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Biomedical subjects

R D Mitchell

Publications and source records attributed to R D Mitchell.

At least 19 recordsLinked to original sources
PubMed2005

Management of patients with Streptococcus milleri brain abscesses.

OBJECTIVES: We evaluated the efficacy of cefotaxime in the management of brain abscesses caused by Streptococcus milleri. Twenty two patients with a S. milleri brain abscess were treated with metronidazole and cefotaxime, in accordance with recent recommendations by the British Society Of Antimicrobial Chemotherapy (BSAC). Seven patients who had Glasgow Coma Scales < or =11 also received rifampicin and high dose cefotaxime. The clinical response of the patients was determined. METHOD: A retrospective study at the Queen Elizabeth Hospital, Birmingham covering the period April 1996-March 2004 was carried out. Neurosurgical and anti-microbial therapeutic approaches were reviewed. Any evidence of improvement of clinical features and radiological disappearance of brain abscesses were determined. RESULTS: Outcome was assessed using the Glasgow Outcome Score (GOS) at 3 and 6 months from the time of surgical intervention. Eighteen patients (82%) had a good outcome by 6 months, with an outcome score of 4-5. Thirteen patients resumed normal life despite minor deficits (GOS 5), while a further five patients had moderate disability though remained independent (GOS 4). One patient had a GOS of 3 and there were three deaths (14). The minimum time to radiological resolution of the abscess was within 1 month in six cases (27) These all represented solitary lesions that required a single drainage procedure in conjunction with 4 weeks of intravenous cefotaxime and metronidazole. Ten cases (45%) had resolution within 4 months and a further three cases took at least 6 months from the time of surgery to show radiological clearance. CONCLUSIONS: This cohort of patients responded favourably to the guidelines recommended by the BSAC. This was confirmed by the Glasgow Outcome Score (GOS 4-5) at 6 months review. Cefotaxime at a higher dose with rifampicin was prescribed for patients presenting with a decreased conscious level (GCS 8-11), subsequent failure of anticipated clinical improvement or clinical deterioration. There was no clinically significant difference in GOS between the two treatment groups. An algorithm for management of brain abscess is presented, based on our clinical experience and review of the literature.

Adolescent↗
PubMed2005

Targeting the subthalamic nucleus for deep brain stimulation: technical approach and fusion of pre- and postoperative MR images to define accuracy of lead placement.

OBJECTIVES: To define the role of magnetic resonance imaging (MRI) and intraoperative electrophysiological recording in targeting the subthalamic nucleus (STN) in Parkinson's disease and to determine accuracy of electrode placement. PATIENTS AND METHODS: We implanted 54 electrodes into the STN in 27 patients. Target planning was done by coordinate guidelines and visualising the STN on MRI and defined in relation to the mid-point of the AC-PC line. Intraoperative microelectrode recording was used. We adjusted electrode positions for placement in the centre of the STN electrical activity and verified this on postoperative MRI in 16 cases, which were fused to the preoperative images to measure actual error in electrode placement in the three axes. RESULTS: Based on coordinate calculation and MRI localisation, the mean of the target was 11.5 mm lateral, 2.5 mm posterior and 4.1 mm inferior to the mid-point of the AC-PC line. Fifty good electrophysiological recordings of the STN (average length 4.65 mm) were achieved and target point adjusted in 90% of lead placements. The mean of the final target after electrophysiological correction was 11.7 mm lateral, 2.1 mm posterior, and 3.8 mm inferior to the mid-point. The distance from the centre of the electrode artefact to the final target used after electrophysiological recording on the fused images was 0.48 mm, 0.69 mm, and 2.9 mm in the x, y, and z axes, respectively. No postoperative MRI related complication was observed. CONCLUSION: Both direct visualisation of the STN on MRI and intraoperative electrophysiological recording are important in defining the best target. Individual variations exist in the location of the STN target. Fewer tracks were required to define STN activity on the side operated first. Our current stereotactic method of electrode placement is relatively accurate.

Adult↗
PubMed2003

Anaplastic oligodendroglioma with metastasis to the spinal cord.

A case of intramedullary spinal metastasis presenting 14 months after excision of the primary anaplastic cerebral oligodendroglioma is presented. To the best of our knowledge, less than 10 cases of spinal metastasis have been reported in the world literature.

Brain Neoplasms↗
PubMed2002

Spontaneous extradural haematoma associated with craniofacial infections: case report and review of the literature.

A 17-year-old male with occult cleft palate presented with depressed-consciousness due to spontaneous frontal extradural haematoma associated with sinusitis. Craniotomy, evacuation of the haematoma and drainage of the frontal sinuses led to a full recovery. Spontaneous extradural haematomas secondary to craniofacial infections are very rare; this appears to be the first described with a coexisting congenital palatal abnormality. The diagnosis should be considered when signs of infection are present with depressed consciousness as a delay in treatment may result in death.

Acute Disease↗
PubMed2000

Systemic indicators of inorganic arsenic toxicity in four animal species.

The effect of arsenic compounds depends on the chemical form and is specific for certain organs. The lack of specific biological indicators for the effects of each arsenic species makes it difficult to differentiate their toxicity. Five prospective biological indicators of systemic toxicity were examined at time points ranging from 15 min to 24 h using male Sprague-Dawley rats, B6C3F1 mice, Golden-Syrian hamsters, and Hartley guinea pigs, following intraperitoneal dosing with 0.1 and 1 mg/kg sodium arsenite. Rats and mice were also dosed with 1 mg/kg sodium arsenate. Total blood arsenic levels were determined in all animal species to show that exposure occurred and as an index of the severity of the change is an indicator of toxicity. Total blood arsenic levels were increased in all animal species. This increase was dose, arsenic species, and animal dependent. Renal pyruvate dehydrogenase activity was significantly decreased at early time points in mice, hamsters, and guinea pigs, and at later time points in rats dosed with arsenite. Rats and mice dosed with arsenate also exhibited PDH decrease at early time points. Blood hematocrit and glucose were increased in the rat and guinea pig, respectively, after arsenite administration. Creatinine and urea nitrogen were found to be unresponsive to arsenic in most animal species. Data suggested that the mouse and secondly the hamster appear to be the most appropriate animal models for the study of acute arsenic toxicity.

Animals↗
PubMed1997

Corynebacterium pseudotuberculosis is a cause of human necrotising granulomatous lymphadenitis.

Corynebacterium pseudotuberculosis is a well recognised pathogen of farm animals, particularly sheep and goats. Human infection is a rare occurrence. This report describes suppurative lymphadenitis occurring in an adolescent boy who had contact with farm animals. The histological differential diagnosis of suppurative granulomatous lymphadenitis is discussed, and the importance of lymph node culture is stressed.

Adolescent↗
PubMed1997

Dietary 1,25-dihydroxycholecalciferol has variable effects on the incidences of leg abnormalities, plasma vitamin D metabolites, and vitamin D receptors in chickens divergently selected for tibial dyschondroplasia.

Three experiments were conducted to examine the efficacy of dietary 1,25-dihydroxycholecalciferol [(1,25-(OH)2D3)] on the development of tibial dyschondroplasia (TD) in chickens divergently selected for high (HTD) and low (LTD) incidences of TD. In Experiment 1, chickens from the two lines were fed two calcium levels (0.75 and 1.0%), with and without 5 micrograms/ kg dietary 1,25-(OH)2D3. In Experiment 2, both lines were fed diets containing 1.0% calcium and 0, 5, 10, or 15 micrograms/kg 1,25-(OH)2D3. The addition of 1,25-(OH)2D3 did not reduce the overall incidence of TD in Experiment 1, but did reduce the incidence of severe TD from 69 to 48% in the chickens receiving the 0.75% calcium diet. In this experiment, LTD chickens had higher plasma phosphorus and bone ash. No line differences were noted between plasma vitamin D metabolites or intestinal vitamin D receptors. In Experiment 2, 5 micrograms/kg of 1,25-(OH)2D3 decreased the incidence of TD from 94 to 76% and number three scores from 69 to 44% (P < or = 0.001). Higher amounts of 1,25-(OH)2D3 further decreased TD, but there was a reduction in body weight above 5 micrograms/kg. Plasma 25-hydroxycholecalciferol [25-(OH)D3] and 1,25-(OH)2D3 were higher and intestinal vitamin D receptors were lower in HTD chickens than in LTD chickens. Plasma 1,25-(OH)2D3 was not affected by dietary treatment, but 25-(OH)D3 was reduced by dietary 1,25-(OH)2D3. Experiment 3 was conducted to examine effects of line and dietary 1,25-(OH)2D3 on plasma vitamin D metabolites and intestinal and growth plate receptors. No effect of genetic line or dietary 1,25-(OH)2D3 was observed for vitamin D receptors concentration or plasma 1,25-(OH)2D3 levels. Plasma 25-(OH)D3 was reduced when 1,25-(OH)2D3 was fed. These results indicate that HTD chickens are somewhat responsive to dietary 1,25-(OH)2D3, but this treatment failed to prevent the lesion in a large portion of the population.

Animal Feed↗
PubMed1997

The effects of ultraviolet light and cholecalciferol and its metabolites on the development of leg abnormalities in chickens genetically selected for a high and low incidence of tibial dyschondroplasia.

Four experiments were conducted to investigate the effects of ultraviolet (UV) light exposure and several cholecalciferol metabolites on the development of tibial dyschondroplasia (TD) and other parameters associated with vitamin D metabolism in chickens selected for high (HTD) and low (LTD) incidence of TD. In Experiment 1, exposure of chickens to UV light reduced the incidence and severity of TD more in LTD chickens than in HTD chickens, as evident by the significant interactions (P < 0.10 and 0.04). In Experiment 2, the addition of cholecalciferol to diets that were deficient in cholecalciferol linearly decreased the incidence of vitamin D rickets and increased bone ash, but increased the incidence of severe TD. The LTD chickens had a higher maximal bone ash of 40.0 +/- 0.7% than did the HTD chickens, which had a maximal bone ash of 37.0 +/- 0.7%. In Experiment 3, the addition of 5 micrograms/kg of 25-hydroxycholecalciferol [25-(OH)D3], 1-alpha-hydroxycholecalciferol, or 1,25- dihydroxycholecalciferol decreased the incidence and severity of TD in the LTD chickens and had no effect on TD in HTD chickens. In Experiment 4, increasing dietary 25-(OH)D3 increased plasma 25-(OH)D3 levels in both lines, but HTD chickens had higher plasma 25-(OH)D3 levels at 20 and 40 micrograms/kg of dietary 25-(OH)D3. The incidence and severity of TD were reduced in the LTD chickens by dietary 25-(OH)D3, but little effect was noted in HTD chickens. The LTD chickens reached a maximal bone ash at 9.7 +/- 1.9 micrograms/kg and HTD chickens reached the same bone ash at 33.0 +/- 7.0 micrograms/kg. These results indicate that UV light and vitamin D metabolites are not effective in preventing TD in HTD chickens, but that altered vitamin D metabolism does exist between HTD and LTD chickens.

Analysis of Variance↗
PubMed1996

Effects of phytase and 1,25-dihydroxycholecalciferol on phytate utilization and the quantitative requirement for calcium and phosphorus in young broiler chickens.

Three experiments were conducted to determine the effects of supplementing 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and a commercial phytase product on Ca and P requirements of 0- to 21-d-old broiler males. These experiments were conducted with four levels of dietary Ca and P in corn-soybean diets with and without supplementation of 5 micrograms/kg of 1,25-(OH)2D3, 600 units/kg of phytase, and the combination of these supplements. The results show that these levels of phytase and 1,25-(OH)2D3 can replace up to 0.1% of the inorganic P for criteria such as BW, bone ash, and plasma P. Both supplements increased phytate P retention, whereas higher levels of Ca and P decreased phytate P retention. The addition of 1,25-(OH)2D3, but not phytase, reduced Ca requirements and decreased the incidence of tibial dyschondroplasia. The combination of these levels of phytase and 1,25-(OH)2D3 replaced 0.2% inorganic P for criteria such as BW, bone ash, and P rickets. Total dietary P requirements are estimated to be between 0.55 and 0.60% at the levels of phytase and 1,25-(OH)2D3, listed above, or 0.45% when the combination is added. The Ca requirements are estimated to be 0.77% when 1,25-(OH)2D3 is added to the diet and 0.9 to 0.95% when phytase is added.

6-Phytase↗
PubMed1996

Additive effects of 1,25-dihydroxycholecalciferol and phytase on phytate phosphorus utilization and related parameters in broiler chickens.

Two experiments were conducted to compare the effects of supplementation with 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and a commercial phytase on P utilization by broiler males. Experiment 1 was conducted with three levels of total dietary P (0.45,0.55, and 0.65%) in corn-soybean meal diets supplemented with 5 micrograms/kg of 1,25-(OH)2D3, 600 units/kg of phytase, or the combination of these supplements in a factorial arrangement from 0 to 21 d in battery brooders. A second experiment was conducted with a similar design except that it was carried out in floor pens for a period of 35 d. In Experiment 1, maximal BW was obtained at 0.65% P in chicks receiving the basal diet, 0.55% P in chicks receiving phytase or 1,25-(OH)2D3, and 0.45% P in chicks fed both supplements. Bone ash for chicks receiving the basal, phytase, 1,25-(OH)2D3, and combination treatments at 0.45% total dietary P were 26.6, 34.9, 35.1, and 38.8%. There were significant interactions between phytase and 1,25-(OH)2D3 for BW, bone ash, and incidence of rickets. Similar results were noticed in Experiment 2, with the exception that 1,25-(OH)2D3 had little influence on BW from 0 to 3 wk, likely due to slightly higher dietary P. From 3 to 5 wk, BW and bone ash were increased by each supplement and further increased by their combination. These interactions suggest different mechanisms of action for these supplements in influencing phytate P utilization.

6-Phytase↗
PubMed1996

Case management in the community setting.

This article describes a federally funded nurse managed community health organization that treats the elderly. The innovative community-focused model uses the nurse as case manager to provide health promotion, screening, and early interventions to clients enrolled in the Community Nursing Organization (CNO). It explains the advantages of integrating advanced practice nurses into the nursing staff to provide both direct care to clients and teaching/conculation to the nursing staff. The CNO demonstrates that advanced practice nurses possess autonomous practice skills and are able to integrate preventive and curative care across practice sites.

Aged↗
PubMed1995

Heat-stable inhibitor protein derived peptide substrate analogs: phosphorylation by cAMP-dependent and cGMP-dependent protein kinases.

The phosphorylation of substrate peptides derived from PKI, the heat-stable inhibitor protein of the cAMP-dependent protein kinase (PKA), has been studied with both PKA and the cGMP-dependent protein kinase (PKG) using a variety of substitution and deletion analogs. On the basis of Km, kcat and kcat/Km values, (Ser21)PKI alpha(14-22) amide (numbering based upon native PKI alpha) is the most effective peptide substrate yet discovered for either kinase, although other peptides, while phosphorylated considerably less efficiently by PKG, are more specific. Although the inhibitory peptide corresponding to this sequence (i.e., with an Ala at position 21) is a much more potent inhibitor of PKA than of PKG (approximately 250-fold), PKG actually exhibits a 60% higher kcat than does PKA with the (Ser21)PKI alpha(14-22) amide substrate peptide, with only a 20-fold higher Km value. The two key PKI residues within this peptide which were found to be essential for substrate activity with both kinases were Arg18 (P-3) and Ile22 (P+1). The Arg19 (P-2) residue, which contributes significantly to both PKI-based peptide inhibitors and substrates of PKA, was only a more minor contributor to PKG substrate efficacy. Of particular note, the Phe10 (P-11) residue, which contributes very substantially to high affinity binding of both PKI and longer PKI peptide inhibitors, neither positively nor negatively affects the kinetics of either PKA or PKG with PKI-based substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Conformationally constrained analogs of protein kinase inhibitor (6-22)amide: effect of turn structures in the center of the peptide on inhibition of cAMP-dependent protein kinase.

The high-affinity interaction between protein kinase inhibitor (PKI)(6-22)amide(Thr6-Tyr-Ala-Asp-Phe-Ile-Ala-Ser-Gly-Arg-Thr-Gly- Arg-Arg-Asn- Ala-Ile22-NH2) and the catalytic subunit of cAMP-dependent protein kinase requires both the N-terminal Thr6 to Ile11 sequence of the inhibitor peptide and its C-terminal pseudosubstrate site comprised of Arg15 to Ile22. Small angle X-ray scattering data indicate that PKI(6-22)amide has a compact, rather than extended, structure in solution (Reed J et al., 1989, Biochem J 264:371-380). CD spectroscopic analysis of the PKI peptide led to the suggestion that a beta-turn structure might be located in the -Ala12-Ser-Gly-Arg15-connecting sequence in the middle of the molecule (Reed J, Kinzel V, Cheng HC, Walsh DA, 1987, Biochemistry 26:7641-7647). To investigate this possibility further, conformationally constrained and flexible analogs of PKI(6-22)amide were synthesized and used to study the structure-function relationships of this central portion of the inhibitor. (Des12-14)PKI(6-22) amide exhibited over a 200-fold loss in inhibitory activity. Replacement of the omitted -Ala12-Ser-Gly14-sequence with aminocaprylic acid yielded an analog that regained more than 90% of the lost binding energy. The D-alanine14 PKI analog was as potent as the parent peptide, whereas the beta-alanine14 and the sarcosine14 analogs were only 10-fold less active. Several peptides that promoted a beta-turn structure at residues 12-15 showed about 200-fold decreases in inhibitory activity. Two constrained analogs that could not assume a beta-turn conformation were only 30-fold less potent than PKI(6-22)amide. Thus, the structure of the central connecting portion of the PKI peptide, encompassing residues 12-15, greatly influences its ability to effectively bind to and inhibit the catalytic subunit. We conclude, however, that a formal beta-turn at this position is not required and is actually detrimental for a high-affinity interaction of PKI(6-22)amide with the enzyme. These results are interpreted in light of the Fourier-transform infrared spectra of the peptide analogs and the crystal structure of the peptide bound at the active site of the protein kinase (Knighton DR et al., 1991b, Science 253:414-420).

Amino Acid Sequence↗
PubMed1995

Staying one step ahead--development of an electronic record.

Participation in a demonstration program allowed the VNS of New York to develop its own electronic records system. This description of the process and the resulting system should give a good picture of the ultimate benefits of such a system.

Ambulatory Care Information Systems↗
PubMed1995

Posthatching growth and pectoralis muscle development in broiler strain chickens, bantam chickens and the reciprocal crosses between them.

Body weight, pectoralis muscle weight, pectoralis protein and DNA concentration, and plasma GH and IGF-I concentrations of broiler chicks (BrBr), bantam chicks (BaBa) and reciprocal crosses between them (BaBr and BrBa) were measured between 0 and 42 days after hatching. At hatch, body weight and pectoralis weight of the two types of chicks from broiler eggs (BrBr and BaBr) were equal to each other but greater than the two types of chicks from bantam eggs (BaBa and BrBa), which were not different from each other. BrBr chicks grew more rapidly than crossbreds and BaBa chicks grew more slowly. Weights of the reciprocal crosses (BaBr and BrBa) were markedly different at day of age, but converged by day 14. The increase in pectoralis muscle mass of BrBr chicks exceeded that of the reciprocal crosses which in turn exceeded that of BaBa chicks. The increase in pectoralis DNA content and protein content followed the same pattern. The DNA unit size, as expressed by the protein:DNA ratio, was markedly lower in pure bantam chicks from 14 to 42 days of ages, whereas the unit size did not differ between the intermediate sized reciprocal crosses and the large bodied broiler chicks. Differences in muscle mass were primarily achieved by differences in the number of DNA units although a difference in unit size was also a factor. There were no clear relationships between growth and plasma growth hormone or insulin-like growth factor I concentrations. Thus while satellite cell proliferation is primarily responsible for genotypic differences in muscle mass, the plasma growth hormone-IGF-I axis does not appear to be regulating their proliferation.

Age Factors↗