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Biomedical subjects

R Miller

Publications and source records attributed to R Miller.

At least 577 records · Page 32Linked to original sources
PubMed1990

The pharmacokinetics of phenobarbitone in fasting and non-fasting dogs.

The pharmacokinetics of oral phenobarbitone was studied in 10 clinically healthy adult dogs. The drug was given once daily in tablet form, at a dose of 5 mg kg-1 of body mass. Serial venous blood samples (n = 9) were collected from each dog on Day 1 (the first day of drug dosing), on Day 22, and on Day 24 after continuous dosing. Trough serum concentrations were determined on Day 7, Day 14 and Day 21. The drug was administered to the dogs on an empty stomach, except on Day 24, when it was given with food, in order to assess the influence of food on its absorption. Drug serum concentrations were described by a one-compartmental open model with first order absorption and elimination. An average steady-state trough serum level of phenobarbitone of 52,96 +/- 8.40 mmol l-1 was achieved after 3 weeks of daily dosing. The mean elimination half-lives for Day 1 and Day 22 were 46.3 +/- 11.3 h and 29.3 +/- 4.6 h respectively. The area under the curve for Day 22 was 1,656.17 +/- 186.45 mumol h-1 l-1 and for Day 24 was 1,493.06 +/- 205.4 mumol h-1 l-1. The mean clearance value for Day 22 was 0.0133 +/- 0.0016 l h-1 kg-1. Side effects of polyphagia, polydipsia, sedation and ataxia were commonly observed in the first 2-9 d, but disappeared thereafter. It was concluded that a dose of 5 mg kg-1 would achieve an average serum concentration of 64.59 mumol l-1 in adult dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

A comparative study of standard and slow-release oral lithium carbonate products.

Lithium serum levels were drawn over one steady-state dosing interval in 8 bipolar disorder patients receiving long-term lithium therapy: (i) after standard-release lithium (STD); and (ii) after changing to 2 weeks' continuous dosing of a slow-release (SR) preparation. Rate of absorption of the SR preparation was significantly slower than the STD preparation measured by the peak/trough difference, percentage peak/trough fluctuation and percentage swing. The extent of absorption measured by the area under the concentration time curve was not significantly different for the two preparations. Serum lithium levels drawn within 2 hours after administration of the SR preparation are likely to be within the range 0- -18% of the 12-hour standard serum lithium with a 95% limit of confidence. The STD preparation shows a deviation in the same period of -14.5-70%. These results suggest that if a patient taking the SR preparation presents within 2 hours after administration a serum lithium level would still be meaningful, whereas for a patient taking the STD preparation it is essential that blood be drawn 12 hours after administration for meaningful interpretation.

Administration, Oral↗
PubMed1989

Mechanisms of T cell activation by the calcium ionophore ionomycin.

We have investigated signaling mechanisms that may underlie the T cell mitogenic properties of the Ca2+ ionophore ionomycin. Ionomycin induces highly purified resting human T cells to proliferate in the presence of monocytes with accompanying IL-2R expression and IL-2 synthesis. Treatment of T cells with ionomycin triggers the hydrolysis of phosphoinositides, as evidenced by the accumulation of the hydrolytic by-products phosphatidic acid and inositol phosphates. Ionomycin also induces the activation of protein kinase C (PKC), as demonstrated by the auto-phosphorylation of PKC and the phosphorylation of the PKC target proteins CD4 and CD8. Ionomycin synergizes with PMA in enhancing the activation of PKC. It is concluded that, in addition to its putative activation of Ca2+/calmodulin-dependent signaling pathways, ionomycin induces the hydrolysis of phosphoinositides and the activation of PKC in human T cells. The synergy of ionomycin with phorbol esters in triggering T cell activation may relate, at least in part, to enhanced activation of PKC.

Calcium↗
PubMed1989

Phenytoin auto-induction? Case reports.

Auto-induction of phenytoin metabolism is considered by many to be insignificant. Two cases, in which elimination of phenytoin apparently increased with continuous use, are presented. The first patient showed an increase in elimination capacity (Vmax) from 511 mg/d to 613 mg/d over a period of 5 months. The second patient showed an increase in Vmax from 512 mg/d to 570 mg/d over a period of 1 year. In neither case was compliance in question. The recognition that therapeutic failure may be due to enzyme induction could obviate expensive diagnostic procedures as well as narrow down the therapeutic alternatives.

Adolescent↗
PubMed1989

An immunodeficiency characterized by defective signal transduction in T lymphocytes.

We studied a nine-year-old boy with severe, recurrent infections. The patient was exposed in utero to azathioprine and prednisone. He had autoimmune hemolytic anemia, bronchiectasis, and Hodgkin's disease. The patient's circulating lymphocytes were normal in number and phenotype, but stimulation of the T-cell receptor by antigens, mitogens, and monoclonal antibodies failed to induce interleukin-2-receptor expression, interleukin-2 synthesis, or lymphocyte proliferation. The early biochemical events necessary to initiate lymphocyte activation--accumulation of the second messenger diacylglycerol, activation of the enzyme protein kinase C, and elevation of the free intracellular calcium concentration--failed to occur in this patient's lymphocytes. The defect in the lymphocyte could be corrected in vitro by two agents that bypass the receptor-mediated signal mechanism (the diacylglycerol analogue phorbol and the calcium ionophore ionomycin). Further studies localized the defect in signal transduction to the interaction between cell-surface receptors and the guanine nucleotide-binding protein. We conclude that this patient's immunodeficiency was caused by a defective coupling of surface receptors to signal-transducing proteins in his T lymphocytes, resulting in failure of lymphocyte activation.

Calcium↗
PubMed1989

Air-filled microballoon manometry for use in anorectal physiology.

Manometry is fundamental to anorectal physiology but the water-filled manometric systems commonly used have several disadvantages. To investigate the 'new' air-filled microballoon system, we compared it with a standard water-filled equivalent by measuring sphincter length, maximum resting pressure (MRP) and maximum voluntary contraction pressure (MVC) in 44 patients using the station pull-through technique. A good correlation was found for all three parameters (Spearman correlation coefficient rs: sphincter length = 0.86, MRP = 0.86 and MVC = 0.94, P less than 0.001). Repeat studies in 15 patients showed excellent reproducibility (rs: sphincter length = 0.97, MRP = 0.96 and MVC = 0.97, P less than 0.001). Air-filled microballoon manometry gives results similar to a water-filled microballoon system and has many advantages.

Adult↗
PubMed1989

Anterior sphincter plication and levatorplasty in the treatment of faecal incontinence.

The surgical treatment of faecal incontinence has been traditionally divided into sphincteroplasty for sphincter disruption and postanal repair for idiopathic cases. However, many studies have failed to show a correlation between outcome and change in the anorectal angle. This study was carried out to determine the effectiveness of anterior sphincteroplasty and levatorplasty in the treatment of faecal incontinence, regardless of aetiology. Thirty consecutive patients underwent surgery, 14 with traumatic sphincter injuries and 16 with idiopathic faecal incontinence. A satisfactory clinical result was obtained in ten (71 per cent) patients in the traumatic group and in ten (62 per cent) in the idiopathic group. This was associated with a significant increase in maximum voluntary contraction pressure in the traumatic group and in those patients who had a good result in the idiopathic group (traumatic: preoperative median 80 cmH2O (range 50-115 cmH2O) versus postoperative 115 cmH2O (75-290 cmH2O), P less than 0.005; idiopathic: preoperative 105 cmH2O (45-190 cmH2O) versus postoperative 120 cmH2O (45-230 cmH2O), P less than 0.05; Wilcoxon paired signed ranks test). There was also significant improvement in anal sensation in the upper anal canal in both groups (traumatic: preoperative mean 17 mA versus postoperative 11 mA, P less than 0.05; idiopathic: preoperative 24 mA versus postoperative 9 mA, P less than 0.02). The anorectal angle increased in the idiopathic group at rest (preoperative median 105 degrees (range 86-152 degrees) versus postoperative 118 degrees (95-180 degrees), P less than 0.05). In conclusion, the type of approach (anterior or posterior) and the anorectal angle are irrelevant to the outcome of surgery for idiopathic faecal incontinence. Success appears to be related more to improved sphincter pressure and anal sensation.

Adult↗
PubMed1989

A multicenter randomized trial of ionic (ioxaglate) and nonionic (iopamidol) low-osmolality contrast agents in cardiac angiography.

A multicentered double-blind randomized study was performed comparing the electrocardiographic and hemodynamic changes induced by two new low osmolar contrast agents used for cardiac angiography. The low osmolar ionic (ioxaglate) contrast agent was compared with a low osmolar nonionic (iopamidol) contrast agent in 150 patients with angina pectoris undergoing angiography. Systolic blood pressure, left ventricular end-diastolic pressure, heart rate, and QT interval were measured just before and for 90 s following the left ventricular angiography and selective coronary angiography. Each group was also evaluated for adverse events and quality of radiographic images. Following left ventricular angiography, the systolic blood pressure dropped slightly in both groups with a greater decrease seen in the iopamidol group at 5 s (p less than 0.05). After selective right and left coronary angiography, systolic blood pressure decreased transiently and equally in both treatment groups. The left ventricular end-diastolic pressure increased after the ventriculogram in both groups (15.9 +/- 6.3 to 18.9 +/- 8.6 mmHg in the ioxaglate group and 16.1 +/- 6.7 to 20.1 +/- 7.8 mmHg in the iopamidol group), the change being significant only in the iopamidol group (p less than 0.05). Heart rate increased slightly but significantly in the ioxaglate-treated patients following left ventricular angiography (71.4 +/- 15.2 to 74.4 +/- 13.7 beats/min) (p less than 0.01). QT interval transiently increased following left ventriculography with ioxaglate (407 +/- 59.5 to 420 +/- 58.3 ms) (p less than 0.05) compared with iopamidol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Polyclonal anti-idiotypes influence macrophage chemotaxis in coxsackievirus-induced murine myocarditis.

Investigation into the mechanism(s) whereby monocytes-macrophages are mobilized to the myocardium of coxsackievirus (CVB3)-infected mice was approached by assessing the role of anti-idiotypic antibodies against specific antiviral IgG molecules. Balb/c mice preinoculated with polyclonal anti-idiotypic, syngeneic antibodies resulted in significantly decreased myocarditis after virus challenge. On the other hand, oil-induced peritoneal exudate cells obtained from virus-exposed animals demonstrated increased chemotaxis in the presence of polyclonal anti-Id preparations, whereas peritoneal exudate cells from normal animals did not. Specificity of the anti-Ids as confirmed by the binding of the syngeneic anti-anti-idiotypic antibodies (antibody 3) to solubilized viral antigen(s) and Fab fragments prepared from the anti-idiotypic antibodies. Paradoxic biological effects of anti-Id, demonstrated in vitro and in vivo, suggest possible and subtle immunoregulation of the macrophage effector arm by anti-idiotypes during the course of virus infection.

Animals↗
PubMed1989

Proliferation of highly purified T cells in response to signaling via surface receptors requires cell-cell contact.

Lymphocyte proliferation is associated with cell-cell aggregation. In order to assess the importance of cell-cell contact in T-cell proliferation we examined the effect of disruption of cellular aggregation by anti LFA-1(4) mAb on T-cell proliferation. Monocyte-dependent T-cell proliferation induced by anti-CD3 mAb, pairs of anti-CD2 mAbs, or PHA was inhibited by anti-LFA-1 mAb. Monocyte-independent proliferation of highly purified T cells to anti-CD3 mAb plus PMA or plus IL-2 and to PHA plus IL-2 was, surprisingly, also inhibited by anti-LFA-1 mAb. Anti-LFA-1 mAb caused the partial inhibition of both low-affinity and high-affinity IL-2 receptor and the complete inhibition of IL-2 synthesis. In contrast to the above, the proliferation of highly purified T cells to PMA plus ionomycin was not inhibited by anti-LFA-1 mAb. These results suggest that optimal activation of highly purified T cells via cell surface receptors requires LFA-1-dependent cell-to-cell contact between proliferating T cells as well as between T cells and accessory cells. Such contact appears to be crucial for initiating IL-2 production and for optimal action of IL-2 through its receptor.

Adult↗
PubMed1989

Differences in anal sensation in continent and incontinent patients with perineal descent.

Neuropathic damage secondary to pelvic floor descent is considered to be an important aetiological factor in idiopathic faecal incontinence. Perineal descent however does not necessarily result in a loss of motor function or incontinence. To elucidate the role of anal sensation in the continence mechanism we measured mucosal electrosensitivity and thermal sensitivity in normal controls and in both continent and incontinent patients with perineal descent. A catheter carrying two platinum electrodes was used to assess mucosal electrosensitivity and a water perfused thermode 1 cm long to measure thermal sensory thresholds. In addition, routine anal manometry was performed. The degree of perineal descent and anorectal angle was assessed radiographically. Anal sensation was largely preserved in continent patients with perineal descent (Controls vs continent perineal descent, Mucosal electrosensitivity (ma), lower anal canal: 4 (2-7) vs 5 (2.6-8) ns; middle anal canal 4 (2-7) vs 4.2 (2-15) ns; upper anal canal 6.5 (4-13) vs 8.3 (3.6-16) p less than 0.05, thermal sensitivity, median threshold (degrees C), lower anal canal 0.92 (0.5-2.5) vs 0.95 (0.3-3.6) ns; middle anal canal 0.83 (0.4-1.5) vs 0.75 (0.2-2) ns; upper anal canal 0.98 (0.6-2.4) vs 2.2 (0.5-4.8) p less than 0.05). There was a severe impairment of anal sensation in the incontinent patients with perineal descent despite a greater degree of perineal descent in the continent group. Loss of anal sensation is associated with the development of incontinence and is likely to be involved in the pathogenesis of the condition.

Adult↗
PubMed1989

Nucleotide sequence of the avian influenza A/Mallard/NY/6750/78 virus polymerase genes.

The avian influenza A/Mallard/NY/6750/78 virus is currently being evaluated as a donor of attenuating genes in the construction of live avian-human influenza A reassortant virus vaccines for use in humans. We determined the nucleotide sequences of the three polymerase gene segments of this virus. This completes the nucleotide sequence of the six transferrable genes of the avian donor virus. Comparison of the nucleotide and deduced amino acid sequences of the non-glycoprotein genes of the avian A/Mallard/78 virus with representative avian and human influenza A viruses suggests that the PB1 gene of H2N2 subtype human influenza A viruses may have been derived from a non-human, possibly avian influenza A virus by genetic reassortment. In addition, several regions of conserved amino acids with potential functional significance were identified in the deduced amino acid sequences of the polymerase proteins.

Amino Acid Sequence↗
PubMed1989

Efficacy of the morantel sustained release trilaminate matrix against gastrointestinal nematodes in beef calves.

The effectiveness of the morantel sustained release trilaminate (MSRT) in controlling gastrointestinal nematodes through a grazing season was evaluated using 60 yearling beef stocker calves randomly divided into 2 groups of 30 animals each. In April 1985, the calves comprising the treatment group each received an MSRT designed to release morantel tartrate continuously for 90 days while those of the control group remained unmedicated. All animals were weighed and samples of rectal feces were taken at 14-day intervals, beginning on Day 0, until trial termination (Day 168). At trial termination, 10 control and 10 treated calves were necropsied for recovery of gastrointestinal nematodes. Three sets of parasite-naïve tracer calves were utilized to evaluate the initial, interim and final levels of pasture contamination by nematode larvae. Overall, the use of the MSRT resulted in a 75.5% reduction (P less than 0.001) in output of nematode eggs from the principals, an 81.8% reduction (P less than 0.001) in numbers of gastrointestinal nematodes in principals (at trial termination), and a 96.9% reduction (P less than 0.05) of pasture larval nematode contamination (as indirectly indicated by parasite burdens in tracer calves). The mean weight advantage of treated calves was 16.6 kg per head (P less than 0.001).

Animals↗
PubMed1989

Paradoxical interventions in counselling for people with an intractable AIDS-worry.

This article has two main objectives. Firstly, consideration is given to the context in which certain individuals become convinced that they have been infected with the Human Immunodeficiency Virus (HIV), despite repeated negative HIV antibody tests and reassurance. Secondly, it is to describe an intervention which is designed to escalate anxiety in individuals with an intractable AIDS-worry, in order to release them from their rigid and distressing beliefs. A case study is presented to illustrate this.

Acquired Immunodeficiency Syndrome↗
PubMed1989

AIDS and children: some of the issues in haemophilia care and how to address them.

Haemophilia is a life-long, life-threatening inherited condition for which there is treatment but no cure. It affects not only the patient but all members of the family. This paper focuses on how AIDS/HIV, which shares these characteristics with haemophilia, has affected children with HIV, their siblings, those who have remained antibody negative and those with HIV infected fathers. The impact of haemophilia and AIDS on the family is considered and the ripple effect of AIDS on health care staff is addressed.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Treatment dilemmas for HIV infected haemophiliacs.

A description of a structured group, held for anti-HIV positive haemophiliacs and their relatives, to discuss the implications of participating in the MRC/INSERM double-blind control trial of zidovudine is given. The group discussion is used to define, evaluate and rank the many treatment dilemmas inherent in participating in this drug trial.

Double-Blind Method↗