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Biomedical subjects

R L Baker

Publications and source records attributed to R L Baker.

At least 19 recordsLinked to original sources

Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature.

Histoplasmosis is a serious opportunistic infection in patients with AIDS, often representing the first manifestation of the syndrome. Most infections occurring within the endemic region are caused by exogenous exposure, while those occurring in nonendemic areas may represent endogenous reactivation of latent foci of infection or exogenous exposure to microfoci located within those nonendemic regions. However, prospective investigations are needed to prove the mode of acquisition. The infection usually begins in the lungs even though the chest roentgenogram may be normal. Clinical findings are nonspecific; most patients present with symptoms of fever and weight loss of at least 1 month's duration. When untreated, many cases eventually develop severe clinical manifestations resembling septicemia. Chest roentgenograms, when abnormal, show interstitial or reticulonodular infiltrates. Many cases have been initially misdiagnosed as disseminated mycobacterial infection or Pneumocystis carinii pneumonia. Patients are often concurrently infected with other opportunistic pathogens, supporting the need for a careful search for co-infections. Useful diagnostic tests include serologic tests for anti-H. capsulatum antibodies and HPA, silver stains of tissue sections or body fluids, and cultures using fungal media from blood, bone marrow, bronchoalveolar lavage fluid, and other tissues or body fluids suspected to be infected on clinical grounds. Treatment with amphotericin B is highly effective, reversing the clinical manifestations of infection in at least 80% of cases. However, nearly all patients relapse within 1 year after completing courses of amphotericin B of 35 mg/kg or more, supporting the use of maintenance treatment to prevent recurrence. Relapse rates are lower (9 to 19%) in patients receiving maintenance therapy with amphotericin B given at doses of about 50 mg weekly or biweekly than with ketoconazole (50-60%), but controlled trials comparing different maintenance regimens have not been conducted. Until results of such trials become available, our current approach is to administer an induction phase of 15 mg/kg of amphotericin B given over 4 to 6 weeks, followed by maintenance therapy with 50 to 100 mg of amphotericin B given once or twice weekly, or biweekly. If results of a prospective National Institutes of Allergy and Infectious Disease study of itraconazole maintenance therapy document its effectiveness, alternatives to amphotericin B may be reasonable.

Acquired Immunodeficiency Syndrome

In vivo tyrosine hydroxylation rate in retina: effects of phenylalanine and tyrosine administration in rats pretreated with p-chlorophenylalanine.

p-Chlorophenylalanine was administered to rats to inhibit hepatic phenylalanine hydroxylase activity. Two days later, phenylalanine injection was noted to produce substantial increases in serum phenylalanine levels, and relatively modest increments in serum tyrosine levels. Rats injected with p-chlorophenylalanine 2 days earlier showed a normal light-induced activation of retinal tyrosine hydroxylase activity in vivo, measured as dihydroxyphenylalanine accumulation following pharmacologic inhibition in vivo of aromatic L-amino acid decarboxylase activity. In addition, tyrosine injection into p-chlorophenylalanine-treated rats in the light produced anticipated increments in retinal tyrosine hydroxylation rate, showing the enzyme to be functionally normal. The acute administration of phenylalanine (62.5-500 mg/kg i.p.) to p-chlorophenylalanine-treated rats produced dose-related increments in retinal phenylalanine. In vivo tyrosine hydroxylation rate in retina was normal at all doses below 300 mg/kg. However, at the highest dose (500 mg/kg), when retinal phenylalanine levels were almost 5-times normal tyrosine hydroxylation rate consistently fell (to about half-normal values). These results demonstrate that very large elevations in tissue phenylalanine levels do not stimulate tyrosine hydroxylation in vivo, and that at extremely high levels phenylalanine inhibits tyrosine hydroxylation rate.

Animals

Interrelationships of vitamin D, bone metabolism and blood calcium concentration in the chick.

It is not known if the effects of vitamin D deficiency on chick bone are due to direct actions of the vitamin or if they are secondary to other changes, such as hypocalcemia. Day-old cockerels were fed either a rachitogenic diet containing no Ca (-D-Ca), 1.4% Ca (-D), or 3% Ca (-DHiCa) and given corn oil (-D groups) or vitamin D3 in corn oil (+D and +D-Ca) p.o. for up to 21 days. Radii were harvested and incubated for 6-8 h in a defined medium. Medium samples were taken every 2 h and analysed for Ca, Pi and lactate. Some bones were incubated in a respirometer to measure O2 consumption. Compared to +D, -D birds showed evidence of D deficiency by decreased plasma Ca concentration (35%), bone and body weight (43%) and Ca release from bone (70%) and by histological changes in bone characteristic of rickets. Increases were seen in total and bone alkaline phosphatase activity in plasma (270 and 706%, respectively), Pi release (23%), O2 consumption (23%) and lactate production (52%) by the -D radii. The marked hypocalcemia seen in the -D chicks did not occur in -DHiCa birds. Nevertheless, bone and body weights were decreased in this group and bone lactate production, O2 consumption and total and bone alkaline phosphatase in plasma were increased. Rachitic bone lesions were only partially corrected by the high-Ca diet. Release of Ca and Pi from the -DHiCa bone was not different than from +D radii. Comparing +D-Ca and -D-Ca groups with +D chicks, both were hypocalcemic with decreased bone weight, body weight and bone Ca release, while showing elevated lactate production and Pi release. The only difference between the +D-Ca and -D-Ca groups was a 50% decrease in Ca release by -D-Ca bone. The results suggest that in chicks: (1) some, but not all, of the effects of vitamin D deficiency on bone can be corrected by normalizing plasma Ca and (2) evaluation of the effects of vitamin D deficiency on bone may require hypocalcemia, since some responses are masked by normocalcemia.

Animals

In vivo effects of Sn-1,2-dioctanoylglycerol, TPA and A23187 on hamster cheek pouch epithelium.

Cheek pouches of male Syrian golden hamsters were topically treated with a single dose of TPA (.5 microgram), calcium ionophore A23187 (75 micrograms) or Sn-1,2-dioctanoylglycerol (DiC8) (500 micrograms) dissolved in 0.25 ml acetone. Acetone-treated animals served as controls. After 48 h the mitotic index for the control group was 1.1 +/- 0.1 per 1 mm of the basement membrane length. All the test congeners exhibited higher mitotic indices than controls: TPA (4.8 +/- 0.4), A23187 (3.9 +/- 0.3), DiC8 (2.1 +/- 0.2). All groups exhibited an increase in the epithelial thickness manifested by cellular hyperplasia. The treatment of the pouches with the anti-inflammatory agent fluocinolone acetonide inhibited the mitogenic and hyperplasiogenic affects on the epithelium induced by the various test chemicals. These studies indicate a possible role of calcium-phospholipid dependent protein kinase (protein kinase C) in the mediation of oral epithelial cell proliferation.

Animals

Birth weight, dystocia and calf mortality in some New Zealand beef breeding herds.

Calf mortality data were summarized from four experiments, including a total of 15,694 birth records over 39 herd-years. Two experiments at Waikite and Waikeria were long-term, straightbred Angus and Hereford selection trials and the other two, at Goudies and Tokanui stations, were comparisons of 11 sire breeds mated to Angus and Herefore cows. The objective of the analyses was to study the relationship between birth weight (BW) and calf mortality for both calf sexes and for different dam age or parity groups. Overall calf death rates from birth to weaning were greater (P less than .01) from 2-yr-old than from older dams at Waikite (13.4 vs 5.3%) and Waikeria (14.7 vs 5.2%). Sex differences in death rate within 2 d of birth were small for calves from older dams. Death rate of males vs females from 2-yr-old dams were 9.1 vs 3.2% (Waikite) and 17.7 vs 10.5% (Waikeria). Mature Angus dams at Goudies had 3.7% calf deaths at birth (4.9 vs 2.4% for males vs females), a further 1.8% calf deaths to weaning and 4.6% assisted births. The BW of calves at Waikite from Angus 2-yr-old vs older dams averaged, respectively, 6.8 and 6.5% of their dam's precalving live weights. Corresponding figures for Waikeria Angus were 7.8 and 6.6% and for Waikite Herefords, 7.3 and 6.9%. Quadratic regressions revealed that, on a whole-herd basis, a small increase in BW would have no effect on total mortality at Waikeria and would decrease total mortality at Waikite; regression lines were different in shape and minimum value for calves from the two dam age groups. Quadratic models also provided an adequate fit to data from Goudies and Tokanui. There was no particular threshold BW.

Animals

Microsurgical anatomy and related techniques to an anterolateral transthoracic approach to thoracic disc herniations.

The microsurgical anatomy and related techniques of a modified anterolateral transthoracic approach to the thoracic disc space is presented. This procedure was performed on at least three thoracic levels of 12 cadavers within a few hours after death. Such an approach allows a safe decompression of the spinal cord and roots under full visual control. There is minimal risk to radiculomedullary vessels, minimal osteoligamental resection, and no compromise of stability of the spinal column. Therefore, this procedure does not require surgical stabilization of the spinal column, postoperative bracing, or prolonged bed rest. The difference between this approach and anterolateral transthoracic, posterolateral, and transpedicular approaches is discussed.

Evaluation Studies as Topic

Interactions between Naegleria fowleri and Legionella pneumophila.

Using electron microscopy we documented some of the intracellular events that occur in Naegleria fowleri suspended in Page amoeba saline after ingestion of Legionella pneumophila. Photomicrographs showed intracellular vacuoles containing bacteria in the process of binary fission that was accompanied by alignment of mitochondria and ribosome-like structures along the vacuole membrane. Although these intracellular events are remarkably similar to that seen in Legionella replication within human monocytes, we could not demonstrate an increase in the number of bacteria by CFU or dark-field microscopy. However, when the Naegleria cells were allowed to ingest Legionella cells while suspended in amoeba culture medium, the number of bacteria increased, and this was contingent upon the presence of viable amoebae.

Amoeba

1,25-Dihydroxyvitamin D3 decreases alkaline phosphatase activity in cultures of embryonic chick tibiae.

The influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the alkaline phosphatase (AlPase) activity in cultures of chick embryo tibiae was determined. A dose-related, decreased release (30-47%) of AlPase from the bones was seen with the metabolite at 0.05-0.5 ng/ml of medium with a similar effect on the bone content of enzyme. The highest dose (1 ng/ml) decreased the bone content by 38% without further effect on AlPase release. Combining a low level of 1,25(OH)2D3 (0.05 ng/ml) with parathyroid hormone (PTH, 1 U/ml) reduced release of enzyme additively, but caused no greater decrease in bone content of activity than PTH alone. No effects of 24,25-dihydroxyvitamin D3 [24,25(OH)2D3, 0.5 ng/ml] on release or bone content of AlPase were found when this metabolite was added alone or in combination with PTH; however, 24,25(OH)2D3 did prevent the inhibition of release of AlPase when added with 1,25(OH)2D3. After a 1-day exposure to 1,25(OH)2D3, continued incubation in metabolite-free medium resulted in an 89% increase in bone content of AlPase. The results suggest that 1,25(OH)2D3, as well as PTH, may have regulatory roles in bone growth through their effects on AlPase.

Alkaline Phosphatase

Cefmenoxime: clinical evaluation.

Cefmenoxime was evaluated in an open trial consisting of 41 patients. Forty infections in 36 patients could be evaluated. Thirteen patients had pyelonephritis due to Escherichia coli (two bacteremic), Pseudomonas aeruginosa, Klebsiella pneumoniae, or Streptococcus faecalis; all improved and 12 of 13 were clinically cured, but one relapse (S. faecalis) occurred at two weeks. Six patients with cystitis due to E. coli, Citrobacter freundii, Serratia marcescens, P. aeruginosa, or S. faecalis all improved, but relapse or reinfection, or both, occurred in five due to P. aeruginosa, S. faecalis, C. fruendii, or E. coli. Neurogenic bladder or other complications were present in five of 13 patients with pyelonephritis and five of six with cystitis. Ten patients with pneumonia and one with tracheobronchitis due to Hemophilus influenzae, S. pneumoniae, S. agalactiae, or Neisseria meningitidis all improved and seven had resolution without relapse, but P. aeruginosa emerged in two patients, one of whom died. Eight soft tissue infections due to Staphylococcus aureus, Peptococcus prevotti, Streptococcus species, or infections of mixed origin resolved in six. Sterility of blood cultures was obtained in one patient with endocarditis due to S. anginosus, but other therapy was substituted. Clinical resolution of the toxic shock syndrome and subsequent negative endocervical cultures for S. aureus occurred in one. Granulocytopenia of unverified cause in four (with less than 1,500 mm3) and two (with less than 2,000 mm3) was reversible. Headache during treatment occurred in six patients and a possible disulfiram-like effect in three. Elevations of serum glutamic oxalacetic transaminase and alkaline phosphatase occurred in five, Coombs' positivity in two, and diarrhea in three. Clinical efficacy of cefmenoxime was significant. Possible side effects require further study.

Abscess

Correlation of in vitro activities of cephalothin and ceftazidime with their efficacies in the treatment of Staphylococcus aureus endocarditis in rabbits.

Rabbits with Staphylococcus aureus endocarditis were treated with cephalothin or ceftazidime to determine whether differences in in vitro activity would result in differences in in vivo efficacy. Antibiotics were administered in doses equivalent to maximum recommended human doses, and results of laboratory tests to predict antimicrobial efficacy were determined during treatment. Cephalothin and ceftazidime MICs for the challenge strain were 0.5 and 8 micrograms/ml, respectively. MBCs were 32 and greater than 128 micrograms/ml, respectively. With peak sera, laboratory results (means) for cephalothin and ceftazidime were as follows: ratios of concentration in serum to MIC, 300 and 16; ratios of concentration in serum to MBC, 4.8 and less than 1; bacteriostatic antibacterial activity titers in serum, 1:256 and 1:16; and bactericidal antibacterial activity titers in serum, 1:16 and 1:4, respectively. Trough sera contained little or no measurable antibiotic and had no antibacterial activity. Both cephalothin and ceftazidime were efficacious in the treatment of infected rabbits. There were no statistically significant differences in efficacy as defined by survival, eradication of bacteremia, or sterilization of cardiac vegetations. Results of laboratory tests which quantitated antimicrobial activity did not correlate with efficacy, either independent of antibiotic or adjusted for antibiotic. Despite their lesser in vitro activities, the new cephalosporins may be equivalent to the older cephalosporins for treating staphylococcal infections in humans, when administered in maximum recommended doses.

Animals

Absence of periodontitis in a population of insulin-dependent diabetes mellitus (IDDM) patients.

The prevalence of periodontitis was studied in a population of insulin-dependent diabetes mellitus (IDDM) patients, aged 10-18, with a variety of disease durations and levels of control. The sample included a number of patients with poorly controlled IDDM of long duration. None of the patients had radiographic signs of periodontitis. When considered in conjunction with previously reported studies, the findings suggest that populations of IDDM patients may differ in susceptibility to the periodontal diseases; thus, generalizations concerning prevalence based on only a few studies may be inappropriate.

Adolescent

Estimates of heritabilities and of genetic and phenotypic correlations among growth and reproductive traits in yearling Angus bulls.

Data from Nichols Farm, Anita , Iowa, collected from 1975 through 1980, were used. Angus Herd Improvement Records with birth, weaning and yearling weights were obtained for 717 bulls by 80 sires. Also available, from Hawkeye Breeders Service, Des Moines , Iowa, were measures of sperm concentration and motility, percentage live sperm, number of sperm/ml, semen score and quality and scrotal circumference on the bulls as yearlings . Heritabilities and genetic and phenotypic correlations were estimated for the above traits from variance and covariance components calculated by restricted maximum likelihood. Estimates of heritability for birth, weaning and yearling weight were .70, .46 and .49, respectively. Heritability estimates for the semen traits were low (0 to .24); the estimate for scrotal circumference was .36. In general, genetic and phenotypic correlations among semen traits were high and favorable, with absolute values ranging between .49 and 1.11. Genetic correlations between semen traits and scrotal circumference were low; corresponding phenotypic correlations were moderate. Semen traits were lowly correlated phenotypically with growth traits (-.08 to .08) and genetic correlation estimates were variable. Estimates of phenotypic and genetic correlations suggested that yearling scrotal circumference was more closely related to yearling weight than to either birth or weaning weight. Estimates of phenotypic and genetic correlations between scrotal circumference and yearling weight were .26 and .68, respectively.

Animals

An electron microscopic study of human neutrophils obtained by crevicular washing.

The Application of electron microscopic methods to the study of neutrophils obtained from single sites by crevicular washing is described. A subsequent preliminary study of neutrophils and neutrophil-bacterial interactions at advanced lesions in patients with juvenile periodontitis and juvenile diabetes indicated that the neutrophils are phagocytically active at these sites. It is suggested that in vitro assays of crevicular neutrophil function may exaggerate the extent of impairment of phagocytosis because of cellular activity which has taken place prior to the time of sampling.

Adolescent

Material adherent to probes during a periodontal examination. Light and electron microscopic observations.

The material adherent to a periodontal probe during the examination of deep periodontal pockets was studied with light and electron microscopy. Most of the specimens contained bacteria with a morphology which has been associated with a pathogenic flora. The findings suggest that periodontal probes may have the potential of transmitting pathogenic bacteria from involved sites to other sites in the mouth, although it remains to be demonstrated that this will result in actual implantation of the organisms at the new sites.

Adult

An ultrastructural study of macrophage-mediated resorption of calcified tissue.

Ultrastructural observations on macrophage-mediated resorption of calcified tissue of killed fetal long bones are described and correlated with increased 45Ca release into the medium. Macrophages disrupt calcified tissue extracellularly and appear to engulf large fragments of mineralized matrix. Ruffled borders, which are common features of osteoclasts at sites of resorption of bone, do not develop in macrophages. However, clear zones are seen in macrophages as well as osteoclasts. These findings provide additional evidence for non-osteoclast-mediated resorption of calcified tissue.

Animals