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Thermoregulatory manifestations of systemic inflammation: lessons from vagotomy.

The multiple effects of vagotomy on the thermoregulatory response to systemic inflammation are reviewed (primarily, for the model of intravenous lipopolysaccharide administration in the rat). The following conclusions are drawn. (1) Vagotomy-associated thermoeffector insufficiency is likely to account for the attenuation of the fever response observed in some--but not all--studies; such an insufficiency is, however, preventable by postoperative care, including the use of a liquid diet. (2) The febrile response to low doses of lipopolysaccharide (monophasic fever) is mediated by the hepatic (but not gastric or celiac) vagal fibers, presumably afferent; the same fibers are likely to be involved in the development of tolerance to low doses of circulating endotoxins. (3) Phase 1 of the polyphasic febrile response to moderate doses of lipopolysaccharide involves capsaicin-sensitive afferents (either nonvagal only or both nonvagal and vagal), does not involve cholecystokinin A-receptors, and may involve peripheral prostaglandins. (4) Febrile phase 2 does not require the integrity of abdominal nerve fibers, either vagal or nonvagal, at least in the rat. (5) Phase 3 of the febrile response to intravenous lipopolysaccharide (and perhaps the response to intraperitoneal lipopolysaccharide) involves capsaicin-insensitive vagal fibers, presumably efferent; the involvement of these fibers in febrigenic mechanisms is strongly modulated by an unknown factor. (6) A hepatoceliac vagal, presumably efferent, mechanism ('an anti-inflammatory pathway') counteracts the development of lipopolysaccharide-induced hypothermia and shock.

Animals↗

Development and initial validation of an instrument to measure perceived coercion to enter treatment for substance abuse.

The present study involved 3 phases that led to the development and initial validation of the Perceived Coercion Questionnaire (PCQ), a scale that researchers use to measure perceptions of coercion of drug and alcohol users to enter drug and alcohol treatment. In Phase 1, the authors used focus groups to generate 48 pilot items. In Phase 2, the items were administered to a sample of 158 drug and alcohol users who were in residential treatment within a therapeutic community setting. Item and exploratory factor analyses reduced the number of items to 32, which represented 6 homogeneous and internally reliable subscales. In Phase 3, the PCQ was administered to a second sample of 362 drug and alcohol users. Confirmatory factor analysis led to a final scale of 30 items across 6 subscales that demonstrated sound consistency and validity. Implications for research and practice are highlighted.

Adaptation, Psychological↗

Influence of acute shortening on the spinal cord: an experimental study.

STUDY DESIGN: Morphometric changes of the spinal cord and influence on spinal cord-evoked potentials and spinal cord blood flow and postoperative function of hind limbs were studied in various degrees of acute spinal column shortening in dogs. OBJECTIVES: To study the morphometric and physiologic effects of acute spinal column shortening on the spinal cord. SUMMARY OF BACKGROUND DATA: The technique of acute spinal column shortening is sometimes applied for correction of spinal deformity, total en bloc spondylectomy operation, or other diseases. However, safe limits and physiologic effects of acute spinal column shortening have not yet been described. METHODS: Total spondylectomy of T13 was performed in dogs after spinal instrumentation placed 2 levels above and 2 levels below the spondylectomy level. Spinal column was gradually shortened until the lower endplate of T12 contacted the L1 upper endplate (maximum of 20 mm). When any morphologic change of the dural sac or the spinal cord was observed, the length of shortening was measured. Spinal cord-evoked potentials were recorded on the exposed dura mater following epidural stimulation at the C7 level in 8 dogs. Spinal cord blood flow was measured during shortening in 6 dogs. Hindlimb function was evaluated 2 weeks after operation in 10 dogs. RESULTS: No morphometric changes occurred in the dural sac and the spinal cord until shortening of 7.2 +/- 1.7 mm (n = 6). From 7.2 +/- 1.7 to 12.5 +/- 1.1 mm shortening, the dural sac was deformed, whereas the spinal cord maintained its shape. Shortening more than 12.5 +/- 1.1 mm buckled the dural sac, and the spinal cord kinked itself and was compressed by the buckled dura in its concave side (n = 6). No changes could be detected in spinal cord-evoked potentials in 5 or 10 mm of shortening. Spinal cord-evoked potential changes were recorded in the 2 of 6 dogs with 15 mm of shortening. At 20 mm of shortening, spinal cord-evoked potential abnormality was observed in 4 of 6 dogs. At shortening of 5, 10, 15, and 20 mm, spinal cord blood flow was 146 +/- 10%, 160 +/- 21%, 102 +/- 17%, and 93 +/- 7% of the control (29.2 +/- 7.9 mL/100 g/min, n = 6), respectively. All 3 dogs with 10 mm ofshortening had normal hindlimb function 2 weeks after operation. One of the 3 dogs with 15 mm of shortening had paraparesis. Three of the 4 dogs with 20 mm of shortening had also paraparesis after operation. CONCLUSIONS: Acute spinal column shortening can be characterized into 3 phases. Phase 1, safe range: occurred during shortening within one-third of the vertebral segment and is characterized by no deformity of the dural sac or the spinal cord. Phase 2, warning range: occurred during spinal shortening between one-third and two-thirds of the vertebral segment and is characterized by shrinking and buckling of the dural sac and no deformity of the spinal cord. Phase 3, dangerous range: occurred after shortening in excess of two-thirds of the vertebral segment and is characterized by spinal cord deformity and compression by the buckled dura. Spinal shortening within the safe range increases spinal cord blood flow.

Animals↗

On the dynamics of periodontal tissue formation in degree III furcation defects. An experimental study in dogs.

The aim of the experiment was to describe the formation of periodontal tissues in degree III furcation defects following GTR therapy. The study was performed in 8 foxhound dogs. The 2nd and 4th premolars in both sides of the mandible were extracted. Furcation defects were produced in the 3rd mandibular premolars. 3 weeks later, reconstructive surgery was performed. The dogs were scheduled for sacrifice 2, 4, 8, and 20 weeks after GTR therapy. Tissue blocks containing the experimental teeth were excised, demineralized in EDTA and embedded in paraffin. Serial sections were cut in the mesio-distal plane and parallel with the long axis of the roots. The microtome was set at 7 microns. The sections were stained in hematoxyline and eosin. From each biopsy, 3 sections representing the central part of the furcation, were selected for light microscopic examination. In the healed furcation sites, descriptive histological analysis of the newly-formed tissues was performed and the relative proportions of the hard and soft tissues were determined. It was demonstrated that at 2 weeks, the furcation defect contained granulation tissue and cell-rich connective tissue, while at 4 weeks the furcation was mainly occupied by connective tissue. At 8 weeks, woven bone occupied the central portion of the furcation, whereas connective tissue and cementum were observed in the lateral portions. The furcation area at 20 weeks was comprised of newly-formed cementum, periodontal ligament and bone. The onset of cementum formation had started as early as 2 weeks after GTR therapy. The cementum formation apparently occurred in 3 phases: organisation of collagen fibers adjacent and perpendicular to the root surface (phase 1), assembly of the collagen fibers and deposition of matrix (phase 2), and addition of cells and collagen fibers organised parallel to the root surface (phase 3). Bone formation took place through a process that included (1) organisation of a fibrous connective tissue, (2) differentiation of this tissue into woven bone and, (3) maturation of the woven bone into lamellar bone and bone marrow.

Alveolar Process↗

Mental health care from the public perspective: the Texas Medication Algorithm Project.

Medication treatment algorithms have been suggested as a strategy to provide uniform care at predictable costs. The Texas Medication Algorithm Project is a 3-phase study designed to provide solid data on the usefulness of medication algorithms. In phase 1, medication algorithms for the treatment of schizophrenia, major depressive disorder, and bipolar disorder were developed. Phase 2 was a feasibility study of these algorithms, and phase 3, now underway, compares the costs and outcome in 3 groups, one using a combination of an algorithm and patient/family education, a second using treatment as usual in a clinic that uses an algorithm for a different disorder, and a third using treatment as usual in a nonalgorithm clinic.

Algorithms↗

Vitamin D and scalp psoriasis.

Calcipotriene has been shown to be safe and effective for the treatment of psoriasis. For scalp psoriasis, the safety advantage of this nonsteroid agent is as important as its efficacy. Even though monotherapy with calcipotriene solution may not always be efficacious for severe scalp psoriasis, many patients are managed effectively with a sequential therapy regimen consisting of 3 phases. In phase 1 (clearing), patients apply clobetasol solution or gel in the morning and calcipotriene solution in the evening daily for 2 weeks. After the scalp psoriasis improves, clobetasol is reduced to weekends and calcipotriene solution is applied on weekdays (phase 2, transitional). Phase 3 is maintenance on calcipotriene solution alone to prevent recurrence. For patients with recalcitrant scalp psoriasis-where only a clobetasol-strength, superpotent topical corticosteroid is effective-a flip-flop therapy regimen has been proposed that allows for the safe, prolonged use of clobetasol solution by limiting its treatment to twice a day for 2-week periods with the use of calcipotriene solution twice a day for a minimum of 2 weeks during the corticosteroid-free in-between periods.

Administration, Topical↗

Effect of triclosan dentifrice on toothbrush contamination.

PURPOSE: The objective of this study was to evaluate by culture and scanning electron microscopy (SEM) the contamination of toothbrushes of 30 children (5-7 years old) by mutans streptococci (MS) when dentifrices with or without triclosan are used. METHODS: The clinical procedures were divided into 3 phases at 1-week intervals. In phase 1 (group I), the children brushed their teeth without dentifrice for 4 minutes; phase 2 (group II) brushed with fluoridated dentifrice (Tandy); phase 3 (group III) brushed with dentifrice containing triclosan (Colgate Total). The toothbrushes were then submitted to microbiological processing for the counting of colony-forming units (CFUs) of MS adhered to the bristles. Four toothbrushes from each group were analyzed by SEM. RESULTS: MS were present on 93% of group I toothbrush bristles and on 77% of group II toothbrush bristles. Only 40% of group III toothbrushes were contaminated with MS. When there was a positive microbiological culture, the formation of cariogenic bacterial biofilm adhered to the bristles of all groups was identified by SEM. CONCLUSIONS: Toothbrush bristles were contaminated by MS after only one use. A dentifrice containing triclosan significantly reduced bacterial contamination of these toothbrushes.

Anti-Infective Agents, Local↗

Musculoskeletal pain, disability and health-seeking behavior in adult Kuwaitis using a validated Arabic version of the WHO-ILAR COPCORD Core Questionnaire.

OBJECTIVE: The WHO-ILAR Community Oriented Program for Control of Rheumatic Diseases (COPCORD) primarily aims to estimate the burden of musculoskeletal symptoms/disorders. We investigated data on musculoskeletal pain, disability and health-seeking behavior in the first community-based COPCORD study in Kuwait. METHODS: The validated Arabic version of the WHO-ILAR COPCORD Core Questionnaire was used in 2,500 randomly selected Kuwaiti households. The target population comprised Kuwaiti nationals aged 15 years and older. Twenty-four trained field workers completed the survey in 8 weeks. Those subjects reporting musculoskeletal pain were identified (Phase 1), and were asked to complete a self-evaluation questionnaire (Phase 2) prior to rheumatological examination (Phase 3). Phase 2 included questions on the site and severity of pain, traumatic events, functional disability, and treatment. Patients marked their pain sites on a mannequin during their interviews. "Sufferers" were defined as those with musculoskeletal pain and no history of trauma. RESULTS: A total of 7,670 adults were interviewed (response rate 88%), of whom 2,057 had musculoskeletal pain not related to trauma. Knees, back, and shoulders were the common sites of pain. Most of the sufferers reported the severity of pain as being moderate to severe. Functional disability was reported in 39.1% of the sufferers. The age-sex population adjusted prevalence rate for musculoskeletal pain was 35.7% in females and 20.2% in males. The most common sources for advice on treatment were physicians in hospitals (68.8%) and general practitioners (30.4%). 82% had prescriptions for their medications, while 19.4% had self prescribed tablets. CONCLUSION: Musculoskeletal pain is a major health problem among Kuwaitis and deserves intense government attention.

Adolescent↗

[Infantile cortical hyperostosis (Caffey-Silverman syndrome). Histologic, histochemical and electron microscopic studies].

Infantile cortical hyperostosis, also known as Caffey's disease or Caffey-Silverman syndrome, is an uncommon clinico-pathological lesion of unknown etiology and uncertain histogenesis. One of the most striking features is the early age of patients at the onset of the disease, showing swelling of the soft tissues overlaying bones, hyperirritability, and, subsequently, periosteal new bone production. The natural history of the disease proves to be self-limiting. Multiple areas are involved in the majority of cases. These polyostic forms are easily clinically diagnosed. But in rare monostic presentations, especially manifestations in the scapular region, there may be a great suspicion of a malignant tumor. Histologically, such lesion may also be misdiagnosed as a malignant neoplasm because of the great variety of microscopic appearances. This study was conducted into 5 cases (biopsies from one male and four female infants, 6 weeks to 4 months of age) to characterize the histological variability in the natural course of the disease. Electron microscopical investigations were additionally performed on two cases. Histologically, the process corresponds to typical ossifying periostitis. Three phases can be distinguished according to the main histological characteristics: 1. Acute inflammatory and proliferating phase; 2. Osteogenic phase; 3. Phase of remodelling. The first phase is characterized by a loss of periost, areas showing proliferation of fibroblast-like cells, and by edema of surrounding musculature. Infiltration by leucocytes was occasionally observed and was accompanied by micro-abscesses. The osteogenic phase was characterized by formation of woven bone. Ultrastructurally proliferations of osteogenic mesenchyma were found and resulted in typical mineralization patterns with matrix vesicles and interfibrillar depositions of hydroxyapatite crystals. Calcification of mitochondria was also detected. Viruses could not be observed. Only thread-like structures were found in the nuclei. At first interpretation, they appeared to be pathological protein depositions. However, further investigations will be necessary to elucidate their genesis. The pathogenesis is discussed. Biopsy still remains indicated in cases of an unclear course of monostic disease.

Bone and Bones↗

Automated technique for sampling milk from farm bulk tanks: collaborative study.

An automated, in-line, mechanical technique for sampling milk from farm bulk tanks was evaluated in a collaborative study. The automated sampling device, which is mounted on the milk intake line, contains an electronically controlled peristaltic pump. The device takes a representative sample of the entire volume pumped through the system. Samples taken can be analyzed for both composition and microbiological quality. The study was performed in 3 phases. In the first 2 phases, samples taken by manual and automated methods were compared in analyses for somatic cell count, antibiotics, fat, protein, lactose, and solids-not-fat. The third phase, using a modified procedure, was designed to compare sampling methods in analyses for total bacteria count (standard plate count), psychrotrophic bacteria count, and coliform count. Evaluation of the data by a nested ANOVA indicated no difference between results for samples taken by the automated and manual methods (P = 0.05) in Phases 1 and 2, irrespective of whether the bulk milk was agitated before sampling. By introducing a sanitizing step between farms in Phase 3, the automated method also provided samples comparable with those taken manually for microbial analyses. The automated method has been adopted first action by AOAC International.

Animals↗

The development and validation of a measure of parent-reported child health and morbidity: the Warwick Child Health and Morbidity Profile.

OBJECTIVE: to validate a simple instrument for the measurement of parent-reported health and morbidity in infancy and childhood suitable for research and service planning purposes and capable of measuring both cross-sectional and longitudinal health and morbidity experience in a child population. SETTING: child health clinic (CHC), child development unit (CDU) and paediatric outpatient department (OPD) in Coventry. DESIGN: 3-phase field testing to establish test-retest reliability, validity and inter-observer variation of the instrument. Field testing samples: phases 1 and 2; 188 parents of pre-school children attending one of the three health service settings-CHC, CDU or paediatric OPD; phase 3; 40 parents of pre-school children attending CHCs. METHODS: test-retest reliability of each domain of the WCHMP was estimated using weighted Kappa; criterion validity was estimated for selected domains against health records; construct validity against medically plausible constructs was tested by comparing responses between domains; Inter-observer variation was estimated using weighted Kappa. RESULTS: the test-retest reliability of the WCHMP varied from 'moderate' for behaviour, functional health and life quality status to 'very good' for acute significant illness and hospital admission status; criterion and construct validity were high; weighted Kappas for all domains for inter-observer variation between the researcher and family health visitor were in the 'good' to 'very good' range and inter-observer variation remained unaffected by change in the order of administration of the WCHMP. CONCLUSIONS: the WCHMP is a simple measure of parent-reported health and illness which, on field-testing, has been shown to be reliable and valid with low inter-observer variation. After further development and validation including incorporation into the parent-held record, it should be suitable for use in infancy and early childhood to collect cross-sectional and longitudinal health and morbidity data for research and service planning purposes.

Chi-Square Distribution↗

Alpha(1)-adrenoceptor subtypes mediate negative inotropy in myocardium from alpha(1A/C)-knockout and wild type mice.

Cardiac alpha(1)-adrenoceptors (AR) have two predominant subtypes (alpha(1A)-AR and alpha(1B)-AR) however, their roles in regulating contraction are unclear. We determined the effects of stimulating alpha(1A)-AR (using the subtype-selective agonist A61603) and alpha(1B)-AR (using a gene knockout mouse lacking alpha(1A)-AR) separately, and together (using phenylephrine) on Ca(2+) transients, intracellular pH, and contraction of mouse cardiac trabeculae. Stimulation of alpha(1)-AR subtypes separately or together caused a triphasic contractile response. After a transient ( approximately 3%) force rise (phase 1), force declined markedly (phase 2), then partially recovered (phase 3). In phase 2, the force decline (% of initial) with combined alpha(1A)-AR plus alpha(1B)-AR stimulation (50+/-3%) was more than with separate subtype stimulation (P<0.01), suggesting alpha(1A)-AR and alpha(1B)-AR mediate additive effects during phase 2. Force decline in phase 2 paralleled decreases of Ca(2+) transients that were reduced more with combined vs. separate subtype stimulation. During phase 3 the final force reduction was similar with stimulation of alpha(1A)-AR (20+/-5%), or alpha(1B)-AR (20+/-3%), or both (26+/-4%) suggesting alpha(1A)-AR and alpha(1B)-AR mediate non-additive effects during phase 3. In contrast, Ca(2+) transients recovered fully in phase 3 suggesting reduced force in phase 3 involved decreased myofilament Ca(2+)-sensitivity. Decreased Ca(2+)-sensitivity was not mediated by changes of intracellular pH since this was not affected by alpha(1)-AR stimulation. In contrast to mouse trabeculae, rat trabeculae demonstrated a positive inotropic response to alpha(1)-AR stimulation. In conclusion, for mouse myocardium in vitro both alpha(1)-adrenoceptor subtypes mediate negative inotropy involving decreased Ca(2+) transients and a decreased Ca(2+) sensitivity that does not involve altered intracellular pH.

Animals↗

Evaluation of secondary poisoning of difethialone, a new second-generation anticoagulant rodenticide to barn owl, Tyto alba Hartert under captivity.

Secondary toxcity of difethialone to Barn owl (Tyto alba) has been investigated. Difethialone was fed to owls for successive periods of 1 (phase 1), 3 (phase 2) and 6 (phase 3) days via-rodenticide dosed rats. The owls survived after the treament of rodenticide on phase 1 and phase 2 experiments but they died during phase 3 experiment. The results suggest that the difethialone could cause more secondary toxicity to owls.

4-Hydroxycoumarins↗

Quantitative cholescintigraphy: selection of random dose for CCK-33 and reproducibility of abnormal results.

UNLABELLED: Dynamic cholescintigraphy (DCG) is a valid technique for evaluating gallbladder emptying. Cholecystokinin (CCK) as a slow infusion is recommended as a contraction stimulus. The normal ejection fraction (EF) has been shown to be reproducible, although the reproducibility of abnormal results has not been investigated. The aims of the present study were to standardize the CCK administration method (phase 1), obtain EF normality values (phase 2), and evaluate the reproducibility of abnormal results in patients with clinically suspected gallbladder dysfunction (phase 3). METHODS: Phase 1 included 40 healthy volunteers divided into 4 groups (n = 10) and subjected to intravenous CCK infusion according to 4 different regimens (0.25, 0.30, 0.40, and 0.60 Ivy dog units [IDU]/kg). Phase 2 comprised 33 healthy volunteers for determining DCG normality values, and phase 3 evaluated the reproducibility of abnormal results in 44 patients having clinical manifestations compatible with gallbladder dysfunction and showing an abnormal EF in a previous study. RESULTS: The most effective CCK infusion regimen was 0.40 IDU/kg (3.07 ng/kg) over 20 min, because it afforded the least variability and a high EF. When this regimen was applied to the healthy population, the EF was found to be 74.2% +/- 17.1% (mean +/- SD); the inferior normality limit was estimated to be 40%. Abnormal results were recorded in 77% (95% confidence interval, 62%-89%) of the patients. When the 2 DCG studies of phase 3 were compared, the EF correlation coefficient between them was 0.439 (P = 0.003). CONCLUSION: Slow CCK infusion is the best regimen for stimulating gallbladder contraction; an EF of less than 40% is estimated to represent abnormality. The abnormal results for the EF in patients with clinically suspected gallbladder dysfunction proved to be reproducible.

Adolescent↗

Nine hexagonal ca(5)pb(3)z phases in stuffed mn(5)si(3)-type structures with transition metal interstitial atoms z. Problems with classical valence States in possible zintl phases.

Ternary hexagonal Ae(5)Tt(3)Z phases have been obtained from high-temperature reactions (1000-1300 degrees C in Ta) only for Ae (alkaline-earth metal) = Ca, Tt (tetrel) = Pb, and Z = V, Cr, Mn, Fe, Co, Ni, Zn, Ru, or Cd. The hexagonal crystal structures (stuffed Mn(5)Si(3)-type, P6(3)/mcm, Z = 2) were refined for Z = Mn and Fe (a = 9.3580(3), 9.3554(5) A, c = 7.009(1), 7.009(1) A, respectively). In contrast, Ca(5)Pb(3)Z for Z = Cu or Ag form only with a trigonal structure (P3c1, Z = 2, a = 9.4130(3) A, c = 7.052(1) A for Cu) in which regular displacements of only the linear strings of Ca1 atoms occur. The existence of these compounds stands in contrast to the nonexistence of all binary Ae(5)Tt(3) products from Ca to Ba (Ae) and Si to Pb (Tt) with a Mn(5)Si(3)-type structure. Therefore, it once seemed attractive to consider the Z elements in these Ca(5)Pb(3)Z compounds as reducing agents (electron donors). The Mn and Fe structures appropriately exhibit greatly enlarged antiprismatic calcium cavities about Z. Other indications of relatively electron-poor environments around Fe are found in its properties, which include soft ferromagnetism with an elevated magnetic moment (6.3 micro(B)) and a large Fe 3p(3/2) binding energy relative to that in La(5)Ge(3)Fe, La(15)Ge(9)Fe, etc. The Ca(5)Pb(3)Mn phase exhibits metallic behavior (rho(295) = 135 microOmega cm) and temperature-independent Pauli paramagnetism. These properties are supported by ab initio band structure calculations for Ca(5)Pb(3)Mn, which show strong Ca-Pb bonding and a broad Pb-based band, with appreciable Ca-Mn and Ca-Pb bonding states at and above E(F). Distortion of the Cu analogue gives strengthened Ca-Pb bonding and reduced Cu-Ca1 repulsions. A Zintl phase description of these compounds and some related compounds in terms of closed Pb bands is not appropriate.

Journal Article↗

Dose conversion and titration with a novel, once-daily, OROS osmotic technology, extended-release hydromorphone formulation in the treatment of chronic malignant or nonmalignant pain.

The objective of this open-label, repeated-dose, single-treatment, multicenter study was to evaluate the outcomes associated with a standardized conversion from prior opioid therapy to a novel, once-daily, OROS osmotic technology, extended-release (ER) hydromorphone formulation in an outpatient population with chronic malignant or nonmalignant pain. The study period was divided into 3 phases: the prior opioid stabilization phase (> or =3 days), the conversion and titration phase (3-21 days), and the maintenance phase (14 days). Patients were evaluated at 5 visits during the study period. Analgesic efficacy was measured using the Brief Pain Inventory (BPI). At baseline, patients were required to have daily oral morphine equivalent requirements of > or =45 mg. Prior oral or transdermal opioid therapy was converted to single daily doses of ER hydromorphone (8, 16, 32, and 64 mg tablets) at a 5:1 (morphine equivalent to hydromorphone) ratio. Immediate-release (IR) hydromorphone was given as rescue medication for breakthrough pain. Among the 445 patients who enrolled, 404 received the study medication. Of these, 73 (18.1%) had chronic malignant pain and 331 (81.9%) had chronic nonmalignant pain. Dose stabilization (defined as a 3-day period during which the total daily dose of ER hydromorphone remained unchanged and < or =3 doses of IR hydromorphone per day were required) was attained by 73.8% of patients (298/404), of whom 70.1% (209/298) were stabilized with < or =2 titration steps. The mean +/- standard deviation (SD) time to dose stabilization was 12.1 +/- 5.7 days (range of 3 to 33 days). The mean +/- SD final daily dose of ER hydromorphone was 63.4 +/- 129.2 mg. The mean +/- SD final daily dose of IR hydromorphone was 11.5 +/- 36.4 mg, and the mean +/- SD final number of daily doses of IR hydromorphone was 1.7 +/- 1.3. Intent-to-treat and completer analysis demonstrated significant improvements in BPI ratings from prior opioid therapy to the end of ER hydromorphone therapy (P < 0.01 for all pairwise comparisons). Adverse events were consistent with those expected of an opioid agonist in such a patient group, affecting primarily the gastrointestinal and central nervous systems. This uncontrolled study delineates a regimen by which patients with chronic malignant or nonmalignant pain can be readily converted from prior opioid therapy and titrated to an appropriate maintenance dose of ER hydromorphone. Controlled longitudinal studies are required to further evaluate the use of ER hydromorphone in patients with discrete chronic malignant or nonmalignant pain conditions.

Adult↗

Double ventricular parasystole: intermittency and its relation to re-entrant premature beats.

Critical analysis of a case of double ventricular parasystole revealed that one parasystolic focus manifested complete protection, whereas the second focus appeared to be intermittent, protected from sinus and other impulse formation both early, as well as late, in the parasystolic cycle. The zone of protection failure, during which extrinsic impulses could penetrate into the parasystolic focus and discharge it, is observed between these early and late phases of protection. When the intermittent parasystolic focus is challenged by the other parasystolic beat, this zone is much wider and is located later in the cycle than the sinus beat. According to this observation, it is supposed that the intermittent parasystolic focus, in this case, is anatomically surrounded by two types of fibers, each showing different degrees of phase 3 and phase 4 block. The fibers located between the major fascicles and the intermittent parasystolic focus may have a shorter phase 3 and a less steep phase 4 depolarization than those located between two parasystolic foci. It is also demonstrated that during the phase 4 depolarization in these fibers around the focus, concealed conduction into this area by the sinus beat evoked exit delay of the parasystolic impulse, resulting in prolongation of the next parasystolic cycle. In this situation, a re-entry movement around the focus was predicted and, as expected, a re-entrant bigeminy coupled with the parasystolic rhythm was observed.

Arrhythmias, Cardiac↗

Characteristics of peripheral microembolization during iliac stenting: Doppler ultrasound monitoring.

OBJECTIVE: To evaluate the characteristics of distal microembolic signals (MES) during iliac stenting using Doppler ultrasound monitoring. DESIGN: Prospective clinical study. METHODS: A 2-MHz probe was used to monitor continuously at the ipsilateral tibioperoneal trunks during technically and hemodynamically successful iliac stenting in 10 patients without infrainguinal occlusive lesion. MESs at guide-wire, balloon, or stent crossing (phase 1), predilatation (phase 2), stent deployment (phase 3), postdilatation (phase 4), and contrast medium or heparinized saline injection (at injection) were analyzed. Differentiation of gaseous emboli from particulate emboli was achieved by calculation of the sample volume length. RESULTS: No distal embolic complications were observed. Five hundred and forty-one MESs were detected. The MES incidence and intensity in phase 3 were significantly higher than those in phase 1, phase 2, and phase 4 (p<0.05). The MES intensity at injection was significantly higher than that in each of four phases (p<0.0001). CONCLUSIONS: Both the MES incidence and intensity were highest at stent deployment. Further study is required of microembolism during endovascular procedures in the lower extremities.

Aged↗