Biomedical subjects
Publications and source records attributed to R Kessler.
Free flow electrophoresis was used to examine the influence of active substances, lipid composition and preparation method on the surface charge of the liposomes. It is also possible to test the homogeneity of a liposome population with FFE.
We reviewed current blood conservation techniques and their use in cardiac surgery. Avoidance of aspirin preoperatively is an important blood conservation measure. Patients scheduled for an elective operation should participate in autologous predonation programs. With careful monitoring, patients with major coronary artery disease can safely donate blood preoperatively. Intraoperative processing of blood withdrawn before cardiopulmonary bypass provides autologous platelet-rich plasma for infusion after reversal of heparin sodium. Blood collected from the field during operation and blood remaining in the oxygenator after bypass can also be processed to yield washed and concentrated red blood cells for reinfusion. Randomized, prospective studies document that postoperative autotransfusion is both safe and effective in reducing homologous blood use. Aprotinin reduces plasma protein activation and platelet damage during bypass. The integration of available blood conservation techniques into a comprehensive program combined with careful consideration of the indications for transfusion may allow more patients to avoid transfusion entirely.
To determine the etiology of self-reported depressive symptoms and their co-occurrence in the general population, multivariate genetic models were fitted to the responses of 771 female twin pairs (463 MZ, 308 DZ) to a 20-item epidemiological depression inventory (CES-D scale). A model which contained one common genetic factor, one shared environmental factor, and four unique environmental factors provided a useful account of symptom covariation. Under this model, the four non-shared environmental factors explained the largest proportion of variance in response to the CES-D scale, whereas a single common genetic factor explained substantially less of the variation in symptomatology. Consistent with previous findings (Kendler, Heath, Martin, & Eaves, Archives of General Psychiatry 43, 213-221, 1986) shared environmental influences were found to play a relatively minor role in the report of depressive symptoms. These results suggest that while genetic factors do contribute to the covariation among symptoms of depression, it is the largely non-shared environmental factors that account for the co-occurrence of symptoms in the general population.
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The release of endothelium-derived relaxing factor (EDRF) from human corpus cavernosum (CC) tissue was confirmed by demonstrating that bradykinin produces endothelium dependent relaxation of human CC tissue. Human CC strips were set in a tissue bath and isometric tension changes were recorded. All strips showed spontaneous contractions and produced tonic contractions by both high potassium solution and noradrenaline (NA) (10(-9) to 10(-4) M) in a dose dependent manner. In preparations precontracted with NA, relaxation was produced by bradykinin (10(-7) to 2 x 10(-6) M). Strips lacking endothelium were contracted by NA but no relaxation was observed with the addition of bradykinin. More direct evidence of the release of EDRF from human CC was demonstrated by a "sandwich" mount. We conclude that bradykinin relaxes human CC by releasing EDRF and that this EDRF may be a factor in erectile function.
The relaxation mechanism of the antispasmodics, papaverine and thiphenamil on isolated human corpus cavernosum (CC) was investigated. CC tissues were obtained from 12 impotent men undergoing surgery for insertion of penile prostheses. CC preparations were mounted in a tissue bath and the isometric tension was recorded. Papaverine and thiphenamil consistently inhibited high-potassium ([K])-induced contractions in a dose-dependent manner. Noradrenaline (NA)-induced contractions were inhibited by both agents in a non-competitive manner. The pD'2 values were 4.77 +/- 0.20 for papaverine and 4.58 +/- 0.13 for thiphenamil. Papaverine at 10(-4) M, the concentration at which high-[K]-induced contraction was abolished, suppressed NA-induced contraction by approximately 85%. In the Ca2(+)-free solution containing two mM EGTA, NA-induced contraction was suppressed by approximately 90%. This contraction was inhibited by papaverine or thiphenamil in a dose-dependent manner and was abolished by papaverine at 10(-4). These results suggest that papaverine and thiphenamil relax CC tissue by the inhibition of extracellular Ca2+ influx (mainly voltage-dependent Ca2+ influx) and by the inhibition of release and/or storage of intracellular stored Ca2+.
The syndrome of ovarian hyperstimulation is a little known aetiology of pleural effusion. It should be thought of in young women who are under treatment to induce ovulation. Serous effusions which occur in these cases are a serious sign. The effusions are exudates and not transudates as occurs in Demons-Meigs syndrome. The treatment which will be undertaken ought to consider the possibility that a pregnancy is underway.
A gentle and rapid isolation procedure is described yielding fractions containing better than 95% pure OmpF porin of Escherichia coli BE with different amounts of bound lipopolysaccharide (LPS). The procedure employs continuous free-flow electrophoresis (FFE) in the presence of detergent above its critical micelle concentration. Total yields of around 45% were typically obtained when porin-enriched membrane extracts were processed. By use of analytical ultracentrifugation a molecular mass of 114,000 and a sedimentation coefficient S20,w of 5.0 S were determined for porin trimers containing approximately 1 mol of tightly bound LPS. This porin readily formed 3D crystals suitable for high-resolution X-ray diffraction analysis. Three other porin-LPS isoforms isolated by FFE revealed molecular masses of 120,000, 124,000, and 151,000, suggesting that, in addition to the tightly bound LPS, 1, 2, and 8 mol of loosely bound LPS were present per mole of porin trimer. Each of the four different isoforms was suitable for reconstitution into highly ordered protein-lipid membrane arrays. The membrane crystals obtained with the 151-kDa isoform exhibited a unit cell polymorphism similar to that previously reported.
Temporal lobe glucose metabolic rate was assessed in 21 off-medication patients with schizophrenia and 19 normal controls by positron emission tomography with 18F-deoxyglucose. Patients with schizophrenia had significantly greater metabolic activity in the left than the right anterior temporal lobe, and the extent of this lateralization was in proportion to the severity of psychopathology.
In permeabilized yeast cells 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase are studied during growth. It is shown that in yeast at least two fructose 2,6-bisphosphate degrading enzyme activities occur, differing in pH profile and in their substrate affinities. The activities of 6-phosphofructo-2-kinase and of fructose-2,6-bisphosphatases drop in the exponential and the transition phase while the activity of the alkaline phosphatases steadily increases. In the stationary phase the activities of 6-phosphofructo-2-kinase and of the low Km fructose-2,6-bisphosphatase increase again. Yeast 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase were purified and separated from each other. The purified 6-phosphofructo-2-kinase was found to exhibit a very high specific activity (1.3 U/mg). The enzyme is efficiently inhibited by ATP. The ATP inhibition is most pronounced at low concentrations of magnesium and fructose-6-phosphate. Phosphoenolpyruvate and sn-glycerol 3-phosphate are inhibitors of the enzyme. The high-affinity yeast fructose-2,6-bisphosphatase releases inorganic phosphate from the 2-position of fructose 2,6-bisphosphate. It displays hyperbolic kinetics towards fructose 2,6-bisphosphate (Km = 0.3 microM) and is strongly inhibited by fructose 6-phosphate. The inhibition is counteracted by sn-glycerol 3-phosphate. The enzyme is shown to be inactivated by cAMP-dependent phosphorylation and reactivated by the action of protein phosphatase 2A.
Our ten-year experience from September, 1975, to December, 1985, with 417 penile prostheses in 290 patients is presented. Arteriosclerosis and diabetes mellitus were the two most common causes of impotence in our patient population. The Scott inflatable penile prosthesis accounted for the majority of all implants and all device failures. Complications leading to device failure and/or reoperation occurred in 36 percent of all prostheses. However, including repairs, 91 percent of patients were left with a functional prosthesis. Examination of reoperated patients showed an average increase in corporeal length of 1.67 cm with repeat prosthesis operations (p less than 0.001). No increase in incidence of prosthesis failure could be shown after multiple reoperations.
We present our experience with implantation of penile prostheses in 6 organ transplant recipients, including 2 patients after renal transplantation and 4 patients after cardiac transplantation. We have seen no problems related to prosthesis surgery in this patient population, and in particular have experienced no infectious complications. All patients received strict perioperative antibiotic and steroid coverage. We conclude that erectile impotence in the male organ transplant patient can be successfully treated with penile prosthesis surgery without incurring undue morbidity and with considerable benefit in terms of quality of life in a generally young patient population.
Between July 1985 and September 1987 we implanted 51 Hydroflex* penile prostheses for treatment of erectile impotence, with a minimum followup of 6 months in all patients and more than 1 year in 43. There have been no mechanical failures and no major complications. Of 47 evaluable patients 38 (81 per cent) are satisfied with the prosthesis. The 9 dissatisfied patients include 3 men who still are experiencing some difficulty operating the pump mechanism and 6 who desired a fuller or stiffer erection than provided by the Hydroflex prosthesis. All of the latter 6 individuals have successfully engaged in intercourse with the Hydroflex device. The patient who previously received a Scott inflatable penile prosthesis may not be as content with the erect state of the Hydroflex device. It also is important to assure adequate distal corporeal length before placement of the Hydroflex prosthesis.
Injectable materials have been used to augment the urethral sphincter and improve urinary continence with some success. However, none of these materials has received widespread use because they are difficult to inject and have been reported to migrate. We investigated the efficacy of transurethral implantation of glutaraldehyde cross-linked collagen, a highly purified bovine collagen. A total of 17 patients (16 men and 1 woman) with urinary incontinence resulting from a previous operation was selected for glutaraldehyde cross-linked collagen injection into the region of the urethral sphincter. Before and after implantation patients underwent urodynamic evaluation. Glutaraldehyde cross-linked collagen was injected into the area of the bladder neck or urinary sphincter under direct endoscopic vision. If no improvement occurred reinjection to increase the implant volume was performed at least 3 months after a previous injection. Of the 17 patients 9 were cured or improved. No complications have been reported. This investigation shows that glutaraldehyde cross-linked collagen can be injected into the urinary tract to correct urinary incontinence without observable or measurable morbidity.
The North-American Trial (NOTT) and the British MRC study clearly indicated that long-term oxygen therapy (LTO) increases the survival rate of patients with severe chronic obstructive long disease (COLD), but O2 must be given for more than 15 h/24 h. At present OT is largely prescribed in COLD patients whose (stable) PaO2 less than or equal to 55 mmHg. The pulmonary haemodynamic effects of OT are still a matter of debate. The first studies, in 1967, indicated that continuous O2 for 6-8 weeks could markedly improve pulmonary hypertension (PH). In the MRC study there was no change in pulmonary artery mean pressure (PAP) in patients receiving O2 for more than 15 h/day, whereas patients not receiving O2 exhibited a progressive increase of PH. In the NOTT study there was a modest but significant improvement of PAP after 6 months in those patients receiving "continuous OT" (in fact greater than 18 h/day), but not in patients receiving only nocturnal OT. In our own study, we found that OT could reverse the progression of PH in COLD patients. In 16 carefully studied patients, PAP increased from 23.3 +/- 6.8 to 28.0 +/- 7.4 mmHg (p less than 0.01) before the initiation of OT (mean duration of follow-up = 48 months) and then decreased to 23.9 +/- 6.6 mmHg (p less than 0.05) during OT (mean duration of follow-up = 31 months). The average yearly change in PAP was +1.5 mmHg before OT, and -2.1 mmHg under OT and the difference was highly significant (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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Cost containment need not be imposed on physicians by government, insurance companies and hospital administrators. Decreases in hospital cost can be achieved voluntarily by physicians without sacrificing quality of care, especially for common procedures with relatively homogeneous patient populations, such as transurethral prostatectomy. Variations in existing practice were identified and shared, and optimal scientific practice was discussed at 5 meetings of the division of urology during a 16-month period. Strict guidelines were not developed; surgeons were encouraged to apply cost-related knowledge individually. Resource use was measured before, during and after the intervention. A total of 356 transurethral prostatectomies was studied. There were significant decreases in preoperative and postoperative length of stay, specific ordering practices and total hospital charges. University faculty differed from community urologists and individual surgeons varied considerably. Suggestions for scientific cost management in prostatectomy are presented.