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Biomedical subjects

D Armstrong

Publications and source records attributed to D Armstrong.

At least 289 records · Page 16Linked to original sources

Catheter-related Malassezia furfur fungemia in immunocompromised patients.

PURPOSE, PATIENTS, AND METHODS: Malassezia furfur has usually been described as a cause of catheter-related sepsis in neonates receiving intravenous lipid emulsion. We report seven cases of catheter-related M. furfur fungemia that occurred in seven immunocompromised patients including four adults and three children who were not neonates. Only two of these patients were receiving concurrent intravenous lipid emulsion. RESULTS: All positive blood cultures were obtained from a central venous access device, one of which was a port device. Quantitative M. furfur colony counts ranged from 50 cfu/mL to greater than 1,000 cfu/mL. All seven patients were treated with amphotericin B. Blood drawn through the central lines of three patients yielded additional organisms. One central venous access device required removal due to persistently positive M. furfur blood cultures despite treatment with amphotericin B. CONCLUSION: We conclude that catheter-related M. furfur fungemia occurs in immunocompromised patients with central venous access devices whether or not they are receiving intravenous lipids. Prompt, aggressive treatment with amphotericin B (1 mg/kg/d) may spare patients removal of their central venous access device. Further studies are needed to determine the role of endogenous lipids in the development of catheter-related M. furfur fungemia and to determine if there is a seasonal incidence in populations other than neonates, since all of our cases occurred between late March and July.

Adult↗

DNA amplification in experimental pneumocystosis: characterization of serum Pneumocystis carinii DNA and potential P. carinii carrier states.

DNA amplification has identified P. carinii DNA in diverse biologic specimens, including the serum of patients with P. carinii pneumonia. To further examine the relationship between P. carinii DNA in serum and P. carinii infection, the corticosteroid-treated rat model of pneumocystosis was studied. By 4 weeks of immunosuppression, P. carinii DNA was detected in rat lungs and by 6 weeks, in their serum. P. carinii DNA persisted in lung tissue as long as 5 months after the withdrawal of steroids. Serum DNA disappeared 2 weeks after steroids were withdrawn. Nonimmunocompromised, sentinel rats housed near immunocompromised, P. carinii-infected rats also were studied. Within 6 weeks, P. carinii DNA became detectable in lung and by 8 weeks, in serum. P. carinii DNA disappeared rapidly from lungs and sera after sentinel rats were isolated away from corticosteroid-treated rats. These findings support the contagious transmission of P. carinii and suggest facile development of P. carinii carrier states.

Animals↗

Early evening nizatidine intake with a meal optimizes the antisecretory effect.

The importance of the temporal relationship between meal and nizatidine intake was studied in a six-armed, double-blind, placebo-controlled trial. Eleven healthy volunteers received early (18.00 hours) or late (21.00 hours) supper, with either placebo, early (18.00 hours) nizatidine, or late (21.00 hours) 300 mg nizatidine. Ambulatory 21-hour gastric pH-metry was performed and plasma nizatidine concentrations were determined by high pressure liquid chromatography. Early-nizatidine/early-supper (median pH 2.50), but not late-nizatidine/late supper (median pH 2.30), produced significantly higher median 21-hour pH values than did early-nizatidine/late-supper (median pH 1.90). Concomitant food delayed the absorption of nizatidine but did not change the drug's bioavailability. Oral nizatidine should be taken with food, preferably early in the evening, to optimize its anti-secretory effect.

Adult↗

Activities of antimicrobial agents against clinical isolates of Mycobacterium haemophilum.

Mycobacterium haemophilum, first described in 1978, can cause severe infections of skin, respiratory tract, bone, and other organs of immunocompromised patients. There is no standardized antimicrobial susceptibility test, and for the 27 reported cases, a variety of test methods have been used. This paper reports the in vitro test results for 17 isolates of M. haemophilum recovered from 12 patients in the New York City area. MICs of 16 antimicrobial agents were determined in microtiter trays containing Middlebrook 7H9 broth plus 60 microM hemin, inoculated with 10(6) CFU of the organism per ml and incubated at 30 degrees C for 10 days. Ethambutol, ethionamide, tetracycline, cefoxitin, and trimethoprim-sulfamethoxazole were inactive against initial isolates from the 12 patients. Isoniazid was weakly active with a MIC for 50% of strains tested (MIC50) of 8 micrograms/ml and a MIC90 of > 32 micrograms/ml. Three quinolones, ciprofloxacin, ofloxacin, and sparfloxacin, were moderately active with MIC50s of 2 to 4 micrograms/ml and MIC90s of 4 to 8 micrograms/ml. Amikacin and clofazamine were active with MIC90s of 4 and 2 micrograms/ml, respectively. Clarithromycin was the most active macrolide with a MIC90 of < or = 0.25 microgram/ml. The MIC90 of azithromycin was 8 micrograms/ml, and the MIC90 of erythromycin was 4 micrograms/ml. The rifamycins were active with a MIC90 of 1 microgram/ml for rifampin and one of < or = 0.03 micrograms/ml for rifabutin. For a second isolate from the skin of one patient and a isolate from an autopsy culture of the spleen of a second patient, MICs of rifampin and rifabutin were > 16 microgram/ml, whereas initial isolates were inactivated by low concentrations of the rifamycins. Both patients had been treated for several months with several antimicrobial agents, including a rifamycin.

Acquired Immunodeficiency Syndrome↗

Azithromycin, rifabutin, and rifapentine for treatment and prophylaxis of Mycobacterium avium complex in rats treated with cyclosporine.

Azithromycin, rifabutin, and rifapentine were used to treat or prevent disseminated Mycobacterium avium complex (MAC) infections produced in rats immunosuppressed with cyclosporine. Animals with bacteremic infections were treated 1 week after intravenous inoculation with 10(7) CFU of MAC with azithromycin, 100 mg/kg of body weight administered subcutaneously for 5 days and then 75 mg/kg on Monday, Wednesday, and Friday, or with rifabutin or rifapentine, 20 mg/kg administered intraperitoneally on Monday through Friday. All three drugs showed efficacy after 1 and 2 months. Rifabutin cleared the organisms from tissues more rapidly than azithromycin or rifapentine. To approximate prophylaxis, treatment was started 2 weeks before intravenous inoculation with 10(4) organisms. MAC infections were undetectable in treated animals after 4 months, while control animals had disseminated infections. These findings support the rationale for clinical trials of treatment and prophylaxis with these agents. The cyclosporine-treated rat appears to be a useful model in which to evaluate compounds for the treatment and prophylaxis of disseminated MAC infections.

Animals↗

Prospective multicentre study of risk factors associated with delayed healing of recurrent duodenal ulcers (RUDER). RUDER Study Group.

Risk factors for delayed duodenal ulcer healing during treatment with ranitidine (300 mg daily) were examined in a multicentre German study of 1923 patients with endoscopically proved, recurrent duodenal ulceration. Healing rates, per protocol, were 39.5% at two weeks, 70.9% at four weeks, and 93.2% at eight weeks. Prospective testing of five, predefined risk factors indicated that smoking (p = 0.0039) was associated with a decreased healing rate at two weeks. Frequent prior recurrence (p = 0.464), a heavy physical workload (p = 0.145), and psychological stress (p = 0.062) were not associated with a decreased healing rate and there were too few patients at risk to allow assessment of the effect of regular NSAID intake. Exploratory analysis identified prior slow healing, a large ulcer, multiple ulcers, and prior ulcer complications, in addition to smoking, as markers of slow healing. In the absence of these risk factors, the mean healing time was 3.3 weeks (95% confidence interval 3.0, 3.5), rising to 3.7 weeks (3.5, 3.9) for one, 4.4 weeks (4.1, 4.7) for two, and 5.1 weeks (4.5, 5.6) for three to five risk factors. Delayed duodenal ulcer healing is associated with multiple factors whose effect is cumulative; for patients with two or more of five easily identified risk factors, more than four weeks' treatment with a histamine H2 receptor antagonist is required to achieve ulcer healing.

Adult↗

Nocturnal oesophageal motor activity is dependent on sleep stage.

Simultaneous overnight oesophageal pH and manometric and sleep electroencephalographic recordings were performed in eight healthy subjects, aged 20-38 years, to test the hypothesis that the frequency of primary, swallow related contractions decreases progressively with deeper sleep stages whereas the frequency of secondary contractions remains constant throughout the night. During the nocturnal period (2300 to 0700), periods of oesophageal motor quiescence were interspersed by clusters of contractions detected 5 and 15 cm above the lower oesophageal sphincter. Primary contractions decreased in frequency from 1.42/min (median) during arousal periods to 0.22/min during stage 1 sleep, 0.05/min during stages 2 to 4 combined, and 0.03/min during rapid eye movement (REM) sleep. Secondary contractions were also most frequent during arousal periods (0.51/min) and they, too, decreased in frequency during stage 1 (0.35/min) and stages 2 to 4 combined (0.08/min). During REM sleep, however, the frequency of secondary contractions increased (0.50/min) to levels noted during arousal and stage 1 sleep. Compared with primary contractions, secondary contractions had a lower amplitude (51.9 hPa v 76.0 hPa; p = 0.0078) and a shorter duration (3.08 v 4.06 s; p = 0.0078). The results of this study suggest that there is no intrinsic oesophageal motor activity in the absence of a stimulatory input from the central nervous system and that the increased number of secondary contractions during REM sleep may be a result of an REM related increase in autonomic nervous system activity although a temporary decrease of efferent inhibitory influences cannot be ruled out. Nocturnal contraction clusters comprise both primary contractions during arousals and stage 1 sleep and secondary contractions during REM sleep.

Adult↗

Effects of ranitidine and cisapride on acid reflux and oesophageal motility in patients with reflux oesophagitis: a 24 hour ambulatory combined pH and manometry study.

The effect of ranitidine and cisapride on acid reflux and oesophageal motility was investigated in 18 patients with endoscopically verified erosive reflux oesophagitis. Each patient was treated with placebo, ranitidine (150 mg twice daily), and ranitidine (150 mg twice daily) plus cisapride (20 mg twice daily) in a double blind, double dummy, within subject, three way cross over design. Oesophageal acidity and motility were monitored under ambulatory conditions for 24 hours on the fourth day of treatment, after a wash out period of 10 days during which patients received only antacids for relief of symptoms. Acid reflux was monitored by a pH electrode located 5 cm above the lower oesophageal sphincter. Intraoesophageal pressure was simultaneously recorded from four transducers placed 20, 15, 10, and 5 cm above the lower oesophageal sphincter. Upright reflux was three times higher than supine reflux (median (range) 13.3 (3.7-35.0)% v 3.7 (0-37.6)% of the time with pH < 4.0, p < 0.01, n = 18). Compared with placebo, ranitidine decreased total reflux (from 10.0 (3.2-32.6)% to 6.4 (1.2-22.9)%, p < 0.01), upright reflux (p < 0.05), supine reflux (p < 0.001), and postprandial reflux (p < 0.01), but did not affect oesophageal motility. The combination of ranitidine with cisapride further diminished the acid reflux found with ranitidine--that is, cisapride led to an additional reduction of total reflux (from 6.4 (1.2-22.9)% to 3.7 (1.0-12.7)%, p < 0.01), supine reflux (p < 0.05), and postprandial reflux (p < 0.05). Cisapride also reduced both the number (p<0.01) and duration (p<0.05) of reflux episodes and significantly increased amplitude, duration, and propagation velocity of oesophageal contractions (p<0.05) but did not affect the number of contractions. The findings show that the 30% reduction of oesophageal acid exposure achieved by a conventional dose of ranitidine (150 mg twice daily) can be improved to more than 60% by combination with cisapride (20 mg twice daily). The cisapride induced increase in oesophageal contractile force and propagation velocity seems to enhance the clearance of gastro-oesophageal reflux. Combination of a histamine H2 receptor antagonist with a prokinetic agent may therefore provide an alternative treatment for reflux oesophagitis.

Adult↗

Continuous measurement of rat gastric blood flow using Doppler flowmeter.

We describe the use of pulsed Doppler flowmetry to permit continuous measurement of gastric blood flow in the anesthetized rat. The aims of this study were: 1) to assess the stability of blood flow during Doppler flowmetry; 2) to assess the ability of Doppler flowmetry to record rapid, transient blood flow changes; and 3) to validate Doppler flowmetry against an established blood flow measurement technique using labeled microspheres. Measurements over 3-h periods with a Doppler probe placed on the left gastric artery showed that there was an initial 30-min stabilization period; after this the mean percentage coefficient of variation, indicating intraindividual variability for blood flow, was < 10% for the remaining 150 min. The infusion of norepinephrine produced rapid, transient blood flow changes, including the typical "autoregulatory escape" and "postinfusion hyperemia," both of which were detected by Doppler flowmetry. The accuracy of pulsed Doppler flowmetry in measuring gastric blood flow was established by the demonstration of a highly significant agreement between blood flow measured by the Doppler flowmetry and microsphere techniques. These data indicate that pulsed Doppler flowmetry is an accurate method for the continuous measurement of left gastric artery blood flow in the rat.

Animals↗

Reconstruction of skull defects in children and adolescents by the use of fixed cranial bone grafts: long-term results.

This article presents the long-term results of skull defect reconstruction in a series of 27 children studied between 1986 and 1990 (mean age, 8.4 yr; range, 1-17 yr). Causes of their defects were encephalocele (six patients), trauma (seven patients), tumor (eight patients), fibrous dysplasia (two patients), postsynostectomy defects (two patients), osteomyelitis (one patient), and Reye's syndrome with bone flap loss (one patient). All patients underwent clinical and computed tomographic scan documentation of their skull defects before and immediately after surgery and at least 1 year later. The average preoperative defect surface area measured 33 cm2 (range, 2.5-114 cm2). Skull defects were reconstructed in all patients with fixed autogenous cranial bone grafts. In the initial five patients, the grafts were fixed with interosseous wires, and in the remainder, they were fixed with a combination of miniplates and microplates and screws. Follow-up ranged from 12 to 66 months (mean, 31.4 mo). Complications were minimal, with no infection, plate or graft exposure, or intracranial injuries. In 24 of 27 patients, clinical examination and computed tomographic scans showed no evidence of skull defect or appreciable irregularity of donor or recipient sites. Two patients had documented small regions of graft resorption. One skull had palpable contour irregularities but without a bony defect. All patients have resumed routine activities and sports without special head protection. Repair of skull defects in children with fixed autogenous cranial grafts is a reliable method of reconstruction with minimal morbidity. Although we prefer miniplates and microplates and screws for fixation, the grafts fixed in place with interosseous wires did equally well.

Adolescent↗

Ear malformation and hearing loss in patients with Treacher Collins syndrome.

Although the hearing loss of patients with Treacher Collins syndrome is well documented, few studies have reported jointly on their hearing loss and ear pathology. This paper reports on the hearing loss and computerized tomography (CT) assessments of ear malformations in a large pediatric series of patients with Treacher Collins. Of the 29 subjects assessed by the Craniofacial Program between 1986 and 1990, paired audiologic and complete CT assessments were available for 23 subjects. The external ear canal abnormalities were largely symmetric, either bilaterally stenotic or atretic. In most cases, the middle ear cavity was bilaterally hypoplastic and dysmorphic, and ossicles were symmetrically dysmorphic or missing. Inner ear structures were normal in all patients. The majority of patients had a unilateral or bilateral moderate or greater degree of hearing loss and almost half had an asymmetric hearing loss. The hearing loss of all subjects was conductive, except for three whose loss was bilateral mixed. Two types of bilaterally symmetric hearing loss configurations, flat and reverse sloping, were noted. Conductive hearing loss in patients with Treacher Collins is mainly attributable to their middle ear malformations, which are similar for those of patients with malformed or missing ossicles.

Adolescent↗

Sagittal synostosis: quantitative assessment of presenting deformity and surgical results based on CT scans.

We reviewed our experience with nine consecutive patients with untreated isolated nonsyndromic sagittal synostosis. Using a method of 14 clinically relevant measurements taken from preoperative and postoperative CT scan images of these patients, we documented their presenting skeletal dysmorphology and the results of surgical correction at least 1 year after operation. Significant preoperative findings included an elongated cranial vault length that averaged 103 percent of normal and a narrowed cranial vault width both anteriorly at 92 percent and posteriorly at 86 percent of normal. Results of surgical correction, as documented by CT scan measurements, included normalization of the cranial length to 100 percent and of the anterior width to 101 percent of normal and improvement (but undercorrection) of the posterior width to 94 percent of normal. Quantitative measurement of CT scan images confirmed clinically observed findings in these patients before suture release and reconstruction and proved useful in assessing the surgical results achieved.

Child, Preschool↗

Crouzon syndrome: quantitative assessment of presenting deformity and surgical results based on CT scans.

We reviewed our experience with 14 children who presented sequentially with untreated Crouzon syndrome and whose cranial vault presentation was with bilateral coronal synostosis. Using a method of 14 measurements in the cranio-orbitozygomatic region taken from preoperative and postoperative CT scans in these patients, we documented their presenting skeletal morphology and the results of surgical correction at least 1 year after operation. Our preoperative measurements confirmed a widened anterior cranial vault at 108 percent of normal and a cranial length averaging only 92 percent of normal. In comparison with age-matched controls, orbital measurements revealed a widened anterior interorbital distance at 122 percent of normal, an increased intertemporal width at 121 percent of normal, globe protrusion at 119 percent of normal, and a short medial orbital wall distance at only 86 percent of normal. The distance between the zygomatic buttresses and the interarch distance were found to be increased at 106 and 103 percent of normal, respectively. The zygomatic arch lengths were substantially shortened at only 87 percent of age-matched control values. These findings confirmed clinical observations of brachycephalic anterior cranial vaults with shallow, hyperteloric orbits and globe proptosis. Generally, in these patients the midface is horizontally retrusive and transversely wide, reflected in wide and shortened zygomas. Assessment of the postoperative results at least 1 year later showed no significant changes in any craniofacial measurements. Our findings indicate that early surgical attempts to decompress and reshape the cranio-orbital regions may limit the effects of increased intracranial pressure but do not correct the deformity as judged by CT scan evaluation at least 1 year later. Over the period of the study, the Crouzon deformity did not worsen after surgery, but the measurements remained far from normal.

Craniofacial Dysostosis↗

Aggregation as well as chemical modification of LDL during oxidation is responsible for poor processing in macrophages.

Aggregation is a characteristic of extensively oxidized (ox-) LDL. We wished to determine whether this structural change contributed even more to the documented poor degradation in macrophages of ox-LDL than the chemical changes. When protein degradation of the soluble and insoluble portions of extensively ox-LDL was compared to that of acetyl LDL in mouse peritoneal macrophages (MPM), we found that the percent of internalized LDL that was degraded was lowest for the insoluble portion (insol. ox-LDL), intermediate for the soluble portion (sol. ox-LDL), and highest for the acetyl LDL, regardless of whether the binding and uptake mechanisms had been excluded, e.g., by performing appropriate pulse-chase studies. As the same order of degradation was found after long-term degradation under cell-free conditions by a mixture of cathepsin B and D, it is likely that poor degradation of ox-LDL by lysosomal proteases is partially responsible for the deficient processing of ox-LDL in MPM. However, when MPM were incubated in a pulse-chase design with LDL that was induced to aggregate by vortexing without oxidizing (vx-LDL), degradation over an 18-h interval of accumulated vx-LDL was almost as low (25%) as that of insol. ox-LDL (18%), in contrast to sol. ox-LDL (60%). Yet, in a cell-free system cathepsin degradation of vx-LDL was as efficient as that of acetyl LDL and LDL. Also, the differences in degradation between sol. and insol. ox-LDL were smaller than in MPM. Thus, it appears that alternative mechanisms to poor proteolysis of substrate were responsible for poor intracellular processing of such aggregated lipoproteins. These results suggest that, although the poorer processing of insol. ox-LDL than sol. ox-LDL may be due, in part, to more deficient proteolytic degradation, particle aggregation per se may play at least as important a role in such deficiencies. This may occur by such mechanisms as altered intracellular trafficking leading to poorer fusion in macrophages of phagosomes containing aggregated lipoproteins with lysosomes.

Acetylation↗

Tumor necrosis factor-alpha induces cell type and tissue-specific expression of chemoattractant cytokines in vivo.

Recombinant murine tumor necrosis factor-alpha (TNF-alpha) was shown to be a strong, systemic stimulus in vivo for members of the chemoattractant cytokine gene families (JE, KC, IP-10). The three genes showed differential sensitivity to TNF-alpha, and their expression demonstrated differential tissue specificity. IP-10 was the most strongly induced messenger RNA and was seen in the liver, kidney, and spleen but very poorly in the lung or skin. JE exhibited a similar pattern, though the magnitude of expression was markedly lower. KC expression was seen only in the liver of TNF-alpha-treated mice. The time course of expression for IP-10 was rapid and transient and showed strong dose dependence. In mice treated with TNF-alpha intravenously, messenger RNA was localized in the splenic stroma but not in adherent macrophages or nonadherent lymphocytes. In situ hybridization found the majority of intercrime expression in the splenic red pulp with little or no expression seen in the white pulp. In vitro, TNF-alpha was a potent stimulus of chemoattractant messenger RNA expression in fibroblasts but not in inflammatory peritoneal macrophages. These results indicate that TNF-alpha may be an important stimulus for chemoattractant cytokine gene expression in vivo, and the primary cell types responsible may be either stromal fibroblasts, microvascular endothelium, and/or a subset of anchored mononuclear phagocytes.

3T3 Cells↗