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Biomedical subjects

K M Smith

Publications and source records attributed to K M Smith.

At least 55 records · Page 3Linked to original sources
PubMed1999

CnOtx, a member of the Otx gene family, has a role in cell movement in hydra.

Otx genes have been identified in a variety of organisms and are commonly associated with the patterning of anterior structures. In some vertebrates, Otx genes are also expressed in the prechordal mesoderm, where they may have a role in cell movement. Here we report the characterization of CnOtx, an Otx gene in hydra, thereby providing evidence that Otx genes appeared early in metazoan evolution. CnOtx is expressed at high levels in developing buds and aggregates, where it appears to have a role in the cell movements that are involved in the formation of new axes. Further, the gene is expressed at a low level throughout the body column of hydra. This latter pattern may reflect a role for CnOtx in specifying tissue as competent to be anterior, although the gene does not have a direct role in the formation of the head.

Amino Acid Sequence↗
PubMed1999

NOS inhibition potentiates norepinephrine but not sympathetic nerve-mediated co-transmission in resistance arteries.

OBJECTIVE: The in vitro interaction between sympathetic nerves and basal nitric oxide release was studied in a resistance artery, since these interact powerfully in large vessels. METHODS: The pharmacological interaction between L-NAME and vasoconstriction to field stimulation of sympathetic nerves or exogenous norepinephrine was studied in rabbit cutaneous resistance arteries in wire myographs. RESULTS: Relaxation of norepinephrine-induced tone by acetylcholine, but not sodium nitroprusside, was blocked by N omega-nitro-L-arginine methyl ester (L-NAME: 100 microM), indicating that the agonist-induced release of nitric oxide could oppose the vasoconstrictor effect of norepinephrine and confirming that L-NAME had no effect on endothelium-independent vasodilatation. L-NAME increased norepinephrine potency indicating basal NO release. With short bursts of electrical field stimulation purinergic transmission was dominant at low frequencies and adrenergic at high frequencies. L-NAME had no effect on nerve-mediated responses, even after blocking the purinergic component with alpha,beta-methylene ATP (3 microM), suggesting that the influence of spontaneously released nitric oxide does not extend to the vascular smooth muscle cells under adrenergic nervous control. CONCLUSION(S): This resistance artery exhibits a highly effective nitric oxide-mediated vasodilatation to acetylcholine. It has basal release of nitric oxide which antagonises exogenous norepinephrine. However, basal nitric oxide did not influence adrenergic nerve transmission, which contrasts with previous studies of larger arteries and veins. We speculate that in small resistance arteries there may be a spatial limitation to the zones of vascular smooth muscle influenced by the adrenergic nerves and by basal nitric oxide from the endothelium, respectively. The role of endogenous nitric oxide in modulating vascular tone may thus be less in resistance arteries than in conducting arteries or capacitance vessels and purinergic transmission appears to be particularly resistant.

Acetylcholine↗
PubMed1999

Hypotension following mild bouts of resistance exercise and submaximal dynamic exercise.

Our purposes were (1) to examine resting arterial blood pressure following an acute bout of resistance exercise and submaximal dynamic exercise, (2) to examine the effects of these exercises on the plasma concentrations of atrial natriuretic peptide ([ANP]), and (3) to evaluate the potential relationship between [ANP] and post-exercise blood pressure. Thirteen males [24.3+/-(2.4) years] performed 15 min of unilateral leg press exercise (65% of their one-repetition maximum) and, I week later, approximately 15 min of cycle ergometry (at 65% of their maximum oxygen consumption). Intra-arterial pressure was monitored during exercise and for 1 h post-exercise. Arterial blood was drawn at rest, during exercise and at intervals up to 60 min post-exercise for analysis of haematocrit and [alphaANP]. No differences occurred in blood pressure between trials, but significant decrements occurred following exercise in both trials. Systolic pressure was approximately 20 mmHg lower than before exercise after 10 min, and mean pressure was approximately 7 mmHg lower from 30 min onwards. Only slight (non-significant) elevations in [alphaANP] were detected immediately following exercise, with the concentrations declining to pre-exercise values by 5 min post-exercise. We conclude that post-exercise hypotension occurs following acute bouts of either resistance or submaximal dynamic exercise and, in this investigation, that this decreased blood pressure was not directly related to the release of alphaANP.

Adult↗
PubMed1999

A virtual reality module for intravenous catheter placement.

BACKGROUND: Virtual reality (VR) is a potential tool for technical skills training. We tested the validity and instructional effectiveness of a prototype VR module for learning intravenous (i.v.) catheter placement. METHODS: First-year medical students (n = 37), third-year medical students (n = 14), and surgical residents (n = 9) attempted two pretest i.v.s into each other, used the VR module for 12 minutes, and subsequently attempted two posttest i.v.s. Success or failure were recorded for each attempt. For each successful attempt, time and global rating of i.v. insertion were also recorded. RESULTS: The pretest success rate was significantly different between groups (chi square = 28.71, P <0.01). VR success rate was not significantly different between groups (F(2,57) = 1.47, ns). Although there was improvement in all groups during VR training (F(2,114) = 44.16, P <0.01), this did not result in improvement in posttest performance. CONCLUSIONS: Significant differences between groups were observed in performance of i.v. insertion in physical reality. However, no significant difference was observed in performance in VR. Thus, performance in VR demonstrated neither construct nor concurrent validity. While performance improved in VR, transfer of skill from VR to physical reality was not observed. Additional development and testing of VR as a training tool is warranted before its widespread use can be recommended.

Catheterization↗
PubMed1999

Perfluorocarbon priming and surfactant: physiologic and pathologic effects.

OBJECTIVE: To test the hypothesis that perfluorocarbon (PFC) priming before surfactant administration improves gas exchange and lung compliance, and also decreases lung injury, more than surfactant alone. DESIGN: Prospective, randomized animal study. SETTING: Animal research laboratory of Children's Hospital of St. Paul. SUBJECTS: Thirty-two newborn piglets, weighing 1.55 +/- 0.18 kg. INTERVENTIONS: We studied four groups of eight animals randomized after anesthesia, paralysis, tracheostomy, and establishment of lung injury using saline washout to receive one of the following treatments: a) surfactant alone (n = 8); b) priming with the PFC perflubron alone (n = 8); c) priming with perflubron followed by surfactant (n = 8); and d) no treatment (control; n = 8). Perflubron priming was achieved by instilling perflubron via the endotracheal tube in an amount estimated to represent the functional residual capacity, ventilating the animal for 30 mins, and then removing perflubron by suctioning. After all treatments were given, animals were mechanically ventilated for 4 hrs. MEASUREMENTS AND MAIN RESULTS: We evaluated oxygenation, airway pressures, respiratory system compliance, and hemodynamics at baseline, after induction of lung injury, and at 30-min intervals for 4 hrs. Histopathologic evaluation was carried out using a semiquantitative scoring system and by computer-assisted morphometric analysis. After all treatments, animals had decreased oxygenation indices (p < .001) and increased respiratory system compliance (p < .05). Animals in PFC groups had similar physiologic responses to treatments as animals treated with surfactant only; both the PFC-treated groups and the surfactant-treated animals required lower mean airway pressures throughout the experiment (p < .001) and had higher pH levels at 90 and 120 mins (p < .05) compared with the control group. Pathologic analysis demonstrated decreased lung injury in surfactant-treated animals compared with animals treated with PFC or the controls (p < .02). CONCLUSIONS: Priming the lung with PFC neither improved the physiologic effects of exogenous surfactant nor improved lung pathology in this animal model.

Animals↗
PubMed1999

Hydroxyurea to inhibit human immunodeficiency virus-1 replication.

Treatment of human immunodeficiency virus (HIV) infection continues to be a challenge. Drug regimens that include two nucleoside reverse transcriptase inhibitors and a protease inhibitor are now the standard of care. These regimens require strict patient adherence and have numerous adverse effects at a high cost, so clinicians must continue to explore other therapeutic options. Hydroxyurea is a ribonucleotide reductase inhibitor that may have efficacy against HIV. We conducted a critical review of the literature to examine the utility of hydroxyurea-based drug combinations.

Anti-HIV Agents↗
PubMed1999

Pilon fractures of the distal tibia.

Pilon fractures are one of the most complicated injuries confronting the lower extremity traumatologist. When faced with the pilon fracture, the surgeon must adhere to the principles of anatomic reduction and rigid stabilization to achieve early range of motion. Open reduction and internal or external fixation or a combination of fixation techniques, expertly placed, ensure the best possible outcome with the least complications. A functional lower extremity following a pilon fracture is possible with meticulous evaluation and repair.

External Fixators↗
PubMed1998

The role for NES1 serine protease as a novel tumor suppressor.

Previously (Liu et al, Cancer Res., 56: 3371-3379, 1996), we isolated a novel serine protease-like gene--Normal Epithelial Cell Specific-1 (NES1)--that is expressed in normal mammary epithelial cells but is down-regulated in most breast cancer cell lines. Here, we demonstrate that stable expression of NES1 in the NES1-negative MDA-MB-231 breast cancer cell line suppressed the oncogenicity as revealed by inhibition of the anchorage-independent growth and tumor formation in nude mice. Fluorescence in situ hybridization localized the NES1 gene to chromosome 19q13.3, a region that contains genes for related proteases (including the prostate-specific antigen) and is rearranged in human cancers. Similar to breast cancer cell lines, prostate cancer cell lines also lacked NES1 mRNA and protein expression. Together, these results strongly suggest a tumor-suppressor role for NES1 in breast and prostate cancer.

Animals↗
PubMed1998

Ly-49D and Ly-49H associate with mouse DAP12 and form activating receptors.

Several members of the Ly-49 receptor family inhibit NK cell-mediated lysis of targets expressing appropriate MHC class I molecules. Ly-49D and Ly-49H, two Ly-49 molecules that lack immunoreceptor tyrosine-based inhibitory motifs (ITIM) in their cytoplasmic domains, associate with mouse DAP12, a molecule that possesses an immunoreceptor tyrosine-based activation motif (ITAM). Cotransfection of either Ly-49D or Ly-49H with DAP12 induces surface expression of both Ly-49 and DAP12. The Ly-49/DAP12 complex was coimmunoprecipitated from the transfected cells, demonstrating a physical association of DAP12 with Ly-49D or Ly-49H in the plasma membrane. Stimulation of transfectants with Abs recognizing either Ly-49D or Ly-49H results in cellular activation, as assessed by induction of tyrosine phosphorylation of multiple cellular substrates.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Amielle vaginal trainers-a patient evaluation.

Ten consecutive patients presenting to a gynaecology clinic with a principal diagnosis of secondary vaginismus and superficial dyspareunia were given a set of Amielle vaginal trainers and instructed in their use. They were subsequently sent a questionnaire asking for their evaluation of the efficacy of the trainers. Nine patients (90%) reported a substantial improvement or complete cure of their symptoms. All patients who used the vaginal trainers gave favourable reports on the physical characteristics of the product. Amielle vaginal trainers seem both effective in the treatment of vaginismus and superficial dyspareunia and aesthetically acceptable to majority of patients.

Journal Article↗
PubMed1998

Pediatric emergency medicine practice patterns: a comparison of pediatric and general emergency physicians.

OBJECTIVE: To determine whether differences exist between general emergency physicians (GEMs) and pediatric emergency physicians (PEMs) in the emergency care of children with common pediatric emergencies. METHODS: We carried out a survey study of all members of the American Academy of Pediatrics Section of Emergency Medicine and the Washington State American College of Emergency Physicians. We identified current therapeutic interventions for croup, asthma, bronchiolitis, seizures, febrile infant, conscious sedation, head trauma, and coin ingestion, and compared the practice patterns of GEMs and PEMs. RESULTS: A total of 66% of the surveys were returned, including 211 GEMs and 329 PEMs. The majority of PEMs practice in children's hospitals, whereas most GEMs practice in general community hospitals. Slightly over half (51%) of PEMs are PEM fellowship-trained versus 1% of GEMs. CROUP: The majority of GEMs and PEMs use racemic epinephrine (RE) in the treatment of a child with stridor at rest; approximately one-third admit to the hospital after RE (39 vs 30%, NS). PEMs are more likely to observe the child for >2 hours after RE (94% vs 79%, P < 0.01). The majority of PEMs and GEMs use steroids in these patients (94 vs 88%, NS). ASTHMA: There is no significant difference in the use of albuterol, aminophylline, or steroids. Steroids are more likely to be given orally by PEMs than GEMs (74 vs 50%, P < 0.01). BRONCHIOLITIS: The majority of both groups of physicians routinely use nebulized beta-agonists; however, significantly more GEMs than PEMs use steroids (68 vs 45 %, P < 0.01). SEIZURES: Half of GEMs vs 78% of PEMs use lorazepam as a first line drug in the treatment of seizures (P < 0.01). There is no significant difference with respect to the use of rectal diazepam in the pre-hospital setting. FEBRILE INFANT: GEMs are less likely than PEMs to admit the febrile infant <4 weeks of age (68 vs 87%; P < 0.01). Admission of older febrile infants (four to six weeks and eight weeks of age) is not significantly different between PEMs and GEMs. CONSCIOUS SEDATION: Both groups use a wide array of drugs alone or in combination to sedate children for complex facial laceration repair, closed fracture reduction, and cranial computed tomography (CT). GEMs are more likely to use ketamine for laceration repair (28 vs 16%, P < 0.01). Both GEMs and PEMs use midazolam plus a narcotic for fracture reduction. For further sedation for cranial CT, after an initial dose of midazolam, GEMs are more likely to use additional midazolam (64 vs 47%, P < 0.01), and PEMs are more likely to add pentobarbital (15 vs 4%, P < 0.01). HEAD TRAUMA: Most GEMs (87%) and PEMs (81%) would obtain a cranial CT on a neurologically normal two year old who had fallen down the stairs with a six-minute loss of consciousness. COIN INGESTION: Most GEMs and PEMs would obtain radiographs on an asymptomatic two year old with a recent coin ingestion. CONCLUSION: With some notable exceptions, GEMs and PEMs have similar pediatric practice patterns despite differences in training and practice environments.

Adult↗
PubMed1998

Muscle performance and enzymatic adaptations to sprint interval training.

Our purpose was to examine the effects of sprint interval training on muscle glycolytic and oxidative enzyme activity and exercise performance. Twelve healthy men (22 +/- 2 yr of age) underwent intense interval training on a cycle ergometer for 7 wk. Training consisted of 30-s maximum sprint efforts (Wingate protocol) interspersed by 2-4 min of recovery, performed three times per week. The program began with four intervals with 4 min of recovery per session in week 1 and progressed to 10 intervals with 2.5 min of recovery per session by week 7. Peak power output and total work over repeated maximal 30-s efforts and maximal oxygen consumption (VO2 max) were measured before and after the training program. Needle biopsies were taken from vastus lateralis of nine subjects before and after the program and assayed for the maximal activity of hexokinase, total glycogen phosphorylase, phosphofructokinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase, malate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase. The training program resulted in significant increases in peak power output, total work over 30 s, and VO2 max. Maximal enzyme activity of hexokinase, phosphofructokinase, citrate synthase, succinate dehydrogenase, and malate dehydrogenase was also significantly (P < 0.05) higher after training. It was concluded that relatively brief but intense sprint training can result in an increase in both glycolytic and oxidative enzyme activity, maximum short-term power output, and VO2 max.

Adaptation, Physiological↗
PubMed1998

Ultrasonographic diagnosis of trisomy 18: is it practical in the early second trimester?

The objective of this paper was to determine the rate of prenatal detection of ultrasonographic abnormalities in fetuses with trisomy 18 during the early second trimester. Our prenatal diagnosis database (encompassing January 1987 to June 1996) was searched for all patients referred for prenatal genetic evaluation between 14 and 22 weeks of gestation and who were found to have a fetus with a trisomy 18 karyotype. The sonographic reports and films were evaluated for the presence or absence of fetal anatomic abnormalities. Thirty-five fetuses were identified with a mean age of 17.3+/-2.0 (standard deviation) weeks. Thirty of the 35 (86%) had at least one detected abnormality. Most fetuses had more than one abnormality, with the mean number of abnormalities per fetus being three (range, 0 to 6). The most common abnormalities noted were persistent abnormal position of fetal fingers (89%); choroid plexus cysts (43%); abnormally shaped fetal head (strawberry or lemon) (43%); two-vessel umbilical cord (40%); cardiac defects (37%); intrauterine growth restriction (29%); omphalocele (20%); neural tube defects (9%); and cystic hygroma or lymphangiectasia (14%). Abnormalities of amniotic fluid volume (12%) and renal defects (9%) were seen less frequently. These data suggest that in the early second trimester, the time of most routine screening ultrasonographic examinations, most but not all fetuses with trisomy 18 have sonographically detectable anatomic abnormalities. The fetal hand appears to be abnormal in most early second trimester fetuses with trisomy 18, but the abnormality may be subtle and or unilateral.

Adolescent↗
PubMed1998

Recent developments in infant formulae: 1--The addition of LCPs.

Long chain polyunsaturated fats (LCPs) are important components of membranes in the human brain and retina. Preterm babies require a dietary source of LCPs, and all preterm formulae in the UK are currently supplemented with LCPs. Supplementation of term infant formulae with AA and DHA has resulted in apparent improvements to visual and cognitive functioning in bottle-fed babies. These improvements may be temporary and more research is needed to determine whether these differences remain in the longer term.

Bottle Feeding↗
PubMed1997

Synthesis, photophysical properties, in vivo photosensitizing efficacy, and human serum albumin binding properties of some novel bacteriochlorins.

The synthesis, photophysical characteristics, in vivo photosensitizing efficacy, human serum albumin (HSA) binding properties, and skin phototoxicity of some stable bacteriochlorins were investigated. The novel bacteriochlorins, obtained from chlorophyll-a, have long-wavelength absorptions in the range lambda max = 734-758 nm. Preferential migration of ethyl over methyl substituents among ketobacteriochlorins obtained in the pinacol-pinacolone rearrangements of vic-dihydroxybacteriochlorins was confirmed by NOE studies. The bacteriochlorins show relatively low fluorescence quantum yields. Among all the bacteriochlorins the triplet states were quenched by ground state molecular oxygen in a relatively similar manner, yielding comparable singlet oxygen quantum yields. In preliminary in vivo studies (DBA/2 mice, transplanted with SMT/F tumors), ketobacteriochlorins were found to be more photodynamically active than the related vic-dihydroxy analogues. Replacement of the methyl ester functionalities with di-tert-butylaspartic acids enhanced the in vivo efficacy. Site specific human serum albumin (HSA) binding studies indicated a direct correlation between the ability of the compound to bind to the diazepam binding site (albumin site II) and the in vivo photosensitizing efficacy.

Animals↗