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Biomedical subjects

J J Miller

Publications and source records attributed to J J Miller.

At least 55 records · Page 3Linked to original sources

Cardiac arrest-induced global cerebral ischemia studied in vitro.

The goal of the present study was to characterize the effects of chest compression-induced global cerebral ischemia on the hippocampal slice preparation. One of the characteristics of rats exposed to such cardiac arrest is a high susceptibility to sound-induced seizures. We tested audiogenic seizures as an in vivo indicator of ischemic cerebral damage and as a possible small animal model of epilepsy. The results of these tests were reported elsewhere. Long-Evans male rats (200-350 g) were subjected to 7 min of chest compression sufficient to stop the pumping action of the heart. The rats were then revived using cardiopulmonary resuscitation. Evaluation of cerebral damage following cardiac arrest and resuscitation was performed in vitro, by testing neuronal responses to electrical stimulation in hippocampal slices prepared from these animals. Sham control animals were used for comparisons. Twenty-one to 146 days after rats were chest-compressed, hippocampal slices were prepared. Sham control rats, anesthetized but not chest-compressed, were sacrificed one week later for preparation of slices. Rats in a second group exposed to 7-min chest compression, were sacrificed at different time intervals after their resuscitation (from 1 h to 7 days); hippocampal slices were prepared for electrophysiological analysis of neuronal damage. The results of these studies indicate that 3 weeks or longer after chest compression the evoked CA1 population spike amplitude in hippocampal slices was significantly attenuated; in 60% of these slices an epileptiform response was evoked. An increased proportion of slices prepared from rats 1 to 48 h after chest compression showed an augmentation in the amplitude of the evoked population spike; 72 h and up to 7 days after chest compression, an attenuation in the evoked CA1 population spike amplitude was observed, signaling delayed neuronal damage.

Animals↗

Three-year follow-up and clinical implications of a mindfulness meditation-based stress reduction intervention in the treatment of anxiety disorders.

A previous study of 22 medical patients with DSM-III-R-defined anxiety disorders showed clinically and statistically significant improvements in subjective and objective symptoms of anxiety and panic following an 8-week outpatient physician-referred group stress reduction intervention based on mindfulness meditation. Twenty subjects demonstrated significant reductions in Hamilton and Beck Anxiety and Depression scores postintervention and at 3-month follow-up. In this study, 3-year follow-up data were obtained and analyzed on 18 of the original 22 subjects to probe long-term effects. Repeated measures analysis showed maintenance of the gains obtained in the original study on the Hamilton [F(2,32) = 13.22; p < 0.001] and Beck [F(2,32) = 9.83; p < 0.001] anxiety scales as well as on their respective depression scales, on the Hamilton panic score, the number and severity of panic attacks, and on the Mobility Index-Accompanied and the Fear Survey. A 3-year follow-up comparison of this cohort with a larger group of subjects from the intervention who had met criteria for screening for the original study suggests generalizability of the results obtained with the smaller, more intensively studied cohort. Ongoing compliance with the meditation practice was also demonstrated in the majority of subjects at 3 years. We conclude that an intensive but time-limited group stress reduction intervention based on mindfulness meditation can have long-term beneficial effects in the treatment of people diagnosed with anxiety disorders.

Adult↗

Treatment of human serum with sulfosalicylic acid structurally alters digoxin and endogenous digoxin-like immunoreactive factor.

Pretreatment of human serum with 5-sulfosalicylic acid (SSA) as used in the Abbott TDx digoxin assay produces deglycosylated congeners of digoxin (DIG) and of endogenous digoxin-like immunoreactive factor (DLIF). Using high-performance liquid chromatography analysis, we observed differences in the degree and pattern of DIG breakdown products among five patients. The aglycone digoxigenin was the major product in several samples. Smaller amounts of the bis- and mono-digitoxosides and unidentified products less polar than DIG were sometimes present. Treatment of DLIF-containing plasma with SSA produced similar patterns of DLIF-breakdown products. Incubation of normal plasma containing DIG with SSA for up to 30 min caused little change in measured DIG by TDx and radioimmunoassay (RIA) but decreased to 50% in the ACS DIG assay. These results are consistent with the near 100% cross-reactivities of deglycosylated DIG congeners in the TDx and RIA assays compared to their lower cross-reactivities in the ACS assay. We conclude that the breakdown of DIG and DLIF during treatment of serum with SSA may compromise the accuracy of TDx DIG assays and may explain discrepancies observed in other studies between digoxin immunoassays. This study underscores the importance of understanding the effects of pretreatment strategies used for analytes measured by immunoassay.

Benzenesulfonates↗

Studies of the specificity and cross-reactions of antibodies to lipid A found in juvenile arthritis.

This work was started to determine whether the immunoglobulin G (IgG) reactions with monophosphoryl lipid A (MPL) found in children with arthritis were due to contaminants, a specific site on lipid A, or polyspecific binding. Different lots of MPL were examined by electrophoresis and immunoblot. Competitive inhibition of enzyme-linked immunosorbent assays (ELISAs) by analogs of MPL and biologic materials of clinical interest was used to determine the specificity of the binding site and potential cross-reactions. IgG in all patient sera tested reacted with a single band just < 6.5 kDa on immunoblots of all lots of MPL tested. The ELISAs were inhibited best by analogs of lipid A with an exposed diglucosamine core and intact polar domains. The anti-MPL was also inhibited by fetal bovine collagen types I and II and in some instances by cardiolipin, but not by keratan sulfate, proteoglycan, or DnaK heat shock protein. Lot variation was a persistent technical problem, but no protein contaminant could be demonstrated in any lot. The ELISA and immunoblot results confirmed each other. Immunoblots detected a single band of MPL reactive with IgG. This antibody remains of interest because of its disease association and correlations and because it cross-reacts with collagen and cardiolipin.

Adult↗

Digoxin immunoassay with cross-reactivity of digoxin metabolites proportional to their biological activity.

Our objective was to identify commercially available digoxin immunoassays whose cross-reactivity with digoxin metabolites paralleled the pharmacological activity of the metabolites. We measured the immunoreactivity of digoxigenin bis- and monodigitoxosides, digoxigenin, and dihydrodigoxin in four immunoassays and compared the immunoactivities with pharmacological activities from studies involving whole-animal and receptor (Na,K-ATPase)-based assays. Correlation coefficients for comparisons of immunoassay reactivity and human heart receptor reactivities were: ACS, 0.96; TDx, 0.60; Stratus, 0.57; and Magic, 0.42. Comparison with other biological assays showed a similar trend. The major difference in metabolite cross-reactivities among the immunoassays was that of digoxigenin (ACS, 0.7%; TDx, 103%; Stratus, 108%; Magic, 153%), which has approximately 10% bioactivity relative to digoxin. Measured recovery of mixtures of digoxin and metabolites confirmed these findings. We conclude that the monoclonal antibody in the ACS digoxin assay closely mimics Na,K-ATPase in detecting digoxin and its metabolites. This finding provides a basis for developing therapeutic drug monitoring immunoassays capable of approximating the true pharmacological activity of a mixture of drug metabolites.

Animals↗

Parental risk and resistance factors among children with juvenile rheumatic disease: a four-year predictive study.

Examined the extent to which baseline functioning and parental risk and resistance factors predicted disease-related (functional disability and pain) and psychosocial functioning (social competence and behavior problems) 4 years later among 172 children with juvenile rheumatic disease. The study also examined the extent to which fathers' risk and resistance factors explained patients' adaptation, above and beyond maternal factors. Poorer baseline functioning was a strong risk factor that predicted poorer functioning 4 years later. In addition, parental risk and resistance factors at baseline predicted patients' adjustment after patients' age and baseline functioning were controlled. Mothers' and fathers' personal strain and depressed mood, and fathers' drinking problems, were associated with poorer patient adjustment; mothers' and fathers' social functioning appeared to aid patients' adjustment. Fathers' risk and resistance factors contributed independently from those of mother, to predict patients' outcome.

Adaptation, Psychological↗

Psychosocial factors related to rheumatic diseases in childhood.

This review discusses those features of psychosocial adjustment which have been found associated with rheumatic diseases in children. In spite of the older literature and widely held intuitive beliefs, children with those diseases tend to do well in both psychological and social development and function. Those who do least well have risk factors which are those which impinge on the adjustments of any healthy child. Those who do best are those who have a strong social support system, particularly maternal competence. Children may cope in part by positive use of denial. Thus, interventions should be tailored to just those children and families at risk and must take into account the individual child's method of coping. It is argued that generalized interventions and education are unnecessary and may be harmful.

Child↗

A technique for developing and photographing ridge impressions on decomposed water-soaked fingers.

One of the most challenging tasks confronting a crime laboratory technician is the fingerprinting and subsequent identification of an unknown homicide or drowning victim whose fingers have been subjected to a long period of exposure to water and the effects of decomposition. If the fingers of the individual have not been exposed to the erosive effects of water and decomposition for a long period of time, they may be allowed to dry, and suitable impressions are often obtainable. In other cases the fingers may have to be removed, with the permission of the Medical Examiners Office, and processed by the Crime Laboratory in an attempt to develop suitable ridge structure for inked impressions or an exact photographic copy of the individual's fingers. In extreme cases the effects of water and decomposition make the fragile ridge structure appear to be nonexistent to the naked eye. The procedure used in this case report, combines the use of cyanoacrylate vapor, commonly called "super glue fuming," and the ninhydrin process in conjunction to develop fragile ridge structure into discernable ridges that are easily seen and photographed for the purpose of making an identification of the individual.

Anthropology, Physical↗

Purification, subunit structure and inhibitor profile of cathepsin A.

Cathepsin A (EC 3.4.16.1), a lysosomal carboxypeptidase, has been purified 1374-fold from pig kidney. Purification steps included concanavalin A-Sepharose and phenyl-Sepharose chromatography and chromatofocusing. The specific activity (16.9 U/mg) of the purified enzyme was significantly higher than previously reported values. The enzyme preparation appeared homogeneous when analyzed by non-denaturing polyacrylamide gel electrophoresis and was free of detectable protease contamination. The molecular mass (M(r) = 97,000), isoelectric point (5.0), and sensitivity to inhibitors were consistent with reported properties of cathepsin A. However, the previously reported three-peptide chain structure was not observed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence or absence of 2-mercaptoethanol demonstrated that the enzyme is composed of two M(r) 47,000 subunits, each of which dissociate in the presence of 2-mercaptoethanol into two polypeptide chains of 19,000 and 31,000.

Amino Acid Sequence↗

Double-blind crossover comparison of human and porcine insulins in patients reporting lack of hypoglycaemia awareness.

There has been much debate about reports that some insulin-treated diabetic patients lose awareness of hypoglycaemic symptoms on changing from porcine to human insulin. In a double-blind, crossover study, we sought differences between porcine and human insulin in the frequency and characteristics of hypoglycaemic episodes among patients who reported a reduction of awareness of hypoglycaemia after changing treatment. We studied 50 patients referred by their physicians because of complaints of lack of awareness of hypoglycaemia on human insulin. They had had diabetes for a mean of 20 (SD 12) years and 70% had good or acceptable glycaemic control. Each patient was treated in a double-blind manner for four 1-month periods, two with human and two with porcine insulin, in random order. Only 2 patients correctly identified the sequence of insulin treatments used; 8 or 9 would have been expected to do so by chance alone. The mean percentage of hypoglycaemic episodes associated with reduced or absent awareness was 64% (SD 30%) for human insulin and 69% (31%) for porcine insulin. We could find no statistically significant differences between the insulin species with respect to glycaemic control or the frequency, timing, severity, or awareness of hypoglycaemia. Reduced hypoglycaemia awareness is common with both human and porcine insulins.

Adolescent↗

The fasciitis-morphea complex in children.

OBJECTIVE: To describe the clinical presentation and treatment of the combined syndrome of fasciitis and morphea in children. SETTING: The rheumatic disease clinic of a university children's hospital. PATIENTS: Six children who were referred for signs or symptoms of fasciitis were observed. SELECTION PROCEDURES: All children who were referred for fasciitis were included in the study. INTERVENTIONS: Therapy included prednisone initially and subsequent long-term treatment with penicillamine and alternate-day doses of prednisone. MEASUREMENTS AND RESULTS: Symptoms of morphea appeared 1 year before to 4 years after the first signs of fasciitis were observed. The fasciitis was characterized by usually symmetrical, centrifugal swelling, pain, and contracture formation. The morphea and fasciitis did not appear in the same areas of the body. CONCLUSIONS: The fasciitis and morphea are clearly linked manifestations. The fasciitis, but not the morphea, appears to respond to treatment with steroids. Treatment with penicillamine may ameliorate the sclerosis of the morphea but does not stop new lesions from appearing.

Adolescent↗