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Biomedical subjects

J Fisher

Publications and source records attributed to J Fisher.

At least 397 records · Page 22Linked to original sources

Surgical technique and pitfalls of breast reconstruction immediately after mastectomy for carcinoma: initial experience.

Breast reconstruction immediately after mastectomy is being used with increasing frequency. In a study of the first 100 consecutive patients at our institution who underwent this procedure, with (21 patients) or without (79 patients) later nipple reconstruction, 85% responded affirmatively on a follow-up questionnaire when asked whether they would recommend the procedure to other patients. Moreover, 32% rated their cosmetic results as "perfect." No deaths occurred in the immediate postoperative period, but 13 patients had major complications--most commonly, wound infection or displacement or partial extrusion of the implant. All infections, however, occurred early in the study, and with increasing experience and improved selection of patients, the associated morbidity decreased. For the entire group, the mean duration of hospitalization was 7.8 days, similar to that for patients who undergo mastectomy without reconstruction (7.5 days). The high patient acceptance and the overall good results in this preliminary study support the use of breast reconstruction immediately after mastectomy.

Adult↗

Experimental comparison of bone revascularization by musculocutaneous and cutaneous flaps.

Revascularization, one of the major components of bone healing, was examined in an experimental model. The radioactive microsphere technique demonstrated that after 4 weeks beneath a musculocutaneous flap, isolated bone segments had significant blood flow, whereas bone beneath a cutaneous flap did not. The muscle flap bone had a blood flow approximately half that of normal control bone. The muscle of the musculocutaneous flap had a blood flow three times that of the skin of the cutaneous flap. The bipedicle cutaneous flap used was designed to have a healthy blood supply, and at 4 weeks it had a blood flow twice that of control skin. Despite this, there was essentially no demonstrable blood flow in the cutaneous flap bone segments at 4 weeks. Only 3 of 17 bone segments underneath cutaneous flaps showed medullary vascularization, whereas 10 of 11 muscle flap bones did. All bone segments underneath muscle flaps showed osteoblasts and osteoclasts at 4 weeks; neither were seen in the cutaneous bone segments. The process of revascularization occurred through an intact cortex and penetrated into the cancellous bone. Because the bone segments were surrounded by an impervious barrier except for one cortical surface, the cellular activity seen is attributed to revascularization by the overlying flap. In this model, a muscle flap was superior to a cutaneous flap in revascularizing isolated bone segments at 4 weeks. This was documented by blood flow measured by the radioactive microsphere technique and by bone histology.

Animals↗

Comparison of electrical measurements on constant voltage and constant current ECT machines.

Electrical measurements were made during treatment of two groups of patients, one group receiving treatment from a constant current ECT machine and the other from a constant voltage machine. The electrical impedance and energy were calculated and compared for the two groups. More energy was delivered by the constant voltage than by the constant current machine, but the spread of energy delivered was comparable. With a consistent technique for applying the electrodes there is little to choose between these machines, but the constant current machine may be preferred where consistency cannot be achieved.

Acute Disease↗

Nifedipine in pulmonary arterial hypertension. Importance of Raynaud's phenomenon.

We studied (via acute vasodilator testing with nifedipine) 27 patients with pulmonary arterial hypertension (PAH) (11 primary, 16 secondary PAH, [including six patients with Raynaud's phenomenon]) in order to identify predictors of hemodynamic response and specifically to assess whether patients with Raynaud's phenomenon and pulmonary hypertension were more likely to respond to nifedipine. Nifedipine decreased resting mean pulmonary artery (PA) pressure and pulmonary vascular resistance (PVR) in patients with Raynaud's phenomenon (delta PA - 6.8 +/- 10.5 mm Hg; delta PAD - PCW gradient - 9.3 +/- 4.7 mm Hg; delta PVR - 255 +/- 201 dynes.s.cm-5, all p less than .05) versus (delta PA 0.3 +/- 4.0 mm Hg; delta PAD - PCW gradient 0.4 +/- 5.0 mm Hg; delta PVR - 58 +/- 132 dynes.sec.cm-5, all NS), in the patients without Raynaud syndrome. These data suggest that patients with both primary and secondary PAH may benefit from nifedipine therapy, but that patients with Raynaud's phenomenon may respond particularly well, perhaps because of vasodilator-reversible pulmonary vasoconstriction. An alternative hypothesis is that prior chronic vasodilator therapy in the majority of our patients with Raynaud's phenomenon preserved pulmonary vasoreactivity.

Female↗

Primary tissue failure in pericardial heart valves.

A number of centers have recorded a significant incidence of primary tissue failure with the standard Ionescu-Shiley pericardial valve. In most cases severe regurgitation was caused by leaflet tears adjacent to the edge of the cloth-covered stent. Our early clinical experience (up to 4 years' follow-up) with two new pericardial valves (Ionescu-Shiley low-profile and Hancock pericardial valves) has shown that primary tissue failure also occurs in these new valves. In vitro accelerated fatigue studies on seven of these valves (size 29 mm) showed that in vitro premature leaflet failure was caused by abrasion of the leaflet on the cloth-covering at the edge of the stent. Clinically, endothelialization and host tissue ingrowth on the cloth and the leaflets at the edge of the frame greatly reduced the amount of abrasion and the incidence of tissue failure. In seven of the eight explanted valves studied, leaflet tears occurred at the top of the stent posts where there was less endothelialization and tissue ingrowth, close to the points where sutures pass through the leaflets. It is likely that both abrasion and stress concentration around these sutures contributed to the tissue failures in the clinical valves.

Adult↗

Autocatalytic quinone methide formation from mitomycin c.

Mitomycin c in the presence of NADPH and brewers' yeast NADPH: (acceptor) oxidoreductase (Old Yellow enzyme, EC 1.6.99.1) is transformed, at pH 8.0 and with anaerobicity, to two major mitosene products (the cis- and trans-1-hydroxy-2,7-diaminomitosenes; respective yields of 45 and 30%). These arise by covalent trapping by solvent of a quinone methide intermediate, obtained by rearrangement of the mitomycin c hydroquinone. At lower pH (6.5), the major product of this reaction is 2,7-diaminomitosene, which arises by covalent trapping of the quinone methide by H+. In the former instance the quinone methide acts as an electrophile and in the latter as a nucleophile. A detailed kinetic analysis indicates that the role of the NADPH and Old Yellow enzyme is to initiate an autocatalytic reaction, propagated by mitomycin c reduction by the mitosene hydroquinones (arising by the electrophilic pathway). The evidence supporting this conclusion is the formation of oxidized mitosene products, under the rigorously anaerobic reaction circumstance, the nonstoichiometric participation of NADPH, a dependence of the velocity on the total mitomycin c concentration, the pH dependence of the reaction, and the accurate simulation of the overall kinetic course with a mathematical model of the autocatalytic pathway. These observations indicate that the autocatalytic pathway may be dominant during in vitro mitomycin c anaerobic reductive activation by other reducing agents and that (as with anthracycline reductive activation) oxidation of the mitosene hydroquinone obtained from nucleophile addition to the quinone methide may be a necessary event for the formation of stable covalent adducts in vivo.

Anaerobiosis↗

Left atrial myxoma: diagnosis by digital subtraction intravenous angiography.

Digital subtraction intravenous angiography (DSIVA) represents an important technical advance in angiographic diagnosis. Herein we present three patients with left atrial myxoma assessed by DSIVA. We review the role of DSIVA in evaluation of patients with suspected cardiac tumors and the importance of careful atrial-phase scrutiny in examinations obtained for other purposes (ie, pulmonary angiography and assessment of ventricular function).

Angiography↗

In vivo modulation of glutathione by buthionine sulfoximine: effect on marrow response to melphalan.

The effect of giving buthionine sulfoximine (BSO), 0.0265 g/mouse (6 mM), at 12 and 6 hr before treatment with melphalan--0.0 mg, 3 mg, 6 mg, and 9 mg/kg, was studied in C3H mice, and was compared with control groups that received normal saline 12 and 6 hr before identical melphalan treatment. BSO treatment resulted in depletion of GSH levels in bone marrow, liver, and muscle to 65, 13, and 41% of control levels, respectively. Hematological toxicity was assessed by measurement of CFU-S survival and peripheral white cell counts. CFU-S survival decreased with increasing doses of melphalan, but no difference was observed with BSO pre-treatment. Likewise, WBC counts following melphalan 9 mg/kg, were similar irrespective of BSO pre-treatment. These data suggest that the marrow toxicity seen with melphalan is not worsened by pre-treatment with BSO and that if tumors can be pre-sensitized with BSO, there may be a clinical role for melphalan/BSO drug combination.

Animals↗

Microvascular reconstruction in the head and neck.

With the advent and refinement of microvascular surgical techniques, the results of reconstruction in the head and neck area have been substantially improved. Free flaps can now be moved in one stage for reconstruction of composite tissue in the head and neck area, whereas multiple procedures were often necessary to accomplish such reconstructions in the past. Skin, fat, muscle, bone, and intraoral lining can all be reestablished by using microvascular techniques. Because of the availability of microvascular surgical procedures, defects caused by cancer, congenital anomalies, or acquired disorders can now be reconstructed successfully. This article summarizes the history of microvascular operations and the development of the techniques and equipment; in addition, free tissue transfer reconstruction is compared with traditional techniques. The selection of the appropriate donor tissues and the assessment of patients preoperatively are discussed, and several illustrative case reports are presented.

Adult↗

7-Deoxydaunomycinone quinone methide reactivity with thiol nucleophiles.

Under anaerobic conditions and with NADPH as a reducing agent, daunomycin is reduced in the presence of spinach ferredoxin: NADP+ oxidoreductase as the enzyme catalyst to its hydroquinone, from which intramolecular elimination of the C-7 glycoside proceeds to provide a quinone methide intermediate. This quinone methide is capable of bimolecular reaction with the thiolate nucleophiles N-acetyl-L-cysteine, N-(tert-butoxycarbonyl)-L-cysteine, and 1-thio-beta-D-glucose, providing a pair of C-7 diastereomers, when the reaction is carried out under the autocatalytic conditions offered by substoichiometric quantities of NADPH. With 0.4 equiv of NADPH, optimal yields of the adducts are obtained of approximately 65%. In each case, the 7S adduct is the major product, with the observed stereoselectivities (7S to 7R) ranging from 2.6 to 1 for N-acetyl-L-cysteine to 4 to 1 for both the N-(tert-butoxycarbonyl)-L-cysteine and 1-thio-beta-D-glucose as nucleophiles. By standard blocking and deblocking procedures, the complete set of complementary functionalized (7S)- and (7R)-N-acetyl and O-methyl 7-L-cysteinyl-7-deoxydaunomycinones is prepared. All efforts to extend this quinone methide trapping reaction to additional nucleophiles (such as I- or N3-), including the use of Fe(III) chelation, are unsuccessful. The Fe(III) chelate of daunomycin is however reduced by ferredoxin reductase and NADPH to the Fe(III) chelate of 7-deoxydaunomycinone, suggesting that quinone reduction of the chelate to the quinone methide has occurred. Of the new compounds prepared, only (7R)-7-S-(beta-D-glucopyranosyl)-7-thio-7-deoxydaunomycinone has biological activity. As an in vitro inhibitor of P388 cell growth, it has a 50% inhibitory concentration 25 times greater than that of daunomycin.

Animals↗

In vitro evaluation of six mechanical and six bioprosthetic valves.

The in vitro function of 6 tissue valves and 6 mechanical valves (all size 29) was assessed in a purpose-built pulse duplicator under different pulsatile flow conditions. Valve function was analyzed by measuring the mean pressure difference across each valve during forward flow, and the reverse flow through each valve during valve closure (dynamic regurgitation) and in the fully closed position (static regurgitation). Although valves of the same type showed similar characteristics, there were significant differences in function between different types of valves. Porcine valves showed much higher forward flow pressure gradients than pericardial, tilting disc, or bileaflet mechanical valves. However, the porcine valves showed least regurgitation, with pericardial valves having less regurgitation than mechanical valves.

Bioprosthesis↗

Design of a function test apparatus for prosthetic heart valves. Initial results in the mitral position.

A test rig has been developed to investigate the function of prosthetic heart valves under pulsatile flow conditions. The rig uses a servo-controlled pump to produce a physiological flow waveform through the valve. The pressure difference across the valve and flow through the valves are measured to assess the valve function. The mean pressure difference, root mean square (RMS) forward flow and regurgitant volumes are calculated on a computer. In the initial study, seven popular mechanical prostheses (sizes 29 and 27 mm) were evaluated in the mitral position under five different flow conditions. The mean pressure difference was dependent on the position of the downstream pressure tapping, the orientation of the valve and the time interval used to average the signals. The orientation of some valves also affected the regurgitant volumes. These variations (10-25%) were similar in size to the differences measured between individual valves. Test conditions have to be specified very carefully for accurate comparison of valve function to be made.

Blood Flow Velocity↗

Comparison of Doppler ultrasound velocity measurements with pressure differences across bioprosthetic valves in a pulsatile flow model.

Continuous wave Doppler ultrasound was used in vitro to assess the pressure differences across four different cardiac bioprosthetic valves in a pulsatile flow test apparatus. Valves were tested under four different flow conditions. Pressure differences were calculated from the maximum flow velocity measured by Doppler ultrasound and correlated well with the pressure differences measured directly in the flow model (r = 0.98). Thus Doppler ultrasound can accurately measure pressure differences across bioprosthetic valves in vitro.

Bioprosthesis↗