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Biomedical subjects

R L Anderson

Publications and source records attributed to R L Anderson.

At least 145 records · Page 8Linked to original sources

Infections and pseudoinfections due to povidone-iodine solution contaminated with Pseudomonas cepacia.

In 1989 we investigated the first instance of Pseudomonas cepacia infections due to intrinsic contamination of a povidone-iodine product. Six patients in a Texas pediatric facility had P. cepacia infection or pseudoinfection (three, peritonitis; one, pseudoperitonitis; and two, pseudobacteremia). Epidemiological studies showed one risk factor for infection of peritoneal fluid with P. cepacia: performance of peritoneal dialysis in the dialysis unit with use of one lot of povidone-iodine later found to be intrinsically contaminated (4/5 vs. 0/16, P = .001). Blood cultures yielded P. cepacia after nurses wiped the tops of blood culture bottles with the povidone-iodine solution before inoculation. P. cepacia was cultured from three povidone-iodine containers used at the hospital and from four containers of the same lot obtained from other health-care facilities in Texas and California. Isolates from patients and the povidone-iodine had similar antibiograms, identical plasmid profiles, and identical DNA banding patterns on the basis of results of ribonucleotide typing. This investigation demonstrates that intrinsic contamination of povidone-iodine solution with P. cepacia can result in infections in addition to colonization and/or pseudoinfection.

Bacteremia↗

Therapeutic bioequivalency study of brand name versus generic carbamazepine.

We performed a randomized double-blind crossover therapeutic bioequivalency study of a generic (Epitol) versus a brand name (Tegretol) carbamazepine product under steady-state conditions in 40 epileptic patients. Each patient received 90-day supplies of Epitol or Tegretol and placebo, which replaced the usual dosage of the alternate product. Group A consisted of 20 seizure-free (from 5 months to 2 years) patients and group B of 20 patients with seizures refractory to drug therapy. In group A, four patients had seizures, two on both Epitol and Tegretol and two on Tegretol. In group B, the average seizure frequencies were 0.25 seizures per day on Epitol and 0.22 seizures per day on Tegretol. Average seizure frequencies were statistically the same (at a 20% difference, p less than 0.05). Areas under the curve were statistically the same (at a 20% difference, p = 0.05). Average peak heights were statistically the same (at a 20% difference, p less than 0.05). Average time to peak was earlier with Epitol. Epitol and Tegretol performed equally well in clinical efficacy and bioequivalency.

Adolescent↗

A comparison of three pulmonary artery oximetry catheters in intensive care unit patients.

OBJECTIVE: To compare the clinical performance of three pulmonary artery oximetry catheters (Oximetrix 3, SAT-2, and HEMOPRO2) in intensive care unit (ICU) patients. DESIGN: Unblinded comparison of performance over 24 h using an IL-282 CO-oximeter as a criterion standard. SETTING: Multispecialty adult ICU at a university teaching hospital. PATIENTS: Thirty critically ill patients selected from those requiring hemodynamic monitoring for medical management. MEASUREMENTS AND MAIN RESULTS: By all measures, performance of the Oximetrix 3 and SAT-2 systems were comparable; bias +/- precision were -1.98 +/- 3.07 and +1.80 +/- 3.49, respectively, vs -2.28 +/- 5.24 for the HEMOPRO2. The Oximetrix 3 and SAT-2 systems demonstrated consistent performance over the range of saturations tested, though Oximetrix 3 tended to underestimate and SAT-2 tended to overestimate the CO-oximeter value. The HEMOPRO2 underestimated the CO-oximetry-derived saturation, although this was not constant across the range of values tested. The 95 percent confidence limits based on intrasubject variability were similar (+/- 4.59, +/- 5.66, and +/- 6.56 for the Oximetrix 3, SAT-2, and HEMOPRO2, respectively); however, the 95 percent confidence limits based on total variability, while similar for Oximetrix 3 (+/- 6.03) and SAT-2 (+/- 6.86), were larger for the HEMOPRO2 (+/- 10.30). The expected SD was similar for the three systems (2.03, 2.50, and 2.90 for the Oximetrix 3, SAT-2, and HEMOPRO2 systems, respectively). None of the systems equaled or exceeded (p greater than 0.05) the manufacturers' published specifications, which, in all cases, are listed as +/- 2 percent (saturation; 1 SD) when compared with bench oximetry. CONCLUSIONS: Although each system measures mixed venous oxygen saturation, the Oximetrix 3 and SAT-2 systems demonstrate closer agreement with CO-oximetry. However, none of these catheters provided statistically significant evidence that they would perform within +/- 2 percent of CO-oximetry. As a continuous monitor used to detect changes or trends, any of the three may be acceptable.

Calibration↗

The epidemiology of low back pain in an adolescent population.

We assessed the prevalence of low back pain (LBP) in a cohort of 1242 adolescents (aged 11 through 17) currently participating in a 4-year prospective study of medically treated injuries. Overall, 30.4% of the adolescents reported LBP. The impact of LBP in adolescents was considerable, with one third resulting in restricted activity and 7.3% seeking medical attention. Life-table analysis demonstrated that by age 15, the prevalence of LBP increased to 36%. There were few differences by gender or race. These results suggest that LBP in adolescents is a serious public health problem.

Absenteeism↗

Cosmetic eyelid surgery and the problem eyelid.

The human eyelid is an amazingly complex structure that is responsible for protecting, moisturizing, and reconstituting the external surface of the eye. Compromise of any of the tarsoligamentous supporting structures of the eyelids can result in eyelid malposition, corneal compromise, and even blindness. Failure to recognize these abnormalities in patients seeking cosmetic eyelid surgery can lead to disastrous results. The most common structural eyelid abnormalities encountered in patients seeking cosmetic eyelid surgery and prophylactic and reconstructive surgical techniques to deal with these difficult problems are discussed.

Eyelids↗

Modifications to the semicircular flap technique in eyelid reconstruction.

The most common reconstructive procedure in the upper and lower eyelid is direct closure of the lid margin. When additional mobilization of tissue is needed to close a defect, lateral canthotomy and cantholysis is suggested. Mobilization of tissue beyond the lateral orbital rim is occasionally required. We have found that in the lower eyelid the mobilized tissue is much better supported if the initial incision is made vertically toward the eyebrow rather than temporally, as is suggested with the semicircular flap technique. We describe modifications to this technique, which we refer to as the vertical-temporal advancement flap, and present the results in 28 consecutive patients followed for 8 months to 3 years.

Eyelid Neoplasms↗

The pigtail probe protected by silicone intubation: a combined approach to canalicular reconstruction.

We have devised a method of single-eyelid canalicular reconstruction using the pigtail probe to facilitate identification of the proximal canalicular segment following silicone stent intubation of the normal, uninjured canaliculus. A series of seven acute and two long-standing canalicular lacerations were successfully reconstructed using this technique, which minimizes the risks associated with the use of the pigtail probe.

Eye Injuries↗

Decentralized operating room pharmacy services in a military teaching hospital.

The development, initiation, and evaluation of a decentralized pharmacy satellite within the operating room, requiring neither additional capital funding nor any major construction, is described. The satellite offers numerous programs to aid the operating room staff. Included in this effort is the complete management of all controlled substances within the operating room, post-anesthesia-care unit, and same-day-surgery unit. Pharmacists function as pharmaceutical resources playing a major role in the pain service unit. Success of the satellite is assessed via a number of parameters including staff survey response, quality assurance impact, and inventory management.

California↗

Hypoxia and resistance to hydrogen peroxide confer resistance to tumor necrosis factor in murine L929 cells.

The mechanism whereby tumor necrosis factor (TNF) kills mammalian cells is not well understood, although oxidative damage has been suggested by several investigators. Further, it is not known why cells vary in their responsiveness to TNF. We show that the cytotoxic effect of TNF toward TNF-sensitive L929 cells is blocked under hypoxic conditions, suggesting a critical role of molecular oxygen and reactive oxygen species. To test whether cellular resistance to reactive oxygen species could provide resistance to TNF, we derived a variant strain from L929 cells by chronic exposure to an oxidizing agent, hydrogen peroxide (H2O2). These cells exhibit marked resistance to TNF as well as to H2O2. This cross-protection provides additional evidence that mechanisms of resistance to oxidative damage are causally related to TNF-induced cell death. Scatchard analysis of TNF binding did not reveal significant differences between the H2O2-resistant line and the wild-type L929 line. On the other hand, analyses of antioxidant enzymes and glutathione levels in cells of the wild-type and the H2O2-resistant lines revealed several potentially important differences. Before exposure to TNF, the H2O2-resistant variants have elevated catalase activity, decreased activity of total glutathione-S-transferase (GST), and similar superoxide dismutase (SOD) activities. Exposure to TNF led to alteration in CuZnSOD activity, and much more so in the variants than in the wild-type L929 cells. However, no significant change in MnSOD activities in cells of either cell line was observed. Total GST activity was not altered appreciably by TNF in either cell line, but Western analysis showed that the level of alpha GST isozyme was increased and mu GST isozyme decreased in the H2O2-resistant variants. Furthermore, alterations in total glutathione content were observed in both the control and the variant cells.

Animals↗

Serratia marcescens surgical wound infection following breast reconstruction.

Surgical wound infections due to gram-negative bacilli have been rarely reported following breast implant surgery. From April to November 1989, four patients from one plastic surgeon's practice developed Serratia marcescens surgical wound infection (SWI) following breast reconstruction procedures with implantation of six expandable mammary implants. All six implants were removed for unabated S. marcescens SWI. Symptoms developed 13-161 days (median, 66 days) after surgery. When compared with nonexpandable silicone breast implants used during the period November 1, 1988, to October 31, 1989, expandable implants were associated with a greater risk of S. marcescens SWI (4/10 versus 0/11 patients, p = 0.04). Epidemiologic studies revealed that infection was associated with saline expansion of the implants performed in the surgeon's office. S. marcescens was cultured from a bag of commercial saline used on at least two of the four patients with SWI; the isolate from the saline and the three available patient isolates had identical serotype (O-undetermined:H4) and antimicrobial susceptibility patterns. Review of office procedures revealed that hands were not routinely washed before and aseptic technique was not used during the expansion procedure. Cultures of unopened bags of saline and an unused expandable implant were sterile. We hypothesize that multiple use of saline bags and nonsterile expansion technique extrinsically contaminated saline solutions and resulted in implant and/or surgical site infection. This investigation underscores the importance of avoiding multiple use of solutions intended for single use and of using aseptic technique when manipulating prosthetic devices.

Adult↗

Isoenzyme analysis of Pseudomonas cepacia as an epidemiologic tool.

Multilocus enzyme electrophoresis has successfully been used to establish basic marker systems for the epidemiologic analysis of a variety of bacterial pathogens. This study was done to determine the efficacy of this technique for characterizing Pseudomonas cepacia, using 31 known-related strains isolated during an outbreak of infections involving intrinsically contaminated povidone-iodine solution, and five outbreak-unrelated strains used in serotyping of P. cepacia. Crude cell extracts were analyzed by starch gel electrophoresis for electrophoretic variants using 13 enzyme substrates; esterase bands were detected using an additional four substrates. The 31 outbreak strains had identical isoenzyme patterns for all enzymes examined. Five electrophoretic types were obtained for the serotyping strains; electrophoretic mobilities of one of the five strains corresponded to the patterns obtained for the outbreak strains. These results suggest that enzyme electrophoretic typing may be a useful adjunct to other typing methods used in epidemiologic analyses of P. cepacia infections.

Burkholderia cepacia↗

Loss of the intrinsic heat resistance of human cells and changes in Mr 70,000 heat shock protein expression in human x hamster hybrids.

Since mammalian cells vary widely in their intrinsic thermoresistance, we have investigated the genetic basis underlying this phenomenon in human and rodent cell lines. Typically, human cells are considerably more resistant to killing by heat than rodent cell lines. To determine whether the heat-resistant phenotype is dominant or recessive and to locate the chromosome(s) bearing determinants for heat resistance, we have prepared hybrids of heat-resistant human HT1080 cells and heat-sensitive Chinese hamster ovary (CHO) cells to test their response to heat. For both mass hybrid cultures and individual clones, the heat response of the hybrids was similar to that of the CHO parent. Analysis by in situ hybridization revealed the presence of five to 20 human chromosomes per cell in the mass hybrids and four to eight intact chromosomes plus some fragments in individual clones isolated from the hybrid cell population. A similar result was obtained using a different human cell line, AG1522. These data suggest that heat resistance is a recessive trait. Consistent with this conclusion are the results from a study of a fusion of HT1080 to a CHO mutant, BL-10, which was found to be hypersensitive to heat-induced killing. These hybrids had a normal CHO heat response and not the more heat-resistant phenotype of HT1080 cells. Two hybrid clones, H2 and H4, from the HT1080/BL-10 fusion were studied in more detail. Both clones possess similar amounts of Mr 70,000 heat shock protein (HSP70), despite the fact that H4 contains three human chromosomes (Nos. 6, 14, and 21) which carry HSP70 genes while H2 contains only one (chromosome 6). Both hybrid cell lines have the same response to heat. Although we found a wide range of sensitivities to heat, all cell lines contained a similar amount of constitutive HSP70, suggesting that HSP70 levels per se are not the critical determinant of intrinsic heat resistance.

Animals↗

Histologic features of human orbicularis oculi treated with botulinum A toxin.

To evaluate muscle histologic features in humans following therapeutic botulinum toxin injections, we studied orbicularis oculi from 11 patients with blepharospasm; nine had previously received botulinum toxin injections and two had not. All muscles had comparable variability in muscle fiber diameter, with no necrosis, inflammation, denervation, or consistent alterations in muscle fiber internal architecture. Botulinum toxin produces no persistent histologic changes in human muscle fibers.

Adult↗

Prenatal diagnosis in multiple gestation: 20 years' experience with amniocentesis.

Three hundred and thirty-nine cases of multiple gestation underwent prenatal diagnosis by amniocentesis. The spontaneous abortion rate (to 28 weeks) in this group was 3.57 per cent compared with our singleton abortion rate of 0.60 per cent. The perinatal mortality rate (PMR) and prematurity rate were not different from the singletons, and compared favourably with the PMR reported in the literature for multiple gestations which did not undergo any intervention during pregnancy. This increased abortion rate following amniocentesis may only represent the increased natural loss rate in multiple gestations, and not indicate any increased risk added by the procedure.

Amniocentesis↗

Expression of carbohydrate binding protein 35 in human fibroblasts: variations in the levels of mRNA, protein, and isoelectric species as a function of replicative competence.

We have compared the expression and localization of carbohydrate binding protein 35 (CBP35) in human SL66 fibroblasts of different replicative capacities. When serum-starved, quiescent young (passage 11, corresponding to approximately 18 cumulative population doublings) SL66 cells were treated with serum, there was a marked stimulation in the expression of CBP35. This was revealed both by an increase in the percentage of cells positively stained with anti-CBP35 under immunofluorescence and by an increase in the amount of the protein in immunoblots, as well as by an increase in the level of accumulated mRNA in Northern blots. The rise in the expression of CBP35 in proliferating cells was manifested most clearly in the nuclear fraction, with elevation in the levels of the nonphosphorylated (pI8.7) protein, as well as the phosphorylated (pI8.2) derivative. In contrast, older (passage 27-35, 55-68 cumulative population doublings) cultures of SL66 fibroblasts appear to have lost the normal proliferation-dependent regulation of CBP35 expression. The level of CBP35 was high in quiescent high-passage cells and decreased somewhat after serum stimulation. Furthermore, the unphosphorylated (pI 8.7) form of the lectin could not be detected in either the nucleus or the cytoplasm of high-passage SL66 cells. Finally, the level of the mRNA for CBP35 was high in quiescent cultures of high-passage cells, but undetectable 17 h after serum stimulation. These results establish that the expression of CBP35 becomes altered as human fibroblasts acquire reduced replicative capacity.

Antigens, Differentiation↗

Binding activity of glucocorticoid receptors after heat shock.

The response of glucocorticoid receptors (GR) to heat was measured by the change in ligand binding activity both in control cells and in cells made tolerant to heat by a prior mild heat exposure. The study was prompted by earlier data showing that one of the heat shock proteins (HSP90) is an essential component of the GR complex and that treatment of mammalian cells with hydrocortisone induces resistance to heat damage. The GR rapidly loses binding activity after commencement of heating. There is a 50% loss of activity after 4 min at 45 degrees C, 8 min at 44 degrees C, or 17 min at 43 degrees C. The reduction in binding is due mainly to a reduction in affinity of binding to the ligand. The ability to bind glucocorticoid recovers quickly after heat treatment. Activity returns to levels 60-80% of normal by 2 h after a heat treatment that initially reduces binding to less than 20% of normal. However, complete restoration of binding activity takes approximately 3 days. The recovery of binding activity does not require protein synthesis. Pretreatment of cells with hydrocortisone, using conditions that induce heat resistance, reduces the activity to 10-20% of control, but residual receptors display a heat sensitivity similar to that of control cells. There was evidence for a limited degree of protection of GR from heat damage in thermotolerant cells.

Animals↗

Early indicators of bladder carcinogenesis produced by non-genotoxic agents.

There are several early indicators of non-genotoxic bladder tumorigenicity. The non-invasive indications are polydipsia, diuresis, changes in urine pH and urinary cation concentrations, especially Na and Ca. The indicators requiring invasive techniques are increased bladder weight and increased cell replication assessed by DNA labeling or histologically as epithelial hyperplasia. SEM has been used to characterize bladder surface changes, and a reduction of bladder tissue Ca has been implicated in one mechanism leading to bladder cancer. Wherever multiple species have been tested, the non-genotoxic bladder carcinogens have induced bladder responses only in rats. This is true whether the criterion was complete carcinogenesis, promotion or short-term indicators. It is also evident that the response can vary greatly within rat strains and is dependent upon the diet being fed. These variables make the relevance of the results obtained in the rat bladder of questionable significance to man. In relation to chronic studies it is clear that as the male rat ages it loses the capacity to concentrate urine, probably because of the endemic, age-progressive loss of functional renal tissue. It is also clear that the bladder grows to accommodate the increase in urine output. Thus it is likely that any agent or treatment that causes bladder damage may be associated with increased neoplasia expression in aged male rats. No other species shows the degree of spontaneous nephrosis seen in the male rat, a condition which is both rat strain- and diet-dependent. Finally, it should be recognized that while there are some early indicators of bladder tumorigenesis that can be useful as warning signs, each compound is likely to yield unique responses when its mechanism is studied in detail. To facilitate discussion of the parameters that have been identified as early indicators of bladder tumorigenesis associated with non-genotoxic agents, the proposed mechanisms of cancer development, the information which led to these proposals and a critique of the mechanisms have been presented.

Animals↗