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Biomedical subjects

M A Jackson

Publications and source records attributed to M A Jackson.

At least 19 recordsLinked to original sources

Pyogenic arthritis associated with adjacent osteomyelitis: identification of the sequela-prone child.

We treated 96 cases of pyogenic arthritis from January 1, 1980, to December 31, 1990, 16 of whom had adjacent osteomyelitis. Presenting symptoms in the latter were indistinguishable from those in 80 cases of primary pyogenic arthritis with regard to involved joints, aspirate findings and pathogens; however, adjacent osteomyelitis patients tended to be younger and were more likely to be symptomatic more than 7 days and to have received prior antibiotics. Prompt joint drainage was done in 15 of 16 cases but adjacent osteomyelitis was recognized in only 5. Bone scan was misleading in 3 of the 4 cases where it was performed as part of the initial evaluation. Persistent pain, swelling and/or fever occurred in 9 patients, 6 of whom underwent further joint drainage. Radiographs were diagnostic in 1 patient at admission, 10 during hospitalization and in 5 at follow-up. Sequelae were found in 8 of 13 patients with bone and joint infections vs. 8 of 41 patients with primary joint infection. Patients with a positive culture from the hip or shoulder who had been pretreated with antibiotics had the worst prognosis. Osteomyelitis should be considered in patients who present with symptoms and signs of pyogenic arthritis for longer than 1 week, especially if they have received prior antibiotics. Earlier recognition and bone debridement may improve outcome.

Adolescent

Complications of varicella requiring hospitalization in previously healthy children.

Between January 1, 1981, and December 31, 1990, 83 previously well children and 20 with stable underlying conditions were hospitalized because of complications of varicella. The mean hospital stay was 4.5 days and one child with pneumonia died. Skin or soft tissue infections and pneumonia were the most common complications. Central nervous system complications (15), dehydration (8) and Reye's syndrome (6) accounted for 75% of the nonsuppurative complications. Cellulitis (7), pneumonia (3) and encephalitis (3) were the most common diagnoses among the 20 children hospitalized greater than or equal to 7 days. No cases of Reye's syndrome were diagnosed after 1984. An increase in the number of soft tissue infections caused by Group A beta-hemolytic streptococci and involving an extremity was noted during the last 5 years. Chickenpox continues to cause significant morbidity in the pediatric population.

Adolescent

Evidence for a NO-rebound mechanism for production of N2O from nitrite by the copper-containing nitrite reductase from Achromobacter cycloclastes.

Reduction of NO2- by the Cu-containing nitrite reductase from Achromobacter cycloclastes produces NO as the primary product initially, but as NO accumulates, NO production levels-off and N2O production becomes significant. Reaction of the enzyme with NO2- in the presence of NO increases the amount of N2O product significantly, while trapping the NO product as nitrosylhemoglobin or rapid removal of NO by sparging results in no detectable N2O production. Reaction of the enzyme with 15NO2- in the presence of 14NO results in rapid formation of the mixed isotope product (14N, 15N)O in ca. 45% yield. In contrast, the presence or absence of NO has no effect on N2O production by a prototypical heme cd1-containing nitrite reductase. These results are consistent with formation of a labile Cu(+)-NO+ species in the copper enzyme, which normally decomposes to NO. Production of N2O requires that the released NO must rebind to the enzyme to combine with a second NO2- or a species derived therefrom.

Alcaligenes

The influence of carbon and nitrogen nutrition on fusarin C biosynthesis by Fusarium moniliforme.

The influence of various carbon and nitrogen sources on fusarin C synthesis was examined in submerged cultures of Fusarium moniliforme NRRL 13616. Using a zinc-deficient, synthetic medium, highest levels of fusarin C were produced by cultures grown with urea or ammonium sulfate as the nitrogen source and fructose, sucrose, or glucose as the carbon source. In media supplemented with various concentrations of glucose and ammonium sulfate, glucose concentrations which provided excess carbohydrate significantly increased fusarin C synthesis, regardless of the ammonium sulfate concentration.

Ammonium Sulfate

Post-operative radiotherapy in invasive thymoma.

The experience of a large Cancer Institute in treating invasive thymoma has been reviewed. Twenty-eight patients received radiotherapy following biopsy or incomplete resection of a thymoma. The overall survival was 53% at 5 years and 44% at 10 years. Treatment was generally well tolerated but three patients (11%) developed significant side effects from the radiotherapy and two of these died. Radiotherapy appeared to be more effective in patients who had a small volume of residual disease after surgery. An attempt was made to identify prognostic factors but none reached statistical significance. The radiation dose, field size and the use of systemic treatment are discussed.

Humans

The Genetic Activity Profile database.

A graphic approach termed a Genetic Activity Profile (GAP) has been developed to display a matrix of data on the genetic and related effects of selected chemical agents. The profiles provide a visual overview of the quantitative (doses) and qualitative (test results) data for each chemical. Either the lowest effective dose (LED) or highest ineffective dose (HID) is recorded for each agent and bioassay. Up to 200 different test systems are represented across the GAP. Bioassay systems are organized according to the phylogeny of the test organisms and the end points of genetic activity. The methodology for the production and evaluation of GAPs has been developed in collaboration with the International Agency for Research on Cancer. Data on individual chemicals have been compiled by IARC and by the U.S. Environmental Protection Agency. Data are available on 299 compounds selected from volumes 1-50 of the IARC Monographs and on 115 compounds identified as Superfund Priority Substances. Software to display the GAPs on an IBM-compatible personal computer is available from the authors. Structurally similar compounds frequently display qualitatively and quantitatively similar GAPs. By examining the patterns of GAPs of pairs and groups of chemicals, it is possible to make more informed decisions regarding the selection of test batteries to be used in evaluating chemical analogs. GAPs have provided useful data for the development of weight-of-evidence hazard ranking schemes. Also, some knowledge of the potential genetic activity of complex environmental mixtures may be gained from assessing the GAPs of component chemicals. The fundamental techniques and computer programs devised for the GAP database may be used to develop similar databases in other disciplines.

Animals

Childhood lawn dart injuries. Summary of 75 patients and patient report.

Lawn dart injuries account for an estimated 675 emergency department visits per year. Seventy-six patients are described herein. The victims ranged from 1 to 18 years of age and were predominantly male (male to female ratio is 3.1:1). The most common sites of injury were head (54%), eye (17%), and face (11%). Hospitalization was required for 54% (41/76) of these patients. Sequelae included unilateral blindness and brain damage. The case fatality rate was 4%. The extent of a head injury was not always clinically apparent at the initial presentation and should be promptly defined by computed tomographic scan. Despite the recent ban on the sale of lawn darts, there remain an estimated 10 to 15 million sets of lawn darts in the homes of Americans. Pediatricians should encourage parents to discard all lawn darts.

Adolescent

Dose-related differences in DNA adduct levels in rodent tissues following skin application of complex mixtures from air pollution sources.

Dose-related differences in the binding of DNA reactive intermediates for three environmentally important complex mixture particulate extracts and a well-studied carcinogen, benzo[a]pyrene (BaP), were examined in female C-57 mice following multiple topical treatments ranging from 1 to 120 mg/mouse. Particulate extracts from coke oven, coal soot and diesel exhaust were selected as model complex mixtures based on short-term mutagenicity assays, animal bioassays for carcinogenicity or epidemiological studies, where increased incidences of lung cancer in exposed populations were detected. Positive and negative control animals were treated with 1.2 mg BaP or acetone respectively. DNA was isolated from skin, lung and liver 24 h following the last application and analyzed for DNA adducts using the nuclease P1 version of the 32P-postlabeling assay. Each of the particulate extracts produced distinct patterns of DNA adducts. A diagonal zone of radioactivity, presumably representing multiple putative DNA adducts, was observed for coke-oven, coal-soot- and diesel-modified DNA samples. One adduct, common to all three complex-mixture-modified DNA samples, co-migrated with the major BaP adduct observed following treatment with BaP alone. Based on the BaP concentration for each of the extracts it seems unlikely that this adduct is derived from BaP alone. It is possible that an adduct is formed with chromatographic properties similar to the major BaP-derived adduct detected in mice treated with BaP alone. This adduct was detected in all tissues examined and represented approximately 12-34% of the total number of adducts detected within the diagonal radioactive zone for all coke-oven- and coal-soot-exposed tissues (skin, lung and liver). In contrast, this adduct represented 49-67% of the total radioactivity recovered from the diagonal zone of DNA isolated from lungs of animals exposed to diesel extract. The highest total number of adducts resulted from the metabolism of coke oven extract followed by coal soot and diesel treatments respectively. A dose-dependent increase in adduct formation was observed for all tissues in the diesel- and coal-soot-treatment mice. Liver and lung, but not skin, DNA adduct levels increased in a dose-dependent manner in the coke-oven-treated mice. The percentage of dose administered, detected as DNA adducts increased in all tissues as the dose decreased for all three complex mixtures. These data have important implications for risk assessment of these complex mixtures.

Adenosine Triphosphate

Production of fumonisin B1 by Fusarium moniliforme NRRL 13616 in submerged culture.

Fumonisin B1, a recently discovered mycotoxin, was synthesized by submerged cultures of Fusarium moniliforme NRRL 13616 grown for 29 days at 28 degrees C and 220 rpm in a basal salts medium (pH 5.0) supplemented with 90 g of glucose per liter and 3.5 g of ammonium sulfate per liter. Under these culture conditions, 74 +/- 23 micrograms of fumonisin B1 per ml was produced by 29-day-old F. moniliforme NRRL 13616 cultures. Fumonisin B1 was detected in liquid culture extracts by high-performance thin-layer chromatography. Fumonisin B1 was confirmed and quantitated by gas chromatography and gas chromatography-mass spectral analysis of the trimethylsilyl derivative. The use of a defined medium for producing fumonisin B1 in a submerged culture facilitates its isolation and provides an excellent method for conducting biosynthetic studies.

Carcinogens, Environmental

Nontypable Haemophilus influenzae nosocomial pulmonary infections in children following intubation.

Twenty-nine intubated pediatric patients were prospectively studied to determine whether nontypable Haemophilus influenzae (NTHI) is associated with the development of nosocomial pneumonia. Throat cultures and tracheal Gram stains, leukocyte counts and cultures were obtained immediately following intubation, then serial studies on tracheal secretions were performed. Median patient age was 13 months. One patient had preexisting lung disease and 14 (48%) had pneumonia when intubated. There were five deaths. NTHI was recovered from the initial throat or tracheal culture in seven patients (24%); none developed a nosocomial lower respiratory tract infection. NTHI was not associated with any of three cases of nosocomial pneumonia. Three of 12 NTHI isolates were beta-lactamase producers. Tracheal leukocyte counts and Gram stains were not predictive of pneumonia, either at the time of intubation or subsequently. We conclude that NTHI in the oropharynx or trachea is not predictive of pneumonia among intubated pediatric patients.

Adolescent

Differences in detection of DNA adducts in the 32P-postlabelling assay after either 1-butanol extraction or nuclease P1 treatment.

The use of nuclease P1 treatment and 1-butanol extraction to increase the sensitivity of the 32P-postlabelling assay for DNA adducts have been compared. Although similar results were obtained with the two methods for standard adducts formed with benzo[a]pyrene diol epoxide I (BPDE-I), nuclease P1 treatment resulted in a significant reduction in detection of major adducts from 1-amino-6-nitropyrene (1-amino-6-NP), 1-amino-8-nitropyrene (1-amino-8-NP), 2-aminofluorene (2-AF), 2-naphthylamine (2-NA) and 4-aminobiphenyl (4-ABP) modified DNAs, but not following the 32P-postlabelling analysis of 2-acetylaminofluorene (2-AAF) modified DNA. These results suggest that, at least initially, both modifications of the 32P-postlabelling assay should be used for the detection of unknown adducts or for adducts derived from nitroaromatics and aromatic amines.

1-Butanol

Alpha-streptococcal septicemia in leukemic children treated with continuous or large dosage intermittent cytosine arabinoside.

During a 2-year period after the introduction of an intensive chemotherapeutic protocol, alpha-hemolytic streptococci accounted for 75% of all episodes of sepsis among children with acute nonlymphocytic leukemia at our institution. Only one case had occurred in the previous 8 years. Fourteen of 15 episodes of streptococcal sepsis occurred after therapy with either continuous or large dosage intermittent cytosine arabinoside. Eleven episodes occurred at two specific treatment points. Septic episodes were complicated by shock (2 of 15), encephalopathy (2 of 15), pneumonia (3 of 15) and death (1 of 15). Oral mucosal lesions may provide a portal of entry for alpha-hemolytic streptococci. These data suggest that children receiving continuous or large dosage intermittent cytosine arabinoside for treatment of acute nonlymphocytic leukemia may be at increased risk for alpha-hemolytic streptococcal sepsis. Empiric antimicrobial therapy in these children when febrile and neutropenic should include antibiotics effective against alpha-hemolytic streptococci.

Anti-Bacterial Agents

Effects of zinc, iron, cobalt, and manganese on Fusarium moniliforme NRRL 13616 growth and fusarin C biosynthesis in submerged cultures.

The influence of zinc, iron, cobalt, and manganese on submerged cultures of Fusarium moniliforme NRRL 13616 was assessed by measuring dry weight accumulation, fusarin C biosynthesis, and ammonia assimilation. Shake flask cultures were grown in a nitrogen-limited defined medium supplemented with various combinations of metal ions according to partial-factorial experimental designs. Zinc (26 to 3,200 ppb [26 to 3,200 ng/ml]) inhibited fusarin C biosynthesis, increased dry weight accumulation, and increased ammonia assimilation. Carbohydrate was found to be the principal component of the increased dry weight in zinc-supplemented cultures. Zinc-deficient cultures synthesized more lipid and lipidlike compounds, such as fusarin C, than did zinc-supplemented cultures. Microscopic examination showed that zinc-deficient hyphae contained numerous lipid globules which were not present in zinc-supplemented cultures. Addition of zinc (3,200 ppb) to 2- and 4-day-old cultures inhibited further fusarin C biosynthesis but did not stimulate additional dry weight accumulation. Iron (10.0 ppm) and cobalt (9.0 ppm) did not affect fusarin C biosynthesis or dry weight accumulation. Manganese (5.1 ppm) did not affect dry weight accumulation but did increase fusarin C biosynthesis in the absence of zinc. Maximum fusarin C levels, 32.3 micrograms/mg (dry weight), were produced when cultures were supplied manganese, whereas minimum fusarin C levels, 0.07 micrograms/mg (dry weight), were produced when zinc, iron, cobalt, and manganese were supplied. These results suggest a multifunctional role for zinc in affecting F. moniliforme metabolism.

Ammonia

Work-related risk factors for hepatitis B virus infection in personnel of a children's hospital.

Seroprevalence of hepatitis B virus markers was examined in employees participating in patient care at The Children's Mercy Hospital in Kansas City, Missouri. Of 377 workers tested in 1985-86, 36 (9.6%) were seropositive for any marker. Among 285 employees who presumably have only work-related hepatitis B exposure, 14 (4.9%) were seropositive. Age 50 years and older, black race, and education no more than 12 years were associated with seropositivity among workers with work-related exposure. Employees in the clinics, laboratories, emergency room, and operating room had an increased prevalence of hepatitis B markers compared to those in other work locations (8 vs. 2%, p less than 0.05). Traditional risk factors for infection were not predictive of seropositivity. Although the risk of acquiring hepatitis B infection from employment in a children's hospital is low, this study does identify work-related risk factors. Possible reasons for this association are discussed.

Adult

Hepatitis B virus vaccine. Cost-benefit analysis of its use in a children's hospital.

A cost-benefit analysis of routine active immunization against hepatitis B virus (HBV) for 500 nursing personnel at The Children's Mercy Hospital in Kansas City, Missouri, is described. Based on outcomes of HBV infection, local charges for medical care and wages lost from illness, the authors calculate the average cost per case of HBV infection to be $1,990. Including the current system of postexposure prophylaxis and an annual attack rate of 1 percent the current annual cost of HBV infection in The Children's Mercy Hospital is $12,630. The HBV immunization program would have to continue for 15 years before its cumulative costs ($189,133) were exceeded by those of the current system ($189,450). Therefore routine immunization of nurses would not be cost effective in the near future. If, however, a subset of high-risk employees with a 2 percent attack rate is identified, or the cost of the HBV vaccine series fell from the current $103 to $27, then routine immunization would become cost beneficial within 6 years.

Cost-Benefit Analysis

Bilirubinuria: an early indicator of gallbladder hydrops associated with Kawasaki disease.

We report four cases of gallbladder hydrops associated with Kawasaki disease diagnosed over a 7.5 year period. Despite varying clinical presentations, all four of these patients had the common finding of bilirubinuria prior to clinical symptoms or at the time of admission. Review of 40 other cases of Kawasaki disease without evidence of hydrops over this time period revealed that urinalysis had been performed in each and bilirubinuria was present in only one case. Bilirubinuria appears to be an early indicator of hydrops in these patients.

Bilirubin