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Biomedical subjects

K Skinner

Publications and source records attributed to K Skinner.

At least 37 records · Page 2Linked to original sources

Comparing generic and disease-specific measures of physical and role functioning: results from the Veterans Health Study.

OBJECTIVES: This study compared the performance of generic measures of Medical Outcome Study Short Form 36-Item Health Survey physical functioning and role limitations with disease-specific measures of physical functioning and role limitations using specific disease attributions for chronic lung disease, chronic low back pain, and osteoarthritis of the knee. METHODS: Data were analyzed from the Veterans Health Study among patients receiving Veteran's Administration ambulatory care. Patients identified as having one of the three study conditions were included in the study (n = 932). RESULTS: The study revealed that the generic physical functioning and role limitations scales had higher correlations with other generic SF-36 scales, whereas disease-specific attribution measures had larger R2 values in explaining variability in symptom-based disease severity and larger t statistic values in discriminating the impacts of patients taking medications and having surgery. CONCLUSIONS: The generic measures of physical functioning and role limitations were more applicable in assessing a broad array of health-related quality-of-life issues, whereas disease-specific measures of physical functioning and role limitations were more useful in evaluating clinical management and limitations associated with specific disease conditions. The results of the study suggest that the use of disease-specific attribution assessments was more cost-efficient than the development of new disease-specific instruments. Disease-specific attribution could be used to complement generic measures in assessing patient outcomes.

Activities of Daily Living↗

Cholecystokinin and enkephalin in brain stem pain modulating circuits.

Neurons in rostral ventromedial medulla and the periaqueductal gray modulate dorsal horn nociceptive transmission. Endogenous peptides implicated in this modulation include enkephalin (ENK), which is antinociceptive, and cholecystokinin (CCK), which has anti-opioid effects. In this study double-label fluorescence immunocytochemistry demonstrated somata and terminals with ENK- or CCK-like immunoreactivity in these regions. Although the distribution of CCK- and ENK-immunoreactive terminal fields overlapped significantly, co-localization was rare. Furthermore, CCK- and ENK-immunoreactive somata had different morphologies and distinct distributions. The overlap of CCK- and ENK- immunoreactive terminals arbors provides a morphological substrate for an antagonistic interaction of CCK and ENK within brainstem pain modulating circuits, as has been demonstrated in the spinal cord.

Animals↗

GABA-immunoreactive boutons contact identified OFF and ON cells in the nucleus raphe magnus.

The pontomedullary raphe magnus (RM) contains two physiologically defined types of neurons that participate in the opioid-induced modulation of dorsal horn nociceptive messages: OFF cells, which decrease, and ON cells, which increase their discharge rates when reflex behavior is evoked by noxious pinch or heat. Because both types of neuron have inhibitory inputs and because there is evidence that gamma-aminobutyric acid (GABA) inhibitory mechanisms within RM contribute to the antinociceptive action of opioids, we have sought anatomical evidence for a direct GABAergic input to OFF and ON cells. In this study, cells of each type located in the RM were electrophysiologically defined and intracellularly filled with horseradish peroxidase or Neurobiotin. One cell of each type was labeled in the cat, and 2-3 cells of each type were labeled in the rat. Thin sections were labeled by a postembedding immunogold procedure by using an antibody directed against glutaraldehyde-conjugated GABA. GABA-immunoreactive (GABA-ir) boutons contained small, round, clear vesicles and made symmetrical synapses with identified dendrites. GABA-ir boutons were apposed to soma and to proximal and distal dendrites of both cell types in both species. These findings demonstrate direct GABAergic input to identified OFF and ON cells in the RM. J. Comp. Neurol. 378:196-204, 1997.

Animals↗

Noradrenergic input to nociceptive modulatory neurons in the rat rostral ventromedial medulla.

Within the rostral ventromedial medulla (RVM), there are two classes of putative pain modulation neurons: ON cells and OFF cells, which respectively burst or pause prior to withdrawal reflexes elicited by noxious stimulation. Alpha-adrenergic agonists injected into the RVM produce changes in the latency of spinal nocifensive reflexes and, when iontophoretically applied, alter the firing of RVM ON but not OFF cells. To provide further information about the contribution of norepinephrine to RVM neuron function, we analyzed the distribution of tyrosine hydroxylase immunoreactive (TH-ir) appositions upon RVM ON and OFF cells. In the lightly anesthetized rat, seven ON and five OFF cells were identified by changes in their discharge rate in relation to nociceptive withdrawal reflexes and were labeled by intracellular injection of neurobiotin. Sections containing labeled cells were visualized by using avidin conjugated to a Texas Red fluorophore. Tissue with labeled cells was subsequently processed for TH-ir by using a Bodipy fluorophore conjugated secondary antibody. The distribution of the Bodipy-labeled fibers and terminals upon the Texas Red-labeled neurons was mapped using a confocal laser-scanning microscope. All the labeled neurons exhibited close TH-ir appositions. Appositions were of two types: swellings and fibers. Although the numbers and density of appositions varied among the cells, there were no consistent differences that correlated with physiological properties. Thus the overall density of appositions for ON cells (29.0 +/- 22.2 x 10(4) microns2) did not differ significantly from that for OFF cells (25.4 +/- 22.2 x 10(4) microns2). Tyrosine hydroxylase immunoreactive (TH-ir) appositions upon ON and OFF cells varied with their location along the dorso-ventral axis with more ventral neurons having a greater density of TH-ir swelling-type appositions. In a separate study, TH-ir and dopamine-beta-hydroxylase-like immunoreactivity (DBH-ir) were mapped in the same sections by using confocal microscopy. Nearly 97% of the TH-ir profiles co-localized with DBH-ir. These observations provide evidence that both ON and OFF cells in the RVM are targeted by noradrenergic inputs.

Adrenergic Fibers↗

Maternal infusion of antioxidants (Trolox and ascorbic acid) protects the fetal heart in rabbit fetal hypoxia.

The antioxidants, Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, a water soluble analog of vitamin E) and ascorbic acid (AA), protect the heart from ischemia-reperfusion injury. We hypothesized that maternal infusion of Trolox and AA, would reduce the fetal bradycardia and myocardial damage observed in fetal hypoxia and increase the total antioxidant activity in fetal plasma. Either i.v. saline (control group) or Trolox + AA (drug group) was randomly administered to 29-d-old pregnant rabbits. Fetal hypoxia was induced by uterine ischemia. Fetal heart rate, plasma CK-MB activity, and plasma total radical antioxidant potential (TRAP) were measured in different sets of animals. Fetal heart rate in the drug group was higher than in the control group for the first 35 min (p < 0.05 at every 5-min interval). Fetal bradycardia (<60 beats/min) occurred after 39 min (median) in the drug group, and 29 min in the control group (p < 0.05). After 50 min of hypoxia, plasma CK-MB was lower in the drug group, 1204 +/- 132 U/L (mean +/- SEM), than in the control group, 2633 +/- 233 U/L (p < 0.05). TRAP was higher in the drug group, 3.01 +/- 0.15 mM (Trolox equivalent concentration), than in the control group, 1.48 +/- 0.27 mM (p < 0.05). Higher TRAP levels (> or = 2.0 mM) were associated with lower CK-MB levels (<2500 U/L) (p < 0.05). Administration of Trolox and AA to the mother has a beneficial effect on fetal myocardial damage after fetal hypoxia, and a small beneficial effect on fetal bradycardia during hypoxia. The beneficial effect may be due to the augmentation of fetal plasma antioxidants from maternal antioxidant pretreatment.

Animals↗

Adhesion formation after laparoscopic anterior resection in a porcine model: a pilot study.

Although decreased adhesion formation is one of the accepted advantages of laparoscopic colorectal surgery, no prospective studies have been done to support this claim. Therefore, we prospectively assessed adhesion formation following laparoscopic anterior resection of the rectum in a porcine model. Five domestic female pigs underwent the procedure with a double-stapled intracorporeal anastomosis. After completion of the laparoscopic procedure, 50 cm of ileum was retrieved through the right lower port site. Controlled serosal abrasion of the antimesenteric surface was performed using a fresh knife. The abraded loop was returned into the peritoneal cavity and the fascia closed at all port sites. All animals underwent a midline laparotomy 3 weeks later to assess adhesions using a 0-3 score according to the density vascularity, and extent of adhesions. All animals survived the study period. The mean level of the anastomosis was 8 cm (range, 7-10) above the anal verge; all anastomoses were intact and completely healed. None of the animals had adhesions to the port sites. The anastomotic site was completely free of adhesions in four animals, and only one animal (20%) had grade 1 adhesions between the urine horns and the anastomosis. Conversely, all animals had adhesions of the abraded loop involving 60 cm (range, 40-75) of bowel and 7 cm (range, 4-9) of the abdominal wall (remote to the port sites); no other adhesions were noted. In this pilot study, serosal abrasion of the small bowel resulted in severe adhesion formation in the porcine model. However, laparoscopic anterior resection of the rectum in the same animals was associated with only minimal insignificant adhesions. Furthermore, unlike in laparotomy incisions, adhesions to port sites did not occur.

Abdomen↗

A hyaluronate based gel for the prevention of postsurgical adhesions: evaluation in two animal species.

OBJECTIVE: To assess in two animal surgery models, the efficacy of a bioabsorbable gel to prevent postoperative adhesions. DESIGN: A randomized, prospective, blinded study using animal abdominal surgery models. SETTING: Two animals species with surgical traumas to induce adhesion formation. INTERVENTIONS: A chemically modified hyaluronate and carboxymethylcellulose-based gel formulation. MAIN OUTCOME MEASURES: The number of animals with no adhesions, mean number of adhesions, and total adhesion score. RESULTS: Treatment with the bioabsorbable gel increased the number of animals without any adhesion by 70% in a rat cecal abrasion model and by > 90% in a rabbit sidewall defect-bowel abrasion model when compared with nontreatment control animals. Other outcome measures showed similar efficacy. CONCLUSION: The modified hyaluronate-carboxymethylcellulose gel was effective in two animal species after surgery in the abdominal cavity. The gel appears to act as a physical barrier between damaged peritoneal tissue and may be appropriate for human clinical trials in open and laparoscopic surgical procedures.

Abdominal Muscles↗

Prevention of tissue injury and postsurgical adhesions by precoating tissues with hyaluronic acid solutions.

The effectiveness of inhibiting serosal tissue damage and preventing surgical adhesions by precoating tissues with dilute solutions of hyaluronic acid (HA) was evaluated in a rat cecal abrasion model. This study was performed at three independent laboratories using the same protocol. Three hundred and seventy-five adult rats were divided into five treatment groups (125 animals at each study site): 0.1% HA, 0.25% HA, 0.4% HA, phosphate-buffered saline solution (PBS), and no solution. The abdominal cavity of each animal was precoated with 4 ml of test solution or no solution, prior to a controlled abrasion of the cecum. One week later, the animals were sacrificed and adhesions were scored on a 0-4 scale. The data were pooled because no statistical difference was found in the trends at the three study sites. The PBS precoating and no tissue precoating treatment groups had the same high incidence of cecal adhesions, which was significantly higher than the incidence of adhesions in the HA treatment groups. As the HA concentration in the precoating solution increased from 0% (PBS group) to 0.4% HA, the mean incidence of cecal adhesions decreased in a concentration-dependent manner from 1.6 +/- 0.11 to 0.7 +/- 0.09 (P < 0.001). The percentage of animals with no cecal adhesions increased from 11% in the PBS group to 50% in the 0.4% HA treatment group (P < 0.001). In a separate histological study employing 150 rats, HA solutions significantly inhibited serosal tissue damage and ameliorated the inflammatory response due to abrasion and desiccation compared to that with no coating or precoating with buffered saline. Together, these studies demonstrate that tissue precoating with dilute HA solutions reduces damage to serosal tissues during surgery and thereby limits formation of postsurgical adhesions.

Administration, Topical↗

Post-Surgical Adhesion Prevention with a Biodegradable Gel Compatible with Laparoscopic Use

A useful laparoscopic product for adhesion prevention must be easy to apply with minimal handling and manipulation of tissue and product. With this objective in mind, we have developed an injectable gel (HALTM) based on hyaluronic acid that is intended to limit adhesion formation after laparoscopic and open surgical procedures. We tested the effectiveness of HALTM gels in a rat sidewall defect model. In 50 adult female rats a 1 cm x 1 cm peritoneal defect was made along the abdominal wall. The defect was enclosed with #3-0 silk suture to induce ischemia. The animals were randomized to gel treatment (0.5 ml placed on defect) or non-treatment control groups. Seven days after surgery the extent (0-4 scale) and severity (0-3 scale) of adhesions were scored. HALTM gel significantly reduced the extent and severity of sidewall adhesions. Moreover, the number of animals with no adhesions was significantly increased compared with non-treatment. These results indicate that HALTM gel, which is easily applied to tissue and organs, may be a useful adjuvant for adhesion prevention in open and laparoscopic surgical procedures. The effectiveness and safety of HALTM gels will be tested in human clinical studies.

Journal Article↗

Depression among female registered nurses.

Depression, the most frequently diagnosed psychiatric illness, is characterized by feelings of sadness, pessimism, self-dislike and loss of energy, motivation and concentration. The relationship of self-esteem, assertiveness and anxiety to depression is studied in a group of female nurses. Recognizing predisposing factors in this high-risk group can begin a process to treat this illness.

Adult↗

Parent satisfaction survey: paediatric physiotherapy services.

The aims of the survey were: to obtain data on children being seen in the department in order to determine whether the needs of parents and children are being met; to discover parents' attitudes to 'parent-based' treatment; and to establish whether physiotherapists' expectations of what parents can do at home are realistic. A parent satisfaction survey was developed and sent to outpatients who had attended the physiotherapy department in the previous 6 months. Results were collated and analysed in the areas of: referral source; appointments; treatment; and general opinion. The results are reported in detail and discussed. Results are generally positive and indicate that the physiotherapists are catering for the needs of parents and children, and have appropriate ideas of what can be achieved at home. Several areas of potential improvement are identified and discussed.

Child↗

Changes in prostaglandin transfer across human fetal membranes obtained after spontaneous labor.

Increased prostaglandin E2 production from amnion is thought to be a critical step in the initiation of human parturition. However, it is not known whether amniotic prostaglandin E2 can reach the decidua and/or myometrium. We examined whether prostaglandin E2 could cross the amnion and full-thickness membranes and whether this capacity changed with active labor. Using an in vitro system we found that there was a time-dependent cumulative transfer of total radioactivity and of radioactivity corresponding chromatographically to prostaglandin E2 across amnion and full-thickness membranes. The rate of transfer across the amnion was faster than across full-thickness membranes and varied according to the site of tissue sampling within the uterus. The permeability constant for prostaglandin E2 transfer across full-thickness membranes was significantly higher in tissue collected after the spontaneous onset of labor than in tissue collected at elective cesarean section at term. We conclude that prostaglandin E2 produced in human amnion at term may escape metabolism in the chorion and reach the decidua and/or myometrium.

Decidua↗

Relation between cyclic adenosine monophosphate and prostaglandin output by dispersed cells from human amnion and decidua.

We have examined the ability of activators of adenylate cyclase and cyclic adenosine monophosphate to affect the output of prostaglandins E and F by dispersed cells of amnion and decidua collected from women following spontaneous labor. Cyclic adenosine monophosphate production by amnion and decidua cells was stimulated in a dose-dependent fashion by cholera toxin and by forskolin in the absence or presence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine. Forskolin and cholera toxin also stimulated prostaglandin E and F output from amnion and decidua cells. Similar effects were seen with cells incubated with dibutyryl cyclic adenosine monophosphate +/- 3-isobutyl-1-methyl xanthine. The beta-adrenergic receptor agonists salbutamol, isoproterenol, and epinephrine all stimulated prostaglandin E and F output from dispersed cells of both tissues. The stimulatory effect of 3-isobutyl-1-methyl xanthine was partially additive with the Ca2+ ionophore A23187. Basal outputs of prostaglandin and outputs stimulated by A23187 and by N6, O2'-dibutyryl adenosine 3':5'-cyclic monophosphate were attenuated by the calmodulin antagonist trifluoperazine in a dose-dependent fashion. We conclude that mechanisms exist for stimulation of adenylate cyclase in human amnion and decidua resulting in enhanced prostaglandin output. This pathway requires basal interaction with Ca2+-calmodulin and may be additive with cyclic adenosine monophosphate-independent mechanisms for prostaglandin stimulation.

1-Methyl-3-isobutylxanthine↗

The structure of the fourth abdominal ganglion of the crayfish, Procambarus clarki (Girard). I. Tracts in the ganglionic core.

The organization of the fourth abdominal ganglion of the crayfish, Procambarus clarki, was studied with the light microscope in serial sections stained with osmium ethyl gallate. This ganglion is composed of a ventral rind of somata and a core of alternating layers of through-tracts and commissures. The longitudinal tracts of the ganglion are named according to the system in use for the orthopteran insects, because the basic plans of the crustacean and insect ventral ganglia exhibit striking anatomical parallels. The dorsal tracts are the largest and the most regular in their path through the ganglion. In the ventral posterior quadrant of the ganglion the tracts diverge from the basic plan to pass around the major synaptic neuropil and the bases of the peripheral nerves. This paper reports the three-dimensional anatomy of the major longitudinal through-tracts, internal tracts and commissures, and bases of peripheral nerves. Landmark features of the ganglion--including the tracts, the major artery of the vascular system, the shape of the ganglionic core in section, and prominent single cells, all of which make it possible to recognize specific regions of the ganglion--are described.

Animals↗

The structure of the fourth abdominal ganglion of the crayfish, Procambarus clarki (Girard). II. Synaptic neuropils.

Four discrete regions of synaptic neuropil in the crayfish fourth abdominal ganglion are described by light and electron microscopy. The largest is the horseshoe neuropil, a horseshoe-shaped mass of synaptic glomeruli that lies horizontally in the ventral ganglionic core. This neuropil has a substructure of three rings of fused glomeruli associated with the entry of small axons from the first and second nerve roots. The lateral neuropils are large, paired bulges of neuropil that define the sides of the ganglionic core. They contain neuronal profiles of various sizes, filled with clear or dense-cored vesicles. The neurons are randomly oriented except for occasional dendritic bundles. The tract neuropil is ultrastructurally similar to the lateral neuropils but it is distributed among the largest axons of the through-tracts and commissures. The midline neuropils are small, U-shaped clumps of uniformly sized neuronal profiles that contain large numbers of dense-cored vesicles and distinctive lamellar inclusions.

Animals↗