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Biomedical subjects

D Miller

Publications and source records attributed to D Miller.

At least 415 records · Page 23Linked to original sources

Biofilm and scleral buckle-associated infections. A mechanism for persistence.

Scleral buckle infections tend to be persistent as well as resistant to antimicrobial treatment. Often, scleral buckle infections require removal of the buckling elements for resolution. To determine if bacteria are able to persist on scleral buckles by elaborating a glycocalyx matrix or biofilm that offers protection against host defenses and antimicrobial treatment, the authors cultured 28 scleral buckle elements removed for infection and extrusion. Bacteria were isolated from 18 elements (64%). The most frequently isolated bacteria were Staphylococcus epidermidis and other coagulase-negative staphylococci (8), Staphylococcus aureus (3), corynebacteria (3), Mycobacterium chelonei (3), and Proteus mirabilis (3). Eleven (65%) of 17 buckles evaluated with scanning electron microscopy demonstrated the presence of bacteria encased in biofilm. Biofilm was demonstrated on the surfaces and ends of solid silicon elements. In the silicon sponges, biofilm also extended into the matrix of the sponges. The authors believe that bacterial production of biofilm offers an explanation for the persistence of scleral buckle infections and their ability to withstand antimicrobial treatment.

Adult↗

Superior sagittal sinus thrombosis after internal jugular vein cannulation.

A case of cerebral venous sinus thrombosis after central venous cannulation is presented. This occurred after a catheter had been in place for 5 days. The patient presented with thrombosis of the left internal jugular vein 4 days after removal of the catheter. Despite anticoagulation, the patient developed symptoms of increased intracranial pressure. Subsequently, a diagnosis of superior sagittal sinus thrombosis was made. The aetiology, diagnosis and management of this uncommon complication of central venous cannulation are discussed.

Brain↗

Modulation of expression of virus-like elements following exposure of mice to high- and low-LET radiations.

Modulation of virus expression has been reported following exposure to a variety of cellular stresses, including UV radiation and heat-shock. The experiments reported here were designed to examine expression of endogenous VL30 (virus-like 30 S) elements following exposure of whole mice to ionizing radiations. Whole mice were exposed to doses of neutrons (50 cGy) or gamma-rays (300 cGy) shown to be equally efficient in cancer production in the whole animal, and tissues were harvested at 10 and 60 min following completion of the exposure. RNA extracted from these tissues and from tissues of untreated controls was examined for VL30 RNA accumulation by dilution dot blot and Northern blot analyses. These studies revealed that neutrons repressed VL30 RNA accumulation evident within 10 min following exposure in brain, gut, thymus and spleen but not in liver, in which VL30 RNA was unaffected by radiation exposure. During this same time interval, gamma-rays induced VL30 expression in gut and brain and to a lesser extent in liver. These experiments suggest the presence of a differential molecular response following whole-body exposure to high- versus low-LET radiations. In addition, this work demonstrates that ionizing radiations may affect expression of murine endogenous viral sequences.

Animals↗

Effect of age on fever response to recombinant tumor necrosis factor alpha in a murine model.

Certain elderly humans show a blunted fever response to infection. A study was designed using a murine model to assess the influence of age on the febrile response to the endogenous pyrogen, tumor necrosis factor alpha (TNF alpha). Twenty (10 young: 4-6 months; 10 old: 24-28 months) BALB/c mice were injected with 50 ng of TNF alpha into the intraperitoneal space; the experiments were repeated one week later with 100 ng TNF alpha. Control animals received intraperitoneal injections of pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 90 minutes post-injection using a thermistor probe and temperature gauge. In the majority of the time intervals following injection, the mean temperature changes of young mice were significantly higher than old mice for both 50 ng and 100 ng doses of TNF alpha. Similarly, peak temperature changes from baseline were consistently higher in young animals following injection of TNF alpha. Moreover, the peak temperature changes in young mice after 50 ng TNF alpha injection were significantly higher than those in old mice following a 100 ng injection of TNF alpha. These findings confirm that (a) TNF alpha has a role in the pathogenesis of fever; (b) aging alters significantly the febrile response; and (c) a mechanism of this age-related blunted febrile response may involve TNF alpha.

Aging↗

The role of calcium ions and calcium channel entry blockers in experimental ischemia-reperfusion-induced liver injury.

Verapamil administered before treatment, but not after treatment, had a beneficial effect on a 90-minute warm ischemia-reperfusion rat liver injury model. The possible activation of proteases converting the xanthine dehydrogenase to xanthine oxidase, the significant mitochondrial calcium loading during the ischemic period, and the potentiation of calcium and oxygen-derived free radicals to promote injury to mitochondria are mechanisms supported by this study, based on both histologic observations and on the pattern of enzyme leak after the acute ischemic event.

Alanine Transaminase↗

Scleral buckle infections due to atypical mycobacteria.

Six cases of scleral buckle infections due to atypical mycobacteria were studied to determine their clinical and microbiologic features and the response of these infections to treatment. All infections were treated with exoplant removal and administration of a variety of antibiotics. Symptoms and clinical signs of infection resolved rapidly after treatment in all cases, and visual acuity returned to the best preoperative level in 5 of 6 cases. There are no clinical features to distinguish mycobacterial infections from other causes of scleral buckle infection, although scleral rupture occurred in 2 of 6 cases. The microbiologic evaluation of these cases showed 5 infections due to Mycobacterium chelonae and 1 infection due to Mycobacterium fortuitum. Species and subspecies differences correlated with different antibiotic susceptibilities. Amikacin most frequently offered the best antibiotic coverage, as cases with M. chelonae were resistant or only marginally sensitive to ciprofloxacin. As in scleral buckle infections caused by other bacteria, prompt exoplant removal and adjustment of antibiotic therapy based on culture sensitivities was the best treatment.

Adult↗

Fever response in elderly nursing home residents: are the older truly colder?

OBJECTIVE: To test the hypothesis that many nursing home residents with an apparently blunted fever response (maximum temperature less than 101 degrees F) may actually have a significant change in temperature (delta T greater than or equal to 2.4 degrees F) which is not recognized because of a low baseline temperature. DESIGN: Retrospective chart review for cases of infection that met specific criteria and for chart-recorded baseline and infection temperatures. Chart-recorded baseline temperatures were prospectively compared with re-measurement of morning temperatures. SETTING: Nursing Home Care Unit of the VAMC West Los Angeles. PATIENTS: Random review of 40 residents' charts resulted in the detection of 69 infections among 26 residents over a 20-month period. Fifty randomly selected residents prospectively underwent comparison of chart-determined and actual re-measurement of baseline temperatures. RESULTS: In 50 randomly selected residents, the mean oral baseline temperature of 97.4 +/- 0.2 (degrees F +/- SEM) closely approximated the mean nurse-recorded measures in the charts (97.6 +/- 0.1). Chart review detected 69 infections among 26 residents, with 53 episodes having a temperature recorded during the infection. The mean maximum temperature (Tmax) during an infection was 101.3 +/- 0.3 (degrees F +/- SEM) but 47% (25/53) of the episodes had a "blunted" fever response (Tmax less than 101 degrees F). Of the 25 "blunted" fevers (Tmax less than 101 degrees F), about one-fourth demonstrated an adequate change in temperature from baseline (delta T greater than or equal to 2.4 degrees F) but failed to reach 101 degrees F because of a low baseline. Most infections (89%) had a Tmax greater than 99 degrees F. CONCLUSION: Establishing a nursing home patient's basal temperature and monitoring for changes in temperature (delta T greater than 2.4 degrees F) and/or lowering the threshold for recognition of fevers (to 99 degrees or 100 degrees F) in nursing home residents with a change in function should assist in early recognition of infections.

Aged↗

Significance of C-terminal cysteine modifications to the biological activity of the Saccharomyces cerevisiae a-factor mating pheromone.

We have undertaken total synthesis of the Saccharomyces cerevisiae a-factor (NH2-YIIKGVFWDPAC[S-farnesyl]-COOCH3) and several Cys-12 analogs to determine the significance of S-farnesylation and carboxy-terminal methyl esterification to the biological activity of this lipopeptide mating pheromone. Replacement of either the farnesyl group or the carboxy-terminal methyl ester by a hydrogen atom resulted in marked reduction but not total loss of bioactivity as measured by a variety of assays. Moreover, both the farnesyl and methyl ester groups could be replaced by other substituents to produce biologically active analogs. The bioactivity of a-factor decreased as the number of prenyl units on the cysteine sulfur decreased from three to one, and an a-factor analog having the S-farnesyl group replaced by an S-hexadecanyl group was more active than an S-methyl a-factor analog. Thus, with two types of modifications, a-factor activity increased as the S-alkyl group became bulkier and more hydrophobic. MATa cells having deletions of the a-factor structural genes (mfal1 mfa2 mutants) were capable of mating with either sst2 or wild-type MAT alpha cells in the presence of exogenous a-factor, indicating that it is not absolutely essential for MATa cells to actively produce a-factor in order to mate. Various a-factor analogs were found to partially restore mating to these strains as well, and their relative activities in the mating restoration assay were similar to their activities in the other assays used in this study. Mating was not restored by addition of exogenous a-factor to a cross of a wild-type MAT alpha strain and a MATaste6 mutant, indicating a role of the STE6 gene product in mating in addition to its secretion of a-factor.

Amino Acid Sequence↗

Do adolescents help and share?

Although developmental and social psychologists have studied prosocial behavior for the past twenty years, its occurrence in adolescents has received little attention. In the present paper, observational and self-report data were collected on 37 nonhandicapped and handicapped (behaviorally disordered) adolescents in public school settings. Helping, sharing, cooperating, comforting, defending, donating, and rescuing were the prosocial behaviors investigated. The adolescents with handicaps displayed significantly more prosocial behavior than did the nonhandicapped adolescents. However, the nonhandicapped adolescents perceived themselves as engaging more frequently in prosocial behavior than did their handicapped peers. The teachers of the handicapped adolescents used a prosocial teaching style more frequently than did the teachers of the nonhandicapped adolescents. Implications for future research and training are discussed.

Adolescent↗

Antibiotic therapy for Bacillus species infections.

We reviewed 36 cases of culture-proven Bacillus species ocular infections occurring between September 1974 and December 1989. Kirby-Bauer disk sensitivities were available in 34 of the 36 cases (95%). All Bacillus species isolates were sensitive to the aminoglycoside antibiotics (N = 34) and to vancomycin hydrochloride (N = 32); resistance to clindamycin was found in four of 18 (22%) of tested isolates. Although B. cereus was uniformly sensitive to these antibiotics, resistance to clindamycin occurred in four cases in the non-B. cereus group. The microbroth dilution technique confirmed the Kirby-Bauer data. The aminoglycosides were uniformly effective, but the cephalosporins (first, second, and third generation drugs) were consistently ineffective against B. cereus and varied from sensitive to moderately sensitive for the non-B. cereus isolates. Our microbiologic laboratory findings suggest that vancomycin hydrochloride in combination with an aminoglycoside ensures more consistent antibiotic coverage of Bacillus species ocular infections.

Anti-Bacterial Agents↗

An optical model to describe image contrast with bifocal intraocular lenses.

We attempted to quantify the decrease in contrast associated with the concentric-style bifocal intraocular lens by using a model eye and bifocal intraocular lens, with a model unifocal intraocular lens as a control. When imaging near objects, pupils smaller than 2.5 mm produced image contrast of 100% of the control; larger pupils degraded contrast to 25% for a 6-mm pupil. For distant objects, pupils smaller than 2.5 mm produced image contrast of 70% to 95% because of the pinhole effect; larger pupils engaged the distance portion of the intraocular lens and maintain 80% contrast on average. Thus, the bifocal intraocular lens produced image contrast greater than 70% in all situations tested, except when imaging near objects with a pupil larger than 3.5 mm. The data suggest that image contrast is highly dependent on pupil size and object distance.

Contrast Sensitivity↗

c-myc amplification in ovarian cancer.

The c-myc oncogene codes for a DNA binding protein that appears to play an important role in the regulation of cell growth. c-myc gene amplification has been documented to occur in both hematopoietic and solid neoplasms and often indicates more biologically aggressive tumors. Southern hybridization analysis was performed on high-molecular-weight DNA isolated from primary ovarian carcinomas. Major structural rearrangements of c-myc were not detected. Five of seventeen (29.4%) tumor samples demonstrated amplification of the myc oncogene. The 5 patients with ovarian carcinomas associated with c-myc amplification exhibited a median survival of 17 months. Of the 12 patients without evidence of tumor-associated c-myc amplification, 5 have exhibited disease-free survival for an average of 36.8 months and are currently alive. The remaining 7 patients, the majority of whom had advanced-stage, poorly differentiated lesions with a normal c-myc copy number, exhibited a median survival of 9 months. There was no apparent relationship between c-myc amplification, grade of tumor differentiation, and response to platinol-based chemotherapy. These data do not suggest a prognostic role for c-myc amplification in primary ovarian cancer. However, c-myc amplification is a common finding in advanced-stage ovarian cancer.

Adult↗

Endogenous Candida endophthalmitis. Management without intravenous amphotericin B.

Eight consecutive cases of culture-proven endogenous Candida endophthalmitis (ECE) were managed between 1980 and 1988. All patients were treated with vitrectomy and injection of intravitreal amphotericin B. Blood cultures were negative in all patients, although Candida albicans was cultured from a foot ulcer in one patient. No systemic therapy was used in three patients, three patients received oral ketoconazole, and two patients received oral flucytosine postoperatively. Intravenous amphotericin B was not used because of lack of evidence of disseminated candidiasis and the systemic toxicity associated with its use. The ECE responded favorably to treatment in all cases. Final vision was better in patients with a shorter interval between onset of symptoms and initiation of antifungal therapy. Posttreatment visual acuities were: four eyes greater than or equal to 20/50, two eyes at 20/80 to 20/200, and two eyes less than 5/200. This series showed that ECE without evidence of disseminated disease can be treated successfully with vitrectomy and intravitreal amphotericin B.

Adult↗