Patterns of structural deterioration due to ischemia in Purkinje fibres and different layers of the working myocardium

Cellular and mitochondrial swelling are regarded as typical intra-ischemic alterations ("IIA"), contraction band lesions (CBL), in contrast, as products of post-ischemic reperfusion. The occurrence of both types of structural deterioration was investigated in Purkinje fibres and subendocardial and intramural working myocardium: initially after St. Thomas- or HTK cardioplegia, then during ensuing global ischemia up to the "practical limit of resuscitability", and following post-ischemic reperfusion. Generally, Purkinje fibres are not better preserved than neighbouring working myocardium. Comparing St. Thomas- and HTK cardioplegia, considerable quantitative, but not qualitative differences in the reaction patterns of different cell types or layers arise. Immediately after cardioplegia, CBL are completely lacking in both cell types. During ischemia, CBL occur occasionally in Purkinje fibres and seldom in subendocardial working myocardium, "IIA" predominate. During post-ischemic reperfusion "IIA" tend to reverse in all layers, whereas CBL are found to remain in the subendocardial cell types. In intramural layers, CBL occur only during reperfusion. Thus, we deduce that cardioplegia only modulates the severity of "IIA" and the frequency of CBL, but cannot abolish the particular sensitivity of subendocardial Purkinje fibres to global ischemia. Prerequisites for the development of irreversible CBL are on the one hand ischemic metabolic alterations and corresponding energy deficits, and, on the other hand, a supply of oxygen. The oxygen may be inadequately supplied via diffusion during ischemia or may be subsequently provided by reperfusion.     

Knochenheilung und dynamischer Interferenzstrom (DIC). —Erste vergleichende tierexperimentelle Studie an Schafen Teil II: Physikalische und chemische Ergebnisse

Zusammenfassung Zusätzlich wurden physikalische und chemische Untersuchungen über den Einfluß von dynamischem Interferenzstrom (DIC) auf die Knochenheilung durchgeführt, nachdem bei 24 Schwarzkopfschafen eine Querosteotomie des Radius vorgenommen worden war. Nach instabiler Osteosynthese wurde die Osteotomiezone wiederholt mit DIC verschiedener mA—Stärken behandelt. (Methodische Einzelheiten sind in Teil I beschrieben). Die Behandlung mit dynamischem Interferenzstrom führte im behandelten Gewebe zu steigenden Temperaturen, die von den mA—Stärken abhängig waren. Weiterhin wurden Zusammenhänge zwischen DIC—mA—Intensität und dem Vorkommen von Hydroxyprolin, einer kollagenspezifischen Aminosäure, nachgewiesen, welches eine erhöhte Calcifizierungsaktivität zur Folge hatte. Messungen des Calcium— und Phosphorgehaltes im neugebildeten Knochengewebe wiesen bei den mit DIC behandelten Tieren vollständige Mineralisation zu einem viel früheren Zeitpunkt als bei den unbehandelten, nach gleichem Verfahren operierten Kontrolltieren auf. Ob DIC einen spezifischen Reiz auf die Knochenneubildung heilender Knochen ausübt, ist noch nicht vollständig geklärt.

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Bone healing and Dynamic Interferential Current (DIC)

Summary In the course of supplementary physical and chemical investigations of the influence ofDynamicInterferential Current (DIC) on bone healing 24 black-head sheep were subjected to transversal osteotomy of the radius. After an instable osteosynthesis the site was exposed to repeated therapy with DIC of varying mA intensity. (Methodological details are described in part 1.) DIC therapy resulted in altering the temperatures in the treated tissue, dependent on the mA intensity. Further associations were verified between DIC intensity and the occurrence of hydroxyprolin, an amino acid specific collagen, which also reflected increased calcifying activity. Measurements of the calcium and phosphorus levels in the regenerated (newly forming) bone tissue documented full mineralization in the DIC-treated animals at a much earlier date than in the untreated controls that had undergone similar operations. Whether DIC specifically stimulates osteogenesis within healing bones is still unclear.

     

Diazepam metabolism in human foetal and adult liver

Summary Diazepam was metabolized by human foetal liver microsomes to N-desmethyldiazepam and N-methyloxazepam as early as the 13th week of gestation. The metabolic activity was lower than that of microsomes from adult human liver. Diazepam was shown mainly to be hydroxylated to N-methyloxazepam at substrate concentrations higher than 0.1 mM. Diazepam levels above 1.0 mM were inhibitory to the overall metabolic reaction. SKF 525-A inhibited diazepam metabolism by foetal liver microsomes at a concentration of 0.1 mM. The addition of diazepam to foetal and adult human liver microsomes resulted in a type II spectral change. Its inhibition by carbon monoxide indicated that biotransformation of diazepam was performed by the cytochrome P-450-linked mono-oxygenase system.     

Predictive control of muscle responses to arm perturbations in cerebellar patients

OBJECTIVES: To examine changes in predictive control of early antagonist responses to limb perturbations in patients with defined lesions of the cerebellum. METHODS: Eight cerebellar patients and eight sex and age matched control subjects participated. Subjects held a handle that was rotated around the elbow joint. They were instructed to hold the forearm at 90 degrees flexion against a mechanical perturbation. Extensor torque (5 Nm) was applied for 140 ms (pulse), or for 1400 ms (step) through an external motor. Motor responses were tested under two different conditions of anticipatory information. In the expected condition, subjects anticipated and received a pulse. Under the unexpected condition, subjects expected steps, but received unexpected pulses. Biceps and triceps EMG as well as angular kinematics were compared between expected and unexpected pulse perturbations to quantify possible effects of prediction. RESULTS: In all healthy subjects, the degree of overshoot in the return flexion movement was significantly less in expected pulse perturbations compared with unexpected trials. The degree of amplitude reduction was significantly smaller in the patient group than in the control group (22.8% v 40.0%). During the expected trials, latency of peak triceps activity was on average 20% shorter in the control group, but 4% larger in the cerebellar patients. CONCLUSIONS: In the expected condition, controls achieved a significant reduction in angular amplitude by generating triceps activity earlier, whereas the ability to use prediction for adjusting early antagonist responses after limb perturbation was impaired in cerebellar patients.     

Neuroanatomical correlates of the near response: voluntary modulation of accommodation/vergence in the human visual system

This study identifies brain regions participating in the execution of eye movements for voluntary positive accommodation (VPA) during open-loop vergence conditions. Neuronal activity was estimated by measurement of changes in regional cerebral blood flow (rCBF) with positron emission tomography and 15O-water. Thirteen naive volunteers viewed a checkerboard pattern with their dominant right eye, while a lens interrupted the line of gaze during alternate 1.5 s intervals. Three counterbalanced tasks required central fixation and viewing of a stationary checkerboard pattern: (i) through a 0.0 diopter (D) lens; (ii) through a -5.0-D lens while avoiding volitional accommodation and permitting blur; and (iii) through a -5. 0-D lens while maintaining maximal focus. The latter required large-amplitude, high-frequency VPA. As an additional control, seven of the subjects viewed passively a digitally blurred checkerboard through a 0.0-D lens as above. Optometric measurements confirmed normal visual acuity and ability to perform the focusing task (VPA). Large-amplitude saccadic eye movements, verified absent by electro-oculography, were inhibited by central fixation. Image averaging across subjects demonstrated multifocal changes in rCBF during VPA: striate and extrastriate visual cortices; superior temporal cortices; and cerebellar cortex and vermis. Decreases in rCBF occurred in the lateral intraparietal area, prefrontal and frontal and/or supplementary eye fields. Analysis of regions of interest in the visual cortex showed systematic and appropriate task dependence of rCBF. Activations may reflect sensorimotor processing along the reflex arc of the accommodation system, while deactivations may indicate inhibition of systems participating in visual search.     

Put more "bite" into health promotion: a campaign to revitalize health promotion in the Army Dental Care System. Part I. The mouthguard, sealant, and nursing caries initiatives

During the course of 1998, the Army Dental Care System launched "Put More 'Bite' into Health Promotion," a campaign to revitalize health promotion in the Army Dental Care System. In this paper, we discuss the content, rationale, and evidence base for three of five health promotion initiatives that are part of the campaign: mouthguard fabrication and counseling, sealant placement and education, and nursing caries education.     

Proliferative activity in primary ovarian carcinoid tumors.

The proliferative potential of six primary ovarian carcinoids with different clinical outcome and histogenetic origin was examined immunohistochemically. The results showed that two cases with extremely high level of proliferative activity were associated with metastatic spread. In the remaining tumors, the examined factor was found to be at low level comparable with excellent prognosis of typical carcinoids in other locations. The preliminary results showed a possibility of a prognosis prediction according to typing of the ovarian carcinoids into two categories, i.e., tumors of low and intermediate malignancy. Topoisomerase II-alpha and Ki-67 are suitable markers giving valuable information about this phenomenon.     

Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients

Background and purpose: Amifostine has been shown to protect against xerostomia induced by radiotherapy for head and neck cancer, but its impact on the therapeutic index is unknown. This is the first report focusing on amifostine related adverse effects leading to discontinuation of amifostine treatment.

Patients and methods: Thirty-nine patients from two centers irradiated for head and neck cancer received i.v.-infusions of amifostine prior to each radiation fraction. In a phase III study, two daily amifostine doses, 200 mg/m² (n=21) and 340 mg/m² (n=18), were compared for protection against radiation induced toxicity. Total radiation dose was 60–70 Gy (2 Gy per fraction), nine patients received concurrent chemotherapy with cisplatin/5-FU. amifostine was usually discontinued after >1 episode of serious toxicity during subsequent treatment sessions.

Results: In 16/39 patients (41%) amifostine was discontinued due to severe adverse effects, which led to discontinuation of the phase III study. In four of 16 patients radiotherapy was delayed due to amifostine related adverse effects for 1–3 days. Discontinuation occurred more often in patients receiving chemotherapy. The results led to a literature review for amifostine treatment during radiotherapy in head and neck cancer patients. Regarding our series and published series using an amifostine schedule comparable to ours, total discontinuation rate was 27% (57/214). Discontinuation was significantly influenced by chemotherapy (P=0.007), but not by amifostine dose (P=0.156).

Conclusion: Daily i.v. administration of amifostine during radiotherapy in head and neck cancer is associated with a high rate of serious adverse effects leading to discontinuation of amifostine treatment and sometimes delay of radiotherapy.