Biomedical subjects
Publications and source records attributed to J H Williams.
There exist numerous temperature-based techniques to calculate the early postmortem interval of human corpses. This paper presents eight commonly used time of death algorithms and describes how they were applied to eight corpses.
1. In malignant hyperthermia susceptible muscle fibers, the calmodulin antagonist, W-7 (10 microM), evoked contractures and potentiated halothene (3%) induced contracture. No effect was seen at 0.1 or 1.0 microM) W-7. 2. Dantrolene sodium (6 microM) prevented and reversed W-7 induced contracture: nifedipine did not. 3. In chemically skinned fibers, 10 microM, 1.0 microM, and 0.1 microM W-7 released 100%, 30%, and 10% of stored calcium respectively, and the effect of 10 microM W-7 was irreversible in that the SR was unable to re-sequestor calcium after exposure to the drug. 4. The release of calcium by W-7 was not prevented by exogenously added calmodulin (3 microM), nor mimicked by mastoparan (10 microM). 5. Calcium release by W-7 appears to be independent of calmodulin inhibition.
This investigation examined the mechanical responses of malignant hyperthermic (MH) and normal porcine skeletal muscle to repetitive stimulation. Twitch and maximal tetanic tensions were not significantly different between muscle types. Tensions produced during stimulation at 20-80 Hz were significantly less in MH muscle than in normal muscle. In addition, MH muscle showed significantly greater force decline (tetanic fade) at the end of contractions evoked by 20-80 Hz stimulation. When stimulated to fatigue, both normal and MH muscle exhibited similar rates of tension decline during the initial minutes. Further stimulation caused additional decline in normal muscle, but a tension plateau in MH muscle. In all cases, normal muscle had greater magnitudes of fatigue than did MH muscle. Results show that there are marked differences between MH and normal muscle in the mechanical responses to repetitive stimulation. Due to its inability to properly regulate intracellular Ca2+ exchange, it is possible that MH muscle might be a useful tool for identifying the mechanisms of muscle fatigue in normal muscle.
OBJECTIVE: Intratracheal instillation of bleomycin in rats has been extensively used as an animal model of pulmonary fibrosis in humans, although it produces a patchy, airway based response. We proposed that the haemodynamic sequelae of the bleomycin model might be less severe than those associated with more diffuse lung injury. METHODS: Pulmonary and systemic haemodynamic indices were examined in adult Sprague-Dawley rats (approximately 400 g, n = 10) both at rest and during submaximal exercise on a rodent treadmill, approximately 60 days after intratracheal bleomycin (6 units.kg-1), and the results compared to a control group (n = 6). RESULTS: Compared to controls, mean pulmonary artery pressure (PPA) was increased by intratracheal bleomycin (p = 0.02) both at rest [24.5 (SEM 2.6) v 18.2(0.9) mm Hg] and during exercise [34.7(3.0) v 26.7(0.7) mm Hg]. PPA-pulse product was also increased, with a similar trend in right ventricular work index, but cardiac index was not altered. Right ventricular hypertrophy was noted on necropsy examination. Consistent with pulmonary fibrosis, lung dry weight, total protein, and hydroxyproline were also raised, and these values correlated strongly with (mean) PPA at rest (r2 = 0.86, 0.81, 0.69, respectively) and during exercise (r2 = 0.81, 0.79, 0.65, respectively). Packed cell volume was increased by intratracheal bleomycin, at 49(1) v 45(1)%, p = 0.02. CaO2 tended to decrease with exercise in the bleomycin group, although this was not statistically significant, while systemic oxygen delivery and consumption were not altered. CONCLUSIONS: Pulmonary hypertension and right ventricular hypertrophy occur in this model of lung fibrosis, and correlate with the severity of fibrosis. However, these sequelae were less severe than those previously demonstrated in association with crotalaria ingestion. We suggest that the haemodynamic sequelae of the intratracheal bleomycin model are consistent with patchy, airway based fibrosis, but reflect less well the haemodynamic sequelae of more diffuse fibrotic injury associated with systemic processes.
The use of quantitative 99Tcm-EHIDA imaging with cholecystokinin and the measurement of gall bladder ejection fraction in a prospective study of 89 patients with right upper quadrant pain is described. Correlation with surgical and histological findings and clinical follow-up suggests that gall bladder ejection fraction < or = 35% is a reliable and accurate indicator of acalculous gall bladder disease.
A series of nine cases of localized amyloidosis of the lower genitourinary tract are reported. The patients comprised six males and three females with an age range of 50-79 years at initial presentation. Clinically and on cystoscopy, the lesions were often diagnosed as neoplasms. Histologically, seven cases had typical features of localized amyloid deposits, while two cases had an unusual appearance with a florid histiocytic and giant cell reaction. Using an immunoperoxidase staining method the deposits were non-reactive with antibodies to serum amyloid A protein, prealbumin and beta 2 microglobulin, while equivocal immunoreactivity was seen with anti-light chain antibodies.
The purpose of this investigation was to determine the effects of reduced pH on Ca(2+)-induced Ca2+ release (CICR) from skeletal muscle sarcoplasmic reticulum (SR). Frog semitendinosus fiber bundles (1-3/bundle) were chemically skinned via saponin treatment (50 micrograms/mL, 20 min), which removes the sarcolemma and leaves the SR functional. The SR was first depleted of Ca2+ then loaded for 2 min at pCa (log free Ca2+ concentration) 6.6. CICR was then evoked by exposing the fibers to pCa 5-7 for 5-60 s. CICR was evoked both in the absence of ATP and Mg2+ and in the presence of beta, gamma-methyleneadenosine-5'-triphosphate (AMPPCP, a nonhydrolyzable form of ATP) and Mg2+. Ca2+ remaining in the SR was then assayed via caffeine (25 mM) contracture. In all cases, CICR evoked at pH 6.5 resulted in larger caffeine contractures than that evoked at 7.0, suggesting that more Ca2+ was released during CICR at the higher pH. Accordingly, rate constants for CICR were significantly greater at pH 7.0 than at pH 6.5. These results indicate that reduced pH depresses CICR from skeletal muscle SR.
The purpose of this paper is to describe a novel and practical technique for endobronchial catheter placement utilizing the flexible fiberoptic bronchoscope. Placement of endobronchial catheters via the flexible bronchoscope is limited by the small dimension of the bronchoscope's internal channel and frequently requires repeated manipulation to verify position endobronchially. We describe preliminary experience with a technique that we call the "bronchoscopic shuttle," which circumvents this limitation. The spectrum of possible clinical uses for this technique is discussed.
The purpose of this study was to evaluate the pain alleviating effect of dexamethasone iontophoresis on delayed onset muscle soreness (DOMS) produced via an eccentric exercise bout, and to determine the effect on muscle function. Baseline data were collected on 18 female subjects for maximum isometric knee extension contraction (MVC), knee extension peak torque (PT), knee extension work (W), and muscle soreness perception (SP). All values were subsequently reassessed 24 and 48 hours after a 10-min bout of bench stepping. Immediately following the 24-hr reassessment, the experimental (E) (N = 6) and placebo (P) (N = 6) groups received iontophoresis treatment while the control (C) group (N = 6) received no treatment. Percent deviation from baseline of SP was significantly less at 48 hours (p less than 0.05) for the E group compared to P and C groups. However, MCV, PT, and W were no different between the three groups at 48 hours post muscle soreness bout.
A university-based hospital serving mainly a developing community readily appreciated that its clientele was from a very different sociological and cultural background than that of the professional staff and that developed and developing communities and their pets exhibit different patterns in their health status, with most diseases being predominantly related to socio-economic predicament. The need for a community-orientated service was recognised. From 1987 to 1988, the small animal outpatient clinic was used for an informal, unstructured sociological observation and interview-based study of the clientele and their pets. During this period, an informal educational programme was implemented to teach basic pet health care, and the efficacy of this programme was empirically gauged by comparing the knowledge and attitudes of first-time clients with those of regular clients. Regular clients appeared to become increasingly concerned about the health and management of their pets and the condition of their animals appeared to improve, with a corresponding decline in the degree of parasitism. The majority of clients however, still regarded the main reason for keeping dogs as the provision of some form of security. It also appeared as if improved attitudes towards household pets paralleled improvements in socio-economic status.
These experiments sought to determine the influence of sarcolemmal Na(+)-Ca2+ exchange on halothane and on caffeine contractures of malignant hyperthermic (MH) skeletal muscle. Fiber bundles excised from MH susceptible pigs (Pietrain) were exposed to halothane (3%) and caffeine (0.5-8.0mM) while Na(+)-Ca2+ exchange was inhibited by reducing extracellular Na+ from 100% to 50, 25 and 0% of control. Halothane contracture magnitude was not altered by 50 or 25% Na+ whereas 0% Na+ increased the contractures by 51%. 0 and 25% Na+ increased the magnitude of caffeine contractures (2-8mM) by 53-176%. These results suggest that external Na+ and the Na(+)-Ca2+ exchange mechanism influences contractures of MH skeletal muscle.
In this study we report the numbers and metachromatic dye-staining characteristics of mast cells (MCs) in the conjunctiva of normal subjects and patients with seasonal allergic conjunctivitis caused by pollenosis. In addition, we have used a monoclonal antibody to the MC-specific enzyme, tryptase, to enumerate tryptase-positive cells immunohistochemically. Tarsal conjunctival MCs were found to be present in increased numbers in the allergic compared to the nonallergic subjects. Most of the MCs exhibited staining that was formaldehyde resistant, compatible with their identification as connective tissue MCs or basophils. The high positive staining for tryptase confirmed that the metachromatic cells stained with toluidine blue were MCs and not basophils, both in normal and allergic subjects.
1. The effects of the calcium agonist, Bay K 8644, on the mechanical output of skeletal muscle were studied in frog semitendinosus fiber bundles and in whole sartorius muscles. 2. Low concentrations of Bay K 8644 (less than or equal to 1 microM) had no significant influence on isometric twitches. Concentrations between 5-20 microM increased peak tension by 28.6 +/- 2.9% while higher concentrations (greater than or equal to 50 microM) initially increased then depressed twitches by 70 +/- 3.5%. 3. 10 microM Bay K 8644 also increased peak tension developed during low frequency stimulation (i.e. less than or equal to 40 Hz), slightly depressed high frequency contractions (i.e. greater than or equal to 80 Hz) but did not reduce maximal tetanic tension which occurred at about 60 Hz. 4. Potentiation of twitches and low frequency tetani and depression of high frequency tetani by Bay K 8644 were partially antagonized by nifedipine (10 microM), low extracellular calcium and D-600 (5 microM). These conditions did not, however, block the depressant actions of greater than or equal to 50 microM Bay K 8644. 5. In skinned fibers, 10 microM Bay K 8644 had no effect on resting or maximal Ca2+ activated tension. Also, 10 microM Bay K 8644 had no effect on caffeine contractures when added to the previous Ca2+ loading solution. 6. These results suggest that Bay K 8644 has both positive and negative inotropic actions on isolated skeletal muscle, which are dependent on drug concentration and muscle activation pattern.
It is well documented that repeated voluntary activity or electrical stimulation of skeletal muscle results in a decline in force production or power output. However, the precise physiological causes of "muscle fatigue" are not yet well understood. It is conceivable that the mechanism(s) may lie either in the conduction of action potentials in the central and peripheral nervous systems or in the transformation of the electrical event into mechanical force production by the muscle itself. In fact, none of the components of the electrical pathway from generation of impulses in the brain to their conduction over the neuron and the excitable membranes of the muscle can as yet be ruled out as potential contributors to the fatigue process. Relative to that on conduction failure, more information exists concerning the possibility that a defect in the excitation contraction coupling process in skeletal muscle, e.g., intracellular acidosis, inadequate supply of energy for contraction, or a disruption in Ca2+ homeostasis may also be significant in compromising force production following sustained activity. Despite this, the amount of conflicting data derived from these experiments has hindered the resolution of this question. In the future more attention must be given to such issues as the type of activity used to elicit fatigue and the fiber composition of the muscles studied. This is imperative as these factors clearly impact the nature of correlations between the biochemical and physiological events in muscle that are required to support prospective fatigue mechanisms.
Immunohistochemical staining of conjunctival biopsies from four normal subjects and five patients with atopic keratoconjunctivitis (AKC) was performed, using a monoclonal antibody to human mast cell tryptase. A massive hyperplasia of mast cells in the patients with AKC was demonstrated. The mean mast cell density in the normal patients was 55.6/mm2 and in the patients with AKC, 172/mm2. The appearance of large numbers of mast cells in the conjunctival epithelium of AKC patients was also demonstrated. The possible pathophysiological significance of these findings is discussed.
The Assessment of Living Skills and Resources (ALSAR), an innovative instrumental activities of daily living tool, systematically evaluates the accomplishment of 11 tasks by separately rating patient skill and resource levels for each task and combining these levels to determine risk. The ALSAR was administered to 75 elderly veterans in a home care program. It predicted change to more supportive living arrangements and a more structured living environment, nursing home placement, hospitalization, and death during the 6-month study period. The ALSAR has proven useful for interdisciplinary problem solving and treatment planning.
BACKGROUND AND METHODS: Pentoxifylline can inhibit blood leukocyte functions in vitro, and some inflammatory processes in the lung in vivo. Therefore, we examined the effects of pentoxifylline on alveolar macrophage functions in vitro. Alveolar macrophages were harvested from normal rat lungs by airway lavage. The dose-response relationship of varying concentrations of pentoxifylline and in vitro cell functions were examined. Macrophage functions studied included adherence to nylon wool, random (unstimulated) and zymosan-activated serum-stimulated migration through 5 microns millipore filters, and superoxide generation induced by zymosan-activated serum as assayed by cytochrome c reduction. RESULTS: Pentoxifylline inhibited superoxide generation and stimulated migration (but not random migration or adherence) in a dose-dependent fashion. Statistically significant inhibition was demonstrated at 0.5 mM and 5.0 mM concentrations of pentoxifylline, respectively, for stimulated migration and superoxide generation. CONCLUSIONS: Pentoxifylline can inhibit some alveolar macrophage functions in vitro. These effects may inhibit some forms of inflammatory lung injury, particularly when iv infusion of high doses of pentoxifylline are utilized. However, potentially adverse effects on inflammatory defense mechanisms must be considered as well.
In an attempt to understand the pathogenesis of corneal changes and conjunctival scarring in trachoma, which are responsible for blindness in some 7 million people worldwide, the surface expression of major histocompatibility complex class II antigens on conjunctival epithelial cells was sought in patients with different clinical features of the disease. Class II expression was significantly associated with active (inflammatory) trachoma, but an independent association with corneal pannus or conjunctival scarring could not be shown. Longitudinal data suggest that class II expression may antedate clinically active disease and persist after it has resolved.