of mice via different routes, a method for collection of secretions directly from mucosal surfaces was developed. Mice were immunized on days 0, 10, 17, and 24 by administration of cholera toxin into the oral cavity, stomach, colon-rectum, or vagina. At sacrifice on day 32, absorbent wicks were placed in the oral cavity and, via an applicator tube, into the vagina and distal colon-rectum and along the entire small intestine after flushing of luminal contents. Protein was quantitatively extracted from wicks, and specific anti-cholera toxin immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay. Concentrations of specific IgA in secretions at various mucosal sites were dramatically influenced by the route of immunization. Oral immunization effectively induced IgA in saliva, and the intragastric route was optimal for induction of IgA in the small intestine. High levels of specific IgA appeared on the colonic-rectal mucosal surface only after rectal delivery of antigen. Oral, gastric, and rectal immunizations also produced distant responses in the vagina. Following vaginal immunization, however, neither local nor distant IgA responses were detected. These results suggest that vaccines intended for protection of colonic-rectal and vaginal mucosal surfaces might best be administered by the rectal route.

Animals↗

Staphylococci express a receptor for human transferrin: identification of a 42-kilodalton cell wall transferrin-binding protein.

Staphylococcus aureus and the coagulase-negative staphylococci are commonly responsible for peritonitis in renal patients undergoing continuous ambulatory peritoneal dialysis. To simulate growth conditions in vivo, staphylococci isolated from peritoneal infections were cultured in used human peritoneal dialysate (HPD). Immunoblotting experiments using cell wall preparations from these staphylococci revealed the presence of the host iron-binding glycoprotein transferrin bound to S. aureus, S. epidermidis, S. capitis, S. haemolyticus, and S. hominis but not to S. warneri or S. saprophyticus. Similar results were obtained by incubating broth-grown staphylococci with human transferrin, although, in contrast to S. aureus, the coagulase-negative staphylococci bound more transferrin after growth in iron-restricted broth. To determine whether the staphylococci express a saturable specific receptor for human transferrin, the interaction of human 125I-transferrin with the staphylococci was examined. Both S. aureus and S. epidermidis bound the radiolabelled iron-saturated ligand in a time- and concentration-dependent manner. From competition binding assays, the affinity (Kd) and number of receptors were estimated for S. epidermidis (Kd, 0.27 microM; 4,200 receptors per cell) and S. aureus (Kd, 0.28 microM; 4,200 receptors per cell). S. epidermidis but not S. aureus receptor activity was partially iron regulated. Human apotransferrin and iron-saturated transferrin and rabbit and rat transferrins competed equally well for the staphylococcal receptor. Bovine and porcine transferrins and ovotransferrin as well as human and bovine lactoferrins were much less effective at competing with human transferrin. Treatment of whole staphylococci with protease abolished transferrin binding, indicating the involvement of cell surface protein. Western blots (immunoblots) of cell wall preparations probed with human transferrin revealed the presence of a 42-kDa transferrin-binding protein common to both S. aureus and S. epidermidis. On Western strip blots, the binding of human transferrin to this protein was blocked by labelled human transferrin but not by albumin, immunoglobulin G, or bovine transferrin or ovotransferrin. To assess the conservation of the 42-kDa transferrin-binding protein, cell wall proteins of S. epidermidis, S. haemolyticus, S. capitis, S. hominis, S. warneri, and S. saprophyticus were Western blotted and probed with human transferrin. Only S. warneri and S. saprophyticus lacked the 42-kDa wall protein, consistent with their inability to bind transferrin. These data show that the staphylococci express a specific receptor for human transferrin based at least in part on a common 42-kDa cell wall protein.

Animals↗

Integrin expression and localization in normal MDCK cells and transformed MDCK cells lacking apical polarity.

Epithelial cells polarize in response to contacts with the extracellular matrix and with neighboring cells. Interactions of cells with the extracellular matrix are mediated mainly by the integrin family of receptors. To begin to understand the role of integrins in polarization, we have investigated the expression and localization of three integrin families in the polarized Madin-Darby canine kidney (MDCK) epithelial cell line and in transformed MDCK cells lacking apical polarity. We find that MDCK cells express several beta 1 integrins, including alpha 2 beta 1, alpha 3 beta 1, and an unidentified integrin designated alpha x beta 1. The beta 1 integrins are the major receptors for collagens I and IV and laminin in MDCK cells, since a blocking anti-beta 1 antibody almost totally abolishes adhesion to these proteins. They also express a vitronectin receptor tentatively identified as alpha v beta 3, and the epithelial-specific integrin alpha 6 beta 4. The latter is not a laminin receptor in MDCK cells because a function blocking anti-alpha 6 antibody has no effect on cell adhesion to laminin. All three integrin families are expressed exclusively on both the basal and lateral surfaces, as determined by immunofluorescence microscopy and surface biotinylation. Transformed MDCK cells express beta 1 integrins as well as alpha v beta 3 and alpha 6 beta 4, but show alterations in the beta 1 family. Expression of alpha x is lacking, and the relative amount of the beta 1 subunit is diminished, resulting in the accumulation of Endo-H-sensitive alpha 3. In addition, surface biotinylation and immunofluorescence indicate that significant amounts of both alpha 2 beta 1 and alpha 3 beta 1 appear on not only the basolateral but also the apical plasma membrane. These results indicate that integrins are the major receptors for the extracellular matrix in MDCK cells, and that they may affect epithelial cell polarization by mediating not only cell-substratum but also cell-cell contacts.

Animals↗

Multilayering and loss of apical polarity in MDCK cells transformed with viral K-ras.

The effects of viral Kirsten ras oncogene expression on the polarized phenotype of MDCK cells were investigated. Stable transformed MDCK cell lines expressing the v-K-ras oncogene were generated via infection with a helper-independent retroviral vector construct. When grown on plastic substrata, transformed cells formed continuous monolayers with epithelial-like morphology. However, on permeable filter supports where normal cells form highly polarized monolayers, transformed MDCK cells detached from the substratum and developed multilayers. Morphological analysis of the multilayers revealed that oncogene expression perturbed the polarized organization of MDCK cells such that the transformed cells lacked an apical--basal axis around which the cytoplasm is normally organized. Evidence for selective disruption of apical membrane polarity was provided by immunolocalization of membrane proteins; a normally apical 114-kD protein was randomly distributed on the cell surface in the transformed cell line, whereas normally basolateral proteins remained exclusively localized to areas of cell contact and did not appear on the free cell surface. The discrete distribution of the tight junction-associated ZO-1 protein as well as transepithelial resistance and flux measurements suggested that tight junctions were also assembled. These findings indicate that v-K-ras transformation alters cell-substratum and cell-cell interactions in MDCK cells. Furthermore, v-K-ras expression perturbs apical polarization but does not interfere with the development of a basolateral domain, suggesting that apical and basolateral polarity in epithelial cells may be regulated independently.

Animals↗