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Biomedical subjects

S Miller

Publications and source records attributed to S Miller.

At least 73 records · Page 4Linked to original sources

Short latency heteronymous excitatory and inhibitory reflexes between antagonist and heteronymous muscles of the human shoulder and upper limb.

The aims were (i) to investigate heteronymous excitatory and inhibitory Group Ia reflexes linking agonist/antagonist muscle pairs acting at the shoulder and elbow; clavicular pectoralis major (Pmajor) and posterior deltoid (Pdeltoid); biceps brachii (Bi) and Tri brachii (Tri), and linking muscles acting at the elbow (Bi and Tri) with muscles acting at the shoulder (Pmajor and Pdeltoid). (ii) To test the hypothesis that the excitability of the reflexes would vary between different tasks in a functionally relevant manner. The study was performed on 45 adults. Reflexes were recorded in the surface EMG when the target muscle was contracting at 10% maximum voluntary contraction. Reflexes were recorded in Bi and Tri with the elbow joint in one of three positions: 105 degrees, 80 degrees, or 55 degrees from full extension. Group Ia reflexes were evoked using a small, brief tap to the tendon of the muscle being stimulated. Reflexes were recorded by cross-correlation of the surface EMG and pseudo-random series of taps. All subjects demonstrated short latency inhibition and excitation between agonist/antagonist muscle pairs; inhibition was significantly more frequent than excitation. Excitation and inhibition occurred with equal frequency between muscle pairs acting between elbow and shoulder. Minimum central delays for excitatory reflexes were 1 ms, consistent with monosynaptic projections and for inhibitory responses were 2 ms consistent with disynaptic linkage. Later excitatory and inhibitory reflexes with central delays of up to 15 ms also occurred. The probability of evoking excitation or inhibition in Tri or Bi changed with the different elbow positions.

Adult↗

Comparison of spinal myotatic reflexes in human adults investigated with cross-correlation and signal averaging methods.

A cross-correlation method for recording spinal myotatic reflexes has been developed to meet the need for brief test periods in babies and children and subjects with central neurological pathology. In normal adult subjects the method has been validated by comparing excitatory and inhibitory reflexes obtained with cross-correlation with those obtained with conventional signal averaging. In the cross-correlation method a pseudo-random binary sequence of 64 brief tendon taps was delivered in <1.5 s, and in the averaging method 20-150 taps at one per second. The reflexes were expressed as unit impulse responses to enable direct, quantitative comparisons to be made. With cross-correlation the responses were slightly expanded in time, had lower peak amplitudes, and onset latencies advanced by 10 ms, the clock period of the pseudo-random binary sequence. The amplitude of biceps phasic stretch reflex increased with muscle contraction in a similar manner with both methods. In tests for stationarity the amplitude of biceps phasic stretch reflex varied <10% in the first six repeats of the pseudo-random binary sequence. The tap force required at threshold for cross-correlation was approximately half that for averaging, but with both methods the magnitude of biceps phasic stretch reflex varied linearly with tap force over the range of one to two times threshold. The validity of responses obtained with cross-correlation was assessed by a statistical procedure. In conclusion, the cross-correlation method is robust and gives similar results to those obtained with averaging.

Adult↗

Reciprocal and Renshaw (recurrent) inhibition are functional in man at birth.

The aims were (1) to determine when in human postnatal development Group Ia reciprocal and Renshaw inhibition can be demonstrated; (2) to explore the relationship between the expression reciprocal inhibition and the disappearance of Group Ia excitatory reflexes between agonist and antagonist muscles. Studies were performed on 99 subjects, aged 1 day to 31 years, of whom 53 were neonates. A longitudinal study was also performed on 29 subjects recruited at birth and studied 3 monthly until 12 months of age. Reciprocal inhibitory and excitatory reflexes were recorded in the surface EMG of contracting biceps brachii (Bi), evoked by taps applied to the tendon of triceps brachii (Tri). Reciprocal excitatory reflexes were recorded in all but one neonate. Reciprocal inhibition was observed in 25% of neonates; evidence is provided that it was likely to have been masked by low threshold reciprocal excitation in the remaining neonates. Reciprocal inhibition was demonstrated in all subjects after 9 months of age. In four neonates there was depression of inhibition of Bi during co-contraction of Bi and Tri implying that Group Ia interneurones may be under segmental and suprasegmental control at birth. Renshaw cells, identified in human postmortem cervical spinal cord by their morphology, location and calbindin D28K immunoreactivity, were present at 11 weeks post-conceptional age (PCA) and by 35 weeks PCA had mature morphological characteristics. In four neonates reciprocal inhibitory responses in Bi disappeared when the tap to Tri evoked its own homonymous phasic stretch reflex, providing neurophysiological evidence for Renshaw inhibition of Group Ia inhibitory interneurones.

Adolescent↗

Water-soluble propofol analogues with intravenous anaesthetic activity.

Propofol (2,6-diisopropylphenol) is a widely used intravenous anaesthetic that is formulated as an emulsion since it lacks water solubility. We report a range of water-soluble analogues of propofol, containing a para-alkylamino substituent, which retain good intravenous anaesthetic activity in rodents.

Anesthetics, Intravenous↗

Pecam-1 is a modulator of stat family member phosphorylation and localization: lessons from a transgenic mouse.

PECAM-1 (CD31) is a member of the immunoglobin (Ig) superfamily of cell adhesion molecules whose expression is restricted to hematopoietic and vascular cells. PECAM-1 can recruit adapter and signaling molecules via its immunoreceptor tyrosine activation motif (ITAM), suggesting that PECAM-1 plays a role in signal transduction pathways. To study the involvement of PECAM-1 in signaling cascades in vivo, we used the major histocompatibility (MHC) I gene promoter to target ectopic PECAM-1 expression in transgenic mice. We noted an attenuation of mammary gland development at early stages of virgin ductal branching morphogenesis. STAT5a, a modulator of milk protein gene expression during lactation, was localized to the nuclei of ductal epithelial cells of 6-week-old virgin PECAM-1 transgenics, but not in control mice. This correlated with decreases in ductal epithelial cell proliferation and induction of p21, an inhibitor of cell cycle progression. Using in vitro model systems we demonstrated PECAM-1/STAT5a association and found that residue Y701 in PECAM-1's cytoplasmic tail is important for PECAM-1/STAT5 association and that PECAM-1 modulates increases in STAT5a tyrosine phosphorylation levels. We suggest that by serving as a scaffolding, PECAM-1 can bring substrates (STAT5a) and enzymes (a kinase) into close proximity, thereby modulating phosphorylation levels of selected proteins, as previously noted for beta-catenin.

Animals↗

Spectroscopy of H3+ and its impact on astrophysics.

Since the original laboratory detection of an H3+ spectrum 20 years ago, the search has been on for astronomical observations of this important and fundamental molecular ion. Successful detection of H3+ in gas-giant planets, supernova ejecta and the interstellar medium as well as the prospects for future observations are discussed. The role H3+ has in determining the atmospheric structure of both the gas giants and cool metal-free planets is explored.

Astronomical Phenomena↗

Spectroscopic characterisation and identification of ecdysteroids using high-performance liquid chromatography combined with on-line UV--diode array, FT-infrared and 1H-nuclear magnetic resonance spectroscopy and time of flight mass spectrometry.

A prototype multiply hyphenated reversed-phase HPLC system has been applied to the analysis of a mixture of pure ecdysteroids and an ecdysteroid-containing plant extract. Characterisation was achieved via a combination of diode array UV, 1H NMR, FT-IR spectroscopy and time of flight (TOF) mass spectrometry. This combination of spectrometers allowed the collection of UV, 1H NMR, IR and mass spectra for a mixture of pure standards enabling almost complete structural characterisation to be performed. The technique was then applied to a partially purified plant extract in which 20-hydroxyecdysone and polypodine B were identified despite incomplete chromatographic resolution and the presence of co-chromatographing interferents. The experimental difficulties in the use of such a systems for these analytes are described.

Chromatography, High Pressure Liquid↗

Compensatory responses in the aging hippocampal serotonergic system following neurodegenerative injury with 5,7-dihydroxytryptamine.

This study utilized a multidisciplinary approach to examine injury-induced compensatory responses in the aging hippocampal serotonin transporter (5-HTT), a membrane protein implicated in a variety of neurodegenerative disorders. Age-dependent cellular, anatomical, and physiological changes of the 5-HTT were evaluated in female Fischer 344 rats (2 and 17 months) following denervation of the serotonergic afferents (fimbria-fornix and cingulum bundle) to the dorsal hippocampus using the neurotoxicant 5,7-dihydroxytryptamine (5,7-DHT). Seven days following 5,7-DHT administration, a uniform loss of the hippocampal 5-HTT immunoreactivity was observed in both age groups. However, at 21 days 5-HTT immunoreactivity in young 5,7-DHT-treated animals was similar to control levels, indicative of recovery, while older animals exposed to 5,7-DHT did not show recovery of hippocampal 5-HTT expression. 5-HTT binding site density, as determined by quantitative autoradiography ([3H]citalopram), supported the immunohistochemical results by demonstrating a recovery of 5-HTT binding sites in young, but not old animals, at 21 days following the lesion (P < 0.001). Furthermore, cellular electrophysiological function of hippocampal CA1 pyramidal neurons in 3- and 18-month-old F344 rats at 21 days following 5,7-DHT or vehicle treatment were assessed using in vivo microiontophoretic application of serotonin (5-HT). Independent of changes in sensitivity to the inhibitory effects of 5-HT application, the time to recovery of cell firing following application of 5-HT was significantly increased in the 18-month 5,7-DHT group compared to the 18-month vehicle and 3-month 5,7-DHT groups (60 and 59% increases, respectively; P < 0.05). Overall, these series of studies comprise a model which can be used to identify cellular events underlying both the formation of injury-induced compensatory processes in younger animals and the lack thereof with advancing age.

Afferent Pathways↗

Preexisting histologic evidence of prostatitis is unrelated to postimplant urinary morbidity.

The presence and extent of prostatitis on the patients' preimplant biopsy slides was correlated with their postimplant course to determine if any relationship exists between histological prostatitis and postimplant morbidity. Biopsy slides from 56 patients treated with I-125 (144 Gy, TG-43), Pd-103 (125 Gy, NIST-1999), or Pd-103 plus supplemental external beam radiation (20-44 Gy) were studied. As part of ongoing prospective protocols, treatment-related morbidity is monitored by mailed questionnaires at 1, 3, 6, 12, and 24 months postimplant, using standard American Urologic Association (I-PSS) and Radiation Therapy Oncology Group criteria. Patient's preimplant biopsies, stained with standard hematoxylin and eosin, were retrieved for review by one uropathologist (LT). Separate evaluations of the degree and extent of inflammation in biopsy cores free of cancer and in cancerous biopsy cores were undertaken. Infiltrates were classified as periglandular if they were within 50 microns of a glandular structure. They were otherwise classified as stromal. Distribution of the inflammation was reported as focal, multifocal, or diffuse. The intensity of inflammation was separately graded as mild if there were fewer than 10 inflammatory cells per high-power field, moderate if there were 10-200 cells per high-power microscopic field, or severe if there were more than 200 cells per field. In all cases the great majority of inflammatory cells were mononuclear, predominantly lymphocytes. Periglandular inflammation was most common, with 18% of patients having focal periglandular and 20% having multifocal periglandular inflammation on their preimplant biopsies. Cancer-related infiltrates were the second most common, with 23% of patients having focal, 13% multifocal, and 13% diffuse cancer-related inflammation on their preimplant biopsies. Eight of the 55 patients developed postimplant urinary retention, requiring catheterization for 2 to 8 days. The overall incidence of postimplant urinary retention was low and there was no obvious relationship between the presence of inflammation on preimplant biopsy and the likelihood of postimplant urinary retention. AUA score changes at 1 and 6 months postimplant were highly variable and unrelated to the presence or severity of periglandular or cancer-related inflammation. Considering the apparent lack of relationship between histological findings and clinical outcomes in the patients reported here, the authors conclude that histologic evidence of prostatitis is not a contraindication to brachytherapy.

Biopsy↗

Subacute myocardial infarction: assessment by STIR T2-weighted MR imaging in comparison to regional function.

PURPOSE: Increased T2 signal intensity (SI) can be regularly observed in myocardial infarction. However, there are controversial reports about the relationship of elevated T2 SI to myocardial viability and some authors propose that high T2 SI serves as a sign of irreversible myocardial injury. This study investigates increased T2 SI compared to myocardial function in patients with reperfused subacute myocardial infarction. Preserved function was used as criterion for viability. METHODS: Ten healthy volunteers and 17 patients with myocardial infarction and patent infarct related coronary artery were examined on a 1.5 T Magnetom Vision system (Siemens). For T2-weighted MR imaging a breath-hold STIR sequence with dark-blood preparation was used. Cine FLASH 2D imaging was applied to assess myocardial function. Signal-to-noise (S/N) in STIR T2 images was measured in normal and infarcted regions and subsequently identified by two independent observers. Based on a 20 segment model of the left ventricle findings were compared to regional myocardial function. RESULTS: Elevated STIR T2 SI was found in all 17 patients and observed in 27% (204/754) of segments. S/N of normal myocardium was 5.1 +/- 0.7 in volunteers and 4.9 +/- 0.8 in patients (P = NS). Infarcted myocardium presented with significantly increased S/N 12.8 +/- 1.9 (P < 0.0001). Significant transmural elevation of T2 SI was noted in 32% of segments with preserved systolic function. CONCLUSION: Increased STIR T2 SI can be observed transmurally in post-ischemic myocardial regions with preserved function. It therefore cannot be used as an exclusive marker for the non-viable region.

Aged↗

The levels of TNF alpha, IL4 and IL10 production by T-cells in B-cell chronic lymphocytic leukaemia (B-CLL).

Tumour necrosis factor alpha (TNF alpha), interleukin (IL) 4 and IL10 are important for the growth and survival of the leukaemic cells in B-cell chronic lymphocytic leukaemia (B-CLL). The present study investigates the production of TNF alpha, IL4 and IL10 in patients with B-CLL. Significant increases in the TNF alpha and IL4 mean levels compared to normal control CD2(+)-cells were observed for B-CLL lymphocytes (TNF alpha: P=0.0004 and IL4: P=0.0026). By contrast, the mean level of IL10 produced by purified B-CLL CD2(+)-cells was significantly lower than that seen with normal control T-cells (P=0.0136). No significant difference in the percentage (%) of T-cells that expressed cytoplasmic TNF alpha, IL4 and IL10 was observed between B-CLL and normal T-cells. However, a significant increase in the mean level of intracellular TNF alpha and IL4 expression was observed in B-CLL compared with normal control T-cells (TNF alpha: P=0.031; IL4: P=0.0027). The increased expression of cytoplasmic TNF alpha and IL4 appeared to be associated with increased cytokine production in the tested samples. The differences observed with some B-CLL cases in the production of TNF alpha, IL4 and IL10 by peripheral blood T-cells may suggest survival mechanisms for the leukaemic cells in these patients.

CD4-CD8 Ratio↗

Parenteral supplementation with a fish-oil emulsion prolongs survival and improves rat lymphocyte function during sepsis.

Nutritional intervention with omega-3 fatty acids during trauma and infection has been shown to improve the clinical outcome of patients and the survival rate in laboratory animals. This study evaluated the effects of parenteral administration of lipid emulsions containing fish oil (FO) or soybean oil (SBO) on survival and T-lymphocyte response during sepsis. Male Sprague-Dawley rats (250-275 g) were prepared for parenteral feeding 4 d before inducing sepsis by cecal ligation and puncture (CLP). Standard resuscitation was provided with normal saline. Thirty minutes after completing CLP, sham control or CLP rats were infused continuously with saline or a parenteral diet containing SBO or a 1:1 FO:SBO emulsion. The survival rate was significantly improved in rats receiving the FO-supplemented diet, with 50% alive by 120 h in comparison with the saline-infused, chow-fed rats (0% alive by 120 h) or the SBO-fed rats (12% alive at 120 h). The T-lymphocyte response was evaluated at 24 h after CLP. Sepsis led to a decline in lymphocyte proliferation in rats infused with saline or the SBO emulsion, which was associated with a greater release of splenocyte interleukin-10, transforming growth factor-beta and prostaglandin E2. Administering the 1:1 FO:SBO parenteral diet during sepsis improved the survival rate and prevented the sepsis-induced suppression of lymphocyte proliferation and interleukin-2 release. The FO effect on lymphocyte function was associated with decreased splenocyte release of transforming growth factor-beta and prostaglandin E2.

Animals↗

Familial aggregation in specific language impairment.

A case-control family study design, in which the current language-related abilities of all biological, primary relatives (mother, father, siblings) of probands with specific language impairment (SLI) and matched controls were assessed, was used to investigate familial aggregation for language disorders. Current test data from each family member showed the rate of language impairment for mothers, fathers, sisters, and brothers of the SLI probands to be significantly higher than for members of control families. Impairment rates for fathers and mothers were approximately equal, whereas rates for brothers were significantly higher than for sisters. In SLI proband families, Language Impairment (LI) occurred in 13.0% of offspring (excluding proband) with neither parent affected, 40% of offspring with one parent affected, and 71.4% of offspring in families in which both parents were language impaired. Rates of impairment as determined in current testing were compared directly to impairment rates estimated from family-history questionnaires collected from the same families. Group data showed impairment rates estimated from the family-history questionnaires to be similar to the rates based on actual testing. Furthermore, both appeared in line with rates based primarily on questionnaire data as reported previously in the literature. However, case-by-case analyses showed poor intrasubject agreement on classification as language impaired on the basis of current testing as compared to history information.

Adolescent↗

A randomized, double-blind, placebo-controlled study of itraconazole capsules for the prevention of deep fungal infections in immunodeficient patients with HIV infection.

OBJECTIVES: To determine whether systemic or deep fungal infections can be prevented, a double-blind, placebo-controlled, phase III trial of itraconazole prophylaxis was undertaken in HIV-infected patients. METHODS: HIV-1 infected patients with CD4 counts < 300 cells/microL were treated with itraconazole (200 mg per day) or matching placebo and followed for 2 years. Development of deep fungal infections, episodes of mucocutaneous candidiasis, change in CD4 count, survival and safety data were collected at each study visit. RESULTS: Three hundred and seventy-four patients received study medication, 187 were given itraconazole and 187 matching placebo. Time to development of deep fungal infection did not differ between groups, in an intention to treat analysis. Low CD4 cell count and prior use of Pneumocystis carinii pneumonia (PCP) prophylaxis were significantly associated with a more rapid development of deep fungal infection (P = 0.044 and 0.017, respectively). Itraconazole treatment significantly reduced the incidence of oral candidosis (25% vs. 48% P < 0.001) and time to development of oral candidosis (508 vs. 413 days, P < 0.001) but not the number of deep fungal infections (11 vs. 13). Survival did not differ significantly between groups (nine vs. 14 deaths). CD4 counts decreased significantly over time in both study arms. Adverse events did not differ between groups; 20% vs. 23% stopped study medication due to an adverse experience. CONCLUSIONS: Although itraconazole prophylaxis significantly reduced the number and time to development of oral candidosis, too few episodes of deep fungal infection were noted to determine whether itraconazole prophylaxis was effective for this condition. Chronic itraconazole treatment is well tolerated in HIV-infected patients with marked immunodeficiency.

AIDS-Related Opportunistic Infections↗

[2D-phase contrast flow evaluation and contrast-enhanced MR angiography for perioperative assessment of internal mammary artery grafts].

PURPOSE: To evaluate LV functional parameters, graft flow and patency in patients with IMA grafts using a combined MR protocol with phase-contrast technique and contrast enhanced MR angiography. MATERIAL AND METHODS: Using a 1.5 T MR system 27 patients with 27 left internal mammary artery (LIMA) and 41 venous grafts were examined before and 6 months after CABG surgery. A T(1)w-TSE sequence (slice thickness 5 mm) was applied for morphological imaging. LV function (EF, CO) was evaluated on cine images (segmented FLASH 2D, TR(eff) 11 ms, TE 4.8 ms, flip angle 25 degrees ). A phase-contrast FLASH 2D (TR 24 ms, TE 5 ms, flip angle 20 degrees ) sequence was applied for aortic and IMA flow measurements. Postoperatively, a contrast enhanced FLASH 3D MR angiography (TR 3.8 ms, TE 1.4 ms, flip angle 30 degrees ) with 25 ml Gd-DTPA was performed to assess bypass patency. RESULTS: In patients with reduced LV function (ejection fraction < 50 %) an improvement of the ejection fraction from 38.4 +/- 10.3 % to 49.8 +/- 15.3 % (p < 0.05) was found postoperatively. LIMA grafts were occluded in 1/27 patients, while 6/41 venous grafts were occluded. Distal LIMA anastomoses were demonstrated in 33 % by MRA. Flow of LIMA decreased from 21.2 +/- 11 ml/min/m(2) preoperatively to 14.4 +/- 9.6 ml/min/m(2) postoperatively (p < 0.01). CONCLUSION: MR imaging allows accurate combined assessment of LV function, bypass patency and flow. The protocol of this study may be applicable for perioperative follow-up studies in patients after CABG surgery.

Aged↗

[Multidetector CT Angiography - is it a valuable screening tool to detect significant renal artery stenosis?].

PURPOSE: To evaluate the diagnostic value of multidetector CT angiography (MDCTA) of the renal arteries. METHODS: 27 patients underwent MDCTA of the renal arteries. Scan parameters were: collimation 4 x 1 mm, pitch 1.5, effective slice thickness 1.25 mm, reconstruction increment 0.8 mm, circulation time measurement, power injection of 80 ml iomeprol 400, flow 4 ml/sec. Independent reading on laser film was done by two radiologists using edited maximum intensity projections, multiplanar reconstructions and source images. Standard of reference was a 3D-FLASH MR angiography (1.5 T, 3.9/1.2, 10 degrees 0.2 mmol GdDTPA/kg bw) in 10 and intraarterial angiography in 17 patients. RESULTS: Analysing 63 arteries, sensitivity, specificity, positive predictive value and negative predictive value in terms of detection of moderate and high grade renal artery stenosis (n = 10) were 90, 98, 90 and 98 % for reader A, and 90 % each for reader B, respectively (kappa = 0.91 interobserver agreement). 1/11 accessory renal arteries was missed by both angiography and MDCTA. Image quality was graded as excellent or good in 26/27 of cases by both readers. CONCLUSION: MDCTA proved to be a highly accurate tool in the detection of therapeutically relevant renal artery stenosis.

Aged↗

A fall prevention program for the home environment.

Falls are the leading cause of injury, death, and disability among people older than 65. When elders fall, they sustain such injuries as hip, spine, hand, and/or pelvic fractures. The prognosis after such a fall is poor--only half of older adults hospitalized for hip fractures are able to return home or live independently again. Even without injury, falls cause a loss of confidence that results in reduced physical activity, increased dependency, and social withdrawal. As a home care agency dealing with a geriatric population, our goal was to develop a user-friendly fall prevention program that would promote multidisciplinary assessment and intervention. We have developed a preventive approach through which clinicians and patients can collaborate on preventing falls in the home and maintaining our patients' first priority: quality of life.

Accidental Falls↗