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Biomedical subjects

J D Miller

Publications and source records attributed to J D Miller.

At least 343 records · Page 19Linked to original sources

Toxigenic potential of some fusarium isolates from southeast Asia.

The isolation and characterization of 10 isolates of six Fusarium spp. from plant and soil samples collected in Southeast Asia is reported. The ability of these isolates to produce trichothecenes both in liquid cultures (CZ, GYEP, and MYRO) and on rice was assessed, and their toxigenic potential was examined by skin assay and gavage studies with culture filtrates. Although culture filtrates of all the isolates caused minor damage to test animals, only that of F. equiseti DAOM 189762 produced trichothecenes.

Journal Article↗

Indomethacin and salicylate modulate effect of insulin on glucose kinetics in dogs.

We studied insulin's effects on glucose production (Ra) and utilization (Rd) in trained, conscious dogs before and during treatment with indomethacin (Indo) and salicylate (S). Ra and Rd (mg X kg-1 X min-1) were calculated by isotope dilution using [3-3H]glucose. Animals were treated with either oral Indo or acetylsalicylic acid for 1 day before the respective studies. On the study day, experimental animals were given a continuous infusion of either saline (control), Indo (5 mg/kg bolus followed by 0.05 mg X kg-1 X min-1), or sodium salicylate (0.45 mg X kg-1 X min-1) for 330 min on separate days; each animal participated in all three protocols. After establishing steady-state specific activity, control (C) and experimental animals (n = 6/group) received insulin, 0.275 mU X kg-1 X min-1 for 150 min, raising serum insulin levels two- to threefold above basal. During insulin infusion in C, plasma glucose (G) fell from 99 +/- 2 to 82 +/- 6 ml/dl (P less than 0.01), associated with a transient fall in Ra from 2.5 +/- 0.3 to 1.9 +/- 0.2 (P less than 0.01) at 30 min, returning to base line at 45 min; Rd did not change. In the Indo and S groups, G also fell by a similar extent. In contrast to C, however, the fall in G was associated with a rise in Rd, commencing at 30 min in the Indo group (P less than 0.05) and at 45 min in the S group (P less than 0.01); Ra did not fall and actually rose above basal (P less than 0.05), although it did not match the rise in Rd.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fifty years of experience with chordomas in southeast Scotland.

We report the clinical presentation and management of 34 patients with a histologically proven chordoma, treated in the neurosurgical departments in Edinburgh and Dundee, over the past 50 years. Although these tumors are commonly regarded as being locally invasive with a variable, but generally slow growth rate, they can metastasize, and this may precede surgical intervention, as in one of our patients. Our cases are compared to those in previously published series, and a comprehensive review of the treatment modalities for tumors at various sites is presented. The optimal treatment to be recommended from our own experience, and that of others, is aggressive operation and radiotherapy. A combination of hyperthermia and chemotherapy has shown some promise, but remains untested, and highlights the need for a multicenter trial with long follow-up to allow the evaluation of new therapeutic approaches.

Adolescent↗

Effect of experimental common carotid arteriotomy on cerebral blood flow in rats.

Cerebral blood flow (CBF) and its reactivity to alterations in arterial carbon dioxide tension were measured in 52 rats. Measurements were made in four groups of rats: 15 were controls, 14 had one carotid artery clamped, 11 had microvascular common carotid arteriotomies, and 12 had sham arteriotomies. Before carotid operation, a flow change of 1 ml/100 g of brain per minute per torr change in CO2 tension was demonstrated in the rats, a value for reactivity similar to that found in normal humans. After unilateral common carotid ligation, CBF was not significantly disturbed in either hemisphere, and reactivity was preserved. In rats subjected to arteriotomy, CBF fell by 30% from the control level in both hemispheres, and carbon dioxide reactivity was reduced by 80%. Very similar reductions in flow (38%) and reactivity (76%) were produced after sham arteriotomy, in which the common carotid artery was isolated between temporary clamps for 30 minutes, but the arteriotomy incision was not made. The observed flow reduction and carbon dioxide reactivity impairment must result from the reperfusion of the brain through the traumatized carotid artery, inasmuch as no impairment of either flow or reactivity followed extravascular dissection and permanent ligation of the vessel. These changes may be mediated by damage to the sympathetic plexus or the innervation of the carotid body chemoreceptors or by the release of histamine, prostaglandins, or other vasoactive substances from the incised vessel wall. If this finding is applicable to humans, it suggests that the entire cerebral circulation in patients with respiratory impairment may be precarious for some hours after a carotid endarterectomy and confirms the danger of hypercapnia during anesthesia for carotid surgery.

Animals↗

Papilledema after acute head injury.

Low grade papilledema after acute, severe head injury was identified in 15 (3.5%) of 426 patients. Papilledema was recognized immediately after head injury in 1 patient, during the 1st week in 10 patients, and in the 2nd week or after in 4 patients. Initial computed tomographic scans showed evidence of brain injury in 11 of these patients. The intracranial pressure (ICP) was monitored continuously for 3 or more days in 9 patients; it was mildly elevated (20 to 40 mm Hg) in 7 patients and moderately elevated (40 to 60 mm Hg) in 2 patients. Intracranial hypertension was controllable in each patient. A sudden, severe, but transient increase in ICP best explained the immediate development of papilledema and survival of 1 patient. Sustained but mild to moderately elevated ICP accounted for papilledema appearing in the 1st week. Papilledema in the 2nd week or after occurred from impaired cerebrospinal fluid absorption and consequent communicating hydrocephalus or delayed focal or diffuse cerebral swelling. A lesser degree of head injury in patients with posttraumatic papilledema was suggested by a higher Glasgow coma score, milder and controllable elevations in ICP, and the absence of any fatality in this group. The favorable outcome was significant compared to the mortality of the more severely injured patients (chi square-4.327; P less than 0.04). Papilledema did not occur in 6 patients with sustained, severely elevated ICP (greater than 60 mm Hg) for 3 or more days. Each of these patients died. The severity of the trauma apparently accounts for the failure of papilledema to develop, possibly by arresting axoplasmic production and transport in retinal nerve fibers.

Acute Disease↗

Validity of measurements of cerebrospinal fluid outflow resistance estimated by the bolus injection method.

Estimation of cerebrospinal fluid (CSF) outflow resistance (Ro) using a bolus injection method was carried out under normal conditions and in a state of artificially increased elastance produced by saline loading into the CSF space. These values of Ro were compared with Ro estimated by the steady state infusion method. Saline loading into the subarachnoid space decreased the buffering capacity significantly, as represented by the pressure-volume index (PVI), which was lowered from 0.72 ml under normal conditions of 0.56 ml during saline loading. The estimated values of Ro under normal conditions and during saline loading were 90.6 and 133.6 mm Hg/ml/minute, respectively. The steady state infusion method yielded an Ro value of 166.3 mm Hg/ml/minute. Ro was therefore considerably underestimated by the bolus method when used under normal conditions of resting intracranial pressure. Moreover, its error was bigger when Ro was higher. On the other hand, during the course of saline loading, the estimated value of Ro using the bolus method was not significantly different from that estimated by the steady state infusion method, even in the higher range of Ro. Estimation of Ro by the bolus injection method was more reliable when the buffering capacity of the craniospinal space was reduced.

Animals↗

Failure of prophylactic barbiturate coma in the treatment of severe head injury.

In certain subgroups of severely head-injured patients, the mortality rate remains unacceptably high. The authors describe a randomized, controlled trial of prophylactic pentobarbital therapy in a group of these patients. Pentobarbital was started as soon as possible after the head injury, regardless of the intracranial pressure (ICP), and was continued for a prescribed period of time. The study included 53 consecutive head-injured patients over the age of 12 years, who had either an acute intradural hematoma (subdural and/or intracerebral, large enough to warrant surgical decompression), or no mass lesion but whose best motor response was abnormal flexion or extension. All patients in the study were randomly assigned to a control group (26 cases) or a pentobarbital-treated group (27 cases) once the diagnosis had been made and informed consent obtained. All patients were treated with the same protocol of aggressive resuscitation, prompt diagnosis and treatment of mass lesions, and intensive care, with close follow-up monitoring. The randomization was effective in producing a close match between the control and treated groups with respect to age, sex distribution, cause of injury, neurological status, intracranial lesions, prevalence of early systemic insults, midline shift, and initial ICP. Outcome was essentially the same in each group. There was no difference between groups in the incidence of elevated ICP, the duration of ICP elevation, or the response of ICP elevations to treatment. Arterial hypotension occurred in 14 patients (54%) in the treated group and only two patients (7%) in the untreated group. Based on these data the authors cannot recommend the prophylactic use of pentobarbital coma in the treatment of patients with severe head injury. They also believe that its use is accompanied by significant side effects which can potentially worsen the condition of a patient with severe head injury.

Adolescent↗

Intracranial pressure monitoring by flaccid-cuff catheter in an animal model.

Several methods of monitoring intracranial pressure (ICP) are in current use, each with its own advantages and disadvantages. The intraventricular line has been most useful because of the ability to withdraw cerebrospinal fluid to assist in control of elevated ICP. However, masses within the brain or generalized increased ICP may compress the lateral ventricle, making insertion of the catheter difficult or impossible. The intracerebral wick records hydrostatic changes too slowly to be used clinically. Swollen cerebral tissue may occlude the subarachnoid bolt thereby dampening the recorded pressure, and epidural monitors may give falsely high recordings because of irregularities of dura or bone. The authors have developed a flaccid-cuff catheter which has proven in animals to be an effective ICP monitor. There are several advantages, such as easy insertion into the centrum semiovale, rapid response to acute pressure changes, and continued sensitivity for periods of up to 3 weeks. The flaccid catheter cuff has no tension so that the pressure across the membrane is equal to zero, simplifying calibration. This type of cuff is necessary for maximum sensitivity to interstitial, brain-tissue, and gross ICP changes. The flaccid-cuff catheter may prove to be useful in a variety of situations such as after closed head trauma or intracranial surgery to assess elevated ICP caused by edema or evolving hematoma.

Animals↗

Effect of naloxone on deficits after aneurysmal subarachnoid hemorrhage.

The opiate antagonist naloxone was suggested for the amelioration of cerebral ischemia after subarachnoid hemorrhage (SAH) following the 1981 report of clinical improvement of ischemic deficits in 2 patients. The deficit in 1 patient was exacerbated by morphine, suggesting that analgesics acting on opiate receptors should be avoided after SAH, and this would include codeine phosphate and dihydrocodeine, both widely used for post-SAH headache. We studied 21 consecutive patients with aneurysmal SAH whose condition was worse than Grade 1 on the Hunt and Hess scale. A single observer graded them to avoid interobserver error, and they were also given a score on the Glasgow coma scale. Each patient was then given an intravenous injection of 0.9% saline as placebo or 0.4 mg (7 patients) or 2.0 mg (14 patients) of naloxone. Five minutes later, the same observer regraded the patient. After 30 minutes, a second injection of placebo or naloxone was given, and the patient was regraded a third time. Each patient received placebo in one injection and naloxone in the other, but the order was randomized and unknown to the observer. There was no beneficial effect of 0.4 mg of naloxone after aneurysmal SAH, and we did not find an elevated level of the endogenous opiate beta-endorphin in the cerebrospinal fluid in the majority (6 of 8 of the patients in whom it was assayed). Five of the patients given 2.0 mg of naloxone did improve transiently, and none deteriorated after the drug, suggesting that naloxone in a high dose may have a place in the management of some post-SAH deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Growth and development of long-term survivors of childhood acute lymphoblastic leukemia treated with and without prophylactic radiation of the central nervous system.

Two groups of patients with at least four years of remission following treatment of acute lymphoblastic leukemia with or without prophylactic cranial irradiation (mean interval of 8 years from diagnosis) were studied. Out of 41 eligible patients, 22 patients were assessed for pubertal staging, growth velocity, cranial computed tomography scanning, and complete endocrinologic status following stimulation with arginine or insulin hypoglycemia, TRH and LHRH. Group I (N = 9, 4 male, 5 female) had received systemic chemotherapy and intratheral methotrexate, but no cranial irradiation. Group II (N = 13, 9 male: 4 female) had additionally received central nervous system irradiation (2400 rads). All patients had undergone normal spontaneous puberty, and had normal levels of thyroxine, thyrotropin, dihydroepiandrosterone sulfate, testosterone or estrogens, luteinizing hormone, follicle stimulating hormone, prolactin, and cortisol. In Group I only one patient decreased his percentile height greater than 25% but he had normal growth hormone responses. In Group II, two younger patients showed growth deceleration with inadequate provocative growth hormone responses, whereas two pubertal patients developed growth arrest post diagnosis and treatment but had normal growth hormone responses. When Groups I and II and controls were compared as to the number of growth hormone samples greater than 5 ng/ml, the peak growth hormone value, or the mean growth hormone concentration during the combined arginine-insulin test, no significant differences were noted. Brain scan abnormalities were noted in 3 out of 9 patients in Group I (33%) and in 5 out of 11 patients in Group II (45%). There was no correlation in either group between abnormal computed tomography scans and abnormal growth hormone secretory dynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Spurious E rosette formation in B cell chronic lymphocytic leukemia due to monoclonal anti-sheep RBC antibody.

The apparent simultaneous presence of surface markers characteristic of both B and T cells is a phenomenon being described with increasing frequency in patients with chronic lymphocytic leukemia (CLL). We describe a patient with CLL whose B lymphocytes possessed surface immunoglobulin reactive with neuraminidase-treated sheep erythrocytes (SRBCs) and produced E rosette formation. Cytofluorography using monoclonal antibodies demonstrated the B cell nature of these cells and the absence of the SRBC receptor. Further documentation that the binding of SRBCs was mediated through immunologic reaction included E rosette formation inhibition by monospecific antisera and hemagglutination of SRBCs by a paraprotein isolated from the patient's serum. Fusion of the CLL cells with a human hypoxanthine-aminopterin-thymidine-sensitive plasma cell line resulted in the production of human hybridomas that secreted the SRBC-reactive IgM antibody. An analysis of clinical histories of CLL patients whose cells exhibited this phenomenon from both immunologic and clinical perspectives is presented.

Animals↗

The nominative technique: a new method of estimating heroin prevalence.

Over the years, nominative estimates of heroin prevalence have been consistently higher than self-reports of heroin use. During this time, nominative data have generally followed mainstream patterns of drug use: nominative estimates for young adults and for males are higher than nominative estimates for older persons, youth, and females; moreover, the recent downward trends in drug use have been replicated by the nominative heroin data. Thus, the overall picture presented by the nominative data--similar patterns but higher levels of prevalence--seems to support the validity of the new approach. Nevertheless, considerable caution should be exercised in interpreting nominative data. This is chiefly because a substantial minority of nominators cannot report the number of other close friends of the heroin user who also "know." While missing data has been handled by a conservative imputation rule, the fact that so many persons are unable to provide an answer to this key question casts doubt on the accuracy of the answers that were given. In fact, the nominative approach might tend to produce over-estimates, because of the potential for undercounts of the numbers of others who "know." Additional tests of validity should be performed, such as application of the nominative approach to nonsensitive behaviors or minimally sensitive behaviors, such as marijuana use or perhaps cocaine use. Certainly, the overall validity of the nominative heroin data would be supported if in future surveys new nominative heroin estimates for relatively unstigmatized forms of drug use proved to be similar to self-reported levels of use, thus pointing to the unique difference in estimates that might be observed for heroin. Finally, in interpreting the heroin estimates presented here, it should be remembered that both the nominative and self-report estimates refer to heroin use in the household population of the United States. Thus, many heroin addicts and other users who reside in various unconventional living arrangements would not be included in the counts presented here. Among the excluded groups are transients residing in rooming houses or "crashing" in the home of one "friend" after another or who are incarcerated in jails or confined to residential drug treatment centers. This is a caution for interpreting the estimates presented in this paper, not a criticism of the nominative technique itself.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

A decade of trends in cocaine use in the household population.

The National Survey provides us with a number of realities about cocaine use in the Nation today: Twenty million or more Americans have now tried it, and half of that number are past-year users. Cocaine use tends to be concentrated in the high-risk 18 to 25 population group. The highest prevalence rates are observed in young white males, in young residents of the West and the Northeast, and among white and college-educated young people. The young adult cocaine user is likely to consume this drug occasionally and to be a more frequent user of alcohol and/or marijuana. It is not unusual for him or her to use marijuana in combination with cocaine. With respect to recent trends, even though dramatic increases in cocaine prevalence among young adults have leveled off, this still means that high levels of cocaine use are being maintained by young Americans. Moreover, small but steady increases in prevalence are continuing for the youth population. And, the overall number of Americans who have used and are using cocaine continues to increase as new cohorts of young persons begin and continue the use of this drug--even as they move into the older age ranges.

Adolescent↗

The attitudes of religious, environmental, and science policy leaders toward biotechnology.

Biotechnology is an increasingly visible and important item on the national science policy agenda. With growing corporate and governmental funding, basic research in recombinant DNA and related technologies is expanding rapidly. In a parallel and related process, new agricultural, medical, and other applications are being developed and a growing list of genetically-engineered products is ready for field testing and market distribution. In the months and years ahead, the flow of genetically-engineered products into the marketplace and the media coverage related to those new products will increase the public's awareness of biotechnology. In addition, it is possible that some public policy debate will occur over the issue of field testing new genetically-engineered materials. Media coverage of this type of controversy will also heighten awareness and influence the aggregate level of public awareness of biotechnology. The prospect of a public debate or controversy over any biotechnology issue illustrates a fundamental problem in the formulation of science policy within a democratic political system. The processes and techniques involved in genetic engineering and complex and require some level of scientific background knowledge. A 1979 study found that only seven per cent of American adults met a minimal definition of scientific literacy. It is clear that the current levels of public awareness and knowledge about biotechnology will not allow a public policy debate similar to those associated with controversies involving Social Security or gasoline prices. How, then, does a democratic society establish public policies on advanced technical issues like biotechnology? This report will outline a model of policy formulation for specialized issues and describe the results of a national study of relevant policy leaders concerning biotechnology. To understand the formulation of public policy toward biotechnology, it is necessary to focus on the role of the policy leaders in a stratified model. In general, when there is agreement on a given policy between the decision-makers and the policy leaders, the policy is implemented and there is no wider involvement in the policy formulation process. A large number of science and technology policy issues have been handled in this manner in the decades since the Second World War and it is likely that most science policy matters will continue to be resolved directly between policy leaders and decision-makers. Looking at the general science policy formulation process, it is clear that policy leaders are an important component.(ABSTRACT TRUNCATED AT 400 WORDS)

Attitude↗

Properties of a phosphorylated intermediate of the Ca,Mg-activated ATPase of microsomal vesicles from uterine smooth muscle.

A phosphorylated intermediate of the CaMg-ATPase is demonstrated in microsomal preparations from uterine smooth muscle. Characterization included the use of activators, inhibitors, and sodium dodecyl sulfate (SDS)-gel electrophoresis. The phosphorylation was a function of the ATP and Ca concentrations. The dissociation constant KATP was 2.7 X 10(-6) M and KCa was 1.7 X 10(-6) M. Mg was obligatory for the reaction. Na azide, ouabain, or the substitution of NaCl for KCl did not affect the reaction. Phosphorylation was inhibited by Salyrgan, ADP, or 20 mM calcium. SDS-polyacrylamide gel electrophoresis at pH 2.4 demonstrated phosphorylation of predominantly one protein with a molecular weight of 100,000. Hydroxylamine and, to a lesser extent, neutral and alkaline pH caused dephosphorylation. This indicates the presence of an acylphosphate bond in the phosphoprotein. The above findings are consistent with the phosphorylated intermediate being a Ca,Mg-ATPase. The inhibition by 20 mM calcium indicates that the Ca,Mg-ATPase of smooth muscle differs from that of striated muscle sarcoplasmic reticulum.

Animals↗