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Biomedical subjects

R Maciewicz

Publications and source records attributed to R Maciewicz.

At least 19 recordsLinked to original sources
PubMed2000

Aerobic fitness testing in patients with chronic low back pain: which test is best?

STUDY DESIGN: This is a randomized comparison of three exercise tests in a sample of 30 patients with chronic low back pain. OBJECTIVES: To determine, by comparing three exercise tests, which test yields the highest peak and predicted oxygen consumption in a sample of patients with chronic low back pain. SUMMARY OF BACKGROUND DATA: Little is known about the level of aerobic fitness in patients with chronic low back pain, although many rehabilitation programs emphasize aerobic exercise as an important part of their therapy. Measurement of aerobic fitness levels in these patients remains a problem. In healthy individuals, the highest oxygen consumption values come from exercise tests that use the largest muscle groups. For a number of reasons, this may not be true in patients with chronic low back pain. METHODS: In this study, 30 participants with chronic low back pain performed three symptom-limited maximal exercise tests: a treadmill, an upper extremity ergometer, and a bicycle ergometer. The tests were administered in randomized order. Heart rate was continuously monitored and oxygen consumption in terms of mL/kg/minute was measured by indirect calorimetry each 30 seconds. RESULTS: The statistical difference among the tests was highly significant (P < 0.0001). The treadmill test yielded the highest peak and predicted oxygen consumption followed by the bicycle and the upper extremity ergometer test, respectively. CONCLUSIONS: The treadmill test is the best test for measuring aerobic fitness levels in patients with chronic low back pain. It yielded the highest peak oxygen consumption compared with the other tests, coming closest to measuring maximal oxygen consumption.

Adolescent↗
PubMed2000

Comorbidity of post-traumatic stress disorder and chronic pain: implications for clinical and forensic assessment.

A summary of the current state of science is presented with reference to post-traumatic stress disorder (PTSD) and pain. Historical development of the diagnosis, current nosology, epidemiology, pathophysiology, and controversies are discussed. Issues of evaluation are reviewed, with specific reference to forensic assessment. Treatment outcome studies are briefly reviewed, with a review of currently accepted treatment interventions, including pharmacologic and behavioral modalities. An emphasis is placed on an integrated treatment plan in which chronic pain and PTSD both are present.

Chronic Disease↗
PubMed2000

Treatment with soluble VEGF receptor reduces disease severity in murine collagen-induced arthritis.

Maintenance of the invasive pannus in rheumatoid arthritis is an integral part of disease progression. The synovial vasculature plays an important role in the delivery of nutrients, oxygen, and inflammatory cells to the synovium. Vascular endothelial growth factor (VEGF), an endothelial mitogen expressed by cells within the synovial membrane, is thought to contribute to the formation of synovial blood vessels. Our objective in this study was to measure the kinetics of VEGF production in a murine model of collagen-induced arthritis and to determine whether VEGF blockade reduces disease progression. Synovial cells isolated from the knee joints of naive or sham-immunized mice, or from mice immunized with collagen but without arthritis, released little or no detectable VEGF. Onset of arthritis was associated with expression of VEGF mRNA and protein. The levels of VEGF secreted by synovial cells isolated from the joints of mice with severe arthritis were significantly higher than from mice with mild disease. To block VEGF activity, animals were treated after arthritis onset with a soluble form of the Flt-1 VEGF receptor (sFlt), which was polyethylene glycol (PEG)-linked to increase its in vivo half-life. Treatment of arthritic mice with sFlt-PEG significantly reduced both clinical score and paw swelling, compared with untreated or control-treated (heat-denatured sFlt-PEG) animals. There was also significantly less joint inflammation and reduced bone and cartilage destruction in sFlt-PEG-treated animals, as assessed by histology. Our data demonstrate that, in collagen-induced arthritis, expression of the potent angiogenic cytokine VEGF correlates with disease severity. Furthermore, specific blockade of VEGF activity results in attenuation of arthritis in both macroscopic and microscopic parameters. These observations indicate that blood vessel formation is integral to the development of arthritis and that blockade of VEGF activity might be of therapeutic benefit in rheumatoid arthritis.

Animals↗
PubMed1999

New alpha-substituted succinate-based hydroxamic acids as TNFalpha convertase inhibitors.

Tumor necrosis factor alpha convertase (TACE), the enzyme responsible for the processing of pro-TNFalpha to TNFalpha, has been reported to be a metalloproteinase closely related to matrix metalloproteinases (MMPs). Current inhibitors of TACE such as succinate-based hydroxamic acids exemplified by Marimastat (TACE IC(50): 3.8 nM; blood IC(50): 7 microM) and BB1101 (TACE IC(50): 0.2 nM; blood IC(50): 2.3 microM) suffer from modest potency in blood and poor in vivo properties. The introduction of new bulky alpha-substituents into these succinate-based hydroxamic acids was studied. Substituents such as thioethers, sulfonamides, and ethers showed improved potency against TACE when compared with Marimastat. Although this improvement did not translate into better blood potency for thioether or ether substituents, the sulfonamide series exhibited improved potency both against TACE and in blood when compared with Marimastat. Optimization of this sulfonamide series has culminated in the identification of heterocyclic bicyclic sulfonamides such as 3t (TACE IC(50): 0.57 nM; blood IC(50): 0.28 microM).

ADAM Proteins↗
PubMed1996

Sustained-release morphine sulfate in the management of pain associated with acquired immune deficiency syndrome.

Sustained-release morphine (SRM) was studied in patients with acquired immune deficiency syndrome (AIDS)-related chronic pain. Outpatients and inpatients with AIDS-related pain were studied for 3-18 days in an open-label prospective survey. Patients were stratified according to prior opioid analgesic use for the purposes of initiating and titrating SRM, which was administered at a 12-hr interval. Immediate-release morphine (IRM) was offered every 2 hr as needed for supplemental analgesia at one-quarter to one-third of the 12-hourly SRM dose. Pain intensity (PI), quality of life (QL), acceptability of therapy (AT), side effects, safety, and morphine usage were evaluated. Of 44 patients enrolled, 40 (91%) were evaluable for intent-to-treat analysis, and 24 (55%) completed the study. PI decreased by 50% (from severe to mild-moderate) in the intent-to-treat patients and by 65% (from severe to mild) in the completed patients. QL was fair to good in 80% and poor in 20% of both groups. AT was good to excellent in 78% of the intent-to-treat and in 96% of the completed patients. Of 61 adverse events reported, 61% required intervention, and 92% were resolved. Total morphine dose remained stable while IRM dosage and frequency of use significantly decreased with escalation of the SRM dose. A significant reduction in PI was achievable with SRM in a variety of painful conditions experienced by AIDS patients, with limited or manageable side effects in most. This study supports the usefulness of opioid analgesia for severe pain in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1991

MK-801 blocks the development of thermal hyperalgesia in a rat model of experimental painful neuropathy.

Loose ligation of the sciatic nerve in the rat can produce behavioral signs of hyperalgesia in the hindpaw. This study examined the effect of an NMDA (N-methyl-D-aspartate) receptor antagonist (MK-801) on the development of hyperalgesia in this model. Rats received i.p. injections of saline or MK-801 (1.0 mg/kg) prior to and then for 7 days after a unilateral sciatic nerve ligation. Testing of each hindpaw for latency to withdrawal from a standardized thermal stimulus was performed prior to ligation and then at 10, 12, 17, 27, and 37 days postoperatively. Hyperalgesia of the operated hindpaw developed in saline-treated animals as measured by a decrease in withdrawal latency. Hyperalgesia did not develop in animals treated with MK-801. MK-801 may therefore prevent the development of hyperalgesia following experimental nerve injury, possibly through an NMDA receptor-mediated effect.

Animals↗
PubMed1990

Ultrastructure of intracellularly labeled trigeminal vascular convergence neurons.

Brainstem trigeminal vascular convergence (TVC) neurons receive an excitatory, nociceptive input from cranial blood vessels as well as the facial skin or cornea. In the present study, a population of cat TVC neurons was electrophysiologically identified and then intracellularly labelled with horseradish peroxidase. One TVC neuron from lamin IV and one from lamina V were processed for electron microscopy. Both cells have extensive axon terminal fields within trigeminal nucleus interpolaris as well as lamina IV and V of trigeminal nucleus caudalis. Analysis of thin sections showed that the soma and dendrites of the TVC neurons are contacted by synaptic terminals of various types. Both cells have myelinated axons and collaterals that give rise to unmyelinated preterminal processes. Within nucleus caudalis, terminals of the TVC cells contain round synaptic vesicles that synapse primarily with dendrites and spines.

Animals↗
PubMed1988

Serotonin immunocytochemistry of physiologically characterized raphe magnus neurons.

To determine if PAG stimulation activates serotonin containing neurons in RM, intracellular techniques were used to identify raphe magnus (RM) cells that are excited by antinociceptive periaqueductal gray (PAG) stimulation in the cat. RM neurons that received a monosynaptic EPSP from PAG shock were intracellularly labeled with ethidium bromide. Intracellularly stained RM cells were large, medium and small sized neurons. To determine if these cells contain serotonin, sections containing intracellularly labeled RM neurons were processed for serotonin immunocytochemistry. None of the RM cells (N = 32) which were intracellularly stained with ethidium bromide contained immunoreactive serotonin. These results are evidence that non-serotonergic RM cells are activated by antinociceptive PAG stimulation; these cells may be important in the relay of PAG induced antinociception.

Action Potentials↗
PubMed1987

Edinger-Westphal nucleus: cells that project to spinal cord contain corticotropin-releasing factor.

Combined retrograde transport and immunocytochemical methods were used to determine whether neurons in the Edinger-Westphal complex (EW) that project to the spinal cord also demonstrate corticotropin-releasing factor-like immunoreactivity (CRF-LI). Large injections of horseradish peroxidase (HRP) into cervical spinal cord retrogradely labeled cells throughout the extent of the EW complex. Most retrogradely labeled EW neurons also exhibited CRF-LI, evidence that EW is the origin of a direct CRF-containing pathway which links the rostral mesencephalon with spinal cord.

Animals↗
PubMed1987

Choline acetyltransferase immunocytochemistry of Edinger-Westphal and ciliary ganglion afferent neurons in the cat.

The distribution of cholinergic neurons in the region of the cat Edinger-Westphal nucleus (EW) was determined by immunocytochemical localization of the acetylcholine-synthesizing enzyme choline acetyltransferase (ChAT). Neurons containing ChAT-like immunoreactivity (ChAT-LI) were densely distributed within EW, the anteromedian nucleus (AM), and the oculomotor nucleus (III), and were also present in immediately adjacent regions of the periaqueductal gray and ventral tegmental region. The majority of labelled neurons in EW and AM showed a markedly lower intensity of ChAT-LI than the labelled neurons in III and adjacent regions. To determine the relationship of cells with ChAT-LI to the distribution of ciliary ganglion afferent neurons, a double labelling immunocytochemistry/retrograde transport technique was also used. These experiments showed that many of the cells located outside of III that stained intensely for ChAT-LI project to ciliary ganglion. Very few ciliary ganglion afferent neurons were found in EW or AM itself; instead, the distribution of lightly labelled ChAT-LI-positive neurons in EW and AM more closely matched the known distribution of peptide-containing cells that have descending, central projections.

Afferent Pathways↗
PubMed1987

Suppression of the jaw-opening reflex by periaqueductal gray stimulation is decreased by paramedian brainstem lesions.

Electrical stimulation of the midbrain periaqueductal gray region (PAG) suppresses the tooth pulp-evoked jaw-opening reflex (TP-JOR). In the present study the pathways that mediate this suppression were investigated by placing brainstem lesions in lightly anesthetized cats. Parasagittal lesions that interrupted the afferent and efferent connections of the medullary and pontine raphe nuclei attenuated (but did not abolish) suppression of the TP-JOR evoked by PAG stimulation. This result provides further evidence that medial brainstem structures partially mediate the effects of PAG stimulation in the trigeminal system.

Animals↗
PubMed1987

Clinical management of neuropathic pain.

Neuropathic pain is often a significant source of protracted suffering, seriously impairing efforts at functional rehabilitation of affected patients. The assessment and treatment of pain symptoms in patients with disease affecting peripheral and central somatosensory pathways is therefore an important problem in clinical management and rehabilitation of patients with neurologic disease.

Animals↗
PubMed1986

Intracellular responses of raphe magnus neurons during the jaw-opening reflex evoked by tooth pulp stimulation.

Neurons in the nucleus raphe magnus (RM) may play an important role in the modulation of nociception. To determine how RM neurons are activated during a nociceptive reflex, the intracellular responses of raphe neurons were studied during the jaw-opening reflex (JOR) elicited by tooth pulp shock in lightly anesthetized cats. Tooth pulp stimulation produces reflex EMG activation of the digastric muscle at a latency of 7-11 ms, resulting in jaw opening. Tooth pulp shock that elicits the JOR also produces an EPSP in a subset of raphe neurons. This EPSP consists of an early small depolarization that occurs at a latency of 10-15 ms followed by a larger depolarization at a latency of 20-60 ms. In all cases the latency to EPSP is longer than the latency to digastric EMG onset. Electrical stimulation of the 4 paws elicits oligosynaptic EPSPs in the same cells at a latency of 16-20 ms. Electrical train stimulation of the midbrain periaqueductal gray region (PAG) suppresses the JOR. Single shock stimulation at the same PAG sites that suppress the JOR evokes monosynaptic EPSPs in the large majority of raphe neurons recorded. In all cases, the threshold for EPSP is below the threshold for suppression of the JOR. The EPSP amplitude is a direct function of PAG stimulus intensity and there is temporal summation of EPSPs evoked by paired PAG shocks. At condition-test intervals of 40-90 ms, train stimulation of PAG suppresses the tooth pulp-evoked EPSP in raphe neurons. The threshold for EPSP suppression occurs at a PAG stimulation intensity below that required for suppression of the JOR. The present findings provide evidence that RM neurons may play an important role in the modulation of the tooth pulp-evoked JOR, but only after the initial withdrawal reflex has occurred.

Animals↗
PubMed1986

Response of brainstem trigeminal neurons to electrical stimulation of the dura.

The extracellular response of medullary trigeminal neurons to electrical stimulation of the dura was studied in anesthetized cats. Fifty-six medullary trigeminal units were excited by stimulation sites near major dural vessels with an average latency of 11.0 ms. Many units also responded to infraorbital nerve shock and had cutaneous receptive fields that included the ipsilateral periorbital region. These cutaneous responses were either wide dynamic range or nociceptive specific in type. Electrical stimulation of the midbrain periaqueductal gray region suppressed the response of medullary trigeminal units to either dural stimulation or infraorbital nerve shock. Medullary trigeminal neurons that receive convergent inputs from dura and facial skin may provide a physiological substrate for the cutaneous referral of dural sensation.

Animals↗
PubMed1985

Pontomedullary raphe neurons: monosynaptic excitation from midbrain sites that suppress the jaw opening reflex.

The intracellular responses of pontomedullary raphe neurons to midbrain stimulation were studied in chloralose anesthetized cats. Electrical stimulation of the periaqueductal gray region at sites that suppressed the nociceptive jaw opening reflex evoked monosynaptic excitatory postsynaptic potentials in the majority of raphe neurons recorded. Intracellular labeling of studied cells demonstrated that recordings were obtained primarily from large and medium sized neurons in nucleus raphe magnus and the rostral nucleus raphe obscurus. These results provide further evidence that analgesia induced by periaqueductal gray stimulation may result in part from the direct activation of caudal raphe neurons.

Analgesia↗