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Biomedical subjects

M J Miller

Publications and source records attributed to M J Miller.

At least 325 records · Page 18Linked to original sources

Symptom control during the last week of life on a palliative care unit.

A recent report suggested that more than 50% of terminal cancer patients have physical suffering that requires sedation in the last days of life. To evaluate this finding on our 14-bed palliative care unit, a retrospective analysis of 100 consecutive patients admitted for 6 days or more was carried out. Information was collected on major symptoms requiring treatment, symptom control at admission and during each of the last 7 days of life, medications used, and changes that may have contributed to sedation. Of the 100 patients, 99 had pain, 46 had dyspnea, 71 had nausea, and 39 experienced delirium. Visual Analogue Scores (VAS) were done twice a day in all patients; mean pain showed a change from 31 +/- 24 on Day 6 to 24 +/- 19 on day of death (DOD) (p less than 0.05); nausea from 19 +/- 18 on Day 6 to 13 +/- 9 on DOD (p less than 0.01); drowsiness from 51 +/- 28 on Day 6 to 85 +/- 45 on DOD (p less than 0.001); symptom distress score from 49 +/- 11 on Day 6 to 52 +/- 9 on DOD (p less than 0.01). On the day of admission (DOA), 69% of VAS were done by the patient and 28% by the nurse as compared to 8% by the patient and 90% by the nurse on DOD. Level of consciousness on DOA was alert (72%), drowsy (28%), unresponsive (0%) and by DOD was alert (2%), drowsy (41%), unresponsive (57%).(ABSTRACT TRUNCATED AT 250 WORDS)

Consciousness↗

Mechanisms of action of ECT: schizophrenia and schizoaffective disorder.

A variety of neurophysiological mechanisms have been suggested to explain the therapeutic action of electroconvulsive therapy (ECT). Processes of kindling, resolution of hemispheric dysfunctions, anticonvulsant effects, and diencephalic stimulation all have been proposed to account for the beneficial effects of ECT. To investigate these, we analyzed clinical, neuropsychological, and electroencephalographic (EEG) data from 110 ECT-treated patients with schizophrenia and schizoaffective disorders, comparing responders with nonresponders. Fifty-four percent of all the patients were rated as very much or much improved. Mechanisms of kindling or anticonvulsant effects were not supported by the data. Dominant hemispheric dysfunctions in schizophrenics were suggested by the neuropsychological test data. There was tenuous support for the sensitization theory and both the neuropsychological and EEG data contradicted the dominant accentuation theory. Taken together with our previous report on ECT-treated patients with affective disorders, we propose that ECT might act by restoration of equilibrium between the hemispheres.

Adult↗

Comparative treatment of experimental Staphylococcus epidermidis endophthalmitis.

We created experimental Staphylococcus epidermidis endophthalmitis of moderate severity in the aphakic rabbit eye by injecting 100,000 organisms of a standardized laboratory strain (ATCC 155) into the mid-vitreous cavity. This model of endophthalmitis self-sterilizes in about 4 days, but inflammatory signs continue to increase 5 to 7 days after the initial bacterial inoculum. Control eyes were compared with eyes treated with five different strategies 24 hours after bacterial inoculation: intravitreal cefazolin sodium, intravitreal cefazolin plus intramuscular corticosteroid, vitrectomy plus intravitreal antibiotics, vitrectomy plus intravitreal antibiotics and intramuscular corticosteroids, and vitrectomy plus intravitreal antibiotics and corticosteroids. Quantitative grading of inflammation and media clarity were compared at the end of weeks 1, 2, and 3 after treatment. At week 1, eyes treated with vitrectomy had significantly lower inflammatory scores; those treated with corticosteroids had significantly lower scores than those without. The two effects were independent. The best results were observed with treatment consisting of vitrectomy, intraocular antibiotics, and corticosteroids. This strategy also produced significantly more eyes with clear media at the end of week 3 than treatment with intravitreal antibiotics alone.

Adrenal Cortex Hormones↗

Hemodynamic and permeability characteristics of acute experimental necrotizing enterocolitis.

We examined the local hemodynamic response of intestinal loops during acute necrotizing enterocolitis (NEC) in anesthetized rabbits. NEC was induced in ileal loops by transmural injection of a solution containing casein (10 mg/ml) and calcium gluconate (50 mg/ml) acidified to pH 4.0 with propionic or acetic acid. Control loops received casein only (pH 5.0). Mucosal damage was quantified by the blood-to-lumen movement of [51Cr]EDTA, fluid shifts into the lumen, and histology. Mean arterial pressure and loop blood flow were steady over the 3-hr period, loop fluid volume decreased, and there was no evidence of necrosis or epithelial damage. In loops receiving acidified casein and calcium gluconate, there was an immediate dramatic increase in loop blood flow that returned to baseline by 50 min. In addition, loop fluid volume was dramatically increased, necrosis was noted in the form of blunting and loss of villi, and sevenfold increase in [51Cr]EDTA permeability was evident. Administration of CV 1808 (30 mg/kg/hr), a selective adenosine2 agonist, which maintained and elevated loop blood flow throughout the 3 hr protocol, failed to alter the changes in loop fluid volume or prevent necrosis. Histamine levels in loop fluid levels were significantly elevated 20-30 min after NEC induction when compared to saline controls, indicating an early activation of mucosal defenses with this luminal insult. Thus, this model of NEC is characterized by a transient, acute hyperemia, increased intestinal permeability, and histamine release. As mucosal damage was independent of ischemia and could not be prevented by vasodilatory therapy, this model supports the clinical findings that NEC is correlated with luminal factors related to feeding and independent of cardiovascular stress.

Acid-Base Imbalance↗

Hypodermoclysis for the administration of fluids and narcotic analgesics in patients with advanced cancer.

Fifty-eight consecutive patients with advanced cancer who required parenteral hydration were treated with hypodermoclysis. A solution of two-thirds 5% dextrose and one-third saline was used in all cases at a rate of 20-100 cc/hr, with 750 units of hyaluronidase per liter, and 20-40 mEq KCl/L were administered in all patients. In 38 patients, morphine (21 cases) or hydromorphone (17 cases) were added. The mean duration of infusion and volume were 14 +/- 9 days and 1.3 +/- 0.8 L/day, respectively (range, 0.5-3 L/day). Mean dose of KCl was 25 +/- 8 mEq/L. The reason for discontinuation was death in 43 cases, oral hydration in 12 cases, and need for fluid restriction in 3 cases. Toxicity consisted in local infection in two cases and bruising in two cases. We conclude that hypodermoclysis is a safe and effective method of hydration in patients with advanced cancer.

Aged↗

The essential carboxyl group in subunit c of the F1F0 ATP synthase can be moved and H(+)-translocating function retained.

The proteolipid subunit c of F1F0-type H(+)-transporting ATP synthases [ATP phosphohydrolase (H(+)-transporting), EC 3.6.1.34] contains a conserved Asp/Glu residue that is thought to function in H+ translocation. To test the importance of the position of this residue in the Escherichia coli enzyme, we used oligonucleotide-directed mutagenesis to move the carboxyl side chain from position 61 to position 58, 60, or 62. Mutant cells with these changes were incapable of growth via oxidative phosphorylation on succinate. An Asp-61----Glu mutant grew on succinate but at 50% the efficiency of wild type. Hence, even minor changes in the position of the carboxyl group can significantly reduce function. In a second approach, slow-growing revertants to an Asp-61----Gly mutant were isolated. In one such revertant, Ala-24 was changed to Asp, while the original Asp-61----Gly mutation remained unchanged. The Asp-24-Gly-61 double mutant grew on succinate at 60% the efficiency of wild type. Hence the essential carboxyl group of subunit c can function when anchored at either position 24 or position 61, and this supports the idea that these residues may neighbor each other when subunit c is folded in the membrane. The rate of ATP-driven H+ translocation by mutant membrane vesicles was estimated by the quenching of 9-amino-6-chloro-2-methoxyacridine fluorescence and corresponded to actual H+ pumping rates less than 25% that of wild type.

Amino Acid Sequence↗

Alcohol protects the diaphragm during dietary restriction.

We recently reported that alcoholic rat diaphragm develops greater contractile force than diaphragm of pair-fed control animals. The present experiment examines whether alcohol or dietary restriction is the more likely cause of this surprising finding. We conditioned 10 rats using a liquid diet containing ethanol as 36% of calories. Ten pair-fed control animals received an equal amount of isocaloric, ethanol-free liquid diet. Ten ad libitum control animals had unrestricted access to lab chow and water. Rats were killed after 30 weeks. Left costal diaphragm strips were studied in vitro at optimal length using direct stimulation at supramaximal voltage. Isometric force was measured and divided by muscle cross-section to compute stress. Maximal tetanic stresses developed by muscle from pair-fed controls were systematically less than alcoholic and ad libitum control values (p less than 0.0001); this did not depend on temperature (25 degrees vs. 37 degrees; p greater than 0.50). Pair-feeding increased twitch half-relaxation times (p less than 0.03) and shifted the tetanic stress-stimulation frequency relationship leftward by 10 Hz (p less than 0.01). Diaphragm of pair-fed rats continued to generate lower stresses during the fatigue caused by repeated contractions (p less than 0.01). We conclude that dietary restriction associated with pair-feeding compromises diaphragm performance in rats. Chronic alcohol consumption prevents or reverses these changes, since diaphragm function of alcoholic and ad libitum control animals was not different.

Alcoholism↗

Effects of nasal CPAP on supraglottic and total pulmonary resistance in preterm infants.

The effects of continuous positive airway pressure (CPAP) on supraglottic and total pulmonary resistance were determined in 10 healthy premature infants (postconceptional age 34 +/- 2 wk, weight at study 1,628 +/- 250 g). Nasal airflow was measured with a mask pneumotachograph, and pressures in the esophagus and oropharynx were measured with a 5-Fr Millar or fluid-filled catheter. Nasal CPAP between 0 and 5 cmH2O correlated well with oropharyngeal pressure (r = 0.94). Total supraglottic resistance, total pulmonary resistance, and supraglottic resistance in inspiration and expiration were measured on increasing CPAP. Total supraglottic resistance decreased from 46 +/- 29 to 17 +/- 16 cmH2O.l-1.s (P less than 0.005) between 0 and 5 cmH2O CPAP, and a delay in return of resistance to control values was seen as CPAP was reciprocally decreased to 0. CPAP produced a decrease in supraglottic resistance in both inspiration and expiration, from 41 +/- 26 to 14 +/- 9 and from 33 +/- 17 to 10 +/- 6 cmH2O.l-1.s, respectively (P less than 0.01). Total pulmonary resistance also decreased from 161 +/- 40 to 95 +/- 24 cmH2O.l-1.s (P less than 0.01) between 0 and 5 cmH2O CPAP. The decrease in total supraglottic resistance in these infants accounted for 60% of the change in total pulmonary resistance, which occurred on CPAP of 5 cmH2O. We speculate that CPAP may decrease supraglottic resistance directly through mechanical splinting of the airway. This effect of CPAP may be the primary mechanism by which this form of therapy reduces apnea with an obstructive component in premature infants.

Airway Resistance↗

Fluoride: benefits and risks of exposure.

This summarizes current knowledge of the benefits and risks of fluoride ingestion. The preponderance of evidence indicates that fluoride can reduce the incidence of dental caries and that fluoridation of drinking water can provide such protection. Due to the ubiquitous nature of exposures to fluoride sources other than drinking water, it is currently impossible to draw firm conclusions regarding the independent effect of fluoride in drinking water on caries prevalence using an ecologic study design. Moderate dental fluorosis occurs in 1 to 2% of the population exposed to fluoride at 1 mg/l in drinking water and in about 10% of the population at 2 mg/l; moderate/severe fluorosis occurs in variable percentages ranging up to 33% of the population exposed to fluoride at 2.4 to 4.1 mg/l in drinking water. The issue of whether moderate or severe dental fluorosis represents an adverse health effect is still controversial. There is no evidence of skeletal fluorosis among the general U.S. population exposed to drinking water fluoride concentrations lower than 4 mg/l. Radiographically detected osteosclerosis after chronic exposure to fluoride in drinking water at 8 mg/l was not associated with clinical symptoms. Reports of crippling skeletal fluorosis associated with low concentrations of fluoride in drinking water in tropical countries have been attributed to other dietary factors. The available data suggest that some individuals may experience hypersensitivity to fluoride-containing agents. Further studies on hypersensitivity are required. There is no evidence of increased incidence of renal disease or renal dysfunction in humans exposed to up to 8 mg fluoride per liter in drinking water. Structural changes in kidneys of experimental animals have been detected at doses exceeding 1 to 5 mg fluoride per kilogram per day. Based on four case reports, individuals with renal insufficiency who consume large volumes of naturally fluoridated water at 2 to 8 mg/l are possibly at increased risk of developing skeletal fluorosis. Studies on the effects of fluoride in individuals with renal insufficiency are needed. There is no evidence that chronic exposure to concentrations of fluoride reported to be greater than 2 mg/l in drinking water increases human cancer mortality or incidence. A study of lifetime exposure to fluoride on cancer incidence in rats and mice has been completed, but assessment for cancer has not been completed. There is no evidence that fluoride is genotoxic except in some in vitro assays at cytotoxic concentrations. There is no in vivo evidence that fluoride affects human cellular enzyme activities.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Casein: a milk protein with diverse biologic consequences.

The consequences of bovine milk consumption are diverse, some of which are potentially deleterious. Although certain cultures shun cow's milk or milk-based products, Western societies consume large quantities of cow's milk. Although there are stronger similarities between bovine whey proteins and human whey proteins, the quantity and nature of casein in cow's milk differ markedly from human milk. We propose that the consequences of diets based on bovine casein should be more closely evaluated and certainly expanded beyond the simplistic approach of growth. What is good for the goose may be good for the gander, but what is good for the cow could be harmful to the human.

Animals↗

Guests or immigrants? Contradiction and change in the German immigration policy debate since the recruitment stop.

The authors review major points in the policy debate over immigration in West Germany since the 1973 recruitment stop legislation. Special emphasis is placed on the labor force effects of migration to West Germany and their impact on migration policy. The authors find that "government immigration policy since 1973 has embraced three contradictory goals: reduce the influx of foreigners, integrate those who intend to settle in West Germany, and encourage the return of migrants who are inclined to leave. The internal contradictions between these policy goals have prevented them from being fulfilled and thereby have generated considerable frustration."

Demography↗

The prevalence of subclinical hypothyroidism in adults with low-normal blood thyroxine levels.

The purpose of this study was to determine whether subclinical hypothyroidism, defined as the state in which there is an elevation of thyrotropin blood level (TSH) with a low-normal blood thyroxine level (T4), can be found in clinically healthy subjects. We identified, by screening of adults in an ambulatory patient care facility, 67 persons with T4 at the lower range of normal (4.5-6.0 micrograms/dL) who were free of acute nonthyroidal illness and who were not on medications known to affect T4, other than long term thyroxine therapy. TSH was determined in all 67 persons, whose ages ranged from 25 to 87 years. Nineteen persons in this population had a history of thyroid disease and 48 did not. Elevation of TSH was found in 13 subjects (19%), seven of whom had a history of thyroid disease. The prevalence of TSH elevation was 50% in those with T4 of 4.5- less than 5.0 micrograms/dL, 26% in those with T4 of 5.0-5.5 micrograms/dL, and 8% in those with T4 of greater than 5.5-6.0 micrograms/dL (p less than 0.02). Three of these 13 patients had been on thyroxine therapy at the time of the survey, and their thyroxine doses were adjusted, whereas five others were started on thyroxine therapy subsequent to the survey. Treatment doses as low as 0.05 mg/day increased the T4 and returned the TSH to normal in six patients. In two of five patients who went untreated, there was a substantial fall in T4 and/or a rise in TSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Spontaneous sterilization in experimental Staphylococcus epidermidis endophthalmitis.

We created a standardized model of endophthalmitis in the aphakic rabbit eye using a laboratory strain of Staphylococcus epidermidis of known characteristics (ATCC 155). Eyes were injected with the following number of organisms: 170, 3760, 8750, 170,000 and 460,000. Serial quantitative cultures, clinical grading of infection and histopathologic studies were performed on days 1, 2, 3, 7 and 14. Bacteria appeared to multiply rapidly during the first 24 hr with peak recovery at 8 to 24 hr. Fewer bacteria were cultured on the third day after injection, and positive cultures were rare after the third day. Inflammatory scores were initially higher with each increased number of injected bacteria and tended to increase for the first 3 to 5 days.

Animals↗