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Biomedical subjects

R McIntosh

Publications and source records attributed to R McIntosh.

At least 19 recordsLinked to original sources
PubMed2005

Visually guided reaching: bilateral posterior parietal lesions cause a switch from fast visuomotor to slow cognitive control.

The visually guided reaching of two patients with bilateral optic ataxia was explored in two experiments. In Experiment 1 simple delayed pointing was compared with immediate pointing. In the immediate pointing task both variable and constant errors increased with target eccentricity. In contrast to the performance of control subjects and contrary to their own beliefs, the patients both showed improved accuracy in the delay condition. This improvement was manifest as a reduction in both pointing variability and in the constant angular error towards the point of fixation. Both angular errors and their improvement with the delay were proportional to target eccentricity. Experiment 2 used a task in which the target was pre-viewed 5s prior to its re-exposure for pointing ('delayed real pointing'). On some trials a conflict was introduced between the present and previous visual information by changing the target's location during the delay. In contrast to control subjects, who ignored the pre-viewed location and aimed directly at the current target, both patients with optic ataxia initiated their movements towards the previously viewed target location. Evidently they relied on off-line information in preference to on-line visual information. In addition, the patients often failed to detect the changes in target location. One of the patients sometimes even guessed incorrectly that the target had changed its location, and her movement trajectory was then more affected by her false belief than by the target's actual location. These findings confirm that posterior parietal lesions severely disrupt direct visuomotor transformations, and suggest that the residual performance is mediated indirectly by expectations or beliefs about target position.

Acoustic Stimulation↗
PubMed2004

WHO Expert Committee on Biological Standardization.

This report presents the recommendations of a WHO Expert Committee commissioned to coordinate activities leading to the adoption of international requirements for the production and control of vaccines and other biologicals and the establishment of international biological reference materials. The report starts with a discussion of general issues brought to the Committee's attention and provides information on the status and development of reference materials for various antibodies, antigens, blood products and related substances, cytokines, growth factors, and endocrinological substances. The second part of the report, of particular relevance to manufacturers and national regulatory authorities, contains recommendations for the production and quality control of meningococcal group C conjugate vaccines, guidelines for regulatory expectations for clinical evaluation of vaccines, guidelines for the production and quality control of inactivated oral cholera vaccines and guidelines on viral inactivation and removal procedures intended to assure the viral safety of human blood plasma products.

Advisory Committees↗
PubMed2001

A series of case studies on the effect of a midfoot control ankle foot orthosis in the prevention of unresolved pressure areas in children with cerebral palsy.

This paper reports on a series of case studies where improvements were sought in muscle tone and gait in children with cerebral palsy. A Midfoot Control Ankle Foot Orthosis (AFO) was developed to control foot position in a cohort of patients with cerebral palsy (CP). The concept of controlling midfoot and hindfoot with an encapsulated internal Supra-Malleolar AFO that fitted into an external AFO was shown to be effective in ambulant children with CP. Some initial problems of compliance were noted and postulated to be due to difficulties associated with previous orthotic devices. Evidence from the case studies suggest that the developed Supra-Malleolar AFO orthoses enables children with CP to maintain mobility without skin tissue damage, delays the need for surgery and at the same time maintains the length of the Triceps Surae (Gastrocnemius and Soleus) complex. Plans for further research are discussed which will contribute to the evidence base for this particular orthotic device.

Ankle↗
PubMed1998

Somatic hypermutation in autoimmune thyroid disease.

Autoimmune thyroid disease is one of the most common autoimmune diseases. There is typically patient antibody (Ab) reactivity to one or more of the antigens thyroglobulin (Tg), thyroid peroxidase (TPO) and the thyroid simulating hormone receptor (TSHr). With the advent of combinatorial library technology, there has been an enormous increase in the number of sequences from Ab to Tg and TPO. The repertoire of both Tg and TPO Ab is restricted and indicates the importance of somatic hypermutation in the development of the high affinity Ab response. However, there are still too few sequences to determine patterns in which the mutation occurs, which residues are introduced during substitution and how individual substitutions affect the affinity of the Ab. Ab to the TSHr are of far greater pathological significance than those to Tg and TPO, but the current repertoire of Ab to the TSHr has yet to include the high affinity IgG Ab characteristic of patient serum Ab. Instructive analysis of the role of somatic hypermutation in the development of TSHr Ab therefore still awaits the isolation of the pathologically active repertoire. Despite this, the Ab response in thyroid autoimmunity remains one of the best characterised of human autoimmune diseases.

Amino Acid Sequence↗
PubMed1993

Recombinant human interleukin-4 (rhu IL-4) administered by the intravenous and subcutaneous routes in patients with advanced cancer--a phase I toxicity study and pharmacokinetic analysis.

19 patients with advanced cancer were entered into a phase I study of recombinant human interleukin-4 (rhu IL-4). The predominant clinical side-effects included flu-like symptoms, gastrointestinal upset, lethargy and transient hypotension. In addition, there were several cases of capillary leak syndrome. 2 cases of gastrointestinal haemorrhage occurred; this was life threatening in 1 patient. The maximum tolerated dose (MTD) was 400 micrograms/m2/day. Biochemical toxicity was limited to asymptomatic elevation of liver enzymes suggesting IL-4 induced liver damage. Pharmacokinetic analysis following the intravenous bolus injection has shown that IL-4 is rapidly cleared (mean T1/2 = 19 +/- 8.7 min) from a small compartment (mean Vd = 4.9 +/- 3.68 l) probably indicating that IL-4 is retained in the systemic circulation or at most the extracellular fluid volume. 2 patients with non-Hodgkin lymphomas (NHL) showed a transient response to IL-4 whilst a third patient with NHL showed transient disease progression.

Adult↗
PubMed1992

Adverse influence of fibrin sealant on the healing of high-risk sutured colonic anastomoses.

The effect of fibrin glue sealing on sutured colonic anastomoses was studied using a 'high-risk' colon anastomosis model in the rat. Animals (n = 104) were randomized to have their sutured anastomosis sealed with fibrin glue or left untreated. They were assessed clinically until they were killed on the fourth day after surgery when contrast radiology, detailed post-mortem examination, anastomotic bursting pressure (ABP) and assessment of adhesion formation were performed. The clinical outcome was worse in the glued group (toxic or death from sepsis: 18 versus seven in the non-glued group; P = 0.0354), which also showed a significantly higher moderate to major leak rate (17 versus two in the non-glued group; P = 0.0009). The median ABP was significantly higher in the glued anastomosis group (96 versus 68 cmH2O in the non-glued group; P = 0.0367). Excessive perianastomotic adhesion formation was significantly greater in the glued group. Microscopic examination showed an extremely intense inflammatory reaction in the glued anastomoses compared with that in the untreated group. These results indicate that sealing of a sutured anastomosis with fibrin glue containing an antiproteinase impairs healing the of anastomotic wound, probably by resisting the ingrowth of vascular granulation tissue during the early stages of repair.

Anastomosis, Surgical↗
PubMed1991

Effect of fibrin glues on the mechanical properties of healing wounds.

Tissue glues are important in clinical practice. Fibrin based glues have many advantages over non-biological adhesives. The optimum formulation of these glues measured by their effect on mechanical properties of healing wounds has not been determined. Using a model involving standard dorsal skin incisions in adult male Wistar rats various glue formulations were compared by varying the fibrinogen, thrombin and factor XIII concentrations. Calcium (40 mumol/ml) and aprotinin (3000 kallidinogenase inactivator units, KIu/ml) concentrations were kept constant. Animals were killed at 8 days and wounds excised. Standard strips of these wounds were mechanically tested using an Instron tensiometer and the stress, strain, elasticity and work required to rupture wounds were calculated. Results indicate that a fibrin glue with a fibrinogen concentration of approximately 39 g/l and a thrombin concentration of 200-600 units/ml with no added factor XIII will result in wounds with significantly increased stress, energy absorption and elasticity values.

Animals↗
PubMed1991

Phase II study with mitomycin, ifosfamide and carboplatin in inoperable non-small cell lung cancer.

In a phase II study of non-small cell lung cancer a new chemotherapy combination of mitomycin 6 mg/m2 intravenously on day 1, carboplatin 400 mg/m2 intravenously on day 1 and ifosfamide with mesna 5 g/m2 intravenously over 24 hours on day 1 was evaluated. A maximum of four chemotherapy cycles was given at intervals of 4 weeks to 34 patients with progressive, inoperable disease. 1 complete and 10 partial remissions were documented, the overall response rate being 32.4%. In a further 13 patients (38.2%) the previously progressing tumours remained stable for at least 6 weeks. The median time to progression for responding patients was 184 days. The median survival time for the whole group has not yet been reached at 293 days. A considerable but easily manageable myelosuppression was the principal toxicity despite a "no dose reduction" policy. Indeed, the dose intensity of the chemotherapy actually given was extremely close (97%) to that intended on protocol. In conclusion, the regimen is active in patients with advanced non-small cell lung cancer but requires regular haematological monitoring to prevent morbidity resulting from myelotoxicity.

Aged↗
PubMed1991

Computed tomographic and ultrasound appearances of focal spared areas in fatty infiltration of the liver.

Computed tomography (CT) and ultrasound (US) appearances of diffuse and focal fatty infiltration of the liver (FIL) are well recognized. We have recently seen 10 cases with "fat spared" areas in FIL presenting as pseudo tumours of the liver. Characteristic appearances of fat free areas in FIL which help differentiate these areas from other focal liver lesions include (i) location in the medial segment of the left lobe of the liver, (ii) absence of mass effect on surrounding vessels and liver tissue, and (iii) presence of typical changes of FIL elsewhere in the liver on CT or US examination.

Fatty Liver↗
PubMed1991

A review of social interventions for students with learning disabilities.

Twenty-two studies are reviewed that report the effects of social skills training and intervention with 572 children identified as learning disabled between 5 and 19 years of age. These studies are reviewed to examine characteristics and components of intervention effectiveness. Age and sex of subjects, grade grouping, group size, intervention duration, intervention procedures, subject selection, and type of interventional model are examined to find patterns that reflect intervention success. Several intervention characteristics and components are associated with social intervention effectiveness: selecting subjects who had social skills difficulties or low peer acceptance, using cognitive-behavioral intervention procedures, providing individual or small group instruction, and applying long-term intervention and training. Discussion focuses on difficulties in comparing studies to determine intervention effectiveness through the examination of outcome measures, a call for revisions in future reporting of social interventions in the literature, and those intervention factors that relate to increases in peer acceptance.

Adolescent↗
PubMed1987

The enhanced induction of metallothionein by zinc, its half-life in the marine fish Pleuronectes platessa, and the influence of stress factors on metallothionein levels.

Intraperitoneal injection of zinc raised levels of a hepatic metallothionein-like species. Assuming that this species was metallothionein (MT) then levels were raised from approximately 20 micrograms/g to 300 micrograms/g in 7 days, and levels thereafter remained high for the next 4 weeks. The half-lives of the protein in liver and kidney from starved fish, measured using in vivo incorporation of 35S cysteine at 11 degrees C, were approximately 27 days and 32 days respectively. The following agents failed to stimulate synthesis of MT in plaice: stress (due to catching), endotoxin, dexamethasone, cortisol and turpentine.

Animals↗
PubMed1986

Operative recovery of vasal sperm from anejaculatory men: preliminary report.

Sperm showing good motility and function, as demonstrated by the in vitro sperm penetration assay using hamster ova, were collected from the vas deferens of 3 men with ejaculatory failure. The collection procedure may be repeated over multiple ovulatory cycles. The sperm may be used to attempt artificial insemination or in vitro fertilization.

Adult↗
PubMed1980

Multiple organ failure: clinical and experimental.

The clinical scenario of multiple organ failure (MOF) is reviewed and its frequent correlation with sepsis emphasized. It is hypothesized that MOF is produced by the formation of immune complexes (IC) in response to infection with deposition on organs such as the liver, lung, and kidney. Such immune complexes trap macrophages which can directly damage endothelium. Such a pathologic picture is in keeping with that of MOF. Granular deposits of IgG, IgM, C3, C5, and fibrinogen have been identified in the organs of four patients dying of MOF and sepsis. Similar deposits have been identified using fluorescent antibody stains in the organs of rabbits following cecal perforation. It is hypothesized that sepsis may produce organ failure at a distance from the site of infection via deposits of immune complexes.

Acute Kidney Injury↗
PubMed1977

Attenuation of canine nephrotoxic glomerulonephritis with an extracorporeal immunoadsorbent.

A novel immunoadsorbent is described in which soluble canine glomerular basement membrane (GBM) antigen was immobilized in collodion membranes adherent to small charcoal particles. As much as 80% of the added GBM antigen was retained in the collodion-charcoal. The binding of GBM antibody to immobilized GBM antigen in vitro and in vivo was demonstrated. For in vivo studies, an extracorporeal circulation system was established, and mongrel dogs were then injected intravenously with GBM collodion-charcoal for 4 h. Renal tissue was examined by fluorescence and light microscopy for the deposition of heterologous gamma globulin and glomerular inflammation before and after the extracorporeal procedure. Results showed less deposition of heterologous IgG and less inflammation in experimental dog kidneys than in control kidneys. There was no evidence of release of 131I-labeled GBM from the immunoadsorbent at the conclusion of perfusion experiments and no significant biochemical or hematologic alterations. Finally, extracorporeal immunoadsorbent treatment was capable of attenuating the early heterologous phase of passive canine nephrotoxic nephritis and may have a potential role in the therapy of anti-GBM-mediated nephropathy.

Animals↗
PubMed1976

Pancreatic islet isografts, allografts, and xenografts: comparison of morphology and function.

Neonatal rat pancreatic islets were transplanted intraperitoneally into adult streptozotocin-diabetic rats and mice. Isologous pancreatic islet recipients (12 of 12) showed consistent and permanent reconstitution of normoglycemia and normal weight gain as well as readjustment to normal of intake of water, urine volume, and glucose excretion for greater than 10 months when compared to age-matched normal (ten) and diabetic (20) controls. Revascularized isologous islet grafts were found to be adherent to both visceral and parietal peritoneum. Pancreatic islet allografts (ten) and allografts and xenografts did not appear to differ markedly; both were characterized by dense round-cell infiltration within 5 days after transplantation.

Animals↗