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Biomedical subjects

J Mitchell

Publications and source records attributed to J Mitchell.

At least 37 records · Page 2Linked to original sources

Congenital diaphragmatic hernia: the hidden morbidity.

It is often thought that survivors of congenital diaphragmatic hernia (CDH) have an isolated problem related to lung hypoplasia, and little data exist regarding the extrapulmonary problems of high-risk CDH patients who do survive. In 1990, the authors began a multidisciplinary follow-up clinic for CDH patients. Members of the program include representatives from the departments of surgery, pulmonary medicine, development, nursing, and nutrition. Since this program began, the authors have followed up on 33 infants who survived after treatment of high-risk CDH, ie, those who were symptomatic within 6 hours of birth. Twenty patients were treated with extracorporeal membrane oxygenation (ECMO). Neurological problems were common in these patients: seven children (21%) required hearing aids, and seven others had abnormal results with brain-stem auditory evoked response (BAER) testing. Extraaxial fluid collections or enlarged ventricles were present on head computed tomography scans of 10 children, and four children had clinical seizure activity. Fifteen patients had developmental delays, which improved rapidly once the children began to thrive. Six patients required eyeglasses or had strabismus, and one patient is congenitally blind. There were a variety of problems related to growth and nutrition, with six patients needing fundoplications, and 13 patients below the fifth percentile for weight. Of 10 patients with patch repairs, two had recurrent hernias. Six others required surgery for bowel obstruction. Eleven patients had pectus excavatum, usually mild, and four had mild to moderate degrees of scoliosis. There were undescended testicles in five boys, vesicoureteral reflux in two patients, and kidney stones in two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Electroencephalography

Fetal liver length in diabetic pregnancy.

OBJECTIVES: Our purpose was to investigate whether liver size is increased in the fetuses of pregnant women with diabetes and whether there is any relationship between fetal liver size and maternal glycemic control. STUDY DESIGN: Eighty pregnant women with diabetes had ultrasonographic measurement of fetal liver length made at 18, 28, and 36 weeks' gestation. Twenty-four obese, nondiabetic women were studied at 36 weeks as controls. RESULTS: Fetal liver length measurements were significantly greater than normal by 18 weeks' gestation (12% above normal mean values; p < 0.001) and increased further (19%, p < 0.02) by 36 weeks. In the obese controls liver length was increased 9% and was significantly lower than in the diabetic subjects (p < 0.001). CONCLUSIONS: Fetal liver size in increased in pregnant women with diabetes and cannot be explained solely by maternal obesity. The major increase in liver size occurs early in pregnancy but appears to be modifiable by glycemic control later in gestation.

Adult

Integration of multiple signals through a complex hormone response unit in the phosphoenolpyruvate carboxykinase gene promoter.

Transcription of the phosphoenolpyruvate carboxykinase gene is stimulated by glucocorticoids, retinoic acid, and cAMP and is dominantly inhibited by insulin and phorbol esters. The glucocorticoid response is mediated by a complex regulatory unit that consists of two glucocorticoid receptor (GR) binding sites (GR1 and GR2) and two adjacent accessory factor elements (AF1 and AF2). Deletion of either the AF1 or the AF2 element results in a 50-75% reduction of the glucocorticoid response. In addition to their accessory role in glucocorticoid action, the AF1 and AF2 elements mediate retinoic acid and insulin/phorbol ester effects, respectively. Site-directed mutagenesis was performed on AF1 and AF2 to precisely locate the sequences responsible for accessory activity in each element. The glucocorticoid accessory activity of the AF1 element maps to the same 12-base pair sequence (TGACCTTTGGCC) involved in the response of the PEPCK gene to retinoic acid. The glucocorticoid accessory activity of the AF2 region maps to the same 10-base pair sequence (TGGTGTTTTG) responsible for mediating the insulin and phorbol ester responses through this element. The AF1 and AF2 elements bind different sets of nuclear proteins, and this binding is not qualitatively or quantitatively affected by treatment of the rat H4IIE hepatoma cells with retinoic acid (AF1) or insulin (AF2). AF2 functions in a heterologous context (a consensus glucocorticoid response element and the thymidine kinase promoter), whereas AF1 functions in this context only if the retinoic acid receptor is overexpressed in the cells. These results show that the AF1 and AF2 elements affect the glucocorticoid response through different protein DNA interactions, and that a small sequence in each serves multiple functions. Together with GR1 and GR2, they form a complex hormone response unit which provides an integrated response of the phosphoenolpyruvate carboxykinase gene to a variety of positive and negative signals.

Animals

Growing up in the hospital: Part I, Let's focus on the child.

Major advances in medical research and technology have made it possible for many children with complex chronic illnesses to survive, including those who just a few years ago would have died (Hobbs & Perrin, 1985). One goal of health care professionals who care for these children is, and continues to be, discharge of the child to the family and community whenever possible. Complex medical and nursing care, elusive diagnoses, complicated psychosocial issues, and inconsistent community resources often mean discharge must be prolonged. Focusing on the creation of innovative methods for integrating the growth and developmental needs of these special children is a challenging and often overlooked aspect of our pediatric nursing practice. This article is one of a series that will address the issues of growing up in the hospital. What are the implications for the child, family, and professional nurse? What strategies can we devise to assist our patients through what may be a very lengthy and complex hospital course?

Adaptation, Psychological

Growing up in the hospital: Part II, Nurturing the philosophy of family-centered care.

This article is the second in a series that addresses the issues of "growing up in the hospital." Whereas the first article focused on the child and the complex growth and development issues surrounding indefinite hospitalization, this article will focus on the family, the philosophy of family-centered care, and how nursing practice can nurture this ideal when working with children who must "grow up in the hospital."

Adaptation, Psychological

Changes in parvalbumin-immunoreactive neurons in the rat hippocampus following a kainic acid lesion.

Changes in a sub-population of hippocampal non-pyramidal neurons following a unilateral lesion with kainic acid were examined using an antibody raised against the Ca-binding protein parvalbumin. A loss of 71-97% of the parvalbumin-immunoreactive neurons occurred at the three post-lesion times studied (1, 2 and 4 weeks) in all areas of the ipsilateral hippocampus, but no such loss was observed in the dentate gyrus. Resistant parvalbumin-immunoreactive neurons occurred principally in stratum pyramidale and displayed altered morphology from the normal with swollen dendrites and dendritic varicosities. The contralateral hippocampus exhibited losses of parvalbumin-immunoreactive cells, but this was restricted to stratum oriens of CA1. This data demonstrates the loss of a specific and important population of non-pyramidal neurons which might be responsible for the chronic loss of functional inhibition seen in this animal model of temporal lobe epilepsy.

Animals

Bilateral reorganisation of mossy fibres in the rat hippocampus after a unilateral intracerebroventricular kainic acid injection.

One month after a unilateral intracerebroventricular injection of the neurotoxin kainic acid (KA) a prominent band of zinc-containing Timm's-stained terminals is present in the inner molecular layer of the ipsilateral dentate gyrus. At 3 months, mossy fibre reorganisation is also seen in the contralateral inner molecular layer of the dentate gyrus and in the infrapyramidal band in the contralateral CA3. The relationship of this reactive plasticity to the CA3 lesion is discussed.

Animals

Nisoldipine: a new dihydropyridine calcium-channel blocker.

Nisoldipine is a new calcium-channel blocker of the dihydropyridine subclass, with a chemical structure similar to nifedipine. It has been used in clinical trials to assess its efficacy and safety in patients with hypertension, angina pectoris, and congestive heart failure. Similar to other dihydropyridines, nisoldipine is a potent peripheral and coronary dilator. The most optimal dosage regimen has not been established in clinical trials. The drug appears to have a favorable side-effect profile.

Angina Pectoris

Microglial and astrocytic cell responses in the rat hippocampus after an intracerebroventricular kainic acid injection.

After central nervous system injury activated microglial cells and reactive astrocytes secrete neurotrophic factors which may provide an environment conducive to axonal sprouting. The present study has used a unilateral intracerebroventricular (ICV) injection of kainic acid (KA) to produce a lesion of the CA3 pyramidal neurons in the rat hippocampus. The time course of the microglial and astrocytic response was studied throughout a 3-month period using an antibody to proliferating cell nuclear antigen to identify proliferating cells as well as OX-42 and GFAP antibodies to identify the activated microglia and reactive astrocytes, respectively. There was no proliferation of reactive astrocytes whereas activated microglial cells continued to proliferate throughout the duration of the study. During the first month there were some activated microglial cells in the CA1 field and in the fascia dentata but this was short-lived in comparison to the persistence of activated microglia and reactive astrocytes in the CA3 field which were still present 3 months after the initial injection. The discussion attempts to correlate this ipsilateral microglial and astrocytic response with the bilateral mossy fiber axonal sprouting, which occurs in the dentate gyrus after a unilateral ICV injection of KA. The discussion concludes that the two events, the microglial and astrocytic response and the mossy fiber sprouting, are not directly related since the contralateral sprouting occurs in the absence of any astrocytic or microglial response.

Animals

The use of sodium sulphide-fixed brain tissue for immunocytochemical staining of activated microglia and reactive astrocytes.

The use of sodium sulphide-perfused material for the immunocytochemical demonstration of microglia and astrocytes is described. An intracerebroventricular injection of kainic acid (KA) was used to induce neuronal degeneration and subsequent axonal sprouting in the hippocampus. Animals under deep anaesthesia were killed by perfusion with either 4% paraformaldehyde alone or with 1% sodium sulphide followed by 4% paraformaldehyde solution. Microglial cells were identified with OX-42, a monoclonal antibody towards CR3 complement receptors, and astrocytes with a polyclonal antibody to glial fibrillary acidic protein (GFAP). The present study reveals a marked enhancement in the immunoreactivity of activated microglial cells in sodium sulphide perfused tissues compared to those observed in tissues fixed in paraformaldehyde alone. GFAP immunoreactivity of the astrocytes was not compromised by the use of sodium sulphide. The results clearly show the suitability of sodium sulphide perfused tissues for immunocytochemical procedures and should provide a useful tool for investigation of the role of neuroglial cells in axonal sprouting.

Animals

Antagonism of [3H]fatty acid incorporation into vimentin by sodium pyruvate: pitfalls of protein acylation.

In the course of studying possible fatty acid acylation of vimentin by cultured bovine lens epithelial cells, several potential pitfalls of protein-fatty acid acylation were recognized. Even exhaustive delipidation of vimentin with organic solvents failed to remove all noncovalently associated [3H]palmitate and [3H]myristate. Hydroxylamine treatment of vimentin, separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), failed to remove either palmitate or myristate derived radiolabel. Hydroxylamine treatment did remove palmitate label from a group of lower molecular weight proteins. The myristate radiolabel associated with vimentin recovered after SDS-PAGE and subjected to acid hydrolysis was shown due to incorporated [3H]amino acids, mainly glutamic acid, generated from the fatty acid. Adding excess sodium pyruvate to labeling media has been used by others to reduce the metabolic conversion of fatty acids to amino acids; however, no direct evidence in support of this antagonism was presented. We observed that inclusion of sodium pyruvate at between 5 and 20 mM in the labeling medium produced a dramatic decrease in incorporation of myristic acid radiolabel into vimentin. However, inclusion of even 20 mM pyruvate did not completely antagonize the metabolic conversion of fatty acid label to amino acids. Furthermore, the sodium pyruvate antagonism could be totally obscured if the exposure of X-ray film by fluorography was even slightly prolonged. The results illustrate the danger in assuming that solvent extraction totally delipidates proteins and that adding sodium pyruvate to labeling media prevents the transfer of fatty acid label to amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Sotalol and type IA drugs in combination prevent recurrence of sustained ventricular tachycardia.

OBJECTIVES: This study assessed the efficacy of the combination of sotalol and either quinidine or procainamide in preventing sustained ventricular tachycardia inducibility and recurrence and prospectively evaluated the ability of the drug combination to prevent ventricular tachycardia recurrence when the arrhythmia remained inducible but was modified. BACKGROUND: Individual antiarrhythmic drugs are often ineffective in preventing the induction and recurrence of sustained ventricular tachycardia. Beta-adrenergic blockade and prolongation of refractoriness may be important components of successful antiarrhythmic therapy in patients with ventricular tachycardia. We reasoned that the combination of sotalol, which has beta-adrenergic blocking properties and prolonged ventricular refractoriness, and quinidine or procainamide, two agents that slow conduction and prolong refractory periods, would be effective therapy in such patients. METHODS: We administered low dose sotalol (205 +/- 84 mg/day) plus quinidine sulfate (1,278 +/- 479 mg/day) or procainamide (2,393 +/- 1,423 mg/day) to 50 patients with spontaneous sustained ventricular tachycardia or fibrillation and inducible ventricular tachycardia. RESULTS: In 21 (46%) of 46 patients, ventricular tachycardia was rendered noninducible at electrophysiologic study (group I), and in 17 patients (37%), inducible tachycardia was modified according to prospectively identified criteria (group II), for a combined 83% response rate. Ventricular refractory periods increased from 252 +/- 24 to 316 +/- 28 ms and from 265 +/- 33 to 316 +/- 24 ms in groups I and II, respectively (p < 0.001), but from 234 +/- 19 to only 286 +/- 13 ms in the group of patients with unmodified ventricular tachycardia inducibility (n = 8, group III, p < 0.001). Cycle length of induced ventricular tachycardia slowed from 324 +/- 62 to 432 +/- 70 ms in group II patients (p < 0.001), whereas it slowed less in group III patients (279 +/- 73 to 314 +/- 63 ms, p = NS). Forty-two of the 50 patients (including all patients in groups I and II) were discharged on treatment with the drug combination. After 25 +/- 19 months of follow-up, the actuarial recurrence rate of ventricular tachycardia was 6%, 6% and 11% at 1, 2 and 3 years, respectively. Among patients in whom this drug combination was unsuccessful at electrophysiologic study (group III) and in those who received alternative therapy after combination therapy was discontinued because of side effects, actuarial recurrence rates were 9%, 14% and 32% at 1, 2 and 3 years, respectively. CONCLUSIONS: The combination of sotalol plus quinidine or procainamide markedly prolongs ventricular refractoriness and slows induced ventricular tachycardia in a high proportion of patients. Patients with modified or noninducible tachycardia have a low rate of arrhythmia recurrence in follow-up. This drug combination deserves further evaluation.

Aged

Analgesic efficacy and potency of two oral controlled-release morphine preparations.

MS Contin tablets and Oramorph SR tablets are two forms of oral controlled-release morphine sulfate available for the alleviation of pain. Our objective was to compare their analgesic effects in a relative potency assay. In this study, 151 patients undergoing caesarean section or abdominal hysterectomy and reporting moderate or severe postoperative pain received a 30 or 90 mg dose of either drug in a balanced, randomized, double-blind, parallel-group, single-dose experimental design. Patients provided self-ratings of analgesia. Relative potency for pain relief were calculated from log dose-effect curves. For total pain relief (rated by visual analog scales) over 12 hours, the log dose relative potency estimate for MS Contin tablets/Oramorph SR tablets was 1.9 (95% confidence limits, 0.89 to 11.1); for peak pain relief (visual analog scales) the relative potency estimate was 1.7 (95% confidence limits, 0.65 to 48.3). Overall, the 90 mg dose of MS Contin was more effective than 30 or 90 mg doses of Oramorph SR and the 30 mg dose of MS Contin at hours 6 to 12. Adverse experiences (mainly drowsiness) were mostly mild to moderate, with no significant differences in their overall incidence or severity between equivalent doses. MS Contin tablets provided greater peak, total, and duration of analgesia, without higher incidence of adverse experiences.

Administration, Oral