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Biomedical subjects

P Simon

Publications and source records attributed to P Simon.

At least 325 records · Page 18Linked to original sources
PubMed1988

Pharmacokinetics of desferrioxamine and of its iron and aluminum chelates in patients on peritoneal dialysis.

We have studied the pharmacokinetics of desferrioxamine (DFA), ferrioxamine (FeA) and aluminoxamine (AlA) in patients with chronic renal failure on continuous ambulatory peritoneal dialysis (CAPD) after 10 mg/kg (15.24 mumol/kg) body weight desferrioxamine (DESFERAL) administration by intramuscular and intraperitoneal routes. The results show an easy exchange of DFA between the plasma and the peritoneal fluid regulated by the relative concentrations of DFA in the two compartments. When the equilibrium is reached, the concentration of DFA are approximately the same in the plasma and the peritoneal fluid.

Aged↗
PubMed1988

Reversal of helpless behavior in rats by putative 5-HT1A agonists.

This study is designed to measure effects of serotonin 1A (5-HT1A) agonists on escape deficits produced by inescapable shock in rats--a model of learned helplessness. Rats were first exposed to 60 inescapable shocks (15-sec duration, 0.8 mA, every 1 min +/- 15 sec), and 48 hr later, they were subjected to daily 15-min shuttle-box sessions (30 trials/day) on 3 consecutive days. Twice daily intraperitoneal injection of buspirone (total daily dose of 0.5 and 1 mg/kg), gepirone (0.06 and 0.125 mg/kg), 8-OH dipropylamino-tetralin (8-OH-DPAT) (0.03, 0.06, 0.125, and 0.25 mg/kg), and ipsapirone (TVXQ 7821) (0.03 and 0.06 mg/kg) eliminated escape failures. This indicates that an antidepressant-like effect--reversal of helpless behavior--can be obtained with drugs assumed to stimulate serotonin 1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Carrier prediction of cystic fibrosis in 36 families by means of restriction fragment length polymorphism.

Transmission of cystic fibrosis (CF) was studied in 36 families with at least one affected and one unaffected child. DNA was prepared from peripheral leukocytes and submitted to restriction fragment length polymorphism (RFLP) analysis with two CF probes (pj3.11 and met). Twenty families were shown to be informative so that accurate predictions could be made of the status of the offspring. Sixteen were only partially informative. The allele frequency was similar to that originally reported except for one Msp I site detected with the pj3.11 probe, for which we found a significantly higher heterozygote frequency, making it more informative than expected in our population sample. Pedigree analysis demonstrated no obligate recombinant between CF and the polymorphic markers.

Cystic Fibrosis↗
PubMed1988

Antidepressant-like effects of triiodothyroacetic acid in mice.

Triiodothyroacetic acid (TA3) is a natural thyroid analogue which possesses some of the properties of triiodothyronine (T3). In particular, it has an inhibitory effect on the thyreotropic axis, but its peripheral effects are reduced. Given the activity of T3 on psychopharmacological models of depression in rodents, we investigated the effects of TA3 on some pharmacological and behavioral tests in mice. TA3 antagonized apomorphine- and oxotremorine-induced hypothermia, potentiated yohimbine-induced toxicity and L-5-hydroxy-tryptophan-induced head twitches, but did not affect forced swimming-induced immobility or reserpine-induced hypothermia. Thus, TA3 was effective on the same psychopharmacological tests which have previously been used to demonstrate the antidepressant-like effects of T3. Moreover, TA3 under the same experimental conditions as T3 has little effect on the metabolic clearance rate parameters, and might, therefore, be preferable to T3 for clinical use in depression.

Animals↗
PubMed1988

Toluene diisocyanate-induced airway hyperresponsiveness to intravenous acetylcholine: a study on single and repeated exposure in guinea-pigs.

We examined the changes in airway responsiveness to increasing doses of intravenous acetylcholine (ACh), in groups of 10 anaesthetized and tracheotomized spontaneously breathing guinea-pigs, 20 h after inhalation exposure to toluene diisocyanate (TDI). TDI exposure consisted of a single 4-h exposure to 1.2 ppm, intermittent exposures to 1.078 and 0.126 ppm for 4 h daily for 2 consecutive days, and continuous exposures to 0.118 ppm for 48 h or to 0.045 and 0.023 ppm for 1 week. Airway resistance (Raw) of the corresponding control groups, which inhaled clean filtered air, was used as baseline, and was similar for air and TDI groups. All the patterns of exposure, except exposure to 0.126 ppm TDI for 4 h daily for 2 consecutive days, significantly reduced by 28-60% the dose of ACh calculated to cause a 200% increase in Raw (ED200). The results indicate that TDI-induced airway hyperresponsiveness to ACh in guinea-pigs can occur at a level of exposure as low as 0.023 ppm for 1 week, and is consistent with the hypothesis of a cumulative effect.

Acetylcholine↗
PubMed1988

Atheromatous renal disease.

PURPOSE: Atheroma as a cause of renal failure has been largely overlooked. We wanted to report our experience with atheromatous renal disease over a 12-year period. PATIENTS AND METHODS: Observations on 32 cases of various forms of renal failure in patients with atheromatous renal disease are presented. These patients had been hypertensive for an average of 10.2 +/- 9.2 years. The length of deterioration was an average of 17 months, and at presentation renal insufficiency was severe, with serum creatinine levels of (mean +/- SD) 616 +/- 358 mumol/liter (6.8 +/- 4.0 mg/dl). At this stage, the clinical picture was indistinguishable from other common causes of chronic renal failure in the elderly. Thus, the precise diagnosis would have been overlooked without an aggressive diagnostic workup. All patients underwent angiography and six patients underwent renal biopsy. RESULTS: In 22 cases, renal insufficiency was mainly due to atheromatous stenosis of renal arteries. In six of six patients, the results of renal biopsy showed cholesterol crystal embolism. In four additional cases, there was clinical or histologic evidence of extrarenal cholesterol embolism. In eight, renal artery plaques coexisted with cholesterol embolism. In two patients, renal failure was due only to cholesterol embolism. Renal atheromatous stenoses were developing, as shown on serial angiographies performed in five cases. In seven cases, stenoses involved both the main trunks of renal arteries and several intrarenal branches of too small a diameter to allow reconstructive surgery or percutaneous transluminal angioplasty. In addition, the general condition of most patients was so poor as to preclude surgery. Dialysis was begun in 11 patients, four other patients died, and renal failure was managed conservatively in 11. When undertaken, reconstructive surgery was successful in five of six patients. CONCLUSIONS: Atheromatous renal disease is a frequent and easily overlooked cause of chronic renal insufficiency. It is not only due to renal artery stenosis but also to complex intrarenal lesions, with multiple stenoses of intrarenal vasculature and cholesterol embolism. It should be diagnosed by early angiography and renal biopsy, before the stage of multivisceral complications and at a time when surgery can still be undertaken.

Aged↗
PubMed1988

Clinical evaluation of pressure-controlled intermittent coronary sinus occlusion: randomized trial during coronary artery surgery.

Pressure-controlled intermittent coronary sinus occlusion (PICSO) was evaluated in a randomized trial in 30 patients undergoing bypass surgery. PICSO was applied for one hour during early reperfusion. Myocardial function was determined from short-axis cross-sectional views of intraoperative two-dimensional echocardiography. Changes of sectional and segmental wall motion during extracorporeal circulation were analyzed. Although sectional wall motion did not change significantly, hypokinetic segments were preserved better in PICSO-treated patients than in controls (-1.3 +/- 2.4 versus -9.1 +/- 2.6 delta% fractional area change; p less than 0.04). Although not significant, the same trend was found for normal and severely hypokinetic segments. Cumulative enzyme release was related to coronary sinus occluded pressure (r = 0.94; p less than 0.006), indicating washout of metabolites during PICSO. Three months after operation, functional classification was similarly favorable in both groups. Long-term effects of PICSO cannot be predicted because PICSO was applied only during early reperfusion. We conclude that PICSO is a safe procedure and that its short-term beneficial effects on myocardial function suggest a preservation of myocardial viability.

Catheterization↗
PubMed1988

Intermittent coronary sinus occlusion in humans: pressure dynamics and calculation of diagnostic quantities.

Pressure controlled intermittent coronary sinus occlusion (PISCO) was applied in 30 patients undergoing coronary artery bypass surgery. The occlusion and release times were manually adjusted according to visual control of the intraoperatively monitored coronary sinus pressure. In six patients the coronary sinus measurements were additionally digitised with a personal computer before postoperative mathematical analysis, which comprised automatic detection of systolic peaks, diastolic troughs, and the calculation of derived quantities. The purpose of the analysis was (a) to assess quantitatively human coronary sinus pressure dynamics, (b) to determine whether visual control and interpretation of coronary sinus pressure rise could be replaced by a mathematical model, and (c) to ascertain whether the occlusion and release cycle lengths were adequate. Numerical estimates for intraindividual and interindividual spread of calculated quantities were produced, the mathematically obtained results were related to a possible physiological interpretation, and the most efficient method of statistical analysis was ascertained. These results form the numerical basis for a closed loop adjustment of pressure controlled intermittent coronary sinus occlusion cycling.

Aged↗
PubMed1988

Complications of plasma exchange in the treatment of polyarteritis nodosa and Churg-Strauss angiitis and the contribution of adjuvant immunosuppressive therapy: a randomized trial in 72 patients.

We recorded side effects and other complications of 813 plasma exchanges used in early treatment of polyarteritis nodosa and Churg-Strauss angiitis in a prospective study of 72 patients (22-75 years old). All the patients were also treated with a corticosteroid (1 mg/kg/day), and half were included in a randomized trial of cyclophosphamide (2 mg/kg/day during 1 year). Centrifugation was used in 678 plasma exchange sessions (83.4%) and filtration in 128 (15.7%) (no data were available about the technique used in seven cases). The replacement fluid in 745 sessions was 4% albumin and in 115 was fresh-frozen plasma; eight patients received both (47 sessions). Two hundred and fifty-one complications were reported in 60 patients during 206 (25.3%) of the 813 completed exchanges; 47 sessions (5.8%) were temporarily stopped as a result of complications. The most common problems were technical difficulties (in 90 sessions), moderate or severe hypotension (in 52), and allergy to the replacement fluid (in 51). Hepatitis B antigen appeared in one patient. In four patients, plasma exchange was stopped permanently because of the severe side effects. No patient died during a session. Twelve of the 72 patients died during the study, six in each of the two groups. In the group treated by a combination of corticosteroid and plasma exchange, deaths were related to the deleterious effects of the disease itself and occurred after 12.8 +/- 11.1 months (1-26 months). In the group treated by the same combination plus cyclophosphamide, four of the six deaths were due to severe infections, which were related to leukopenia in three patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Long-term variations of serum beta 2-microglobulin levels in hemodialysed uremics according to permeability and bioincompatibility of dialysis membranes.

Hemodialysis (HD) amyloidosis is due to beta 2-microglobulin (beta 2M) storage, the importance of which could vary with the permeability of dialysis membranes. We studied long-term variations of beta 2M in 52 patients who had been dialyzed over 1.5-20 years (mean +/- SD = 7.5 +/- 5.2), 3 X 4 h weekly. Serum samples had been stored at 30 degrees C and RIAs were done in one run with the same kits (Immunotech). At least 2 assays were done for each patient in samples collected 1-9.5 years apart. Mean beta 2M concentration in 26 ESRF patients was 31 +/- 18 mg/l. According to duration of HD and membranes used, Cuprophan (CUP) versus polyacrylonitrile (AN69), mean concentrations of beta 2M were (mg/l +/- SD): at 6 months, 55 +/- 36 vs. 54 +/- 20 (n.s.); 2 years, 55 +/- 24 vs. 61 +/- 23 (n.s.); 4 years, 79 +/- 18 vs. 64 +/- 19 (n.s.); 6 years, 69 +/- 17 vs. 55 +/- 17 (n.s.); 8 years, 76 +/- 18 vs. 54 +/- 12 (less than 0.01); 10 years, 77 +/- 17 vs. 54 +/- 14 (less than 0.02). The effect of changing membranes was also studied: CUP-AN69 (69 +/- 28 months), 79 +/- 21 vs. 54 +/- 14 (less than 0.01). Serum beta 2M (1) increased rapidly after the beginning of HD; (2) reached a plateau after 2 years in patients treated with AN69 and 4 years with CUP; (3) were significantly lower after 8 years with AN69 than with CUP, and (4) decreased significantly after changing CUP for AN69.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗
PubMed1988

Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study.

Clinical investigations using the adoptive transfer of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) to treat patients with advanced cancer have yielded encouraging results. We have thus sought ways to enhance the effectiveness of adoptive immunotherapy while minimizing its toxic side effects. Murine experiments have identified tumor-infiltrating lymphocytes (TIL) as killer cells more effective than LAK cells and less dependent on adjunctive systemically administered IL-2 to mediate antitumor effects. Accordingly, we performed a pilot protocol to investigate the feasibility and practicality of administering IL-2-expanded TIL to humans with metastatic cancers. Twelve patients, including six with melanoma, four with renal cell carcinoma, one with breast carcinoma, and one with colon carcinoma, were treated with varying doses and combinations of TIL (8.0 X 10(9) to 2.3 X 10(11) cells per patient), IL-2 (10,000 to 100,000 U/kg three times daily to dose-limiting toxicity), and cyclophosphamide (CPM) (up to 50 mg/kg). Two partial responses (PR) to therapy were observed: pulmonary and mediastinal masses regressed in a patient with melanoma, and a lymph node mass regressed in a patient with renal cell carcinoma. One additional patient with breast cancer experienced a partial regression of disease in lymph nodal and cutaneous sites with complete elimination of malignant cells from a pleural effusion, although cutaneous disease recurred at 4 weeks. The toxicities of therapy were similar to those ascribed to IL-2; no toxic effects were directly attributable to TIL infusions. In five of six melanoma patients, TIL demonstrated lytic activity specific for the autologous tumor target in short-term chromium-release assays, distinct from the nonspecific lytic activity characteristic of LAK cells. This study represents an initial attempt to identify and use lymphocyte subsets with enhanced tumoricidal capacity in the adoptive immunotherapy of human malignancies.

Adult↗
PubMed1988

Effect of melatonin implantation on the seasonal variation of FSH secretion in the male blue fox (Alopex lagopus).

A heterologous radioimmunoassay system developed for the sheep was shown to measure FSH in the plasma of the blue fox. FSH concentrations throughout the year showed a circannual rhythm with the highest values (61.6 +/- 14.8 ng/ml) occurring shortly before or at the onset of the mating season, a pattern similar to that of LH. The concentration of FSH then declined when androgen concentrations and testicular development were maximal at the time of the mating season (March to May). Thereafter, concentrations remained low (25.2 +/- 4.1 ng/ml) in contrast to those of LH. Implantation of melatonin in August and in February maintained high plasma values of FSH after the mating season (142.3 +/- 16.5 ng/ml) in association with a maintenance of testicular development and of the winter coat. The spring rise of prolactin was suppressed by melatonin treatment. The release of FSH after LHRH injection was also increased during this post-mating period in melatonin-treated animals, in contrast to the response of the control animals which remained low or undetectable. These results suggest that changes both in the secretions of FSH and prolactin may be involved in the prolongation of testicular activity and in the suppression of the spring moult after melatonin administration.

Animals↗
PubMed1988

[Retrocecal mucus-secreting tumors of the appendix (mucoceles). Apropos of 3 radiologically diagnosed cases].

The term of appendiceal mucocele has been applied to a group of lesions distending the lumen of the appendix; filled with mucus. About 15% of these lesions are malignant tumors (cystadenocarcinomas). All these lesions may lead to pseudomyxoma peritonei, but only the peritoneal involvement due to a malignant tumor (adenocarcinoma) has multiple recurrences and poor prognosis. Benign lesions are cured by appendicectomy, even if a peritoneal "gelatinous" effusion is present. These lesions can usually be early diagnosed by US and CT features if the mucocele extends behind the cecum in the retroperitoneal space, especially if the wall is calcified. A colic examination (with barium enema or colonoscopy) must be taken event if the diagnosis is made by US or CT means, because of the significant association of mucocele with other colonic tumors.

Adult↗
PubMed1988

Treatment of corticoresistant idiopathic nephrotic syndrome in the adult: minimal change disease and focal segmental glomerulosclerosis.

We undertook a review of the literature concerning idiopathic NS in the adult (with MGL or due to FSGS) in an effort to assess the results obtained with corticosteroid and/or conventional immunosuppressive treatments. We found few usable published works and we were left with an impression of great imprecision. This imprecision stems both from frequently deficient definition of glomerular lesions and from different evaluations of responses to treatment. The almost total absence of controlled series, due to the rarity of nephrosis in the adult, hinders any firm conclusions with regard to the effect of treatments. It limits evaluation to mere tendencies, formulated in such vague terms as "complete remission," "partial remission," and "treatment failure," in a disease whose natural history is sometimes so whimsical that the same clinical case, over a period of years, can be both a success and a failure of the same treatment. In the adult, there is a significant difference in the incidence of complete remissions obtained by corticosteroids according to whether the NS is due to MGL or to FSGS. Nevertheless, the published data are difficult to interpret because dosage and length of treatment vary among authors. A high percentage of corticoresistant, corticodependent, or multirelapsing nephroses responds to immunosuppressive treatment. Efficacy has been documented for three drugs. Chlorambucil is easy to use but entails some long-term oncogenic hazards. Cyclophosphamide has more short-term side effects, but its long-term risk of malignancy appears less. Both of these alkylating agents may definitively compromise fertility. Azathioprine, easy to use but prescribed surprisingly little in NS, may have considerable advantages over alkylating drugs, which would justify reconsidering its use in nephrosis. An open, cooperative study was launched to determine the efficacy and the tolerance of cyclosporine in 45 patients who had been considered as failures of corticosteroid and/or conventional immunosuppressive therapy. The preliminary results of this trial showed that two thirds of the patients with cases of MGL and half of those with FSGS had total or partial remission after long-term treatment with cyclosporine. It is not yet known whether this may eventually lead to lasting remission after treatment is progressively tapered to a stop, or only represent reappearance of low-dose corticosensitivity. In case of dependence on this new immunosuppressive drug, long-term tolerance remains to be determined.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical Trials as Topic↗
PubMed1988

[Increase of the frequency of HLA DR4 antigens in recurrent arterial hypertension of pregnancy].

We studied the frequency of HLA DR antigens in 96 women whose 50 with preeclampsia (PE = proteinuria greater than 0.5 g/l + HTA) and 46 with gestational HTA (GHTA = pregnancy-induced HTA without proteinuria). Sixty had later pregnancies (28 PE and 32 GHTA) and were followed for from 3 to 23 years (m = 8.5 yrs) after the first pregnancy. HLA DR antigen distribution was determined by a search on B lymphocytes for the 10 antigens of locus DR. The normal population included 38 control couples (76 mothers and fathers) with normotensive pregnancies (A) and 200 healthy controls recruited from a local blood donor population (B). The frequency of alleles was compared to that of the different group of primiparous women and whole group of women with later pregnancies. Significant variations were evaluated by the chi 2 test, using Woolf's method: the p values obtained was multiplied by the number of antigens looked for (p corrected or pc). Only the DR4 antigen, present in 19.7% of control couples (A) and 26.5% of the blood donor population (B), was increased in proportions that depended on clinical classification: 54.3% (pc less than 0.005 with A, less than 0.007 with B) in all primiparous women with GHTA, 38% (NS) in all primiparous women with PE. However significant variation was also observed when the frequency of DR4 in PE women was compared to that in only women of A (38% vs 5.2%, pc less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗