Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Collateral sensitivity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources

Late gestational changes in sympathomimetic sensitivity in primagravid rabbit ligaments.

The adrenoceptor profile of blood vessels supplying the medial collateral ligament (MCL) of virgin and primagravid (day 29 of pregnancy) rabbit knees was examined. Topical bolus administration of the alpha1-adrenoceptor agonists methoxamine and phenylephrine, and the alpha2-adrenoceptor agonist clonidine, to exposed knee joints resulted in a dose-dependent vasoconstriction of ligamentous vessels. The rank order of potency for the alpha-agonists was found to be phenylephrine > methoxamine > clonidine. Dobutamine, which acts on beta1-adrenoceptors, and ritodrine, which is a beta2-agonist, imparted a mild vasodilatatory effect on MCL blood vessels with the efficacy of ritodrine being greater than that of dobutamine. In primagravid rabbits, the constrictor effects of methoxamine and phenylephrine were significantly attenuated compared with virgin control animals (P < 0.0001), whereas clonidine-mediated vasoconstriction was unaltered in the gravid animal (P = 0.3957). With respect to beta-adrenoceptor activity, the dilatational effect of dobutamine was the same as in controls (P = 0.5294), while ritodrine vasoactivity was completely abolished in primagravid knees (P < 0.005). These findings suggest that the adrenergic control of rabbit MCL blood flow is predominantly mediated by postjunctional alpha1 and beta2-adrenoceptors. Pregnancy leads to either downregulation and (or) desensitisation of alpha1 and beta2-adrenoceptors in the ligament which could disrupt normal joint homeostasis.

Animals↗

Activity-sensitive signaling by muscle-derived insulin-like growth factors in the developing and regenerating neuromuscular system.

In the nervous system, activity-sensitive retrograde signaling pathways couple the status of postsynaptic activation to elimination of collaterals during development and collateral sprouting in the adult. This article presents evidence supporting the hypothesis that in the neuromuscular system, skeletal muscle fiber derived insulin-like growth factors play a central role in such signaling. This evidence includes (1) timing and activity-sensitive expression of IGFs in skeletal muscle fibers, (2) identification of an IGF- and activity-sensitive retrograde signaling pathway from developing muscle to motoneurons in the spinal cord, (3) demonstration that IGFs in the muscle are both sufficient and necessary to induce interstitial cell proliferation and intramuscular nerve sprouting in adult muscle.

Aging↗

Evaluation of coronary arterial stenoses using 2D magnetic resonance coronary angiography.

This study investigated the usefulness and limitations of magnetic resonance coronary angiography (MRCA). MRCA was performed with an electrocardiographically gated gradient echo sequence with k-space segmentation. Coronary angiography (CAG) was performed using a conventional system. We had three protocols. In protocol one, 160 consecutive patients (279 coronary arteries) who underwent initial CAG for diagnosing coronary artery disease were enrolled. Out of the 279 coronary arteries, 235 arteries (84.2%) were visualised with an image quality suitable for further analysis. In these 235 arteries, the validity for diagnosing over 75% arterial stenosis was 98%, and sensitivity and specificity was 79%. In protocol two, 48 stenoses were evaluated for restenosis after balloon angioplasty. The validity for diagnosing restenosis by MRCA was 93% in sensitivity and 33% in specificity. In protocol three, comprising 18 coronary arteries with total obstruction, the presence of collaterals was evaluated. The development of collateral circulation improved MRCA findings in the distal portion of obstructed coronary arteries. We conclude that MRCA provides useful information with acceptable sensitivity and specificity before balloon angioplasty. However, MRCA has a tendency to over-estimate restenosis after balloon angioplasty.

Journal Article↗

Analysis of skiing accidents involving combined injuries to the medial collateral and anterior cruciate ligaments.

Two types of ligament injuries common in skiing are the isolated ruptures of the anterior cruciate and ruptures of the medial collateral, either with or without rupture of the anterior cruciate. Based on research related to ligament injury mechanics and two-mode release binding function, the purpose of this paper was to critically assess the ability of two-mode release bindings to prevent combined medial collateral and anterior cruciate ligament injuries. Making this assessment entailed several steps. First, I determined the loads typically transmitted by the knee during falls in which combined injuries occurred. Because more than one load was transmitted, the next step was to discern which of the loads was more damaging. Finally, heel-toe type bindings were evaluated for their potential to release in response to damaging loads. I concluded that combined medial collateral and anterior cruciate ligament injuries typically occur in forward, twisting-type falls in which the primary loads are external axial and valgus moments. An external axial moment is more damaging than a valgus moment, both to the medial collateral ligament when the joint is intact and to the anterior cruciate ligament when the medial collateral ligament is damaged. Because heel-toe type bindings offer release sensitivity to this moment, the release level of the toepiece in twist is an important factor in the prevention of these injuries.

Accidents↗

Proposed mechanisms for cerebellar coordination, stabilization and monitoring of movements and posture.

In this paper cerebellar mechanisms have been proposed for the coordination of all movements, for the learning effect of training on movements, for the effect of mental set on posture and voluntary movements, for the detection of velocity and acceleration, and for the stabilization of movements and posture. Coordination of agonist, antagonist, fixation and synergistic muscles during a movement could occur via a cerebellar matrix which connects agonist efferent feedback from the Motor Cortex to the appropriate antagonist motor cortical neurons. Improved efficiency through repetition (learning) occurs through suggested changes at the molecular and synaptic levels. The Inferior O-live-Climbing Fibre System is seen as a dynamic oscillator; indicating when a movement begins, its velocity and acceleration, and its stability. According to this view, the cerebellum stabilizes movements, and adds the effect of mental set on posture and voluntary movements, by inducing changes in the gain of stretch reflexes. Inhibitory interneurons add versatility to movements, while excitatory collaterals from cerebellar afferents directly to cerebellar deep nuclei improve sensitivity of the system. These mechanisms work for all movements whether active, passive, or reflexive.

Action Potentials↗

Correlation of MR imaging findings and open exploration of medial patellofemoral ligament injuries in acute patellar dislocations.

The purpose of this investigation was to correlate magnetic resonance (MR) images of medial patellofemoral ligament (MPFL) injuries with gross macroscopic findings. Twenty-seven knees with MPFL injury following an initial patellar dislocation were examined using axial proton-density and T2-weighted fast spin-echo MR imaging. MR findings were subsequently correlated with open exploration. MPFL injury was observed in 26 (96%) of the 27 knees. From the MR images, discontinuity, irregularity and/or high-signal intensity changes anterior to the femoral attachment were seen in 13 (82%) of the 16 knees with substantial-tear type injuries of the MPFL. In 8 (80%) of the 10 knees with avulsion-tear type injuries, detachment of the MPFL from the femoral attachment, accompanied with or without high-signal intensity changes, was confirmed. MPFL injury types could be accurately diagnosed on 21 (81%) out of 26 knees using MR imaging. MR imaging was an acceptable method in diagnosing MPFL injury types.

Acute Disease↗

Exposure to 1 ppm ozone attenuates the immediate antigenic response of canine peripheral airways.

The effect of oxidant exposure on the immediate airway response to immunologic challenge is controversial. We investigated the response of canine peripheral airways to antigen aerosol, 1-3 h and 24 h after a 5-min exposure to 1 ppm ozone. In dogs that were natively sensitive to Ascaris suum antigen, resistance to flow through the collateral system (Rcs) was measured using the wedged bronchoscope technique. In eight dogs, four sublobar segments of each lung were wedged: two were exposed to ozone for 5 min and two (control) received air with 5% CO2. Ozone caused a mean ( +/- SE) increase in Rcs of 75 +/- 15%, which returned to baseline after 1-3 h. The increase in Rcs elicited by subsequent administration of antigen aerosol (25 microliters, 0.27 mg protein/ml) to the ozone-exposed segments (312.0 +/- 70.6%) was attenuated by 22% compared to controls (398.9 +/- 83.0%; p less than .05). In another series of experiments (n = 5), segments were exposed to ozone or air and challenged with antigen 24 h later and a significant attenuation (38%) of the antigen-induced increase in Rcs was detected compared to controls (178.5 +/- 57.9 vs 289.0 +/- 62.2; p less than .05). Cellular influx of polymorphonuclear leukocytes (PMNs) was not detected by bronchoalveolar lavage (BAL) 1-3 h after ozone, but was found after 24 h (19.8 vs. 4.7%; p less than .01). A significant increase in PMNs was detected in exposed subepithelial tissues 1-3 h after ozone compared to unexposed tissues. Tissue PMNs were not significantly different from unexposed tissues after 24 h, but a shift toward degranulation of mast cells was detected in ozone-exposed tissues at this time. These data suggest that the Rcs response to antigen is attenuated 1-3 h and 24 h after acute (5 min) exposure to 1 ppm ozone, and this effect occurs independently of PMNs in the airways.

Administration, Inhalation↗

Basilar artery occlusion in rats.

The basilar artery is one of the three major sources of blood supply to the circle of Willis. To investigate the effects of basilar artery occlusion, we surgically exposed and coagulated the basilar artery in 25 rats. Basilar artery occlusion at any single point between the foramen magnum and the circle of Willis in 11 rats did not produce histologically detectable infarcts in the brain at 12-24 hours. Two-point occlusions of the basilar artery in 12 rats produced variable infarcts between the occlusion sites but no ischemic lesions elsewhere. After either single- or double-point occlusions, the proximal basilar artery refilled within 2-3 minutes. When the basilar artery was occluded above and below the origins of the anterior inferior cerebellar arteries, the artery segments between the occlusion points initially collapsed but refilled within 2-3 minutes in two rats. Basilar artery occlusions invariably suppressed cortical somatosensory evoked potentials by greater than 50%. Regardless of whether a brain stem infarct developed, somatosensory evoked potential amplitudes recovered to greater than baseline levels by 4 hours in seven of 17 rats and returned to baseline levels by 24 hours in every rat tested. We conclude that the occluded basilar artery receives extensive retrograde collateral blood flow and that somatosensory evoked potentials are exquisitely sensitive to basilar artery occlusion but are insensitive to whether brain stem infarcts develop.

Animals↗

Dry air-induced bronchoconstriction--a role for voltage-sensitive calcium channels?

We examined the role played by voltage-sensitive calcium channels (VSCC) in airflow-induced bronchoconstriction (AIB). Collateral resistance (Rcs) in anesthetized male mongrel dogs was measured before and after periods of elevated airflow, or before and after hypocapnic challenge, using a wedged bronchoscope technique. A dihydropyridine calcium channel antagonist (nifedipine) was ineffective in preventing or even attenuating AIB in the canine lung periphery. Treatment with nifedipine did not affect the response of peripheral airways to aerosolized acetylcholine, indicating that receptor-operated calcium channels (ROCC) and/or release of calcium from intracellular stores were unaffected by this drug. Despite the ability of a calcium agonist (BAY K8644) to enhance responses to a hypocapnic challenge, it did not alter peripheral airway responses to dry air. Neither nifedipine nor BAY K8644 affected airway wall temperature at any time during the dry air experiments. We conclude that dihydropyridine receptors do not play a significant role in initiating AIB in the canine lung periphery.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Clinical features of hepatopulmonary syndrome in cirrhotic patients.

AIM: To evaluate the frequency, clinical and paraclinical features of hepatopulmonary syndrome (HPS) and to determine their predictive values in diagnosis of this syndrome in patients in Iran. METHODS: Fifty four cirrhotic patients underwent contrast enhanced echocardiography to detect intrapulmonary and intracardiac shunts by two cardiologists. Arterial blood oxygen, O(2) gradient (A-a) and orthodoxy were measured by arterial blood gas (ABG) test. The patients positive for diagnostic criteria of HPS were defined as clinical HPS cases and those manifesting the intrapulmonary arterial dilation but no other criteria (arterial blood hypoxemia) were defined as lHPS cases. HPS frequency, sensitivity, positive and negative predictive values of clinical and paraclinical features were studied. RESULTS: Ten (18.5%) and seven (13%) cases had clinical and subclinical HPS, respectively. The most common etiology was hepatitis B. Dyspnea (100%) and cyanosis (90%) were the most prevalent clinical features. Dyspnea and clubbing were the most sensitive and specific clinical features respectively. No significant relationship was found between HPS and splenomegaly, ascites, edema, jaundice, oliguria, and collateral veins. HPS was more prevalent in hepatitis B. PaO(2)< 70 and arterial-alveolar gradient had the highest sensitivity in HPS patients. Orthodoxy specificity was 100%. CONCLUSION: Clubbing with positive predictive value (PPV) of 75% and dyspnea with negative predictive value (NPV) of 75% are the best clinical factors in diagnosis of HPS syndrome. PaO(2)< 70 and P (A-a) O(2)> 30 and their sum, are the most valuable negative and positive predictive values in HPS patients.

Adult↗

[Magnetic resonance and arthroscopy of the knee. A double-blind study in 40 patients].

To evaluate the capabilities of ultra-low-field MR for the high-resolution imaging of the knee with a short acquisition time, a prospective double-blind study was carried out on 40 consecutive patients with acute or chronic articular conditions who were examined with both MR imaging and arthroscopy. Three-dimensional gradient-echo MR sequences were employed which allow many thin high-resolution slices to be obtained in a relatively short time. To evaluate the results arthroscopy, performed the day after MR imaging, was considered the gold standard. MR imaging and arthroscopy were in agreement in 84.6% of meniscal tears with 91.6% sensitivity and 80% specificity, in 82% of anterior cruciate ligament lesions with 100% sensitivity and 80% specificity and in 81% of cartilage lesions with 100% sensitivity and 61% specificity. On the whole, MR imaging and arthroscopy were in agreement in 82.5% of cases with 97.2% sensitivity and 75.3% specificity. MR imaging gave more information about collateral ligament, muscle and bone involvement. These results confirm the capabilities of ultra-low-field MR imaging in the study of the knee: the technique allows diagnostic studies to be performed in a short time, at a low cost, and with similar results to those obtained with higher field strengths.

Anterior Cruciate Ligament↗

[The effect of ultrasonic therapy in rheumatoid arthritis of the temporomandibular joint].

The mouth opening distance, the joint pressure sensitiveness and the biting strength have been measured. In the treated group all three examined parameters showed significant improvement while in the placebo group two parameters (pressure sensitiveness and mouth opening distance) changed significantly. The placebo effect collateral to the real therapeutic effect is not a rare phenomenon in physico-therapy. However, the real effect of the physico-therapeutic treatment can be judged only by means of double blind examination.

Adult↗

[Oculo-cutaneous albinism in man. Biochemical, genetic, clinical, and population aspects].

Oculocutaneous albinism comprises hereditary disorders in which there is a congenital absence or reduction of melanin in the skin, hair and eyes, coupled with nystagmus, photophobia and reduced visual acuity. The body is unable to make melanin (a compound derived from the metabolism of tyrosine) due to the functional absence of the enzyme tyrosinase. The disease is transmitted as an autosomal recessive character. In man, there are six conditions distinguishable in relation to their frequency, and their clinical, biochemical, ultrastructural, and genetic characteristics. The attempt to identify the heterozygote has led to contradictory results. Abnormal transparency of the iris has only been observed in some heterozygotes, and this feature cannot be used to recognise carriers. As far as treatment is concerned, the two main problems are sensitivity to sunlight, with concomitant susceptibility to skin tumors, and collateral vision disturbances. Subjects should avoid direct sunlight. Photophobia can be reduced by wearing sunglasses.

Albinism↗

A new device and method for controlling the load in rabbit medial collateral ligament reconstructions.

In order to study the effect of intra-operative tensioning on the laxity and strength of healing ligament grafts in an animal model, a method of quantifying graft tension was needed. In this study a sensitive ligament tensioning device was developed to measure accurately the prefixation loads in the rabbit medial collateral ligament (MCL) graft. To verify that reproducible changes in ligament tension could be created with the tensioning device, a group of animals had their MCL grafts replaced at one of three different graft loads (tight, anatomic, or loose). The tensioning device consists of two posts which move relative to one another by means of an axial screw. The movable post, which is inserted into the tibial bone island of the MCL graft has a series of strain gauges which can measure the tension applied to the graft. The stationary post attaches to the tibial shaft, permitting the ligament graft to be tensioned relative to this fixed point. After graft tensioning and fixation, the animals were euthanized immediately postoperatively and their ligament load-deformation behavior was measured using an Instron materials testing machine. Specific measures of low load behavior was taken to quantify ligament laxity. Our results demonstrate that the tensioning device was capable of reproducibly altering prefixation graft load intra-operatively as well as MCL laxity immediately postoperatively. A baseline of laxity values was thus developed to follow changes in this laxity measure for future studies of MCL graft healing in this model.

Animals↗

Analysis in yeast of antimalaria drugs that target the dihydrofolate reductase of Plasmodium falciparum.

Pyrimethamine and cycloguanil are competitive inhibitors of the Plasmodium enzyme dihydrofolate reductase (DHFR). They have been effective treatments for malaria, but rapid selection of populations of the parasite resistant to these drugs has compromised their effectiveness. Parasites resistant to either drug usually have point mutations in the dhfr gene, but the frequency of these mutations is unknown. To study drug resistance more effectively, we transferred the DHFR domain of the dhfr-thymidylate synthase gene from a drug-sensitive line of P. falciparum to a strain of the budding yeast, Saccharomyces cerevisiae, that lacks endogenous DHFR activity. Expression of the P. falciparum dhfr is controlled by the yeast dhfr 5' and 3' regulatory regions and the heterologous enzyme provided all of the functions of the yeast dhfr gene. These yeast were susceptible to pyrimethamine and cycloguanil at low concentrations that inhibit P. falciparum (IC50 about 10(-8) and 10(-7) M, respectively). Yeast expressing constructs with dhfr alleles from pyrimethamine-resistant strains were resistant to both pyrimethamine and cycloguanil (IC50 > 10(-6) M); resistance of the yeast depended on the dhfr allele they expressed. The experimental drug WR99210 efficiently killed all three yeast strains (IC50 about 10(-8) M) but the pyrR strains showed collateral hypersensitivity to drug. The yeast transformants carrying the drug-sensitive allele can now be screened quickly and quantitatively to identify new drugs or combinations of drugs and determine which drugs select resistant parasites least efficiently. Such compounds would be excellent candidates for development of treatments with a longer life in clinical practice.

Animals↗

Factors influencing the diagnostic sensitivity of the exercise test in coronary artery disease.

A continuous multistage bicycle ergometer test was performed on 50 patients with coronary artery disease. Selective cinecoronary angiography and left ventriculography were performed within a week of the test in all patients. Overall, 62% had a positive ischemic response, defined as 1 mm or greater depression of the ST segment. Patients with 75% or greater stenosis in any vessel and those with triple-vessel involvement had a higher incidence of positive tests. Those with low systolic ejection fractions and areas of asynergy had fewer positive tests than patients with normal ejection fractions and normal or minimal segmental wall motion abnormalities. The level of exercise, location of arterial disease and the presence of collateral blood supply to the diseased vessels did not appear to influence the sensitivity of the exercise stress test.

Adult↗

Factors that determine the occurrence of arrhythmias during acute myocardial ischemia.

To elucidate the determinants of arrhythmias during acute myocardial ischemia, a 25-minute coronary artery occlusion was performed in 101 open-chest dogs. Heart rate correlated positively with the number of premature ventricular complexes (PVCs) and the occurrence of ventricular tachycardia (VT) and fibrillation (VF). The size of the occluded coronary bed was positively correlated with the occurrence of VF, but exhibited only a weak association with PVCs and VT. Coronary collateral flow exhibited a strong negative correlation with all forms of arrhythmias. Importantly, a sensitive coupling was present, whereby small differences in flow were associated with large differences in rhythm disorders. VT occurred in all ranges of occluded bed size examined, but within any given range, its incidence was inversely related to collateral flow. Thus, VT is relatively independent of occluded bed size, and is determined primarily by the degree of myocardial hypoperfusion. In contrast, even in the presence of low flows, VF did not develop with occluded beds less than 28% of left ventricular mass; above this critical occluded bed size, the incidence of VF was inversely related to collateral perfusion. VF is therefore determined by the association of a large occluded bed with a poor collateral function. This study identifies and systematically analyzes three major determinants of arrhythmias during acute myocardial ischemia: the heart rate, the amount of ischemic myocardium, and the severity of myocardial flow reduction. The finding that these factors account for most of the variability in the occurrence of malignant tachyarrhythmias has important methodological and clinical implications.

Animals↗

Coactivation of Local Circuit NMDA Receptor Mediated epsps Induces Lasting Enhancement of Minimal Schaffer Collateral epsps in Slices of Rat Hippocampus.

Lasting enhancement of minimal Schaffer collateral epsps in CA1 pyramidal neurons was induced when these epsps were coactivated with putative local circuit N-methyl-d-aspartate (NMDA) receptor-mediated epsps. In transverse slices of hippocampus, minimal epsps were evoked by stimulating the Schaffer collateral/commissural pathway within CA3 stratum radiatum and the local circuit axons were stimulated within CA1 stratum oriens or alveus using fine, two barrel glass micropipettes. Minimal Schaffer collateral epsps were insensitive to d-2-amino-5-phosphonovalerate (AP-5) and displayed conventional voltage relations. Local epsps were sensitive to AP-5 and increased in amplitude and duration with membrane depolarization. High frequency tetanic stimulation of the minimal Schaffer collateral epsps induced no lasting enhancement. However, pairing of the Schaffer epsp with a frequency potentiated local epsp resulted in a delayed, but lasting increase in the Schaffer epsp. When the local epsp did not exhibit frequency potentiation during pairing, no enhancement resulted. When either epsp was contaminated with an ipsp, no lasting increase resulted. When transmission through the alveus was blocked by focal application of local anaesthetic, traditional protocols for long-term potentiation (LTP) induction were relatively ineffective. These results indicate that a significant source of the NMDA receptor activation required for the induction of LTP in the Schaffer collateral input to CA1 derives from local circuit connections between CA1 pyramidal neurons and, moreover, that lasting enhancement can be induced with low frequency activation, at postsynaptic resting potential, in the presence of Mg2+ and with local inhibition intact.

Journal Article↗