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Biomedical subjects

C R Smith

Publications and source records attributed to C R Smith.

At least 271 records · Page 15Linked to original sources
PubMed1985

Colchicine effect on bile canalicular motility: long-term study using isolated cultured hepatocytes and time-lapse cinephotomicrography.

The effect of colchicine on spontaneous in vitro contractions of bile canaliculi was assessed using time-lapse cinephotomicrography. Colchicine 2.5 microM and/or taurocholate 5 microM were added to the culture medium. The experiment was long-term, lasting for 13 h. Frame-by-frame analysis revealed that colchicine, after a lag period of 4 h, suppressed the number of contractions over the remainder of the 13-h experimental period, even in the presence of taurocholate (p less than 0.001). The number of contractions per hour decreased in both the colchicine and combined colchicine-plus-taurocholate-treated groups compared to untreated and taurocholate-treated controls. These results do not necessarily mean that colchicine has an effect on the contractile process per se, since the contractions, when they occurred, appeared normal. It is likely that the canalicular motility events are related to bile secretion. The reduction in contractions after a lag period likely indicates that secretion is impaired, and hence the need for contractions is reduced. These results support the view that for normal canalicular bile secretory function, microtubules as well as a normal microfilament system are required.

Animals↗
PubMed1985

Lack of evidence for interaction between tobramycin and shock in their effect on renal function.

We sought to determine whether there was an interaction between aminoglycoside use and shock in their effect on renal function among seriously ill patients suspected of having gram-negative sepsis. Serial serum creatinine determinations were used to estimate changes in creatinine clearance rates in 179 patients entered onto a prospective randomized trial of tobramycin-nafcillin versus cefotaxime. A 25% decline in estimated creatinine clearance was considered to be clinically important. Univariate chi-square analysis showed that both shock (P less than 0.01) and tobramycin use (P less than 0.001) were independently associated with decline in estimated creatinine clearance. A two-way analysis of variance showed that both shock (F = 10.44, P less than 0.01) and tobramycin use (F = 42.6, P less than 0.001) continued to be significantly associated with renal dysfunction in the presence of each other, but there was no significant interaction between shock and tobramycin in their effect (F = 0.62, P less than 0.43). A multiple logistic regression with an interaction term representing the occurrence of shock and tobramycin use simultaneously yielded similar results. Our study provided no analytic evidence supporting the existence of an interaction between shock and aminoglycoside use in their effect on renal function.

Analysis of Variance↗
PubMed1985

Effect of low level direct current on in vivo tumor growth in hamsters.

A preliminary study has been carried out on the effect of low level direct current on tumor growth using an experimental tumor model developed from an amelanotic melanoma (T1-4) in the hamster. An inoculum of 2 X 10(6) viable cells was injected s.c. on day 0; on day 7 the tumor-bearing animals were randomly divided into treatment and control groups. On days 7 through 11 inclusive, the treatment group was subjected to electrical current (direct current) at levels from 0.1 to 2.4 mA, for 1 h/day under general anesthesia. Control groups were subjected to the same procedures, with the exception that the electrodes were not connected to the current source. On day 14, the animals were killed and autopsied; their tumors were removed, weighed, and sectioned. Treated tumors decreased in mass (as a percentage of controls) from 89% at 0.1 mA to 2% at 2.4 mA. Increased necrosis of the treated tumors was noted macroscopically and microscopically. On histological examination, it was observed that a thin rim of viable cells remained around the periphery after treatment even at the highest current levels. Similar results were obtained with both stainless steel and platinum-30% iridium electrodes. In separate experiments where the animals were allowed to survive after a treatment period (1 h/day for 5 days at 2.4 mA), the viable cells at the periphery developed into tumors whose mass at 28 days posttreatment averaged only 52% of that of the control tumors. The mechanism of growth reduction is unknown but hyperthermia was shown not to be a factor.

Animals↗
PubMed1985

Reduced infection in cardiac transplant recipients.

Despite the introduction of cyclosporine immunosuppression, infectious morbidity and mortality in cardiac transplant recipients has remained high. To decrease infectious complications, lower doses of cyclosporine and oral prednisone than previously reported were used for maintenance immunosuppression in 22 operative survivors of orthotopic cardiac transplantation. Twelve infections occurred in 10 patients followed 8 +/- 5 months. Fifty-five percent of patients had no infectious complications. There were no deaths. Seven infections required hospitalization for a mean of 12 days. Infection rate per patient for the first 3 months after transplantation was 0.23 compared with a range of 0.82 to 1.06 in series previously reported in which higher doses of steroids were used. Lowered doses of steroid can be used for maintenance immunosuppression and treatment of rejection with acceptable short-term results. With such a protocol, a low incidence of controllable infectious complications with no deaths has been observed.

Adolescent↗
PubMed1985

Technique for primate heterotopic cardiac xenotransplantation.

Heterotopic cardiac transplantation in the primate is a valuable method for the evaluation of immuno-suppressive regimens. This report describes our technique for heterotopic transplantation of cardiac grafts into the neck of baboons. Preliminary experience with cross-genus cardiac transplantation in the nonhuman primate is discussed.

Animals↗
PubMed1985

Coordination of the contractile activity of bile canaliculi. Evidence from spontaneous contractions in vitro.

Rat hepatocytes, when isolated and maintained in primary culture, are capable of producing forceful contractions of their bile canaliculi, with contractions occurring on a regular basis once every 5.5 minutes. To determine whether the contraction of one bile canaliculus affected the contraction of a neighboring canaliculus, cinephotomicrographic studies of pairs of contiguous canaliculi were undertaken. The activity of 10 pairs of contiguous canaliculi, and 10 pairs of noncontiguous canaliculi which served as a control group, was recorded for a period of 12.5 hours at the rate of 1 frame every 15 seconds. Using frame-by-frame analysis of this period of observation, we determined the time of contraction of each of the canaliculi in the pairs. Cross-correlations were obtained for the contraction times of each of the 10 pairs of contiguous canaliculi and 10 control pairs. A peak in activity was found, with that peak occurring five frames or 75 seconds from the midline, whereas the noncontiguous controls showed no correlation in contractile activity. This finding indicates that, when one bile canaliculus contracts, a neighboring canaliculus is likely to contract after an interval of 1.25 minutes. That there is coordination of contractile activity of bile canaliculi suggests that, within the intact liver lobule, ordered motility function of the bile canaliculi may facilitate bile flow.

Animals↗
PubMed1985

Coordination of the contractile activity of bile canaliculi. Evidence from calcium microinjection of triplet hepatocytes.

The discovery that bile canaliculi are capable of spontaneous contractile activity has led to their use in the investigation of the physiology of the liver cell. The contraction of a bile canaliculus is dependent on the network of actin, which is found in the pericanalicular region of the hepatocyte, and agents that inhibit actin filaments interfere with canalicular contraction. Injection of calcium directly into the cytoplasm of one hepatocyte of a cell pair results in contraction. Injection of calcium directly into the cytoplasm of one hepatocyte of a cell pair results in contraction of the canaliculus. To determine whether the contractile activity of adjacent bile canaliculi was coordinated, calcium was injected into one cell of a group of three hepatocytes that formed two neighboring bile canaliculi. Calcium microinjection resulted in contraction of the bile canaliculus contiguous with the microinjected cell and was followed by a contraction of the second, adjacent canaliculus. These secondary contractions occurred after an interval of approximately 45 seconds. The finding that bile canalicular contractions are coordinated with contractions occurring in a sequential fashion supports the hypothesis that, within the liver lobule, transport of bile within the canalicular network results from the coordinated contractions of the canaliculi.

Animals↗
PubMed1984

Open lung biopsy in immunocompromised children with pulmonary infiltrates.

We assessed the diagnostic value of 46 open lung biopsies performed on 44 immunocompromised children with acute pulmonary infiltrates. We assessed also how frequently the results of these biopsies resulted in a change of therapy. A histological diagnosis was established for all of our patients. At least one infectious agent was found in 72% of the specimens. Nonspecific interstitial pneumonitis was observed in 24%, and two biopsy specimens demonstrated relapsed malignancy. In this series, the empirically chosen preoperative therapy was altered on 30 (65%) of 46 occasions. Specific therapy, not provided before surgery, was initiated in 26% of our patients, and broad-spectrum preoperative therapy was discontinued in 43%. Open lung biopsy is a valuable diagnostic procedure in the immunocompromised host with pulmonary infiltrates.

Adolescent↗
PubMed1984

Association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia.

To determine the association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia, the case reports of 37 patients from four prospective, randomized, controlled trials of gentamicin, tobramycin, and amikacin were analyzed. Twenty (54 percent) of these patients had a favorable outcome. Patients with maximal one-hour postinfusion (peak) levels of 7 micrograms/ml or greater for gentamicin and tobramycin or 28 micrograms/ml or greater for amikacin more often had successful outcomes (14 of 20, 70 percent) than those with levels less than this (six of 19, 32 percent) (p less than 0.006). Patients with overall mean peak levels of 6 micrograms/ml or greater for gentamicin and tobramycin or 24 micrograms/ml or greater for amikacin more often had successful outcomes than those with levels less than this (six of 17, 35 percent) (p less than 0.04). The initial patient temperature, serum urea nitrogen/creatinine ratio, initial polymorphonuclear leukocyte count, and age were also associated with outcome; but by multivariate analysis, achieving an adequate peak concentration was the most important discriminating factor. These results suggest the potential importance of achieving adequate aminoglycoside levels in patients with gram-negative pneumonia.

Adult↗
PubMed1984

Risk factors for the development of auditory toxicity in patients receiving aminoglycosides.

Risk factors for the development of auditory toxicity in patients receiving aminoglycosides were determined from the analysis of 135 patients enrolled in three prospective, randomized, double-blind clinical trials of gentamicin, tobramycin, and amikacin. Auditory toxicity, defined as a decrease in auditory acuity of greater than or equal to 15 dB, occurred in 30 patients (22.3%). Patients with auditory toxicity underwent therapy for a longer period, were more likely to be bacteremic, and had, on the average, a higher temperature (P less than 0.05). Using stepwise discriminant analysis, we selected these factors with liver dysfunction and the serum urea nitrogen:serum creatinine ratio in a function that accurately discriminates between toxic and nontoxic patients. Factors not adding significantly to the predictive accuracy of the equation were plasma aminoglycoside levels, aminoglycoside type, furosemide use, diabetes, age, sex, renal function, initial auditory acuity, hematocrit value, and shock. This analysis may be important both for determining the pathophysiology of auditory toxicity and for the prognostic stratification of patients receiving aminoglycosides in clinical trials.

Amikacin↗
PubMed1984

The association of aminoglycoside plasma levels with mortality in patients with gram-negative bacteremia.

To determine the association of aminoglycoside levels with mortality from gram-negative bacteremia, we analyzed the case reports of patients from four prospective, randomized, and controlled clinical trials of gentamicin, tobramycin, and amikacin. Twelve (13.5%) of 89 patients died. One (2.4%) death occurred in 41 patients with early (1-hr postinfusion) peak concentrations of greater than 5 micrograms/ml of gentamicin and tobramycin and of greater than 20 micrograms of amikacin/ml; nine deaths (20.9%) occurred in 43 patients with lower concentrations. Five (8.3%) deaths occurred in 60 patients with mean peak concentrations for the entire course of therapy of greater than 5 micrograms/ml of gentamicin and tobramycin and of greater than 20 micrograms of amikacin/ml; five (20.8%) deaths occurred in 24 patients with lower concentrations. Stepwise discriminant analysis showed that therapeutic early peak concentration was a significant factor in the presence of three other factors: severity of underlying illness, peak temperature, and initial leukocyte count. The results suggest the importance of achieving adequate early aminoglycoside levels in patients with gram-negative bacteremia.

Adult↗
PubMed1984

Iris color and hearing loss.

This study investigated the relation between iris color and hearing loss in 261 adult textile workers exposed to either a low-noise environment (below 85 dB) or a high-noise environment (above 102 dB). The subjects included 48% white males, 28% white females, 15% black males, and 9% black females. No relation was found between iris color and hearing loss in the control or low-noise group. A significant relation between iris color and hearing loss or hearing threshold levels was found for workers in the high-noise environment. Other variables, however, were found to predict susceptibility to hearing loss better than iris color alone.

Adolescent↗
PubMed1984

Field testing of a minimal record of disability in multiple sclerosis: the United States and Canada.

The IFMSS Minimal Record of Disability (MRD) in Multiple Sclerosis was field tested at eight medical centers in the U.S. and Canada. The goals were to conduct a qualitative and quantitative evaluation of the MRD. Assessment were completed on 249 patients with definite MS by neurologists and allied health professionals. Effective administration required some study and practice. Refinement of some unclear wording and awkward format will improve ease of administration. The MRD fit well into clinic routines and was accepted by staff and patients. Scoring presented few problems and these were related to overlap among the MRD scales, poor wording, and content not appropriate to MS. Quantitative evaluation of the MRD indicated that Incapacity Status primarily reflects disability in mobility and self-care when used as a composite score. Heterogeneity of content in Incapacity Status suggests that summed scores be used cautiously. Both Incapacity and Environmental Status had high levels of reliability and high correlations with established measures of impairment in MS. Inter-rater agreement of the ISS and ESS were also high. Once some necessary revisions are made, the MRD should be well on its way to achieving the IFMSS goal of developing a brief, reliable, valid, and appropriate instrument acceptable to a wide variety of workers in MS.

Activities of Daily Living↗
PubMed1984

Risk factors for nephrotoxicity in patients treated with aminoglycosides.

Risk factors for nephrotoxicity in patients treated with aminoglycosides were determined from the case records of 214 patients in two prospective, randomized clinical trials of gentamicin and tobramycin. Nephrotoxicity, defined as a 50% or greater fall in calculated creatinine clearance, developed in 30 patients (14.1%). Patients with nephrotoxicity had higher initial calculated creatinine clearances, were more often women, and were more likely to have liver disease. Using stepwise discriminant analysis, these factors were selected with the initial 1-hour post-dose aminoglycoside level, patient age, and shock. An equation was generated that was accurate in discriminating between patients with and without nephrotoxicity when validated in an independent population. Factors that did not add significantly to the equation were diabetes, dehydration, serum bicarbonate, bacteremia, urinary tract infection, gentamicin or tobramycin use, duration of therapy, total aminoglycoside dose, or the use of clindamycin, furosemide, or cephalothin.

Aged↗
PubMed1984

Cefotaxime compared with nafcillin plus tobramycin for serious bacterial infections. A randomized, double-blind trial.

In a prospective, randomized, double-blind study, we compared cefotaxime with nafcillin plus tobramycin in the treatment of serious bacterial infections. Of 195 patients with suspected or proven infections who were not neutropenic, definite bacterial infections were identified in 81; 34 of 38 patients given cefotaxime and 26 of 43 given nafcillin plus tobramycin (p less than 0.01) responded to treatment. The difference in response rates occurred primarily in patients with rapidly fatal underlying disease or with an infection outside the urinary tract. A logistic regression analysis showed that treatment with cefotaxime was still associated with a higher response rate after adjusting for several potential confounding factors. Among patients treated for 3 days or more, our criteria for nephrotoxicity were met in 2 of 68 (2.9%) given cefotaxime and 16 of 57 (28.1%) given nafcillin plus tobramycin (p less than 0.001). Prolongation of the prothrombin time and enterococcal colonization did not occur more frequently with cefotaxime. We conclude that cefotaxime may be more effective and less toxic than nafcillin plus tobramycin for patients with serious bacterial infections.

Adult↗
PubMed1984

Comparative cost effectiveness of gentamicin and tobramycin.

Gentamicin and tobramycin were compared for cost effectiveness in the treatment of adult patients with serious infections in a general medical service. We used data from a randomized double-blind trial in which the only observed difference between the clinical effects of these aminoglycosides was the incidence of nephrotoxicity (26% with gentamicin and 12% with tobramycin). According to 1984 cost data, the combined average drug and nephrotoxicity costs per patient were $127 for tobramycin and $72 for gentamicin. An extensive sensitivity analysis--varying frequency and cost of nephrotoxicity, dialysis requirements, aminoglycoside acquisition costs, and length of hospitalization--showed gentamicin to be more cost effective than tobramycin, unless hospitalization is prolonged by an average of at least 15 days for patients with severe nephrotoxicity or at least 3 days for all patients with moderate or severe nephrotoxicity.

Adult↗