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C Bowles

Publications and source records attributed to C Bowles.

At least 19 recordsLinked to original sources
PubMed2001

Quantitative myocardial cytokine expression and activation of the apoptotic pathway in patients who require left ventricular assist devices.

BACKGROUND: Molecular mechanisms underlying the deterioration of patients undergoing LV assist device (LVAD) implantation remain poorly understood. We studied the cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta and IL-6 and the terminal stage of the apoptotic pathway in patients with decompensating heart failure who required LVAD support and compared them with patients with less severe heart failure undergoing elective heart transplantation. METHODS AND RESULTS: Myocardial and serum samples from 23 patients undergoing LVAD implantation were compared with those from 36 patients undergoing elective heart transplantation. Myocardial TNF-alpha mRNA (1.71-fold; P<0.05) and protein (3.43+/-0.19 versus 2.95+/-0.10 pg/mg protein; P<0.05) were elevated in the LVAD patients. Immunocytochemistry demonstrated TNF expression in the myocytes. Serum TNF-alpha was also elevated (12.5+/-1.9 versus 4.0+/-0.4 pg/mL; P<0.0001) in the LVAD patients. IL-6 mRNA (2.57-fold higher; P<0.005) and protein (27.83+/-9.35 versus 4.26+/-1.24 pg/mg protein; P<0.001) were higher in the LVAD candidates, as was serum IL-6 (79.3+/-23.6 versus 7.1+/-1.6 pg/mL; P<0.0001). Interleukin-1beta mRNA expression was 9.78-fold higher in the LVAD patients (P<0.001). iNOS mRNA expression was similar to that in advanced heart failure patients and was not further elevated in the LVAD patients. Levels of procaspase-9 (8.02+/-0.91 versus 6.16+/-0.43 oligodeoxynucleotide [OD] units; P<0.01), cleaved caspase-9 (10.02+/-1.0 versus 7.34+/-0.40 OD units; P<0.05), intact and spliced DFF-45 (4.58+/-0.75 versus 2.84+/-0.23 OD units; P<0.05) were raised in LVAD patients, but caspase-3 and human nuclease CPAN were not. CONCLUSIONS: Elevated TNF-alpha, IL-1beta, and IL-6 and alterations in the apoptotic pathway were found in the myocardium and elevated TNF-alpha and IL-6 in serum of deteriorating patients who required LVAD support. These occurrences may have therapeutic implications and influence the timing of LVAD insertion.

Adolescent↗
PubMed2000

A stereological method for testing whether or not there is random deposition of perivillous fibrin-type fibrinoid at the villous surface: description and pilot applications to term placentae.

We present a stereological method for testing whether or not there is random deposition of fibrin-type fibrinoid (FTF) at the villous surface of human placenta. The method requires random sampling of tissue with test lattice lines superimposed on microscopic fields at random positions and orientations. Test lines are used to generate chance intersections with specified sub-domains of the villous surface. At least three sub-domains are distinguishable: non-syncytial knots (nonSK), syncytial knots (SK) and areas of trophoblast de-epithelialization (DEP). Other sub-domains may be included to suit individual circumstances and project aims. The relative numbers of intersections with sub-domains provide the basis for an 'expected' distribution. Subsequently, this is compared with an 'observed' distribution which can be calculated from empirical estimates of the numbers of intersections with sub-domains associated with perivillous FTF (e.g. nonSK+FTF, SK+FTF and DEP+FTF). Expected and observed distributions can be compared by a chi-squared analysis. If the null hypothesis (no difference) is rejected, chi-squared values for individual sub-domains can be analysed in order to localize and interpret sites of preferential deposition. Comparisons may be drawn for individual placentae as well as a group of placentae, thereby permitting assessment of inter-placental variability. Finally, between-group comparisons may be drawn in order to test whether or not FTF deposition patterns differ in control and other pregnancies. Worked examples of the statistical procedures are provided. Preliminary results of applications to placentae from normal and complicated (hypobaric hypoxia) pregnancies are presented. They show that FTF deposition is non-random and preferentially located at sites of de-epithelialization. De-epithelialization may be a consequence of syncytial degeneration but also, at least in part, of continuous trophoblast turnover in which syncytial fragments rich in (pre-) apoptotic nuclei detach from the epithelium and are deported from the maternal intervillous space. The nascent detachment site is immediately covered by FTF prior to repair by re-epithelialization.

Altitude↗
PubMed1999

Clenbuterol increases stroke power and contractile speed of skeletal muscle for cardiac assist.

BACKGROUND: Skeletal muscle assist (SMA) may be limited by loss of power, slowing of contraction and relaxation, and atrophy of the transformed latissimus dorsi muscle (LD). Clenbuterol (clen), a beta2-adrenergic receptor agonist, was used to improve the performance of trained skeletal muscle in sheep. METHODS AND RESULTS: The following 4 groups were used: A (n=6), untrained controls; B (n=6), left LD progressively transformed toward a slow-twitch and fatigue-resistant phenotype by electrical stimulation over 12 weeks (2.5 to 5 V, 240- microsec pulse duration, 35 Hz, 3 to 6 pulses per burst, and up to 40 bursts per minute); C (n=6), clen-treated (0.5 mg/kg SC) for 12 weeks; and D (n=6), clen+trained. In a terminal experiment, the mobilized LD was wrapped around a rubber aorta of a mock circulation and stimulated to contract 40 times per minute. Group A had an initial mean pressure augmentation (DeltaP) of 24.6 mm Hg and stroke power of 2.28 W/kg, but both fell to <20% of their original values by 15 minutes because of fatigue (P<0.005). Group B was fatigue-resistant, with a DeltaP and stroke power at 60 minutes of 13 mm Hg (70% of initial) and 0.34 W/kg (39% of initial), respectively. The performance of group C was similar to that of controls. In group D, however, the muscles were stronger at all time points than in B, with a DeltaP of 23 mm Hg and stroke power of 2.66 W/kg at 60 minutes (P<0.01). The speeds of contraction (+dP/dt:DeltaP) and relaxation (-dP/dt:DeltaP) were significantly greater in group D than B. Protein analyses showed group D to have only a trend toward greater abundance of the fast isoforms of myosin heavy chain and sarcoplasmic reticulum Ca2+-ATPase (P>0.1). CONCLUSIOINS: ++Clen improves the performance of trained skeletal muscle in a model of aortomyoplasty by unknown mechanisms. These findings may have important implications in SMA.

Adrenergic beta-Agonists↗
PubMed1998

An in vitro study of the correlation between aortic valve diameter and mitral intertrigonal distance: a simple method to select the correct mitral annuloplasty ring size.

BACKGROUND AND AIMS OF THE STUDY: The application of the flexible Duran mitral annuloplasty ring in the treatment of various mitral valvular diseases is a physiologically appealing method of surgical repair. However, accurate identification of the trigonal structures, which is crucial in selecting the proper ring size, cannot always be made with certainty. A method is proposed to calculate the intertrigonal distance (ITD) from the aortic diameter. METHODS: Using digital calipers, the linear intertrigonal distance was measured in human homograft (n = 10) and sheep (n = 10) aortic root specimens. The aortic diameter was obtained from the circumference of the pressurized aortic root. A conversion factor was acquired for each specimen by dividing the aortic diameter with the measured ITD. A single constant conversion factor, which closely approximated the mean of the conversion factors in both groups, was then applied broadly to derive the ITD by calculation from the aortic diameter, which is known. The validity of using this constant conversion factor was tested by comparing the degree of variation of the calculated ITD from the direct measurements of the ITD. RESULTS: The mean of the conversion factors was 0.79 and 0.80 in the human and the sheep roots, respectively. The value 0.80 was used as the constant conversion factor in both groups for calculating the ITD. A paired comparison t-test in each group showed the difference between the calculated intertrigonal distance and the direct measurements of the ITD to be insignificant, validating the use of 0.80 as a constant conversion factor. CONCLUSIONS: The results of the study suggest that the conversion factor of 0.80 can be reliably used to obtain a calculated value of the intertrigonal distance; this method has the potential to aid the surgeon in determining the intertrigonal distance and the proper ring size.

Animals↗
PubMed1997

Comparative study of the biomechanical performance of trained and untrained skeletal muscle.

UNLABELLED: Changes in contraction and relaxation parameters during chronic electrical stimulation can exert profound effects on diastolic augmentation during skeletal muscle assistance (SMA) of the circulation, in both short and long term. The physiological properties of latissimus dorsi muscle (LD) performance in a system that mimics the clinical setting has not been adequately studied. OBJECTIVE: To quantify changes in the biomechanical performance of trained and untrained skeletal muscle in relation to circulatory assistance using an ex-vivo Windkessel mock circulation. METHODS: Twelve Welsh Mountain sheep were divided into 2 groups: Group A (n = 6) underwent implantation of intramuscular electrodes into the left LD connected to a myostimulator (Telectronics Pacing Systems, Inc., Colorado) and progressively trained by burst stimulation over a 12-week period using standard stimulation parameters (2.5-5 V, 35 Hz, 6 pulses per burst, 240 microseconds per pulse); Group B (n = 6) were the untrained controls. At the end of 12 weeks, the LD was mobilised on its neurovascular pedicle and wrapped around a latex rubber aorta connected to two Windkessel chambers pressurised to 70 mmHg and stimulated to contract 40 times per minute continuously for 60 min. Pressure change per contraction (augmentation, delta P), volume displacement, contraction (Ct) and relaxation to 90% (Rt90) times, and the standardised rate of change of pressure generation (+dP/dt: delta P) and decay (-dP/dt: delta P) were determined and assessed for potential clinical efficacy. RESULTS: In Group A, the LD was fatigue-resistant in all 6 animals with a mean pressure augmentation of 13.7 (s.e.m. 1.3) mmHg and mean stroke volume of 12.5 (s.e.m. 1.0) ml. These muscles were slow with a mean Ct and +dP/dt: delta max of 243.2 (s.e.m. 6.1) ms and + 6.5s-1, respectively, and Rt90 and -dP/dt: delta max of 261.0 (s.e.m. 4.8) ms and -7.8s-1, respectively. In contrast, the LD in Group B was fatiguable with a mean pressure augmentation and stroke volume of 24.6 (s.e.m. 0.9) mmHg and 21.1 (s.e.m. 0.7) ml at 1 min and only 5.4 (s.e.m. 0.3) mmHg and 5.2 (s.e.m. 0.3) ml, respectively, at 30 min (P < 0.001). These muscles were faster at all time points compared to group A (P < 0.02). Acute diminution of power output per contraction in Group B coincided with a prolongation in the Rt90 by 101% compared to the Ct which decreased by less than 5% (P < 0.001). The Ct/Rt90 ratio did not significantly change during performance testing in Group A (fatigue-resistant animals) (P > 0.1). CONCLUSIONS: Using a mock circulation system, we have identified significant differences in biomechanical properties of trained and untrained skeletal muscle. Optimisation of these parameters during and after electrical training may alter the clinical efficacy of SMA.

Animals↗
PubMed1983

Treatment of systemic mycoses with ketoconazole: emphasis on toxicity and clinical response in 52 patients. National Institute of Allergy and Infectious Diseases collaborative antifungal study.

The pharmacology, in vitro mycologic activity, toxicity, and efficacy of ketoconazole were studied in a Phase-II evaluation by the National Institutes of Health and National Institute of Allergy and Infectious Disease Mycoses Study Group. This report emphasizes the toxicity and clinical response data in 52 patients with the following systemic mycoses: blastomycosis in 16 patients; nonmeningeal coccidioidomycosis in 13; histoplasmosis in 8; nonmeningeal cryptococcosis in 7; sporotrichosis in 7; and both blastomycosis and nonmeningeal coccidioidomycosis in 1. Maximum daily doses of ketoconazole were 100 mg in 1 patient; 200 mg in 23; 400 mg in 12; and 600 mg in 16. In 52% of the patients, duration of therapy ranged from less than 1 to 6 months, whereas in 35%, duration ranged from 7 to 12 months, and in 13%, from 12 to 22 months. In 35 patients (67%), evidence of toxicity was not seen. Nausea, anorexia, or vomiting occurred in 21%. Cure or marked improvement was shown in 27 patients (52%), whereas failure of the primary course was seen in 14 (27%) and relapse after ketoconazole was discontinued in 11 (21%). Although this evaluation did not provide clear-cut clinical response data, our results indicate that ketoconazole, in the dosage regimens used, was more effective in patients with histoplasmosis and nonmeningeal cryptococcosis than in patients with blastomycosis and nonmeningeal coccidioidomycosis, and least effective in patients with sporotrichosis.

Adolescent↗
PubMed1983

Prognostic indicators of tumor response to Staphylococcus aureus Cowan strain I plasma perfusion.

Ten tumor-bearing dogs were treated with passage of autologous plasma over fixed Staphylococcus aureus Cowan strain I. Five similar dogs were treated identically except for the exposure to S. aureus. These animals have been assessed to identify positive and negative prognostic variables for response. Nonresponder treated animals had significantly larger chest wall tumor bulk than did the responder and control groups (P less than .01). Responder animals had fewer initial circulating immune complexes than did the nonresponders, though each group had similar reductions in immune complexes with therapy. Nonresponder animals had smaller volumes of plasma processed per kilogram of body weight per procedure than did controls (P = .016), whereas responder and control animals had similar volumes processed per kilogram of body weight per procedure (P = .84). These data suggest that the response observed in our original series was significantly related to the larger amount of plasma treated per procedure and suggest that a factor may be eluted from the S. aureus cartridge that mediates this response.

Adenocarcinoma↗
PubMed1982

Regression of canine mammary carcinoma after immunoadsorption therapy.

The plasma of dogs afflicted with mammary carcinoma was perfused through chambers bearing Staphylococcus aureus Cowan strain I in an attempt to remove tumor-promoting, immunosuppressive immune complexes from the peripheral blood of these animals. In this canine model of spontaneous mammary carcinoma, reduction of breast and/or soft-tissue tumor (posttreatment size equal to 0 to 50% of pretreatment tumor size) was observed in five of the ten animals so treated. Immune complexes capable of blocking lymphocytotoxicity were measured pre- and postimmunoadsorption; removal was more efficient in the five responders (four of six complexes) than in nonresponders (one of ten complexes), although statistical significance was not attained. The reduction of tumor size seen in soft-tissue sites was not always accompanied by a similar reduction of tumor size in visceral sites, and surgical resection of residual soft-tissue tumor nodules remaining after immunoadsorption treatment was required to achieve a complete response in two responding animals. No significant decrease in tumor size was observed in the control group, perfused without immunoadsorbent, nor in five additional tumor-bearing animals infused with normal dog plasma which had been passed through S. aureus Cowan strain I-containing chambers. These data indicate that immunoadsorption of tumor-bearing host plasma can result in reduction in size of canine mammary adenocarcinoma but that the response is dependent on the site of the tumor (s.c. versus visceral) and may require utilization of other modalities to achieve a complete disappearance of the tumor.

Adenocarcinoma↗
PubMed1982

Phase I trial of Staphylococcus aureus Cowan I immunoperfusion.

Staphylococcus aureus Cowan I has shown antitumor activity in in vitro and in animal tumor models. It is hypothesized that this antineoplastic effect results from the interaction of protein A on the cell surface of Cowan I strain S. aureus and immunosuppressive circulating immune complexes. Therefore, we treated five patients with ex vivo plasma immuno-perfusion over killed and fixed S. aureus Cowan I. Toxic effects were marked in all patients and appeared to be related to the plasma volume infused and rate of infusion. Toxic reactions occurred in the cardiovascular, respiratory, and hematopoietic systems. No responses even minimal or transient, were observed in this phase I trial. This toxicity may be reduced if the rate of plasma infusion decreases.

Adult↗
PubMed1981

Cyclophosphamide treatment expands the circulating hematopoietic stem cell pool in dogs.

Increased numbers of circulating granulocyte-monocyte precursor cells (CFUc) have been observed in the peripheral blood of man after antineoplastic chemotherapy. We have developed a canine model to study the biologic significance of this phenomenon for hematopoietic reconstitution following hematopoietically lethal exposure to total body irradiation (TBI). After cyclophosphamide administration, a 16-fold expansion of circulating CFUc numbers was observed during the period of rapid leukocyte recovery that occurred after the chemotherapy-induced leukocyte nadir. We had previously noted this association between leukocyte recovery and CFUc expansion in our human studies. After 900 rad TBI hematopoietic reconstitution was attempted with autologous, cryopreserved collections of peripheral blood mononuclear cells obtained either at times of post-cyclophosphamide CFUc expansion (group A, 14 dogs) or without CFUc expansion (group B, 12 dogs). Asd compared to group B collections, group A collections contained 11-fold more CFUc and were 12.5-fold more potent in fostering hematopoietic recovery after TBI. These results suggest that the expansion of CFUc numbers we observed was accompanied by a similar expansion of more primitive hematopoietic stem cell numbers. We conclude that chemotherapy-induced expansion of circulating CFUc numbers appears to be of substantial import in effecting hematopoietic reconstitution--an observation that may be of significance for further studies of autologous hematopoietic reconstitution in man.

Animals↗