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Biomedical subjects

J M Donovan

Publications and source records attributed to J M Donovan.

At least 55 records · Page 3Linked to original sources

Physical-chemical basis of gallstone formation.

The broad outlines of the physical chemistry of cholesterol solubilization are well understood, but minor components of native biles probably alter the equilibrium solubility of cholesterol in bile and, more importantly, profoundly affect the kinetics of cholesterol crystal formation. The physical chemistry of UCB solubilization is much less clear; two decades after the limits of cholesterol solubilization in bile were reported, we still cannot provide accurate information on the limits of UCB solubility in bile. Although UCB is predominantly solubilized by the same biliary aggregates as cholesterol, the ionic nature of UCB implies that other, quantitatively minor biliary components profoundly alter UCB solubilization. Understanding UCB solubilization in bile and the prevention of black pigment stone formation await further studies. An understanding of the physical chemistry of cholesterol and UCB, both as solubilized in bile and as precipitated in gallstones, is basic to an understanding of the pathogenesis of gallstone disease, as well as current and potential chemical methods of gallstone dissolution and prevention.

Bile Acids and Salts↗

Identifying types of female incontinence with retrograde urethrocystography.

The most specific radiographic findings characterizing stress incontinence (SI) on upright retrograde urethrocystography include replacement of a flat or rounded bladder base with a concave funnelled base; patency of the bladder neck with contrast material pooling in the proximal urethra; the descent of the intravesical Foley balloon beyond the internal meatus and into the proximal urethra. We found that neither a cystocele nor the dependent position of the urethra at the bottom of the bladder were diagnostic of SI if the above stigmata were absent. On the other hand the defect of urgency incontinence (UI) is functional. The bladder can usually be filled by retrograde urethral infusion (though in severe UI this may not be the case). An alert technician can frequently obtain a film when the patient is experiencing uninhibited voiding. The finding of contrast material throughout the urethra, in the distal urethra alone, or in the parameatal area is strongly suspicious for UI, especially when trabeculation is also seen. These findings in association with the stigmata of SI give warning of combined SI and UI.

Diagnosis, Differential↗

Treatment of pacemaker patients with extracorporeal shock wave lithotripsy: experience from 2 continents.

Patients with cardiac pacemakers currently are treated by extracorporeal shock wave lithotripsy only by agreement between individual physicians and patients. We present the results of a survey of patterns of extracorporeal shock wave lithotripsy treatment (or nontreatment) of patients with pacemakers in the United States and Europe. Letters of inquiry regarding treatment of pacemaker patients were sent to 141 United States extracorporeal shock wave lithotripsy sites and 55 sites in Europe. Responses were received from 81 (57%) and 17 (31%) sites, respectively. A total of 131 patients received 142 treatments and pacemaker-related complications occurred in 4 (none was lethal, 3 were minor and all were corrected immediately). No patient required replacement of the pacemaker. No correlation existed between complications and pacemaker type or manufacturer. Urologists who treat patients with a pacemaker required previous clearance of the patients by the cardiologist, a cardiologist in or near the extracorporeal shock wave lithotripsy suite and standby of corrective equipment or temporary pacemakers.

Europe↗

Microvascular changes in rabbit kidneys after extracorporeal shock wave treatment.

Concerns about the safety of extracorporeal shock wave lithotripsy include the risk of vascular damage and the genesis of hypertension. We evaluated gross specimens and barium microangiograms of the right kidneys of 14 rabbits exposed to shock waves; the untreated left kidneys served as controls. Six rabbits were assessed immediately after shock wave treatment, whereas the other eight rabbits had the same procedure 3 months later. All six acute phase animals showed microangiographic changes indicative of shock wave trauma, including cortical, subcapsular, and medullary extravasation of barium and patchy loss of efferent vessels. No significant vascular abnormalities were seen in the control kidneys. All kidneys treated from the animals that had delayed microangiography showed macroscopic evidence of fibrotic capsular thickening and parenchymal scarring. Microscopically, there was crowding of glomeruli and areas of avascularity. In this model, shock waves damaged the cortical circulation and resulted in persistent alterations of the microvasculature that potentially could be responsible for the abnormal secretion of renin.

Animals↗

Separation and quantitation of cholesterol "carriers" in bile.

On the basis of phase equilibria theory and experimental data, we discuss the identity, separation and quantitation of cholesterol-solubilizing lipid aggregates in bile, trivially known as cholesterol "carriers." We first describe analogies (as well as lack of correspondence) between equilibrium phase diagrams of aqueous bile salt, lecithin and cholesterol systems and phase equilibria in native biles. At equilibrium, the possible number and types of different cholesterol "carriers" are limited by constraints placed by the phase rule. These "carriers" include simple micelles (bile salts without lecithin), mixed micelles (bile salts plus lecithin), a lecithin plus cholesterol lamellar phase composed of single bilayer structures (vesicles) or multilamellar structures (liquid crystals) and possibly fragments of a hexagonal phase. Clearly, in this context, cholesterol monohydrate crystals, no matter how small, cannot be considered "carriers." We also use a metastable "phase diagram" for aqueous taurocholate-egg yolk lecithin-cholesterol systems to interpret physicochemical studies on the formation and stability of native biles. In biliary lipid systems, bile salt monomers with or without simple bile salt micelles are present in the aqueous "phase" in equilibrium with mixed micelles/or vesicles. This bile salt concentration is designated the intermicellar concentration but actually represents the total nonmixed micellar/nonvesicular concentration of bile salts (i.e., bile salt monomers and simple bile salt micelles when present) and may be a value that falls below, equal to or above the critical micellar concentration of the bile salts. Experimental estimates of the intermicellar-intervesicular bile salt concentration in model systems are compared with the range of bile salt concentrations that has been used in the literature to separate the presently accepted cholesterol "carriers" (mixed micelles and vesicles) in both model and native biles. We also reinterpret published lipid compositions of phases separated from human bile, using both a nonequilibrium "phase diagram" and an equilibrium phase diagram for the model system, taurocholate-egg yolk lecithin-cholesterol. From these analyses, we conclude that precise quantitation of cholesterol "carriers" in bile awaits methods to accurately determine the intermicellar-intervesicular concentration of bile salts in any individual bile, as well as advances in nonperturbing separatory procedures, and methods to control the thermal and temporal history of native bile samples.

Animals↗

Release of prostaglandin E2 from cells by photodynamic treatment in vitro.

Photodynamic treatment in vitro, using the photosensitizer Photofrin II and light at 630 nm, was found to liberate large amounts of prostaglandin E2 (PGE2) from mouse radiation-induced fibrosarcoma tumor cells and peritoneal macrophages, but not from L929 fibroblasts. PGE2 release was dose dependent and directly related to cell membrane disruption. It occurred rapidly and was complete within 30 min of treatment. PGE2 release could be inhibited by indomethacin, meclofenamate and extended prior exposure to dexamethasone, indicating that it was due to new production involving both the phospholipase and cyclooxygenase enzyme systems. Removal of calcium ions, necessary for phospholipase activation, from the medium did not inhibit the photodynamically induced elevated PGE2 production, possibly because of Ca2+ resupply from leaking intracellular pools.

Animals↗

Ulnar variance in children--standard measurements for evaluation of ulnar shortening in juvenile rheumatoid arthritis, hereditary multiple exostosis and other bone or joint disorders in childhood.

Measurements for radioulnar variance in adults cannot be used in children because the epiphyses are not fully ossified. We describe a method of determining ulnar variance in children by using the distance from the distal metaphysis of the radius to the distal metaphysis of the ulna. Standards for this measurement are presented for ages 1.5 to 15.5 years in boys and girls. These measurements change little with age and may be helpful in establishing shortening of the ulna which may been seen in juvenile rheumatoid arthritis, hereditary multiple exostosis, or other bone and joint diseases with childhood onset.

Adolescent↗

Short-term changes of laboratory values after extracorporeal shock wave lithotripsy: a comparative study.

Since the inception of extracorporeal shock wave lithotripsy 9 years ago treatment strategies have changed. Patients currently are receiving larger numbers of higher voltage shock waves. However, upper limits of safety for these treatments have not been established. In an attempt to address this question a comparative study of effects of extracorporeal shock wave lithotripsy on laboratory values between 2 stone centers, Munich and Tucson, using different treatment strategies 3 to 4 years apart was done to identify possible differing effects. Patient stone burdens were similar. However, Tucson patients received almost twice the number of shock waves. Both groups showed a significant decrease in hematocrit (by 8.7 per cent in Munich and 6.4 per cent in Tucson). Both groups had a significant increase in white blood count (14.5 per cent in Munich and 22.7 per cent in Tucson). In addition, both groups had increased serum levels of glutamic oxaloacetic transaminase of 43.3 and 59.7 per cent, respectively. However, only the Tucson group showed increases in serum glutamic pyruvic transaminase, lactic dehydrogenase and total bilirubin in 51.5, 40.8 and 46 per cent of the patients, respectively. Further analysis indicated that extracorporeal shock wave lithotripsy was associated with 2 significant short-term changes of blood or serum laboratory values: 1) those presumed to be dilutional from related infusions, rather than extracorporeal shock wave lithotripsy treatments themselves and 2) those presumed to be related to cellular injury after high energy treatments. Elevated serum glutamic pyruvic transaminase, lactic dehydrogenase and total bilirubin values of Tucson patients clearly were related to higher kilovolts and number of shocks or to treatments on the right side.(ABSTRACT TRUNCATED AT 250 WORDS)

Arizona↗

Effects of extracorporeal shock wave lithotripsy on the structure and function of rabbit kidney.

An animal model was developed to investigate the effect of extracorporeal shock wave lithotripsy (ESWL) on a normal kidney. Rabbits were treated with 3,000 shock waves at 18 kV to each kidney. Blood and urine samples were collected daily before and after shock wave treatment. Serum levels of hemoglobin, creatinine, lactic dehydrogenase (LDH), creatinine phosphokinase (CPK), and total protein were determined. Urine determination of volume, total protein, hemoglobin, and creatinine were also made. All kidneys, after sacrifice, were subjected to histologic analysis. The average pre-treatment creatinine clearance of our rabbits was 8.3 ml./min. After the treatment, a significant (p less than 0.01) reduction in creatinine clearance was noted for four days. The reduction was to 0.61 ml./min. on day one, 0.87 on day two, 1.04 on day three, and so forth. Urine hemoglobin rose significantly (p less than 0.01) for the first three days from 0.0 to 1.5 gm./dl. Histologic examination at seven days showed focal subcapsular hemorrhage, tubular dilation, and interstitial hemorrhage. Histologic evaluation at two months revealed focal interstitial fibrosis. In conclusion, this study reveals that shock waves to the kidney have short term physiologic effects on renal function and permanent focal histologic effects, which do not effect long term physiologic function. Further research on the effects of ESWL on renal function and structure could be facilitated with the use of this model.

Animals↗

Brief dynamic psychotherapy: characterologic intervention and the physical position of the patient.

BRIEF dynamic psychotherapy has achieved widespread acceptance in the past 20 years but as yet has formed no satisfactory approach to effecting character change. The most frequently chosen path has been to select for treatment only those who readily demonstrate the capacity to investigate focal conflict, thus bypassing character armor. The strategy here flows in the opposite direction. Within brief dynamic treatment, what technical alterations might more effectively engage characterologic difficulty? I report on one such innovation. When patients are asked to sit close to but turned at 180 degrees from the therapist, those with character disorders--particularly patients suffering from mid-level disorders--can often suspend their defenses sufficiently to permit specific types of new material into the treatment. This alteration in process appears, in turn, to abet outcome.

Adult↗

Urosound. In-office ultrasonography for pediatric urology.

Ultrasound has proved to be very accurate in evaluating children with common urologic problems such as renal obstruction and urinary infection and in screening for uropathology among children with siblings known to have urologic disease. The benefits of ultrasound in a pediatric population include diagnostic accuracy, ease of use, absence of radiation exposure, and no risk of adverse reactions to contrast agents. As a consequence, ultrasound has become routine in the evaluation of children with urologic conditions, and its use has been expanded to screening of healthy infants for urinary tract abnormalities. One (1.3 per cent) of 73 otherwise-healthy babies studied had urologic problems severe enough to warrant surgery. Steinhart and associates recommended the routine use of ultrasound in healthy infants, because a significant number of infants harbor silent urinary tract abnormalities that can be detected by ultrasound at a low cost. Obstetricians and other primary-care physicians as well as urologists have incorporated the office use of ultrasound into the care for their patients and thus avoid the inconvenience and difficulties of outside referral. In addition, the clinician as a sonographer occupies a unique position that permits sonographic information to be related directly to the clinical problem. In this review, we have included more than three times the number of patients studied in the initial report. The ease and accuracy of office ultrasound that we described initially have been confirmed by subsequent experience. The urosound examination is indicated for the initial evaluation of patients with voiding symptoms, urine infection, or hematuria, as well as to screen patients with known congenital anomalies, such as hypospadias. Urosound can be employed in the surveillance of children with dysfunctional voiding to measure the completeness of bladder emptying and hydronephrosis. The degree of hydronephrosis in cases of ureteropelvic junction obstruction, megaureters, ectopic ureters, and ureteroceles and that remaining after surgery may be documented by urosound examination. We have found that when the urosound study is abnormal, further diagnostic evaluation is more efficiently planned. Office-based pediatric urologist-operated ultrasound supplements the information elicited from routine history, physical examination, laboratory studies, and other radiologic investigations.

Adolescent↗

Clinical experience with a self-contained inflatable penile implant: the Flexi-Flate.

We implanted 23 Flexi-Flate penile prostheses during a 15-month period beginning July 1985. Of the implants 22 were followed for a mean of 16.1 months and 19 (86 per cent) function well. Satisfaction of individuals with a functioning prosthesis, as determined by interview and questionnaire (79 per cent response rate), has been good. Deflation sometimes occurs with penile shaft bending during sexual activity but this is managed satisfactorily by most couples via technique adjustments with minimal disruption of enjoyment. Reliable preoperative prosthesis size selection based on pubis to mid glans measurements was not possible in our hands secondary to broad variation in intracorporeal lengths found in the population studied.

Adult↗

Torulopsis glabrata urinary infections: a review.

During a 12-year prospective period 9 referral patients were treated for proved Torulopsis urinary infections. Of the 9 patients 7 had irritative voiding symptoms and pyuria was present in 8. To estimate incidence of infection, a retrospective review was performed between January 1982 and December 1983. A total of 105 urine specimens from 57 hospitalized patients yielded Torulopsis glabrata. Two patients suffered symptomatic invasive infections. Patients were treated with antifungal therapy only when invasive symptomatic infections persisted despite elimination of predisposing factors. 5-Fluorocytosine eradicated Torulopsis funguria in 4 of 6 patients in whom it was used. Prolonged therapy with ketoconazole was also successful. Surgical removal of associated stones or fungal coagulum was sometimes required.

Adult↗

Self-association of human apolipoproteins A-I and A-II and interactions of apolipoprotein A-I with bile salts: quasi-elastic light scattering studies.

We employed quasi-elastic light scattering (QLS) to systematically study the aqueous self-association of human apolipoproteins A-I and A-II (apo A-I and apo A-II) and the interactions of apo A-I with common taurine-conjugated bile salts. Self-association of apo A-I was promoted by increases in apolipoprotein concentration (0.09-2.2 mg/mL) and ionic strength (0.15-2.0 M NaCl), inhibited by increases in temperature (5-50 degrees C) and guanidine hydrochloride concentration (0-2.0 M), and unaffected by hydrostatic pressures up to 500 atm. The mean hydrodynamic radius (Rh) of apo A-I micelles ranged from 38 A to a maximum asymptotic value of 68 A. We examined several possible models of apo A-I self-association; the model that best fitted the Rh values assumed that apo A-I monomers first interacted at low concentrations to form dimers, which then further associated to form ring-shaped limiting octamers. Comparison of the temperature-dependent and ionic strength dependent free energy changes for the formation of octamers from apo A-I dimers suggested that hydrophobic forces strongly favored self-association and that electrostatic repulsive forces were only weakly counteractive. Apo A-II self-association was also promoted by increases in apolipoprotein concentration (0.2-1.8 mg/mL) and inhibited by increases in guanidine hydrochloride concentration (0-1.0 M) but was unaffected by variations in temperature (10-37 degrees C): the largest Rh values observed were consistent with limiting tetramers. As demonstrated by equilibrium dialysis, bile salts in concentrations below their critical micellar concentrations (cmc) bound to apo A-I micelles but had no effect upon apo A-I self-association, as inferred from constant Rh values. When bile salt concentrations exceeded their aqueous cmc values, a dissociation of apo A-I micelles resulted with the formation of mixed bile salt/apo A-I micelles. These studies support the concepts that apo A-I and apo A-II form small dimeric micelles at low concentrations that grow sharply to reach limiting sizes over a narrow concentration range. The influences of bile salt concentration and species upon these micelles have relevance to the plasma transport of bile salts in high-density lipoproteins and to the physical-chemical state of apo A-I and apo A-II molecules in native biles.

Apolipoprotein A-I↗

Formation of mixed micelles and vesicles of human apolipoproteins A-I and A-II with synthetic and natural lecithins and the bile salt sodium taurocholate: quasi-elastic light scattering studies.

We employed quasi-elastic light scattering to systematically study the interactions of human apolipoproteins A-I and A-II (apo A-I and apo A-II) with synthetic and natural lecithins, analogues of the major membrane lipids found in high-density lipoproteins (HDL). Equilibrium values of the mean hydrodynamic radius (Rh) of systems with varying concentrations of dimyristoylphosphatidylcholine (DMPC) to apolipoprotein showed that as the percentage of DMPC was increased, three distinct regions were observed. At low DMPC to apolipoprotein ratios, Rh values either increased, remained constant, or decreased, depending upon the total apolipoprotein concentration, which influenced the size of pure apolipoprotein micelles [Donovan, J. M., Benedek, G. B., & Carey, M. C. (1987) Biochemistry (preceding paper in this issue)]. When the percentage of DMPC approached the micellar phase boundary, Rh values uniformly diverged (50 to approximately 150 A); with the percentage of DMPC in excess of the micellar phase boundary, large Rh values (200-300 A) were observed that were consistent with unilamellar apo A-I/DMPC or apo A-II/DMPC vesicles. Decreases in total solute concentration (1.0-0.25 mg/mL) and/or elevations in temperature (25-37 degrees C) shifted micellar phase limits to lower percentages of DMPC in the case of both apolipoproteins. Although apo A-I interacted spontaneously with DMPC at 25 degrees C, it was necessary to dilute mixed micellar solutions of sodium taurocholate (TC) and egg yolk phosphatidylcholine (EYPC) with apo A-I solutions to form apo A-I/EYPC mixed micelles. Despite the presence of submicellar concentrations of TC (below 3 mM, the lower limit of its critical micellar concentration), Rh values of apo A-I/EYPC mixed micelles were similar to those observed for the apo A-I/DMPC system. Dilution of micellar TC/EYPC solutions with low concentrations of apo A-I (0.001-0.10 mg/mL) influenced the width of the mixed micellar zone, the kinetics of micelle-to-vesicle transitions, and the size of metastable vesicles. Dilution with higher apo A-I concentrations (0.05 and 0.1 mg/mL) resulted in the transformation of bile salt rich EYPC micelles into apo A-I rich EYPC micelles with an intervening zone of metastable vesicles. The micelle-to-vesicle transition was abolished by dilution with an apo A-I concentration of 0.5 mg/mL, suggesting that bile salts and apo A-I can directly interchange in micellar solubilization of EYPC.(ABSTRACT TRUNCATED AT 400 WORDS)

Apolipoprotein A-I↗

5-year experience with intravesical therapy of carcinoma in situ: an inquiry into the risks of "conservative" management.

Recent reports of disease progression in patients being treated with intravesical agents for carcinoma in situ of the bladder led us to examine our 5-year experience with 26 consecutive patients with carcinoma in situ treated with intravesical therapy for this lesion. Nine patients with isolated carcinoma in situ and 17 with carcinoma in situ associated with papillary lesions were treated intravesically with a variety of agents in a closely monitored program for a mean of 22 months. All patients wished to exhaust conservative options before accepting cystectomy. Of 26 patients treated 9 (35 per cent) have no evidence of disease with a functional bladder after 27 months, 13 (50 per cent) are treatment failures and 4 (15 per cent) maintain an equivocal status to date. Successful treatment results with each drug were 6 of 24 thiotepa, 0 of 7 mitomycin, 0 of 6 doxorubicin and 3 of 8 bacillus Calmette-Guerin. Treatment failure was associated with disease progression to muscle invasion, adjacent organ invasion or metastases in 7 patients (27 per cent). Significant reduction in bladder capacity after prolonged therapy occurred in 3 patients. Our results suggest that persistent, intensive, "conservative" intravesical therapy in the face of recurrent or persistent disease is associated with substantial patient risk.

Administration, Intravesical↗

Brief dynamic psychotherapy: toward a more comprehensive model.

Previous schools of brief dynamic psychotherapy, however valuable, have rejected the majority of potential patients. When the brief therapy method was experimentally extended to include most who applied, a new, more comprehensive model emerged. I discovered that many patients arrive in therapy not simply with a focal issue but, beneath that, with a pathogenic belief, i.e., a negative conviction about self engendered by unconscious guilt toward primary objects. I have found this pathogenic belief to be a most economic subject for brief therapy. Moreover, unverbalized but specific relationship interventions often represent a more effective treatment strategy to combat pathogenic belief than does interpretation alone. Critical review of previous work and a case illustration demonstrate that the new model speaks to important controversies in the theory and the practice of brief psychotherapy.

Adult↗

An etiologic model of alcoholism.

As we await a successful model of the etiology of alcoholism, research and intervention strategies founder. The author critically reviews the present etiologic models, particularly those bearing on alcoholic personality. The central shortcoming of these models is that they pay only lip service to the multidimensional etiology of alcoholism. Hereditary, environmental, and psychostructural risk factors have never been adequately integrated into any one design. The author explains the difficulties that this problem and others have introduced into the previous etiologic research. In the conclusion, he constructs a new model from the positive findings thus far. This, in turn, suggests the studies needed next and has definite diagnostic and therapeutic implications.

Alcohol Drinking↗