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Biomedical subjects

J Griffiths

Publications and source records attributed to J Griffiths.

At least 91 records · Page 5Linked to original sources

Evaluation of an animal model system for cryptosporidiosis: therapeutic efficacy of paromomycin and hyperimmune bovine colostrum-immunoglobulin.

Several immunodeficient rodent models currently exist in which persistent, largely asymptomatic, Cryptosporidium parvum infections can be established. Piglets, in contrast, develop a self-limiting diarrheal illness. We have consequently developed an animal model system in which scid mice were used to screen drugs for inhibitory activity against C. parvum, after which the drugs' therapeutic potential was evaluated with piglets. Paromomycin and hyperimmune bovine colostrum-immunoglobulin were selected to evaluate this system. C. paravum infections in suckling scid mice tended to be associated with villus surfaces, while in weaned and in older scid mice infections were more commonly localized in abscessed crypts. Rates of oocyst shedding in suckling scid mice were 50 to 200 times higher than in weaned mice and therefore made suckling mice a considerably more sensitive model for drug testing. Paromomycin given in high doses over 9 to 10 days was not toxic to either scid mice (3,000 mg/kg of body weight per day) or piglets (500 mg/kg/day). Paromomycin treatment was very effective against villus surface infections in suckling mice and considerably less effective against infections in inaccessible sites such as abscessed crypts and stomach pits seen in weaned and adult scid mice. The therapeutic efficacy of paromomycin in piglets depended on the severity of the diarrheal illness. Mild to moderate diarrhea and infection were cleared after paromomycin treatment of piglets infected with one C. parvum isolate. However, paromomycin had no impact on severely affected piglets infected with a second isolate, presumably because of a rapid transit time through the gut. In contrast to paromomycin hyperimmune bovine colostrum-immunoglobulin treatment reduced the rate of C. parvum infection moderately in scid mice and only slightly in piglets, again probably because of a rapid transit time through the gut and inactivation in the stomach. It was also clear that the impact of effective drugs against C. parvum can be detected within 5 days after the onset of treatment in either model.

Animals↗

Characterization of histogranin receptors in human peripheral blood lymphocytes.

Histogranin (HN), a peptide recently isolated from bovine adrenal medulla, is also present in the spleen. In present studies, specific high affinity binding sites for HN were characterized on membrane preparations of human lymphocytes by radioligand binding. [125I]-[Ser1]HN binding was found to be dependent on time and protein concentration and to be sensitive to trypsin treatment. The binding displayed high affinity (Kd = 1.1 +/- 0.3 nM) and saturability (Bmax = 40.2 +/- 5.0 fmol/mg protein), and it was reversed upon addition of unlabelled [Ser1]HN and closely related peptides. The relative potency of various fragments in displacing [125I][Ser1]HN binding indicated that the active core of the molecule resides inside the C-terminal fragment, HN-(6-15). Interestingly, depressed patients displayed a marked decrease in the binding activity (from 15.4 to 8.55 fmol/mg protein at 0.5 nM of [125I][Ser1]HN). The presence of high affinity HN binding sites on lymphocytes provides evidence for a modulatory role for HN in the regulation of lymphocyte functions.

Adult↗

General practitioners in partnership with management: an organisational model for debate.

The role of general practitioners is changing and expanding. Doctors have more control over the treatment received by their patients but remain largely unaccountable to the public and management. This article proposes an organisational model for integrating primary and secondary care which retains the advantages of fund-holding while giving management control over overall strategy. It proposes that general practitioners control funds for all primary and secondary care. Secondary care will be contracted through a joint team of managers and an elected general practice executive committee. A new health care purchasing authority will contract for primary services with individual practices or primary care provider units. General practitioners will have local contracts reflecting their desire to provide an expanded range of services and the needs of the community.

Capital Financing↗

Biodistribution of a methylene blue derivative in tumor and normal tissues of rats.

By using a chemical extraction procedure and confocal laser scanning fluorescence microscopy we have investigated the kinetic patterns of uptake and biolocalization of a methylene blue derivative (MBD) in tumors and various normal tissues of Wistar rats bearing fibrosarcoma (Leeds ovarian tumor) after intravenous injection of MBD (10 mg kg-1 body weight). Similar kinetics of accumulation and elimination of MBD fluorescence were found in tumor tissue and surrounding normal skin and muscle tissues. However, the tumor:skin and tumor:muscle ratios of the MBD fluorescence intensity were found to be 9 and 4, respectively, 4 h after intravenous injection, indicating selective uptake of MBD by the tumor tissue. MBD was localized on the walls of all the vessels and extensively in the area of neoplastic cellular and tumorigenic fibrous components in the tumor tissue. Interestingly, no MBD fluorescence could be detected in the metastatic neoplastic cells in the remote lymph nodes. In the skin, MBD was mainly distributed in the keratinized epithelium of the epidermis, hair follicles and their accessories, while little was found both in the epidermis and dermis. In most other tissues, the maximal fluorescence intensity of MBD was found 1-4 h after injection, after which it decreased dramatically to almost undetectable levels 120 h postinjection. Strong fluorescence of MBD was seen in the tracheal mucosal epithelium, while little fluorescence was noted in the transitional epithelium of bladder. The kinetics of biolocalization of MBD in some other tissues (liver, spleen, kidney, brain, muscle, lung, heart) were also studied.

Animals↗

Exogenous chromophores for the argon and Nd:YAG lasers: a potential application to laser-tissue interactions.

Chromophore dyes can be employed to modify laser-tissue interaction. A number of dyes have been investigated for their effect on the absorption and transmission of argon and Nd:YAG laser energy by vascular tissue in vitro. Three histological dyes have been assessed as potential chromophores for the argon laser and four infrared dyes for the Nd:YAG. Segments of porcine coronary artery to which dye had been applied were lased (1,064 nm, 2.5 W, 83 W/cm2, 60 s and 488/514 nm, 400 mW, 10.5 W/cm2, 60s) and the tissue temperature measured remotely using an infrared thermometer. In addition, energy transmission was measured with a photodiode and tissue morphological changes assessed histologically. All three argon dyes significantly increased energy absorption (typically 60 degrees C v. 20 degrees C at 60 s, P less than 0.001, 2-way ANOVA). Three of the four infrared dyes behaved similarly (40-70 degrees C v. 20 degrees C, P less than 0.001). All dyes significantly increased the initial rate of rise in tissue temperature during lasing. A reduction in energy transmission was observed for each of the Argon dyes but not for the Nd:YAG dyes. Histological evidence of thermal damage in control tissue first occurred for the argon and Nd:YAG lasers at 800 mW and 7.5 W without chromophore and at 400 mW and 2.5 W with the chromophore, respectively. A number of effective chromophores have therefore been identified at each wavelength.

Absorption↗

Strain-specific alterations in consumption of a palatable diet following repeated stressor exposure.

Exposure to acute inescapable shock caused reductions in the consumption of a highly palatable diet. The magnitude and duration of the reduction varied across strains of mice. With repeated exposure to footshock, consumption of the diet returned to baseline levels, although alterations of weight appeared to be more persistent. The course of the adaptation varied across strains of mice; however, the rate of adaptation was unrelated to the extent of the alterations of consumption induced by the acute stressor. When mice were exposed to a series of different stressors, the adaptation progressed less readily, and reductions of diet consumption were apparent in strains that had not shown such an effect following acute stressor application or when repeatedly exposed to a single type of stressor. Data were discussed with respect to the mechanisms that might be operative in subserving stressor-induced anhedonia.

Animals↗

Different techniques of residual composite removal following debonding--time taken and surface enamel appearance.

Four different methods of in vitro residual composite removal following debonding performed by two different operators (an orthodontist and a hygienist) were assessed for enamel surface damage (using scanning electron microscopy) and the time involved. There was no difference in the quality of enamel surface appearance between the two operators, regardless of the method used for composite removal. There was a statistically significant difference (P less than 0.05) for the time taken for composite removal between the two operators using a tungsten carbide bur method only. It is suggested that an expanded duties auxiliary with the practical skills of the hygienist would be able to remove residual composite debris and produce a satisfactory polished enamel surface using tungsten carbide burs and aluminium oxide polishing discs, thus becoming a safe and cost-effective member of the orthodontic team.

Composite Resins↗

Automation and other recent developments in clinical chemistry.

The decade 1980 to 1990 was the most progressive period in the short, but turbulent, history of clinical chemistry. New techniques and the instrumentation needed to perform assays have opened a chemical Pandora's box. Multichannel analyzers, the base spectrophotometric key to automated laboratories, have become almost perfect. The extended use of the antigen-monoclonal antibody reaction with increasing sensitive labels has extended analyte detection routinely into the picomole/liter range. Devices that aid the automation of serum processing and distribution of specimens are emerging. Laboratory computerization has significantly matured, permitting better integration of laboratory instruments, improving communication between laboratory personnel and the patient's physician, and facilitating the use of expert systems and robotics in the chemistry laboratory.

Automation↗

An alternate origin for the placental isoenzyme of alkaline phosphatase.

By means of an electrofocusing technique, the serum specimens of pregnant women routinely revealed three bands of alkaline phosphatase (ALP) that were released by placental syncytiotrophoblast, germ cell (ovary), and fetal intestine at pl of 4.73, 4.65, and 4.55, respectively. When defining reference ranges for ostensibly healthy persons of all decades of age and investigating patients with elevated total ALP activity, we found the isoenzyme at pl 4.73 to be above the established reference range in some nonpregnant women and in men. Evidence suggests that T lymphocytes from whole blood or in vivo tissue were the origin of this pl 4.73 ALP band; the isoenzyme being released during cell lysis, in cellular turmoil from any cause, or when active cell division occurs. A designation of lymphocyte ALP is proposed for this ALP band that is observed in a broad group of diseases associated with abnormal lymphocyte function.

Acquired Immunodeficiency Syndrome↗

Lessons in class.

In the second of two articles, Jenny Griffiths and colleagues look at the evolution of health promotion in Oxford region over five years in the light of The Health of the Nation.

Community Participation↗

Steroid-eluting epicardial leads in pediatrics: improved epicardial thresholds in the first year.

From 1986 to 1991, we evaluated the clinical use of three new epicardial lead designs incorporating a steroid-eluting electrode. Medtronic models SP2114 (bipolar high profile), 10320 (bipolar low profile), 10295A/4965 (unipolar low profile) steroid epicardial (SE) leads were used on either atrium or ventricle for a total of 21 lead placements in 17 patients. Energy thresholds (T) were calculated and compared with our most recent 16 nonsteroid epicardial (NE) Medtronic model 4951 lead implants for which T was available. SE leads demonstrated no acute T rise and continued T improvements at 1 year of follow-up. We conclude that epicardial application of SE lead technology offers a major improvement in pacing lead function and potential pacemaker longevity over NE leads in pediatric patients in whom endocardial pacing is precluded by size or anatomy.

Animals↗

Mouse strain differences in plasma corticosterone following uncontrollable footshock.

Exposure to acute inescapable footshock provoked marked increases of plasma corticosterone concentrations in six strains of mice (A/J, Balb/cByJ, C57BL/6J, C3H/HeJ, DBA/2J and CD-1). However, the magnitude of the increase, as well as the time required for corticosterone to return to control values, varied appreciably across strains. Moreover, it appeared that the strain-specific corticoid increases ordinarily observed after acute shock were also evidence following a chronic stressor regimen. The data were related to previously observed strain differences in stressor-induced alterations of brain norepinephrine, dopamine and serotonin, as well as variations in performance in several behavioral paradigms.

Animals↗

Management of supracondylar fractures of the femur with Zickel supracondylar nails.

Twenty-one cases of supracondylar fracture of the femur treated at St Vincent's Hospital, Melbourne, during 1983-86, by intramedullary Zickel supracondylar nails were reviewed. The causes were high energy trauma in young patients (six), minor trauma in elderly patients (13), and metastatic malignant fracture (two). The functional results were considered excellent in 10, good in six and poor in five. There were two cases of superficial wound infection. All cases united after 3-6 months. The best functional results were in those patients below 60 years or with pathological fractures. It is concluded that internal fixation of supracondylar fractures of the femur with Zickel supracondylar nails is a successful technique and can be performed by open and closed methods. It is most useful in osteoporotic or pathological bone which is unsuitable for bone plating.

Aged↗

Alkaline phosphatases. Newer concepts in isoenzymes and clinical applications.

ALP is a profoundly ubiquitous enzyme that originates in many, if not all, mammalian tissues. The development of a simple ISEF technique has allowed reflection of at least 12 cellular components. Improvements in technique may add further zones of information. The aura of darkness surrounding ALP is being slowly dissipated.

Alkaline Phosphatase↗