Biomedical subjects

M J Miller

Publications and source records attributed to M J Miller.

At least 307 records · Page 17Linked to original sources

PubMed1991

Adherence of Pseudomonas aeruginosa to rigid gas-permeable contact lenses.

We examined the adherence of a human corneal isolate of Pseudomonas aeruginosa to unused rigid gas-permeable and hydrogel contact lenses. Adherence to rigid gas-permeable lenses was greater than the adherence to hydrogels. The lower incidence of microbial keratitis associated with rigid gas-permeable lenses, as compared with hydrogel lenses, may be attributed to the more rigorous cleaning and disinfection possible for rigid gas-permeable lenses and/or patient noncompliance with complicated disinfection systems used with hydrogel lenses.

Bacterial Adhesion↗

PubMed1991

Carbamazepine compared with lithium in the treatment of mania.

Fifty-two hospitalized manic patients were randomized to treatment with either carbamazepine or lithium carbonate after a 2-week drug withdrawal period. All of the probands were tertiary referrals with a high proportion of failures of previous lithium and other treatment. Weekly ratings of manic, depressive, and psychotic symptoms were obtained for 8 weeks, and responders were followed up for up to 2 years. One third of patients responded favorably. Double-blind assessments revealed no statistically reliable differences between the two treatment groups. Patients receiving carbamazepine were somewhat more manageable than patients treated with lithium early in the study, whereas lithium-treated patients remained longer in the follow-up phase. However, numbers of long-term survivors were too small to be conclusive. This study adds to the growing body of evidence that acutely manic patients respond as well to carbamazepine as to lithium. However, monotherapy with either drug is not sufficient for the majority of manic patients who are referred for tertiary care.

Acute Disease↗

PubMed1991

Cost analysis of microsurgical reconstruction in the head and neck.

In a cost-conscious environment, pressure exists to justify the use of expensive techniques such as reconstructive microsurgery in head and neck patients. Therefore, the costs and effectiveness of 39 consecutive free tissue transfers in patients with head and neck defects due to neoplasia (77%), trauma (13%), or congenital causes (10%) were assessed by reviewing clinical and billing records. The technical success rate was 95% with a 29% rate of complications. Most patients returned to preoperative levels of social activities, and none admitted dissatisfaction with their results. Average cost was $27,000 per case with 16 days of hospitalization. Average cost for aerodigestive tract tumors was $37,400 with 21 days of hospitalization. Costs were directly related to the etiology of the defect and incidence of complications. Applying cost-effectiveness principles we believe that these costs are justified by the high level of patient satisfaction and enhanced quality of life.

Adult↗

PubMed1991

The design, synthesis and study of siderophore-antibiotic conjugates. Siderophore mediated drug transport.

The use of conjugates of microbial iron chelators (siderophores) and antibiotics for illicit transport of antibiotics into cells is a potentially powerful method for the rational design of therapeutic agents. The structural complexity of most natural siderophores has impeded progress in this area. Described here are the design, syntheses and preliminary biological studies of several siderophore-beta-lactam antibiotic conjugates. Both hydroxamic-acid-based and catechol-based conjugates with and without amino acid spacers to carbacephalosporins were synthesized and demonstrated to be effective inhibitors of Escherichia coli X580. Mutant selection was noted for each class of conjugates. Mutants selected from exposure of the E. coli to the hydroxamate conjugates were susceptible to the catechol conjugates and vice versa. Combinations of hydroxamate- and catechol-carbacephalosporin conjugates were most effective inhibitors of E. coli X580.

Anti-Bacterial Agents↗

PubMed1991

Histamine is a transient marker of small intestinal injury induced by luminal acetic acid and casein.

We compared the time course of histamine release with other markers of intestinal injury in a rabbit model of necrotizing enterocolitis. Injury was induced by luminal acetic acid (200 mM) and casein (10 mg/ml) and experiments terminated after 45 min or 3 hr. Compared to saline controls there was a significant elevation of epithelial permeability (51Cr-EDTA clearance) and luminal protein levels at both time points. Luminal fluid histamine levels were approximately 120-fold greater than saline controls at 45 min but were indistinguishable from control values at 3 hr. We conclude that although mast cell activation is a characteristic of this model, elevations in histamine levels are transient.

Acetates↗

PubMed1991

Misoprostol attenuates acetic acid-induced damage in rabbit distal small intestine.

The influence of misoprostol pretreatment (100 micrograms/loop intraluminally) on small intestinal damage induced by acetic acid was evaluated in anesthetized rabbits. In this model injury was induced by intraluminal administration into loops of distal small intestine, of a solution of calcium gluconate (50 mg/ml) and acetic (200 mM). After 3 hr damage was associated with increase in loop fluid volume, loop fluid protein levels and epithelial permeability to 51Cr-EDTA, all of which were attenuated by misoprostol pretreatment. Similar protective effects were noted 45 min after the insult, suggesting that misoprostol may be therapeutically useful in conditions where the epithelial barrier is compromised.

Acetates↗

PubMed1991

Bioassay for siderophore utilization by Candida albicans.

A convenient plate assay which is sensitive to medium pH has been developed to evaluate potential siderophores of Candida albicans. Adding a siderophore to a filter paper disk on chemically defined Lee's agar (final pH 7.2) seeded with the test strain reversed the growth inhibitory effects of the supplemented (25-100 micrograms/ml) iron chelator ethylenediaminedi(o-hydroxyphenylacetic acid), to provide a zone of growth stimulation. This bioassay has been used to demonstrate the structure-activity relationships of ferrichrome and several water-soluble hydroxamate peptide building blocks of this natural siderophore. Of all compounds so evaluated, ferrichrome exhibited the best activity.

Candida albicans↗

PubMed1991

Acute intestinal injury induced by acetic acid and casein: prevention by intraluminal misoprostol.

Acute injury was established in anesthetized rabbits by intraluminal administration of acetic acid with and without bovine casein, into loops of distal small intestine. Damage was quantified after 45 minutes by the blood-to-lumen movement of 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) and fluorescein isothiocyanate-tagged bovine serum albumin as well as luminal fluid histamine levels. The amount of titratable acetic acid used to lower the pH of the treatment solutions to pH 4.0 was increased by the addition of calcium gluconate. Luminal acetic acid caused a 19-fold increase in 51Cr-EDTA accumulation over saline controls; casein did not modify this effect. In saline controls, loop fluid histamine levels bordered on the limits of detection (1 ng/g) but were elevated 19-fold by acetic acid exposure and markedly increased (118-fold) by the combination of acid and casein. Intraluminal misoprostol (3 or 30 micrograms/mL), administered 30 minutes before acetic acid, significantly attenuated the increase in epithelial permeability (luminal 51Cr-EDTA, fluorescein isothiocyanate-bovine serum albumin accumulation) and histamine release (P less than 0.05). Diphenhydramine, alone or in combination with cimetidine, and indomethacin (5 mg/kg IV) were not protective. It is concluded that exposure of the epithelium to acetic acid promotes the transepithelial movement of casein leading to enhanced mast cell activation and mucosal injury. Damage to the epithelial barrier can be prevented by misoprostol.

Acetates↗

PubMed1991

The hand in Charcot-Marie-Tooth disease.

The upper extremity was evaluated in 68 symptomatic individuals previously diagnosed as having Charcot-Marie-Tooth disease. Consistent patterns of motor and sensory involvement were found noted as well as a predictable progression of neuromuscular deficits. Improved understanding of the clinical behaviour of this disorder is necessary to develop better treatment strategies.

Adolescent↗

PubMed1991

Synthesis and siderophore activity of albomycin-like peptides derived from N5-acetyl-N5-hydroxy-L-ornithine.

N5-Acetyl-N5-hydroxy-L-ornithine (1), the key constituent of several microbial siderophores, has been synthesized in 23% yield overall from N-Cbz-L-glutamic acid 1-tert-butyl ester (6) derived from L-glutamic acid. Reduction of 6 to 7 and treatment with N-[(trichloroethoxy)carbonyl]-O-benzylhydroxylamine (8), and diethyl azodicarboxylate and triphenylphosphine followed by deprotection produced the protected N5-acetyl-N5-hydroxy-L-ornithine derivatives 11 and 12 in large quantities (10-20 g). Following alpha-amino and alpha-carboxyl deprotections of 11 and 12, EEDQ [2-ethoxy-N-(ethoxycarbonyl)-1,2-dihydroquinoline] mediated peptide coupling and final deprotection provided amino acid 1 and six albomycin-like peptides (20, 23, 25, 28, 35, and 36). The growth-promoting ability of each was evaluated with the siderophore biosynthesis mutant Shigella flexneri SA240 (SA 100 iucD:Tn5). These results indicate that substantial modification of the framework of peptide-based siderophores can be tolerated by microbial iron-transport systems.

Anti-Bacterial Agents↗

PubMed1991

Synthesis and siderophore and antibacterial activity of N5-acetyl-N5-hydroxy-L-ornithine-derived siderophore-beta-lactam conjugates: iron-transport-mediated drug delivery.

N5-Acetyl-N5-hydroxy-L-ornithyl-N5-acetyl-N5-hydroxy-L-ornithyl-N5-acety l- N5-hydroxy-L-ornithine, the functionally instrumental component of the albomycins and ferrichromes, has been incorporated as a "carrier" substructure into both carbacephalosporin and oxamazin type beta-lactam antibiotics. The previously synthesized protected version of this tripeptide (14) was coupled with various beta-lactam analogues 17, 19, 24, and 25 to give protected conjugates 21, 22, 26, and 27. Final deprotection by hydrogenolysis provided the deprotected siderophore-beta-lactam antibiotic conjugates 1-4. The growth-promoting ability of each has been evaluated using either the siderophore-deficient mutant Shigella flexneri SA 100 or S. flexneri SA240 (SA 100 iucD:Tn5). Measurement of the growth-promoting activity using two isogenic Escherichia coli strains differing only in the presence or absence of fhuA (hydroxamate ferrichrome receptor) suggests uptake by the hydroxamate iron-transport system. The antibacterial activity of these conjugates has been investigated, and the potential for use of the ferrichrome iron-transport system as a means of drug delivery is discussed.

Anti-Bacterial Agents↗

PubMed1991

Effect of chronic resistive loading on inspiratory muscles in rats.

The development of animal models of respiratory muscle training would be useful in studying the physiological effects of training. Hence, we studied the effects of chronic resistive loading (CRL) for 5 wk on mass, composition, and mechanics of inspiratory muscles in laboratory rats. CRL was produced by means of a tracheal cannula (loaded animals) and results were compared with sham-operated controls. Acutely, upper airway obstruction led to a doubling of inspiratory pleural pressure excursion and 25% decrease in respiratory rate. We observed no changes in lung pressure-volume curves, nor in the geometry of the respiratory system in loaded compared with control animals. Muscle mass normalized for body mass increased in the diaphragm (DI) and the wet weight-to-dry weight ratio increased in the sternomastoid (SM) in loaded compared with control animals. Loaded animals demonstrated a decrease in ether extractable (fat) content of the DI and SM muscles but not the gastrocnemius. For the DI there was no change in length at which active tension was maximal (Lo), but there was an increase in maximum tension at lengths close to Lo in loaded compared with control rats. Endurance did not change, although twitch tensions remained higher in loaded compared with control rats. We conclude that 1) alteration of inspiratory muscle structure and function occurs in rats with CRL; 2) the DI and SM demonstrate different adaptive responses to CRL; and 3) although maximum tension increases, endurance does not.

Animals↗

PubMed1991

Maturation of respiratory reflex responses in the piglet.

Stimulation of chemo-, irritant, and pulmonary C-fiber receptors reflexly constricts airway smooth muscle and alters ventilation in mature animals. These reflex responses of airway smooth muscle have, however, not been clearly characterized during early development. In this study we compared the maturation of reflex pathways regulating airway smooth muscle tone and ventilation in anesthetized, paralyzed, and artificially ventilated 2- to 3- and 10-wk-old piglets. Tracheal smooth muscle tension was measured from an open tracheal segment by use of a force transducer, and phrenic nerve activity was measured from a proximal cut end of the phrenic nerve. Inhalation of 7% CO2 caused a transient increase in tracheal tension in both age groups, whereas hypoxia caused no airway smooth muscle response in either group. The phrenic responses to 7% CO2 and 12% O2 were comparable in both age groups. Lung deflation and capsaicin (20 micrograms/kg iv) administration did not alter tracheal tension in the younger piglets but caused tracheal tension to increase by 87 +/- 28 and 31 +/- 10%, respectively, in the older animals (both P less than 0.05). In contrast, phrenic response to both stimuli was comparable between ages: deflation increased phrenic activity while capsaicin induced neural apnea. Laryngeal stimulation did not increase tracheal tension but induced neural apnea in both age groups. These data demonstrate that between 2 and 10 wk of life, piglets exhibit developmental changes in the reflex responses of airway smooth muscle situated in the larger airways in response to irritant and C-fiber but not chemoreceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effects of CO2 rebreathing on pulmonary mechanics in premature infants.

The effects of hypercapnia produced by CO2 rebreathing on total pulmonary, supraglottic, and lower airway (larynx and lungs) resistance were determined in eight premature infants [gestational age at birth 32 +/- 3 (SE) wk, weight at study 1,950 +/- 150 g]. Nasal airflow was measured with a mask pneumotachograph, and pressures in the esophagus and oropharynx were measured with a fluid-filled or 5-Fr Millar pressure catheter. Trials of hyperoxic (40% inspired O2 fraction) CO2 rebreathing were performed during quiet sleep. Total pulmonary resistance decreased progressively as end-tidal PCO2 (PETCO2) increased from 63 +/- 23 to 23 +/- 15 cmH2O.l-1.s in inspiration and from 115 +/- 82 to 42 +/- 27 cmH2O.l-1.s in expiration between room air (PETCO2 37 Torr) and PETCO2 of 55 Torr (P less than 0.05). Lower airway resistance (larynx and lungs) also decreased from 52 +/- 22 to 18 +/- 14 cmH2O.l-1.s in inspiration and from 88 +/- 45 to 30 +/- 22 cmH2O.l-1.s in expiration between PETCO2 of 37 and 55 Torr, respectively (P less than 0.05). Resistance of the supraglottic airway also decreased during inspiration from 7.2 +/- 2.5 to 3.6 +/- 2.5 cmH2O.l-1.s and in expiration from 7.6 +/- 3.3 to 5.3 +/- 4.7 cmH2O.l-1.s at PETCO2 of 37 and 55 Torr (P less than 0.05). The decrease in resistance that occurs within the airway in response to inhaled CO2 may permit greater airflow at any level of respiratory drive, thereby improving the infant's response to CO2.

Airway Resistance↗

PubMed1991

Exaggerated intestinal histamine release by casein and casein hydrolysate but not whey hydrolysate.

Loops of rabbit distal small intestine received luminal acetic acid (pH 4.0) alone or in combination with bovine casein, casein hydrolysate, or whey hydrolysate. Blood-to-lumen movement of 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) (an index of epithelial permeability) and loop fluid histamine levels were quantified after 45 min. Luminal acetic acid caused a marked increase in 51Cr-EDTA accumulation which was not modified by the addition of bovine casein or hydrolysates by of casein or whey. However, acetic acid-induced histamine release was potentiated by casein and casein hydrolysate (six- and four-fold respectively) but was not altered by whey hydrolysate. Casein hydrolysate-dependent histamine release was evident in naloxone-pretreated rabbits, suggesting that beta-casomorphins were not solely responsible. We conclude that luminal casein or casein hydrolysate, but not whey hydrolysate. can activate intestinal mast cells under conditions of enhanced epithelial permeability. This effect appears to involve components other than beta-casomorphins.

Caseins↗

PubMed1991

Potential role of histamine monochloramine in a rabbit model of ileitis.

Histamine chloramines, derived from the chlorination of histamine by granulocyte-derived oxidants, are potential mediators of intestinal injury and dysfunction in states of atopy or inflammation. We assessed the ability of histamine monochloramine to increase epithelial permeability in rabbit distal small intestine and determined whether the conditions for histamine chloramine formation are favorable in a rabbit model of ileitis. Epithelial permeability, quantified by the blood-to-lumen clearance of 51Cr-labeled ethylenediaminetetraacetic acid, was enhanced by luminal perfusion with either histamine or histamine monochloramine (10 microM), although the latter was twice as effective (p less than 0.05). In a rabbit model of ileitis induced by a luminal solution of acetic acid (200 mM) and casein (10 mg/ml) there was a marked increase in epithelial permeability and in the release into the lumen of histamine, myeloperoxidase, 6-keto-prostaglandin F1 alpha and protein. These results suggest that the conditions are favorable for histamine chloramine formation and that histamine and histamine chloramine may impair the integrity of the epithelial barrier.

Acute Disease↗

PubMed1991

Clozapine: a novel antipsychotic with a controversial introduction.

Last year's introduction of clozapine, an atypical antipsychotic, in the United States was the most significant advance in schizoprenia treatment since the advent of chlopromazine in the 1950s. However, clozapine has a disturbingly high incidence of agranulocytosis. The drug manufacturer designed a complex and expensive mandatory blood monitoring system that was dismantled after public pressure earlier this year. There is hope that clozapine will become more widely available to schizoprenic patients.

Antipsychotic Agents↗

PubMed1991

The Edmonton Symptom Assessment System (ESAS): a simple method for the assessment of palliative care patients.

We describe a simple method for the assessment of symptoms twice a day in patients admitted to a palliative care unit. Eight visual analog scales (VAS) 0-100 mm are completed either by the patient alone, by the patient with nurse's assistance, or by the nurses or relatives at 10:00 and 18:00 hours, in order to indicate the levels of pain, activity, nausea, depression, anxiety, drowsiness, appetite, and sensation of well-being. The information is then transferred to a graph that contains the assessments of up to 21 days on each page. The sum of the scores for all symptoms is defined as the symptom distress score. The Edmonton Symptom Assessment System (ESAS) was carried out for 101 consecutive patients for the length of their admission to our unit. Of these, 84% were able to make their own assessment sometime during their admission. However, before death 83% of assessments were completed by a nurse or relative. Mean symptom distress score was 410 +/- 95 during day 1 of the admission, versus 362 +/- 83 during day 5 (p less than 0.01). Mean symptom distress scores throughout the hospitalization were 359 +/- 105, 374 +/- 93, 359 +/- 91 and 406 +/- 81 when the ESAS was completed by the patient alone, patient with nurse's assistance (p = N.S.), nurse alone (p = N.S.), or relative (p less than 0.01) respectively. We conclude that this is a simple and useful method for the regular assessment of symptom distress in the palliative care setting.

Activities of Daily Living↗