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R Simon

Publications and source records attributed to R Simon.

At least 37 records · Page 2Linked to original sources
PubMed1994

Prospects for reform of hospital fees in sub-Saharan Africa: a case study of Niamey National Hospital in Niger.

Hospital finance in developing countries has attracted increasing attention in recent years as economists and health planners have examined whether financial reforms will make public hospitals more financially autonomous and consequently reduce (or limit the increase in) their share of government health budgets. This paper presents estimates of the effects of some reforms of hospital user fees on total hospital revenue and on the amount of fees paid by patients in various payor categories. The reforms include special fees for non-referred patients and changes in exemptions for some categories of patients and types of care. The estimates show that doubling fees for non-referred patients increases revenue more than charging them prices equal to operating costs, because current fees are not uniformly less than operating costs. Eliminating exemptions can be as important as changing fees. For example, eliminating exemptions for surgery and inpatient diagnostic exams increases the percentage of operating costs recovered by the same amount as doubling prices for non-referred patients in estimates with an elasticity of demand equal to zero.

Fees, Medical↗
PubMed1994

Evidence for partial sympathetic cardiac reinnervation following cardiac transplantation.

Heart transplantation causes total cardiac denervation. Measurements of plasma concentrations of the main presynaptic noradrenal metabolite, dihydroxyphenylglycol (DOPEG, exclusively neuronal in origin), were used to examine the possibility of sympathetic reinnervation of the transplanted human heart. We determined arterial and coronary-venous plasma concentrations of DOPEG in 15 heart transplant recipients (28-68 years of age at the time of transplantation with the transplant ageing from 0.5 to 4 years at the time of investigation) and in nine control patients (45-75 years of age). In each of the control patients the DOPEG concentration was higher in coronary venous plasma than in arterial plasma (mean arteriovenous increment: 60 +/- 10%; P < 0.001). In the heart transplant recipients nine patients showed an arteriovenous increment in plasma DOPEG. For the mean group results it was found that the ratio of the coronary-venous to arterial DOPEG concentration was positively correlated with the time after transplantation (r = 0.92; n = 5; P < 0.05). Thus, our data provide neurochemical evidence for partial sympathetic reinnervation in some of the heart transplants. Moreover, it is suggested that the time after transplantation is unlikely to be the only determinant for the occurrence and extent of sympathetic reinnervation.

Adult↗
PubMed1994

A possible vulnerability locus for bipolar affective disorder on chromosome 21q22.3.

In a preliminary genome scan of 47 bipolar disorder families, we detected in one family a lod score of 3.41 at the PFKL locus on chromosome 21q22.3. The lod score is robust to marker allele frequencies, phenocopy rates and age-dependent penetrance, and remains strongly positive with changes in affection status. Fourteen other markers in 21q22.3 were tested on this family, with largely positive lod scores. Five of the other 46 families also show positive, but modest lod scores with PFKL. When all 47 families are analysed together, there is little support for linkage to PFKL under homogeneity or heterogeneity using lod score analysis, but the model-free affected-pedigree-member method yields statistically significant results (p < 0.0003). Our results are consistent with the presence of a gene in 21q22.3 predisposing at least one family to bipolar disorder.

Adolescent↗
PubMed1994

A pedigree series for mapping disease genes in bipolar affective disorder: sampling, assessment, and analytic considerations.

A series of 57 extended pedigrees with high density of bipolar affective disorder is described. Ascertainment and diagnostic procedures are documented and simulation studies to assess statistical power are carried out. The pedigrees, obtained in the US and Israel, are comprised of 1508 adult individuals with best estimate consensus diagnoses (12-71 relatives per pedigree), 490 of whom (including 401 sib pairs) meet criteria for a conservative disease definition (bipolar disorder or recurrent major depression). Cell lines have been established on 1324 of these individuals. Statistical power to detect linkage with lod score analysis, assuming autosomal dominant transmission and highly polymorphic DNA markers, is nearly 100% for alpha (proportion of linked families) = 30%, and 75% for alpha = 20%. This is the largest bipolar pedigree series reported to date; its unique features make it amenable to various gene detection techniques.

Bipolar Disorder↗
PubMed1994

Further analysis of cytoplasmic polyadenylation in Xenopus embryos and identification of embryonic cytoplasmic polyadenylation element-binding proteins.

Early development in Xenopus laevis is programmed in part by maternally inherited mRNAs that are synthesized and stored in the growing oocyte. During oocyte maturation, several of these messages are translationally activated by poly(A) elongation, which in turn is regulated by two cis elements in the 3' untranslated region, the hexanucleotide AAUAAA and a cytoplasmic polyadenylation element (CPE) consisting of UUUUUAU or similar sequence. In the early embryo, a different set of maternal mRNAs is translationally activated. We have shown previously that one of these, C12, requires a CPE consisting of at least 12 uridine residues, in addition to the hexanucleotide, for its cytoplasmic polyadenylation and subsequent translation (R. Simon, J.-P. Tassan, and J.D. Richter, Genes Dev. 6:2580-2591, 1992). To assess whether this embryonic CPE functions in other maternal mRNAs, we have chosen Cl1 RNA, which is known to be polyadenylated during early embryogenesis (J. Paris, B. Osborne, A. Couturier, R. LeGuellec, and M. Philippe, Gene 72:169-176, 1988). Wild-type as well as mutated versions of Cl1 RNA were injected into fertilized eggs and were analyzed for cytoplasmic polyadenylation at times up to the gastrula stage. This RNA also required a poly(U) CPE for cytoplasmic polyadenylation in embryos, but in this case the CPE consisted of 18 uridine residues. In addition, the timing and extent of cytoplasmic poly(A) elongation during early embryogenesis were dependent upon the distance between the CPE and the hexanucleotide. Further, as was the case with Cl2 RNA, Cl1 RNA contains a large masking element that prevents premature cytoplasmic polyadenylation during oocyte maturation. To examine the factors that may be involved in the cytoplasmic polyadenylation of both C12 and C11 RNAs, we performed UV cross-linking experiments in egg extracts. Two proteins with sizes of ~36 and ~45 kDa interacted specifically with the CPEs of both RNAs, although they bound preferentially to the C12 CPE. The role that these proteins might play in cytoplasmic polyadenylation is discussed.

Age Factors↗
PubMed1994

[Hemodynamic effects of non-ionic iomeprol 350 and ionic diatrizoate 370 during levocardiography and coronary angiography--double-blind randomized comparison of 2 contrast media].

A double-blind randomized study was performed in 49 patients to compare the hemodynamic changes induced by two contrast agents: non-ionic low osmolar lomeprol 350 (IO, n = 25) and ionic high osmolar Diatrizoat 370 (DIA, n = 24). We observed significant changes in hemodynamic parameters after laevocardiography with DIA: a decrease in LVSP from 125 +/- 14 to 113 +/- 14 mmHg, a decrease in mean aortic pressure from 96 +/- 9 to 84 +/- 10 mmHg and in max dp/dt from 2086 +/- 628 to 1861 +/- 654 mm Hg/sec. LVEDP increased from 13 +/- 5 to 17 +/- 6 mmHg and cardiac output from 5.9 +/- 1.2 to 7.7 +/- 1.2 l/min. Heart-rate also rose slightly, but insignificant. IO did not alter these parameters. After selective coronary angiography both groups did not differ significantly in systolic aortic pressure, but DIA caused a drop in diastolic aortic pressure after 10 to 15 sec and a bradycardia in the first five sec, in contrast to IO. These effects can be explained by a cardiodepressive action of contrast agents on left ventricular function, an increase in circulating volume and a reduced peripheral vessel resistance. Differences between both agents are probably due to their different osmolality. IO is a safe contrast agent, compatible in contrast to DIA. In patients with borderline left-ventricular function, IO is preferable, it exerts only very slight effects on cardiovascular function.

Adult↗
PubMed1994

[Directional coronary atherectomy: effect of vessel size on primary results and long-term results].

Of 325 consecutive patients undergoing DCA, 263 patients with 277 stenoses were successfully treated with DCA alone and had angiographic follow-up 3-6 months later. Depending upon the initial reference diameter (RD) patients were divided into two subgroups: group I (n = 159) with a RD > 3 mm and group II (n = 104) showing a RD < or = 3 mm. In contrast to other series DCA was predominantly performed with 7F atherectomy devices using balloon inflation pressures of approximately 5 atm. Angiographic data including the minimal luminal diameter (MLD), percentage of stenosis (%D) and reference diameter (RD) were assessed by quantitative computer-assisted analysis before (pre), after (post) DCA and at a 3-6 months angiographic follow-up (FU). The percentage of diameter stenosis pre/post/FU in group I was 59.9 +/- 12.6%/18.4 +/- 12.8%/29.8 +/- 17.6%, and in group II 55.6 +/- 10.8%/17.8 +/- 12.3%/33.7 +/- 16.1% with a net gain at FU of 1.0 +/- 0.89 mm for group I and 0.86 +/- 0.66 mm for group II. Based on an angiographic restenosis criterion of at least 50% diameter obstruction at FU and or recurrence of symptoms warranting interventional re-treatment of the target lesion, the incidence of restenosis in group I was 20.6% and in group II 28.0% (p: n.s.). There was no significant difference between the two groups concerning complications. Our data show that DCA leads to a satisfying long-term result.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Bicaval versus atrial anastomoses in cardiac transplantation. Right atrial dimension and tricuspid valve function at rest and during exercise up to thirty-six months after transplantation.

Conventional cardiac transplantation with atrial anastomoses alters atrial integrity, geometry, and possibly function. Theoretically, this may also contribute to the development of tricuspid insufficiency that is frequently observed after the operation. Thus more anatomic transplantation techniques using bicaval anastomoses were recently introduced into clinical practice. Knowledge of their efficacy, however, is scarce. Therefore right atrial size and tricuspid valve function were compared in patients with bicaval (group A) and standard atrial (group B) anastomoses in a randomized, prospective study. The results of this echocardiographic study at rest and exercise in 18 patients (bicaval n = 8; atrial n = 10) on the average 28 months after transplantation are presented. The right atrial dimension was comparable between group A patients and control subjects and larger in group B patients (p < 0.05). The incidence of tricuspid regurgitation was not different between the two groups at rest, but it was at exercise (50 watts of workload) (p < 0.05). This study suggests that up to 36 months after cardiac transplantation the technique of bicaval in contrast to atrial anastomoses preserves right atrial size and reduces tricuspid regurgitation during exercise. Whether this leads to improved hemodynamics and increased exercise capacity remains to be evaluated in a larger series of patients.

Cardiac Output, Low↗
PubMed1994

Cyclosporin A and transplant coronary disease after heart transplantation: facts and fiction.

From published data in the currently available literature on animal experiments, it can be concluded that CyA may be involved in the development of hypertension and renal dysfunction. These side effects are probably related to a disturbed vasomotor tone and a pathologic reaction to physiologic vasoconstrictive and vasodilative agents following administration of high doses of CyA. These effects are dose related and reversible and were undetected at clinically applied levels of immunosuppression. It therefore appears to be unlikely that this pathologic response is operative in precipitating or promoting TCD, which is supported by findings of in vivo and in vitro studies on human coronary arteries as well as by comparison of immunosuppressive protocols comparing series with and without application of CyA. Chronic graft dysfunction, as depicted by late mortality in heart and isolated lung transplant recipients and by loss of kidney allograft survival, yields an annual rate of between 4 and 6% per year. It is only in heart transplantation that TCD has been tried to be associated with CyA application. If CyA-related damage were to occur in coronary arteries independent from immunologic factors, the incidence of coronary disease should be similar in heart, lung, liver, and kidney transplants. This is not the case. Although continuous investigation on the side effects of immunosuppressive agents is definitely necessary, we should concentrate our research activities on potential prophylactic and therapeutic measures to overcome the single most important risk factor of long-term surviving patients after solid organ transplantation: chronic rejection.

Animals↗
PubMed1994

[Dynamic online quantification of left ventricular function by automated boundary detection: validation of a new echocardiography method].

A recently developed ultrasonic integrated backscatter imaging system allows automated border detection (ABD) of the blood-tissue interface in real time and provides instantaneous measurement of left ventricle cavity area in a beat-to-beat fashion. Three validations of this new system have been performed. 1) In 70 subjects (38 normal volunteers and 32 patients) the on-line ABD-derived areas (end-diastole, -systole = EDA, ESA) and the resulting fractional area change (FAC) of the left ventricle (apical four-chamber view) were compared with the off-line areas and FAC traced manually. All correlations were close (EDA r = 0.97, ESA r = 0.98, FAC r = 0.92; p < 0.0001). 2) In 36 patients with mitral regurgitation (MR), ABD-FAC was compared to the Doppler-derived systolic rate of pressure rise (RPR) which corresponds to systolic dP/dt, as simultaneous studies with high-fidelity pressure measurements have shown. Linear regression analysis yielded a significant correlation with r = 0.91; p < 0.0001. 3) In 26 patients undergoing routine heart catheterization, ABD-echo was performed on the same day. ABD-derived areas (end-diastole, -systole) and FAC (apical two- and four-chamber view) were compared to the corresponding angiographic data derived from biplane projection in 30 degrees RAO and 60 degrees LAO. Linear regression analysis yielded significant values for all correlations (EDA r = 0.88, ESA r = 0.95, FAC 0.90; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Echocardiography online quantification of left and right ventricular function by automatic boundary detection: reference values and reproducibility in healthy probands].

UNLABELLED: Automated border detection (ABD) is a new on-line technique that instantaneously calculates cavity areas from automatic tracking of the endocardial-blood interface with a modified ultrasonic integrated backscatter imaging system. After validation of this new method in comparison with off-line echocardiographic, Doppler- and angiographic analyses, we studied dynamic systolic and diastolic function of the left (LV) and right ventricle (RV) in 50 normal volunteers (31 +/- 9 years) in order to establish ranges of normality for the ABD-parameter. The averaged areas of the LV (apical chamber view) were 25.7 +/- 4.9 sq cm in end-diastole and 14.7 +/- 3.3 sq cm in end-systole, resulting in a fractional area change (FAC) of 43.2 +/- 4.8%. The peak filling (PFR) and peak ejection rate (PER) were 69.3 +/- 11.2 and -61.5 +/- 11.1 sq cm/s. Normalization for end-diastolic area (EDA) yielded 2.7 +/- 0.28 and -2.4 +/- 0.42 EDA/s. The areas of the RV (apical chamber view) were 17.1 +/- 3.8 sq cm in end-diastole and 9.0 +/- 2.0 sq cm in end-systole, resulting in a FAC of 47.3 +/- 9.2%. PFR and PER were 58.2 +/- 13.7 and -51.6 +/- 10.1 sq cm/s. Normalization for EDA yielded 3.4 +/- 0.74 and -2.9 +/- 0.62 EDA/s. The interobserver- and day-to-day-variability for all measured values was less than 10%. CONCLUSION: ABD permits reproducible on-line quantification of systolic and diastolic ventricular function and offers a non-invasive approach for longitudinal monitoring of cardiac patients.

Adult↗
PubMed1994

[Neurochemical studies of adrenergic reinnervation after heart transplantation].

Heart transplantation causes sympathetic cardiac denervation. Measurements of plasma concentrations of the main presynaptic noradrenaline metabolite, dihydroxyphenylglycol (DOPEG, the plasma pool of which is exclusively neuronal in origin), were used to examine sympathetic reinnervation of the transplanted human heart. We determined arterial and coronary-venous plasma concentrations of DOPEG in 27 heart transplant recipients (transplant age ranging from 0.5 to 5 years) and in 9 control patients. In each of the control patients the DOPEG concentration was higher in coronary venous plasma than in arterial plasma (mean arterio-venous increment: 57.3 +/- 8.7%; p < 0.001). However, in heart transplant recipients, 18 out of 27 patients showed an arteriovenous increment in plasma DOPEG (mean increment in all patients 12.6 +/- 2.0%; p < 0.05). The ratio of the coronary-venous to arterial DOPEG concentration was positively correlated with the time after transplantation (p = 0.02 for individual results and p < 0.01 for mean group results). Thus, our data provide evidence for a time-dependent partial sympathetic reinnervation of the transplanted heart.

Adrenergic Fibers↗
PubMed1994

Practical Bayesian guidelines for phase IIB clinical trials.

A Phase IIB clinical trial typically is a single-arm study aimed at deciding whether a new treatment E is sufficiently promising, relative to a standard therapy, S, to include in a large-scale randomized trial. Thus, Phase IIB trials are inherently comparative even though a standard therapy arm usually is not included. Uncertainty regarding the response rate theta s of S is rarely made explicit, either in planning the trial or interpreting its results. We propose practical Bayesian guidelines for deciding whether E is promising relative to S in settings where patient response is binary and the data are monitored continuously. The design requires specification of an informative prior for theta s, a targeted improvement for E, and bounds on the allowed sample size. No explicit specification of a loss function is required. Sampling continues until E is shown to be either promising or not promising relative to S with high posterior probability, or the maximum sample size is reached. The design provides decision boundaries, a probability distribution for the sample size at termination, and operating characteristics under fixed response probabilities with E.

Bayes Theorem↗
PubMed1992

[An aortopulmonary shunt after a knife wound].

An extensive hemopneumothorax developed in a 23-year-old man after having been knifed in the region of the left nipple. After general surgical care a Bülau suction drain was inserted. Cardiological examination became necessary a week later when a chest X-ray film demonstrated an enlarged cardiac silhouette. Echocardiography revealed pericardial effusion (about 600 ml) which was removed by pericardial aspiration. Cross-sectional and colour Doppler echocardiography showed a shunt between the aorta and right ventricular outflow tract at the origin of the pulmonary artery. At surgery a fistula between the root of the aorta and the pulmonary artery was identified (the posterior sinus near the anulus was nearly completely detached). The fistula was closed and the pulmonary valve reconstructed. The early and late postoperative course was unremarkable.

Adult↗
PubMed1992

[Colonic complications of acute necrotizing pancreatitis].

Among 126 patients operated upon for acute necrotizing pancreatitis in our department over a 10-year period starting in November 1979, 17 had a colonic resection. Colectomy was made mandatory by a necrotic or ischaemic appearance (12 cases, including 3 bowel perforations), an isolated perforation (2 cases) or extensive fat necrosis of the pericolonic atmosphere (3 cases). The hospital mortality was 5 out of the 17 cases. In 6 patients, the pathological results suggested that colonic resection was unnecessary. Since May 1988, a diverting loop ileostomy has been performed whenever colonic viability was found to be dubious at laparotomy. After this policy was introduced no case of secondary colonic complication was encountered. Nevertheless, there still are "abusive" colectomies unjustified by the pathology. Their number should be reduced by a more cautious indication of colonic resection in acute necrotizing pancreatitis.

Acute Disease↗
PubMed1992

Statistical model to determine the relationship of response and survival in patients with advanced ovarian cancer treated with chemotherapy.

BACKGROUND: A statistically appropriate analysis of the association between survival and response measures in patients with ovarian cancer could help to define the role of response rate in planning, monitoring, and interpreting the results of clinical trials. PURPOSE: This study was designed to investigate the relationship between antitumor response determined by clinical or pathological means and survival in patients with advanced ovarian cancer with no previous treatment. We focused on avoiding the limitations of the usual approach of comparing durations of survival for patients responding to therapy with those for nonresponders. METHODS: A new meta-analytic statistical model we developed was used to analyze data from 26 randomized clinical trials published between 1975 and 1989. Our model incorporates intra-study and inter-study sources of variability in the estimates of response and survival. The study also addresses the methodological problems of evaluating response as a surrogate end point and the relevance of this association to clinical decision making and the design of clinical trials. RESULTS: For 13 studies in which response was pathologically assessed, an improvement in surgically documented complete response rate was associated with an increase in median survival. A similar but apparently smaller effect was found for the association between objective clinical response and median survival in the 25 studies reporting these data. CONCLUSIONS: These results suggest that therapeutic measures must produce large improvements in clinical response rates to achieve meaningful effects on median survival. Improvement in surgically documented complete response rate appears to be more strongly associated with increased median survival and, hence, might be used for interim monitoring in clinical trials, but the role of second-look procedures in clinical management is controversial.

Antineoplastic Combined Chemotherapy Protocols↗