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Biomedical subjects

C W Jones

Publications and source records attributed to C W Jones.

At least 55 records · Page 3Linked to original sources

Etiology and prevention of topical cardiac hypothermia-induced phrenic nerve injury and left lower lobe atelectasis during cardiac surgery.

Left hemidiaphragm elevation is frequently noted following cardiac surgery employing topical hypothermia. We speculate that contact of the left phrenic nerve with ice causes nerve injury, resulting in left hemidiaphragm paresis or paralysis and left lower lobe atelectasis. Left diaphragm elevation was noted on postoperative chest x-ray examination of 36 of 60 (60 percent) consecutive patients in whom topical cooling of the heart with a cold slush solution was administered prior to use of a cardiac insulation pad (CIP, Shiley Laboratories, Irvine, California). Following the use of the CIP in a similar group of 60 consecutive patients, only five (8 percent) showed evidence of diaphragmatic elevation. The difference in the incidence of diaphragmatic elevation between these two groups is statistically significant (p less than 0.001). A comparison of postoperative left lower lobe atelectasis prior to the use of the CIP was also statistically significant (p less than 0.001). There was no significant difference in the aortic cross-clamp time or the volume of intraaortic cardioplegia used in these two groups. The use of topical cardiac hypothermia has been shown to protect the myocardium. Phrenic nerve injury secondary to the use of ice in this method has been documented. The use of a cold solution without ice chips or slush, or the insertion of a CIP prior to the use of topical cardiac hypothermia (when ice chips or slush are used) decreases the exposure of the phrenic nerve to cold injury and decreases the incidence of paresis of the left diaphragm and resultant atelectasis.

Cardiac Surgical Procedures↗

The pathophysiology of experimental insulin-deficient diabetes in the monkey. Implications for pancreatic transplantation.

In an 11-year study of experimental insulin-deficient diabetes (IDDM) induced in rhesus monkeys by streptozotocin or total pancreatectomy, the authors have found that pathophysiologic changes occur in eye and kidney, which closely resemble the early stages of human insulin deficient diabetes mellitus (IDDM). In addition, morphologic changes of thickening of glomerular capillary basement membrane and expansion of mesangial matrix (by light microscopy) appear within 3 years of onset of hyperglycemia. However, progression to irreversible complications of advanced diabetic nephropathy or proliferative retinopathy, have not occurred. This animal model resembles human disease in that the animals tend to become ketotic unless maintained with exogenous insulin; C-peptide production is low to absent, and large amounts of glycosylated hemoglobin develop within a month of onset. The monkeys differ from humans in the absence of hypertension and hyperlipidemia. The authors suggest that the abnormalities in basement membrane form and function caused by hyperglycemia form the necessary background upon which other factors, such as hypertension and hyperlipidemia, then act to cause irreversible complications. The role of pancreatic transplantation is in prevention of these background changes.

Animals↗

Which cephalosporin for wound prophylaxis? An experimental comparison of three drugs.

An experimental wound model was used to evaluate the effectiveness of cefazolin, cefamandole, and cefotaxime in the prevention of wound infection. Incisions were contaminated with Staphylococcus aureus, Escherichia coli, or a standardized fecal suspension. Regardless of the contaminant employed, the prophylactic use of either cefazolin, cefamandole, or cefotaxime yielded lower concentrations of bacteria in the wounds and fewer infections compared with treatment with saline solution. Within the context of this experimental model, cefazolin proved equally as effective as the newer and more expensive cephalosporins, cefamandole and cefotaxime.

Animals↗

Infectivity of vascular sutures.

Bacterial adherence to vascular sutures was evaluated in vitro using radioactively labeled Staphylococcus aureus. The following suture materials were tested: polypropylene, silicone-treated braided polyester, and Teflon-treated braided polyester. Significantly fewer bacteria adhered to the monofilament polypropylene than either of the braided polyester sutures. There was no significant difference between silicone-treated and Teflon-treated polyester from the standpoint of bacterial adherence. Vascular sutures were evaluated in vivo using a mouse wound model. Sutures were tested with and without knots. When tested without knots, fewer bacteria were recovered from wounds containing polypropylene suture compared to either of the braided materials, although this apparent advantage did not prove to be statistically significant. When studied with knots, the differences among types of suture were much less marked and, again, not significant. The purported contribution of the monofilament structure of a suture to its infection resistance may have been overstated.

Adhesiveness↗

Effect of age on the efficacy of Zn-diethylenetriaminepentaacetic acid therapy for removal of Am and Pu from beagles.

Decorporation of intravenously injected monomeric 241Am and 237+239Pu by the administration of 30 mumole Zn-diethylenetriaminepentaacetic acid (DTPA)/kg each day beginning 2 weeks after radionuclide injection was compared in beagles entered into the experiment when 3 months (juveniles). 1.9 years (young adults), or 10 years (mature adults) old and studied for about 5 months. DTPA therapy was most effective in the juvenile dogs and least effective in the mature adults. Retention of 241Am in the liver decreased from a pretreatment value for adults of about 50% of the injected activity to about 10% in the mature adults and less than 1% in the young adults at 140 days of treatment, while the liver retention of juveniles decreased from pretreatment values of about 16% to undetectable levels by 28 days of treatment. Plutonium retention in the liver decreased from adult pretreatment levels of about 30% of the injected activity (corrected for radioactive decay) to near 10% in the mature adults and 6% in the young adults at 140 days of treatment, while juvenile liver retention decreased from pretreatment values near 15% to undetectable levels by 56 days of treatment. Nonliver Am retention (mainly skeleton) decreased in mature adults from pretreatment values of about 45% of the injected activity to near 25%, in young adults from 35 to 20%, and in juveniles from roughly 70 to 9% by 140 days of DTPA administration. Nonliver Pu retention decreased from pretreatment values of about 50% of the injected activity (corrected for radioactive decay) for mature and young adults to about 30% by 140 days and from 75 to 16% in juveniles over the time period.

Aging↗

243,244Cm studies in C57BL/Do mice.

Three groups of C57BL/Do mice were injected with different activities of 243,244Cm so that the long-term biological effects could be evaluated. The biological retention, R, of injected curium in the skeleton at t days after injection could be represented by the equations R = 0.245e-0.000379t and R = 0.208e-0.000494t for male and female mice, respectively. Effective skeletal retention equations were used to calculate the cumulative mean skeletal dose in rad at 140 days before death in each group of mice. The primary objective of this study was to determine the relative biological effectiveness (RBE) of 243,244Cm compared to 226Ra, using bone sarcoma induction as the end point. Combined data (bone sarcomas per 10(6) mouse-rad) for male and female mice permitted the RBE value +/- SD for 243,244Cm to be calculated as 4.4 +/- 1.8 compared to 1.0 for 226Ra. A comparison of RBE values form a previous study in this mouse strain and the value for 243,244Cm from this study suggests that the trivalent actinides 241Am, 243,244Cm, and 249Cf are about three times less effective for bone sarcoma induction than 239Pu.

Animals↗

The effect of EDTA and related chelating agents on the oxidation of methanol by the methylotrophic bacterium, Methylophilus methylotrophus.

The effects of EDTA and related metal-chelating agents on the respiratory system of the methylotrophic bacterium Methylophilus methylotrophus have been investigated. EDTA completely inhibited whole cell methanol oxidase activity and concomitantly decreased the aerobic steady-state reduction level of cytochrome c, but only partially inhibited methanol dehydrogenase activity. Analysis of the inhibition kinetics of EDTA and other chelating agents on methanol oxidase activity indicated that they were effective in the order CDTA greater than EDTA greater than HEDTA greater than EGTA greater than EDDA, and that they inhibited in an uncompetitive manner. Inhibition by EDTA varied as a function of the ambient cell mass in the assay, and could be partly reversed by the addition of divalent cations. EDTA had no effect on the activity of solubilised methanol dehydrogenase. These and other results indicate that EDTA binds a divalent metal ion, probably Mg2+, which is involved in the functional association of methanol dehydrogenase with the respiratory membrane. This concept is discussed in terms of the electron transfer properties and spatial organisation of the terminal respiratory chain of M. methylotrophus.

Alcohol Oxidoreductases↗

Pathophysiology of the blood-retinal barrier in experimental diabetes. Vitreous fluorophotometry using carboxyfluorescein and fluorescein.

Carboxyfluorescein resembles fluorescein in size and spectral characteristics but is much less lipid soluble. Both dyes were used to differentiate between two groups of factors that influence penetration across the blood-retinal barrier: (1) factors that depend on lipid solubility, such as the area of the barrier, and (2) factors independent of lipid solubility, such as opened intercellular junctions or necrotic cells. Vitreous fluorophotometry was performed on normal and diabetic rats after injection of either dye. After the results were adjusted for sources of error, midvitreous-plasma dye ratios for carboxyfluorescein and fluorescein were of the same order of magnitude in normal rats. Ratios for both dyes increased in diabetic rats, and the increases were similar in magnitude. Our results suggest that lipid solubility contributes little to inward transport of these dyes in both the normal and diabetic states.

Animals↗

A comparison of topical and systemic cefazolin for wound prophylaxis.

An experimental wound infection model was used to compare the effectiveness of topical and systemic cefazolin in the prevention of wound infection. Studies were conducted using both Staphylococcus aureus and Escherichia coli as the contaminating organisms. Regardless of the wound pathogen studied, there were no significant differences between topical and systemic cefazolin with regard to wound bacterial concentrations and the incidence of wound infection.

Administration, Topical↗

Peripheral glomerular basement membrane thickness in the normal and diabetic monkey.

Diabetes of varying severity was induced in a colony of rhesus monkeys by streptozotocin injection or total pancreatectomy. Peripheral glomerular basement membrane thickness was determined using a reproducible and efficient procedure. Four groups of monkeys formed on the basis of sex, age, severity, and duration of treatment were analyzed. In control animals peripheral glomerular basement membrane thickness increased with age from 3 to 7 years, whereas monkeys aged 11 to 18 years had relatively constant measurements. Mean values did not differ between control and age-matched non-insulin-dependent streptozotocin-injected animals treated up to 13 years previously. Insulin-dependent streptozotocin-treated or pancreatectomized monkeys with a treatment duration of 10 to 27 months were not different from age-matched controls, whereas insulin-dependent monkeys treated 2 to 12.5 years earlier showed significantly increased peripheral glomerular basement membrane thickness. The peripheral glomerular basement membrane thickening observed in the insulin-dependent monkey is easily measured and is similar to changes observed in human diabetes mellitus.

Analysis of Variance↗

228Th retention and dosimetry in beagles.

Total-body and skeletal retention of 228Th were determined in a group of 104 young adult male and female beagles for about the first 7 years after the injection of 0.00159 to 2.76 muCi/kg. Ratios of 224Ra / 228Th , 212Pb / 228Th , and 212Bi / 228Th in the skeleton and in soft tissues of 20 beagles were measured as a function of time after injection. A humerus, femur, and ulna from 20 dogs dying 7 to 554 days after injection were sectioned, and the 228Th concentration was obtained for each piece. Percentage biological retention in the skeleton of 228Th at t days after injection could be described as 68.1 e-0. 000180t . Ratios of daughter-to-parent activity in soft tissue showed no definite trend with dose level or time and averaged Ra/Th = 0.56, Pb/Th = 0.83, and Bi/Th = 0.91, whereas the ratios for the skeleton varied with both dose level and time. Ratios of activity in the skeleton from lowest to highest dose level after 2 years following injection ranged between Ra/Th = 0.88 to 0.95, Pb/Th = 0.78 to 0.92, and Bi/Th = 0.77 to 0.90. Retained 228Th was deposited most heavily in parts of the skeleton with much trabecular bone, much bone surface area, and high bone remodeling rates. No changes in this deposition pattern could be discerned during the 554 days over which the measurements of sectioned long bones were made.

Animals↗

Retention and dosimetry of injected 241Am in beagles.

Equations have been derived, from the results of total-body and partial-body counting and gamma-ray counting of individual bones and soft tissues, which describe the retention of injected 241Am in the liver, in the nonliver tissue (including skeleton), and in the skeleton of young adult beagles. Retention was found to be dependent upon injection level, and different sets of equations were developed for dogs given about (a) 2.8 microCi/kg (b) 0.9 microCi/kg (c) 0.3 microCi/kg, and (d) 0.1 microCi/kg and less. Liver rention, RL, was characterized by a single exponential equation of the form RL = ce-beta t, with c = 0.49 +/- 0.04 and beta = a function of injection level. Nonliver tissue was assigned a retention equation of the form RNL = d + alpha + J(l - e-mt), with d = 0.102 +/- 0.024 e-1.22t, alpha = 0.41 +/- 0.04, and both J and m as a function of injection level. Skeletal retention was found to be about 0.885 +/- 0.037 of nonliver retention with no significant dependence upon either injection level or time after 241Am injection. Dosimetry equations based on these retention expressions were derived. Individual bones of 55 beagles were assayed at death for their 241Am content for a determination of 241Am distribution within the skeleton.

Americium↗

Removal of Pu and am from beagles and mice by 3,4,3-LICAM(C) or 3,4,3-LICAM(S).

Decorporation of Pu and Am by tetrameric catechoylamide (CAM) ligands has been investigated in beagles and mice. Eight dogs were injected intravenously (iv) with 237 + 239Pu(IV) + 241Am(III) citrate, and 30 min later, pairs of dogs were injected iv with 30 mumole/kg of 3,4,3-LICAM(C) [N1,N5,N10,N14-tetrakis(2,3-dihydroxy-5-sulfobenzoyl)tetr aazatetradecane, tetrasodium salt], 3,4,3-LICAM(S) [N1,N5,N10,N14-tetrakis(2,3-dihydroxy-4-carboxybenzoyl)te traazatetradecane, tetrasodium salt], CaNa3-DTPA, or each of the latter two ligands. Blood was sampled, and excreta were collected for 7 days, at which time the dogs were sacrificed and nuclide retention in liver and nonliver tissue was measured. Groups of five mice were each given 238Pu(IV) or 241Am(III) citrate iv; 3 min later 30 mumole/kg of a CAM ligand was injected intraperitoneally, mice were killed at 24 hr, and separated excreta and tissues were analyzed. In the dogs, average retention at 7 days of the injected Pu and Am, respectively, was as follows: 12 and 70% after treatment with a CAM ligand alone; 30 and 20% after DTPA; 12 and 20% after LICAM(S) plus DTPA; 90 and 89% without a ligand. In the mice, mean retention of the injected Pu and Am, respectively, was as follows: 14 and 66% after treatment with LICAM(C); 21 and 54% after LICAM(S); 91 and 87% without a ligand. In both species, about 99% of net Pu excretion (excretion with ligand - excretion without ligand) promoted in 24 hr by DTPA or LICAM(S) was in the urine, whereas about 10% of net Pu excretion promoted by the less hydrophilic LICAM(C) was in feces. Delayed excretion of both Am and Pu was significant in all ligand-treated dogs. Comparison of the nuclide content of tissues of ligand-treated mice with those of mice killed 3 min after nuclide injection indicated that the CAM ligands chelated circulating Pu and Am and prevented further deposition. In addition, the CAM ligands removed much of the presumably loosely bound Pu present in liver and skeleton at the time of ligand injection. LICAM(C) was more effective in removing Pu from liver and LICAM(S) was more effective in the skeleton. Moderate to severe uremia and histological evidence of cell killing in the distal tubules of the kidney were observed in the four dogs injected once with 30 mumole/kg of LICAM(S).(ABSTRACT TRUNCATED AT 400 WORDS)

Americium↗

The terminal respiratory chain of the methylotrophic bacterium Methylophilus methylotrophus.

Cytochrome oxidase o has been isolated from the obligately aerobic, methylotrophic bacterium Methylophilus methylotrophus in the form of a cytochrome cL-o complex. The latter is comprised of cytochrome cL (Mr 21 000) and cytochrome o (Mr 29 000) in a 1-2:1 ratio, possibly in association with one or more minor polypeptides; the complex exhibits a high ascorbate-TMPD oxidase activity which is inhibited non-competitively by cyanide (Ki approximately 2 microM). In contrast, the oxidation of methanol by whole cells is inhibited uncompetitively by cyanide (Ki approximately 4 microM), thus indicating the involvement in methanol oxidation of cytochrome oxidase aa3 rather than o.

Bacteria↗

Protection from postsplenectomy sepsis: Effect of prophylactic penicillin and pneumococcal vaccine on clearance of type 3 Pneumococcus.

The intravascular clearance of type 3 Streptococcus pneumoniae was studied in Sprague-Dawley rats. One hundred animals were divided into the following five equal groups: I--splenic mobilization, II--splenectomy, III--splenectomy plus pneumococcal vaccine, IV--splenectomy plus 50,000 U of penicillin prophylaxis, V--splenectomy plus 300,000 U of penicillin prophylaxis. Bacteremia was induced by intraperitoneal injection of 10(6) type 3 S. pneumoniae. Serial cultures of peripheral blood were obtained. Splenectomy produced significant impairment of intravascular clearance of Pneumonococcus compared to clearance in control animals (P less than 0.01). Neither dose of penicillin, administered prophylactically prior to induction of bacteremia, significantly altered pneumococcal clearance of asplenic animals. Administration of polyvalent pneumococcal vaccine to splenectomized rats resulted in measurable antibody titers. More importantly, such immunization of asplenic animals significantly improved pneumococcal clearance compared to clearance in asplenic, nonimmunized rats (P less than 0.03). Although in both groups I and III animals S. pneumoniae organisms were effectively removed from the peripheral blood, the clearance curves are significantly different (P less than 0.01). This represents the difference between phagocytosis by the reticuloendothelial cells of the liver and those of the spleen.

Animals↗