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Biomedical subjects

C Miller

Publications and source records attributed to C Miller.

At least 577 records · Page 32Linked to original sources

Improved neurologic function after long-term correction of vitamin E deficiency in children with chronic cholestasis.

We studied the effect of long-term correction of vitamin E deficiency on neurologic function in 14 children with chronic cholestasis. Vitamin E repletion was achieved in all, either by large oral doses (up to 120 IU per kilogram of body weight per day) or by intramuscular administration of dl-alpha-tocopherol (0.8 to 2.0 IU per kilogram per day). With early institution of therapy, neurologic function remained normal in two asymptomatic children below the age of three years after 15 and 18 months of therapy. Neurologic function became normal in three symptomatic children below age three after 18 to 32 months of therapy. Restitution of neurologic function was more limited in nine symptomatic children 5 to 17 1/2 years old after 18 to 48 months of therapy. We conclude that vitamin E repletion therapy should be initiated at an early age in children with chronic cholestasis complicated by vitamin E deficiency, to prevent irreversible neurologic injury.

Adolescent↗

Psychosocial correlates of survival in advanced malignant disease?

Prospective studies of the general population have isolated specific social and psychological factors as independent predictors of longevity. This study assesses the ability of these factors, plus two others said to influence survival in patients with cancer, to predict survival and the time to relapse after a diagnosis of cancer. Patients with unresectable cancers (n = 204) were followed to determine the length of survival. Patients with Stage I or II melanoma or Stage II breast cancer (n = 155) were followed to determine the time to relapse. Analysis of data on these 359 patients indicates that social and psychological factors individually or in combination do not influence the length of survival or the time to relapse (P less than 0.10). The specific diagnosis (F = 2.0, P = 0.06), performance status (F = 0.66, P = 0.62), extent of disease (F = 1.12, P = 0.89), and therapy (F = 1.08, P = 0.35) were also unrelated to the psychosocial factors studied. Although these factors may contribute to the initiation of morbidity, the biology of the disease appears to predominate and to override the potential influence of life-style and psychosocial variables once the disease process is established.

Attitude↗

Severe compression neuropathy following sudden onset of parkinsonian immobility.

Prolonged immobility with adoption of unusual fixed body postures may lead to compression neuropathy. Although parkinsonism has not been considered to predispose to nerve compression, we report three patients with Parkinson's disease and on-off motor fluctuations who developed severe compression neuropathy following a sudden onset off period. The stereotyped posture assumed by parkinsonian patients during an off period appears to make them especially prone to injury of the radial nerve in the upper arm and the brachial plexus.

Aged↗

Frequency and clinical progression of the vitamin E deficiency neurologic disorder in children with prolonged neonatal cholestasis.

To determine the frequency of biochemical vitamin E deficiency and of the clinical signs of the vitamin E deficiency neurologic syndrome in children with prolonged neonatal cholestatic disorders, we studied 46 children (aged 1 month to 17.0 years) with chronic forms of intrahepatic neonatal cholestasis and 47 children (aged 4 months to 8.0 years) with extrahepatic biliary atresia. Based on serum vitamin E concentrations and the ratios of serum vitamin E concentration to total serum lipid concentration, 64% of the intrahepatic and 77% of the extrahepatic cholestasis groups were vitamin E deficient. Prior to age 1 year, neurologic function was normal in all children. Between ages 1 and 3 years, neurologic abnormalities were present in approximately 50% of the vitamin E-deficient children; after age 3 years, neurologic abnormalities were present in all vitamin E-deficient children. Areflexia was the first abnormality to develop between ages 1 and 4 years; truncal and limb ataxia, peripheral neuropathy, and ophthalmoplegia developed between ages 3 and 6 years. Neurologic dysfunction progressed to a disabling combination of findings by ages 8 to 10 years in the majority of vitamin E-deficient children. Neurologic function was normal in the vitamin E-sufficient children. We conclude that vitamin E status should be evaluated in infants in whom cholestasis is diagnosed, and effective therapy should be initiated to prevent or treat vitamin E deficiency at an early age.

Adolescent↗

Synthesis and characterization of methylbromoamiloride, a potential biochemical probe of epithelial Na+ channels.

We report the synthesis of a radioactive, methylated analog of bromoamiloride which inhibits the amiloride-sensitive, epithelial Na+ channel reversibly and with high affinity. This synthesis was achieved by methylation of a nitrogen in the acylguanidinium moiety with tritiated methyliodide of high specific activity. This methylated bromoamiloride molecule (CH3BrA) was purified by both thin layer and high performance liquid chromatography. Proton nuclear magnetic resonance and mass spectroscopy techniques were used to determine the structure of this analog. This compound inhibited both short-circuit current of in vitro frog skin and 22Na+ influx into apical plasma membrane vesicles made from cultured toad kidney cells (line A6) with the same or lower apparent inhibitory dissociation constant as bromoamiloride. Irradiation with ultraviolet light rendered this inhibition irreversible in both A6 vesicles and frog skin. Preparation of radioactive CH3BrA yielded specific activities in excess of 1 Ci/mmol. We suggest that this compound will be useful in the isolation and purification of this ubiquitous Na+ channel.

Amiloride↗

The K+ channel of sarcoplasmic reticulum. A new look at Cs+ block.

K+-selective ion channels from mammalian sarcoplasmic reticulum were inserted into planar phospholipid bilayers, and single-channel currents measured in solutions containing Cs+. Current through this channel can be observed in symmetrical solutions containing only Cs+ salts. At zero voltage, the Cs+ conductance is approximately 15-fold lower than the corresponding K+ conductance. The open channel rectifies strongly in symmetrical Cs+ solutions, and the Cs+ currents are independent of Cs+ concentration in the range 18-600 mM. Biionic (Cs+/K+) reversal potentials are only 10 mV, showing that Cs+ is nearly as permeant as K+, though much less conductive. Addition of Cs+ to symmetrical K+ solutions reduces current through the channel in a voltage-dependent way. The results can be explained by a free energy profile in which the channel's selectivity filter acts in two ways: to provide binding sites for the conducting ions and to serve as a major rate-determining structure. According to this picture, the main difference between high-conductance K+ and low-conductance Cs+ is that Cs+ binds to an asymmetrically positioned site approximately 20-fold more tightly than does K+.

Animals↗

Long-term experience with pergolide therapy of advanced parkinsonism.

Nine patients with idiopathic Parkinson's disease were treated with pergolide to a daily maintenance dose of 2.2 +/- 0.9 mg (mean +/- SD) for 17.3 +/- 8.3 months. After 1 month, there was an average 68% increase in mobile on-time, but the improvement declined to 30% by 6 months, 23% by 1 year, and virtually disappeared by 18 months of therapy. Pergolide was discontinued in seven patients because of loss of efficacy (4 patients), confusion (1 patient), or myocardial infarction or ventricular ectopy (2 patients). Partial but temporary restoration of mobility was observed in seven patients who were switched to an alternate-day dosing schedule after 9.2 +/- 2.4 months. Two patients with advanced Shy-Drager syndrome were treated with pergolide without benefit.

Aged↗

[Application of computerized tomography to transthoracic puncture].

Transthoracic puncture for peripheral pulmonary lesions not diagnosed by fibroscopy were performed on 70 patients under computed tomographic (CT) control. Sixty four cases had a simple cytological puncture associated in 23 cases with a tru-cut biopsy. Six patients had a needle biopsy. The CT enabled us to localise the tumour to be punctured very accurately, whatever its size or topography in relation to the thoracic wall or mediastinum. It also distinguished necrotic zones within the body of the tumour whose biopsy would lead to false negative results. The sensibility for detecting malign tumours by this method was 83% for cytology and 90% when a biopsy was associated with cytology by needle aspirate. The specificity was 94%. A more precise histological diagnosis was correctly suggested by simple cytology in 7 patients (20%). A tru-cut biopsy enabled histological characterisation in all the neoplastic cases; amongst the benign lesions a specific diagnosis was made on the biopsy in 4 out of 10 cases. There were complications -9% overall. None of the pneumothoraces produced required surgical drainage. There were no fatal complications. In conclusion, transthoracic puncture under CT control is a sensitive method for detecting peripheral malignant tumours and is associated with a low level of complications.

Biopsy, Needle↗

Serial studies of protein C and its plasma inhibitor in patients with disseminated intravascular coagulation.

This study was undertaken to determine the levels of protein C antigen and activity and protein C inhibitor in sequential plasma samples of disseminated intravascular coagulation (DIC) patients. Our normal range for both protein C antigen and activity is 70 to 130 U/dL, and protein C inhibitor is 65 to 135 U/dL. A decreased level of protein C activity was found in 96% of the plasma samples from individuals with DIC; the protein C antigen was decreased in 73%. The inhibitor of protein C was decreased in all samples. Analysis of serial samples from patients with DIC reveals that protein C activity and antigen and protein C inhibitor decrease progressively during the initial stages of DIC and remain at a low level for 24 to 48 hours before gradually returning toward normal in nonfatal cases. The protein C activity decreases in parallel with protein C inhibitor and is lower than protein C antigen. In a fatal case of DIC, protein C activity and protein C inhibitor rapidly decreased to undetectable levels; however, protein C antigen was gradually decreasing but still detectable at time of death. In DIC, a discrepancy initially occurs between the activity and antigen of protein C, suggesting a complex with the inhibitor or other inactive forms of protein C. Protein C appears to play a major role in the control of DIC.

Blood Coagulation Factors↗

Human apolipoprotein B: partial amino acid sequence.

A successful approach has been developed for the sequencing of apolipoprotein B based upon the procedure of Cleveland et al. [(1977) J. Biol. Chem. 252, 1102-1106] involving limited proteolysis in the presence of sodium dodecyl sulfate. Staphylococcus aureus protease was employed to produce large peptides which were isolated in relatively pure form by preparative gel electrophoresis. Two peptides were partially sequenced using spinning-cup microsequencing techniques. The sequences are: Peptide R2-5, -Ala-Leu-Val-Gly-Ile-Asn- Gly-Glu-Ala-Asn-Leu-Asp-Phe-Leu-Asn-Ile-Pro-Leu-Arg-Ile-Pro-Pro- Met-Arg-(Arg)-; Peptide R3-1, -Leu-Val-Ala-Lys-Pro-Ser-Val-Ser-Val-Glu- Phe-Val-Thr-Asn-Met-Gly-Ile-Ile-Pro-Lys-Phe-Ala-Arg-. Several stretches of residues suitable for the construction of oligonucleotide probes have been identified.

Amino Acid Sequence↗