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Biomedical subjects

M L Kennedy

Publications and source records attributed to M L Kennedy.

36 records · Page 2Linked to original sources

Basal pressure patterns and reflexive motor responses in the human ileocolonic junction.

This study aimed to determine whether a sustained high-pressure zone exists at the human ileocolonic junction (ICJ) and whether the motor responses of ICJ are consistent with sphincteric function. In 10 subjects with temporary ileostomies, a high-pressure zone was identified using a manometric pull-through with a mean pressure of 9. 7 +/- 3.2 mmHg and length of 4.8 +/- 1.2 cm. Prolonged recordings using a sleeve sensor confirmed sustained tone in the ICJ and superimposed phasic pressure waves (4-8 counts/min) occupying 35% of fasted state. A meal increased ICJ tone (P = 0.0001) and the proportion of time occupied by phasic activity to 50% (P = 0.013). Terminal ileal propagating pressure wave sequences inhibited ICJ phasic activity, and sequences not extending to the cecum reduced ICJ tone (9.0 +/- 7.2 to 5.6 +/- 6.3 mmHg; P = 0.04). Cecal distension increased ICJ tone (8.9 +/- 4.4 mmHg to 11.7 +/- 4.9 mmHg; P = 0.005). The ICJ response to ileal distension was variable and depended on resting tone at the time of distension. We conclude that the human ICJ has sustained tone with superimposed phasic activity. Tone is augmented by cecal distension or a meal and is inhibited by ileal propagating pressure waves. Response to ileal distension is variable but suggests control by descending excitatory and inhibitory pathways.

Adult↗

Relationship between terminal ileal pressure waves and propagating proximal colonic pressure waves.

The relationship between propagating distal ileal and proximal colonic motor patterns has not been systematically examined in humans. Our aim was to define the relationships, if any, between prolonged propagating contractions or discrete clustered contractions and cecal propagating sequences using multiple manometric recording sites spanning the distal ileum and unprepared colon. In 14 healthy volunteers, a 17-lumen-perfused silicon catheter was positioned pernasally such that at least three recording sites lay in the ileum and the remainder in the colon. Intersidehole distance was 7.5 cm. In 271 h of recording, 30% of the terminal ileal propagating events was temporally associated with cecal propagating sequences. Significantly more prolonged propagating contractions (11 of 24, 46%; P = 0.02) were associated with cecal propagating sequences than were associated with ileal discrete clustered contractions (4 of 26, 15%). This trend was more pronounced at night. Of 159 cecal propagating sequences, 15 (9%) were preceded by an ileal propagating event. The remaining 91% was preceded by increased nonpropagating activity commencing 2 min before the cecal propagating sequence (P = 0.0002). We conclude that distal ileal propagating motor patterns are one stimulus for cecal propagating sequences, with the association being stronger for prolonged propagating contractions than for discrete clustered contractions.

Adult↗

A comparison of nine WAIS-R short forms in individuals with mild to severe traumatic brain injury.

Scores from nine WAIS-R short forms were calculated for a sample of 75 adults with mild to severe traumatic brain injury (TBI). Although all nine of the short forms were significantly correlated with the WAIS-R Full Scale IQ, three of the short forms (Vocabulary-Block Design; Vocabulary-Block Design-Arithmetic-Similarities; Vocabulary-Arithmetic-Picture Arrangement-Block Design) significantly overestimated the WAIS-R IQ and thus may be inappropriate to use with this population. The remaining six short forms did not differ significantly from the WAIS-R Full Scale IQ. Among these six, Ward s seven-subtest short form appeared to exhibit the least variability in predicting the WAIS-R Full Scale IQ. Information is presented and discussed regarding the absolute difference scores between short form IQ estimates and the WAIS-R as well as the proportion of short forms which significantly under- and overestimate the Full Scale IQ.

Adult↗

Effect of iron on transferrin receptor expression by human placental syncytiotrophoblast cells.

Transferrin receptor expression has been examined in primary cultures of morphologically differentiated placental syncytiotrophoblast cells. More than 90% of the cells were multinucleated. Incubation of syncytiotrophoblast for 4 days in the presence of iron salts had no effect on receptor expression assessed by measuring the binding of 125I-labelled transferrin. However, incubation of cells in the presence of human diferric transferrin (10-100 microM) led to a 50% decrease in surface and intracellular receptor expression. This down-regulation was not accompanied by a significant decrease in receptor synthesis. In contrast to syncytiotrophoblast, expression of intracellular transferrin receptors in non-differentiated cytotrophoblast cells decreased when cells were cultured with iron salts; this was accompanied by decreased receptor synthesis. Addition of diferric transferrin to cytotrophoblast cells led to a 50% reduction in surface and intracellular receptor expression, similar to that seen in the syncytiotrophoblast. This reduction was accompanied by a decrease in receptor synthesis. In contrast to that of most cell types, the expression and distribution of trophoblast transferrin receptors were not altered by insulin, epidermal growth factor or hydrocortisone. These characteristics of syncytiotrophoblast transferrin receptor expression may assist in ensuring a supply of iron to the fetus regardless of the maternal iron status.

Cells, Cultured↗

Robertsonian chromosomal rearrangements in the short-tailed shrew, Blarina carolinensis, in western Tennessee.

We report significant heterozygosity for numerous Robertsonian translocations in the southern short-tailed shrew (Blarina carolinensis) in western Tennessee. Eight Robertsonian rearrangements were documented using G-banding techniques that explain the variability in diploid numbers from 46 throughout most of the range of the species to 34-40 in western Tennessee. These fusions resulted in the loss of telomere sequences and were not associated with nucleolar organizer regions. When heterozygocity is considered, the lowest diploid number possibly present would be 30. Four localities with distances of over 180 km apart were sampled, and 80-90% of the collected animals were heterozygous for at least one rearrangement. No putative parental type was found in western Tennessee. Heterozygosity for the same rearrangements was found in these different localities, and no monobrachial fusions were noted. Thus, this is a very wide hybrid zone with rare or absent parental types in the areas sampled or is an evolutionary stage preceding establishment of Robertsonian races. Selective forces, if any, were minimal, as evidenced by the wide area of polymorphism, significant heterozygosity, and the fact that the Robertsonian translocations were in Hardy-Weinberg equilibrium. The origin of such extensive polymorphism in western Tennessee is discussed, especially in light of putative effects of the New Madrid seismic activity. Similarities and differences are noted between the Blarina model and the well-documented variation in the European common shrew (Sorex araneus) and Mus musculus groups.

Animals↗

Chromosomal variation in the southern short-tailed shrew (Blarina carolinensis).

Chromosomal polymorphism was assessed in the southern short-tailed shrew (Blarina carolinensis) using standard metaphase chromosome and G-banding techniques. Twenty-one animals (11 males, 10 females) from the Meeman Biological Station in Shelby Co., Tennessee, were examined for diploid number. Results showed diploid numbers of 35, 36, 37, 38, 39, 40 and 41 and fundamental numbers of 41, 42, 43, 44 and 45. No diploid numbers or fundamental numbers were unique to a specific collecting locality. The first G-banded karyotypes are reported for the species. These results indicate that Robertsonian polymorphisms, inversions, and possibly other events are responsible for chromosomal variation in B. carolinensis.

Animals↗

Rectal mucosal electrosensitivity - what is being tested?

The results of rectal mucosal electrosensitivity (RME) testing have been used to support theories regarding the aetiology of both idiopathic constipation and bowel dysfunction following rectopexy. The aim of this study was to assess the validity of tests of RME. Sixty-eight patients, comprising three groups (group 1: 50 patients undergoing assessment in the Anorectal Physiology Unit, group 2: 10 patients with coloanal or ileoanal anastomosis, group 3: 8 patients with a stoma) underwent mucosal electrosensitivity testing, with the threshold stimulus required to elicit sensation being recorded. In addition the RME was measured in groups 1 and 2 when placing the electrode, mounted on a catheter with a central wire, against the anterior, posterior, right and left rectal or neorectal walls. To asses the influence on this test of loss of mucosal contact due to faeces, a further 8 cases with a normal rectum had RME performed with and without a layer of water soaked gauze around the electrode to stimulate faeces and prevent the electrode from making contact with the rectal mucosa. There was marked variance in the sensitivity of the different regions of rectal wall tested (P < 0.001). In group 1 patients the mean sensitivities were: central 36.6 mA, anterior 27.4 mA, posterior 37.9 mA, right 22.3 mA and left 25.6 mA. This circumferential variation suggests that the pelvic floor rather than rectal mucosa was being stimulated. All patients in group 2 had recordable sensitivities, and the mean sensitivity threshold was significantly higher than group 1 patients in the central (P = 0.03), right (P = 0.03) and left (P = 0.007) positions. In group 3 the sensitivity was greater within the stoma at the level of the abdominal wall muscle than intra-abdominally or subcutaneously, again suggesting an extra-colonic origin of the sensation. The sensitivity threshold was significantly greater with the electrode wrapped in gauze (P < 0.01), and loss of mucosal contact was not detected by the EMG machine. Therefore RME testing would seem not to measure mucosal sensitivity, and is probably influenced by the presence of faeces.

Electric Stimulation↗

Results of colectomy for severe slow transit constipation.

PURPOSE: This study assesses the outcome of a standardized operation performed by two surgeons for severe idiopathic slow transit constipation that was resistant to laxative treatment. METHODS: Fifty-nine consecutive patients, 4 men and 55 women, with a mean age of 42.3 years, underwent colectomy with ileorectal anastomosis. Slow colonic transit was demonstrated in each case. Fifty-two patients were available for follow-up, with median time to follow-up being 42 (range, 3-81) months. RESULTS: Median bowel frequency was 4 per 24 hours. Sixty-nine percent had four or less bowel movements daily. Ten percent used antidiarrheal medication regularly. One patient had a stoma for recurrent severe constipation. Mean continence score was 1.8 (on a scale of 0-20); six patients were incontinent, and four of these six had normal preoperative anal manometry. Fourteen patients (27 percent) had difficulty with rectal evacuation. Preoperative defecating proctography was a poor predictor of postoperative evacuation difficulties. Twenty-seven patients (52 percent) had persisting abdominal pain, but there was a significant improvement in the degree of pain (P <0.00001). Forty-seven patients (90 percent) were satisfied with the outcome of the operation (and would elect to have it done again). Dissatisfied patients had recurrent constipation or diarrhea and incontinence. CONCLUSION: Colectomy with ileorectal anastomosis produces a satisfactory functional outcome in the majority of patients undergoing surgery for severe constipation with proven slow colonic transit.

Adolescent↗

Stimulated gracilis neosphincter: a new procedure for anal incontinence.

BACKGROUND: The gracilis muscle has been used previously to construct an anal neosphincter, but this was not successful since a short-lived muscle contraction was insufficient to restore continence. Recently, a procedure was described in which conversion to a fatigue-resistant muscle was achieved by chronic low frequency electrical stimulation, and the resultant ability to sustain a constant contraction was associated with improved continence. Our initial results with this procedure, using a standardized operation and treatment protocol in 12 consecutive patients, is reported. METHODS: Seven women (mean age 50 years, range 22-71 years) had faecal incontinence, and five patients (F:M, 3:2; aged 53-72 years) underwent reconstruction after abdominoperineal excision of the rectum for cancer. A detailed questionnaire including continence score was completed pre-operatively. Eight patients have been assessed after ileostomy closure at a mean time of 10 months. RESULTS: Slow-twitch muscle conversion was achieved in each case and all patients have a functional neosphincter. Mean continence score was 6.8 (range 4-12), and seven patients were continent. There was significant improvement in continence in the non-cancer group (p = 0.03). Mean pre-operative resting anal pressure, functional neosphincter pressure (NPfunc), and maximal neosphincter pressure (NP(max)) were 36, 102 and 207 cmH2O, respectively. There was a significant improvement in pressure comparing NPfunc (P = 0.03) and NP(max) (P = 0.03) with pre-operative pressure. Complications included deep vein thrombosis, pulmonary embolism, saphenous nerve injury, leg wound haematoma, and late pacemaker infection. CONCLUSION: The stimulated gracilis neosphincter achieves satisfactory continence in a majority of patients.

Adult↗

Iron metabolism in genetically obese (ob/ob) mice.

Several reports in the clinical literature suggest that obese children may be at risk for developing iron deficiency. Here the absorption, retention, tissue distribution and tissue levels of iron were compared in lean (+/?) and obese (ob/ob) C57BL/6J mice to examine the impact of obesity on the iron status of this animal model. Obese mice absorbed and retained approximately twice as much 59Fe as lean mice after receiving a solution containing 1 mumol iron per os. This difference was independent of age, severity of obesity and mass of the gastrointestinal tract. Obese mice fed ad libitum had higher levels of 59Fe in blood and fat pads, but lower amounts of 59Fe in the skeletal-muscular system, than lean mice 6 d after subcutaneous injection of 1 mumol of the metal. At least 30% of carcass 59Fe was present in the liver of obese and lean mice 6 d after injection. Despite significantly lower concentrations of iron in liver and bone, blood hemoglobin and hematocrit were significantly higher in obese mice fed ad libitum than in lean mice at 10 wk of age. Plasma iron and transferrin were not affected by chronic obesity. Although several characteristics of iron metabolism differed in obese and lean mice, the results indicate that ob/ob mice were not iron deficient when fed a diet containing an adequate level of this micronutrient. The increased absorption of iron by obese mice probably represents an adaptive response that is required to supply additional micronutrient for the expanded blood volume in these animals.

Absorption↗

Hematology, intestinal parasites, and selected disease antibodies from a population of bobcats (Felis rufus) in central Arkansas.

Eight bobcats with adjoining or overlapping home ranges were examined. Hematological values were within previously reported ranges. Six bobcats demonstrated antibody titers to Toxoplasma gondii. Isospora spp., Taenia taeniaeformis, Spirometra mansoides, Physoloptera rara, Toxocara cati, Strongyloides spp., Trichurus spp., Capillaria spp., and Ancyclostoma spp. were found also in the animals examined. The mean number of parasite species per host was 4.1. All bobcats tested negative for serum antibodies to Rocky Mountain spotted fever (Rickettsia rickettsii). Two bobcats had titers less than or equal to 1:20 for tularemia (Francisiella tularensis), and two were positive for leptospirosis (Leptospira spp.).

Animals↗

Zinc metabolism in genetically obese (ob/ob) mice.

Recent reports indicate that the concentrations and total amounts of several essential trace metals in various tissues of genetically obese rodents differ markedly from those in lean controls. In the present studies the absorption, retention and tissue distribution of zinc and constitutive levels of zinc-metallothionein (Zn-MT) in selected tissues were compared in obese (ob/ob) and lean (+/?) C57BL/6J mice. When 5-, 10- and 22-wk-old mice were administered 1.2 mumol 65Zn by stomach tube the apparent absorption of 65Zn by obese mice was 1.5, 2.2 and 3.9 times higher, respectively, than that in age-matched lean mice. Retention of orally administered 65Zn after 96 h was also substantially higher in obese mice than in lean mice. To assess the possible influences of hyperphagia and intestinal hypertrophy on the enhanced apparent absorption of 65Zn by obese mice food intake by an additional group of obese mice was restricted to that of age-matched lean controls. When actual absorption of zinc was determined according to the method of Heth and Hoekstra, groups of ad libitum--fed obese, pair-fed obese and lean mice absorbed 38, 32 and 18% of administered 65Zn, respectively. In contrast, the rate of 65Zn excretion 2-6 d after oral or subcutaneous administration of the metal was similar for obese and lean mice. Unrestricted and pair-fed obese mice had significantly lower percentages of carcass 65Zn present in skin, muscle plus bone, spleen and testes and higher percentages present in liver, small intestine and adipose tissue than lean mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Helminth parasites of the coyote (Canis latrans) in Tennessee.

From 1980 to 1984, 267 coyotes (Canis latrans) from Tennessee were examined for helminth parasites. Hearts were examined for the presence of Dirofilaria immitis, diaphragms for Trichinella spiralis, and digestive tracts for other helminths. Six species were found including 5 nematodes (D. immitis, Physaloptera rara, Trichuris vulpis, Ancylostoma caninum, and Toxascaris leonina) and 1 cestode (Taenia pisiformis). Univariate and multivariate statistical techniques were used to assess parasite prevalence and intensity. For prevalence data, a matrix of correlation among characters was computed, and the first 3 principal components were extracted from the original distance matrix. These accounted for 93.7% of the variation in the character set. Three-dimensional projections of localities showed spatial variability on each component. Significant relationships were found between principal component I and longitude, component II and latitude and mean January temperature, and component III and mean July precipitation and mean January actual evapotranspiration. For intensity data, no spatial variability was determined.

Animals↗

Influence of genetic obesity on tissue concentrations of zinc, copper, manganese and iron in mice.

The concentrations (micrograms/gram dry wt) of four essential trace metals in various tissues from C57BL/6J lean (+/?) and obese (ob/ob) mice were determined. Lower concentrations of zinc were found in liver, femur, small intestine and muscle from obese mice than in those from lean mice at 22 wk of age. The concentrations of copper in liver, femur, small intestine, muscle and testes, iron in liver, femur, muscle and plasma, and manganese in liver, femur and small intestine from adult obese mice were also significantly below the concentrations present in tissues from age-matched lean mice. Hepatic concentrations of zinc, copper and manganese in obese mice were also lower than those in lean mice when the different amounts of neutral lipid in obese and lean liver were considered. In contrast with the trend towards lower concentrations of trace metals in tissues from adult obese mice, plasma zinc and copper levels and ceruloplasmin activity were higher in adult obese mice than in lean controls. The effect of genetic obesity on tissue trace metals concentrations was similar in male and female mice. Several tissues from young (5-6 wk of age) obese mice also had lower concentrations of the trace metals than age-matched lean mice, although the differences were not as great as in adults. These data demonstrate that chronic obesity in the genetically obese (ob/ob) mouse is associated with lower concentrations, but not necessarily lower total quantities, of several inorganic micronutrients in tissues. The possibility tht chronic obesity alters the nutritional requirements for these trace metals is discussed.

Animals↗

Geographic variation in helminth parasites from the digestive tract of Tennessee raccoons, Procyon lotor.

The stomachs and intestinal tracts of 253 raccoons, Procyon lotor, were examined for helminth parasites. Sixteen species of helminths were found including eight trematodes, two cestodes, five nematodes, and one acanthocephalan. Fourteen of these helminths are new geographic records for the state of Tennessee. Multivariate statistical techniques were used to analyze two-state and multistate character sets. Matrices of correlation among characters were computed and the first three principal components were extracted, accounting for 79.7% and 66.5% of the variation in the respective character sets. Three-dimensional projections of Tennessee's eight geographic localities onto two-state and multistate principal components demonstrated that raccoons in western localities were parasitized most heavily by Atriotaenia procyonis. Mesocestoides variabilis, Gnathostoma procyonis, and Pharyngostomoides procyonis. Parallelorchis diglossus, Euparyphium beaveri. Eurytrema procyonis, Euryhelmis squamala, Molineus barbatus, and Macracanthorhynchus ingens were most common to P. lotor from eastern areas.

Acanthocephala↗

Winter ecology of ectoparasites collected from hibernating Myotis velifer (Allen) in southwestern Oklahoma (Chiroptera: Vespertilionidae.

During the winter of 1971-72, Trichobius major, T, corynorhini, Mydopsylla collinsi, Macronyssus crosbyi, M. unidens, Paraspinturnix globosus, Spinturnix carloshoffmani, Ornithodoros sp., Albeckia senase, Nycteriglyphus sp. A, and Olabidocarpus sp. were quantitatively collected from hibernating Myotis velifer, Plecotus townsendii, and Pipistrellus subflavus. Significantly greater numbers of S. carloshoffmani and M. crosbyi were found on female M. velifer, while greater numbers of P. globosus were found on males. With the exception of T. major and P. globosus which were radomly distributed, all ectoparasites exhibited a contagious distribution on M. velifer. Only T. major and S. carloshoffmani had a 1:1 sex ratio, the remaining species had significantly fewer males. M. unidens, M. crosbyi, and N. species A were positively associated, while M. collinsi was negatively associated with both Macronyssus; the remaining species were not signficantly associated. With the exception of T. major and P. globosus, ectoparasite densities decreased during the winter.

Animals↗

Expression of transferrin receptors during differentiation of human placental trophoblast cells in vitro.

In most cell types, transferrin receptor expression is correlated with the proliferation rate, being increased by growth stimulation, or decreased by induction of terminal differentiation. In the human placenta the multinucleated syncytiotrophoblast, in direct contact with maternal blood, is derived by differentiation from mononucleated cytotrophoblast. In this study we examined changes in transferrin receptor expression during in vitro differentiation of trophoblast. Cells cultured in Ham's/Waymouth's medium (HWM) remained primarily mononuclear throughout the study, whereas incubation in keratinocyte growth medium (KGM) led to formation of multinucleate masses within 2-3 days of culture. Cell surface binding of 125I-labelled transferrin increased fivefold between days 1-5 of culture in both media and surface receptors were saturated at 7-14 micrograms/ml (90-200 fM). At saturation, the amount of transferrin bound to syncytiotrophoblast was 37 per cent lower than in cytotrophoblast. Scatchard analysis revealed a reduction in the number of surface transferrin receptors in syncytiotrophoblast compared to cytotrophoblast. A corresponding 29 per cent reduction in the binding of transferrin to intracellular sites was observed in syncytiotrophoblast. Distribution of receptors between surface and intracellular sites was therefore similar in both cytotrophoblast and syncytiotrophoblast. The affinity of transferrin for transferrin receptors was 3.7-fold higher in syncytiotrophoblast when compared to cytotrophoblast. Observed differences between the two cell types were not due to the presence of growth factors or higher iron levels in KGM. Expression of a high number of surface transferrin receptors in syncytiotrophoblast (1.5 x 10(12)/mg protein), along with a high affinity of these receptors for iron-saturated transferrin, could help explain the efficient transport of large amounts of iron from mother to fetus.

Binding Sites↗

Interaction of 125I-labelled ceruloplasmin with human trophoblast cells in vitro.

In vitro binding, internalization and release of the plasma protein ceruloplasmin was investigated using primary cultures of human placental trophoblast cells. Binding of 125I-labelled ceruloplasmin at 4 degrees C reached equilibrium by 5-6 h; binding was linear throughout all concentrations tested (1 nM-3.3 microM). Addition of greater than 5-10 microM unlabelled ceruloplasmin or a variety of other proteins (albumin, transferrin, IgG) were equally effective in displacing bound ceruloplasmin in a concentration-dependent manner. When cells were incubated at 37 degrees C, the majority of surface-bound 125I-labelled ceruloplasmin was released directly to the extracellular medium. Trypsin-resistant radioactivity increased to 18 per cent of initially bound ceruloplasmin within 1 min, declining to 5 per cent by 2 h. The acquisition of trypsin-resistant radioactivity was unaffected by the addition of a variety of metabolic inhibitors and no evidence of intracellular degradation of ceruloplasmin was found. In summary, our results suggest that the majority of ceruloplasmin binding to trophoblast cells is nonspecific, of low affinity, and easily dissociable at 4 degrees C. Only a small amount of ceruloplasmin appeared to be internalized, by an as yet unknown mechanism.

Ammonium Chloride↗