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A 35-year-old woman undergoing laparoscopic sterilisation developed prolonged apnoea after suxamethonium. Fresh frozen plasma was given to replenish plasma cholinesterase, but recovery of neuromuscular transmission was not accelerated. Routine use of quantitative neuromuscular monitoring simplified her postoperative management.
The development of a sensitive radioimmunoassay has enabled measurements of pregnancy-associated plasma protein-A (PAPP-A) to be performed from early pregnancy. The present paper compares the plasma concentrations of PAPP-A with the levels of two trophoblastic proteins, human placental lactogen (hPL) and the beta-subunit of human chorionic gonadotrophin (beta-hCG), with a steroid of fetoplacental origin, total oestriol (total E3), and with a fetal protein, alpha-fetoprotein (AFP). PAPP-A was also measured in amniotic fluid and in maternal urine. In contrast with the secretion of the other substances studied, which either reach a plateau or even decrease during the last 4 weeks of pregnancy, PAPP-A steadily increased in the maternal circulation from 7 to 40 weeks gestation. It is proposed that PAPP-A production is either not related to placental mass or that PAPP-A is not of trophoblastic origin. The increase of PAPP-A in amniotic fluids parallels the increase in maternal blood; virtually no PAPP-A is excreted in urine.
BACKGROUND: Photochemical treatment of fresh-frozen plasma (FFP) with amotosalen and ultraviolet (UV) A light (PCT FFP) results in inactivation of a broad spectrum of pathogens while retaining coagulation factor activity, antithrombotic proteins, and von Willebrand factor-cleaving protease (VWF-CP) activity. STUDY DESIGN AND METHODS: A randomized, controlled, double-blind Phase III trial was conducted with PCT FFP or control FFP for therapeutic plasma exchange (TPE) in patients with thrombotic thrombocytopenic purpura (TTP). Owing to the rarity of this diagnosis, the trial was not powered to demonstrate small differences between treatment groups. Patients were treated with study FFP for a maximum of 35 days until remission was achieved (for a maximum of 30 daily study TPEs with no remission) plus an additional 5 days after remission. RESULTS: Among the 35 patients treated, the primary endpoint, remission within 30 days, was achieved by 14 of 17 (82%) PCT patients and 16 of 18 (89%) control patients (p = 0.658) The 90 percent confidence interval for treatment difference in remission rate for test - control was (-0.291 to 0.163). Time to remission, relapse rates, time to relapse, total volume and number of FFP units exchanged, and number of study TPEs were not significantly different between groups. Improvement in VWF-CP and inhibitors was similar for both groups. The overall safety profile of PCT FFP was similar to control FFP. No antibodies to amotosalen neoantigens were detected. CONCLUSION: The comparable results between treatment groups observed from this small trial suggest that TPE with PCT FFP was safe and effective for treatment of TTP.
A patient with a plasma cell proliferative disorder and a monoclonal IgG-kappa protein in the serum was observed over a period of four years. Two unusual features were seen in this patient: (1) An apparently benign course in spite of relatively large and slowly increasing amounts of Bence Jones protein (monoclonal kappa light chains) in the urine, and (2) crystalline structures located outside the cisternae of the endoplasmic reticulum in a large number of bone marrow plasma cells. The crystals, which ultrastructurally appeared to be composed of protein material, were not stained by immunofluorescent antisera to immunoglobulins. They were, however, observed only in cells staining for gamma heavy and kappa light chains. This suggest an association between the crystalline structures and the synthesis of monoclonal immunoglobulin proteins.
The relationship between plasma osmolality (pOsm) and plasma vasopressin (pAVP) was studied in 13 human subjects during dehydration. The fit of linear, log-linear, parabolic, and exponential models was tested. For all of the data, the nonlinear models had the best fit. However, when individual differences in either gain or threshold were allowed for, the linear models were better than log-linear models. Finally, analyses were made with individual data points. Linear models had the best fit in half of the subjects, whereas for the others the parabolic model gave the best fit. For those subjects investigated in the low range of the osmoregulatory curve, a linear relationship was found, whereas, for those having the most pronounced increase in pOsm, the most significant improvement was found with the parabolic model. This finding indicates that the relationship is not stable during dehydration in the whole range and that hypovolemia probably can influence the secretion rate and/or metabolic clearance rate and thereby the relationship.
Therapeutic plasma exchange is an effective empiric treatment for thrombotic thrombocytopenic purpura (TTP), but how therapy affects the level of a disintegrin and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) or inhibitor has not been reported in many patients. We prospectively analyzed ADAMTS13 activity and inhibitor levels in 37 adults with TTP. ADAMTS13 level at presentation was lower than 5% in 16 of 20 patients with idiopathic TTP and in none of 17 patients with TTP associated with hematopoietic stem cell transplantation, cancer, drugs, or pregnancy (P <.00001). Seven of the 16 patients with ADAMTS13 activity lower than 5% ( approximately 44%) had inhibitors. For 8 patients followed serially with ADAMTS13 activity lower than 5% but no inhibitor at presentation, plasma exchange led to complete clinical remission and a rise in ADAMTS13 level. In contrast, 4 patients with low ADAMTS13 activity but high-titer inhibitor (> 5 units/mL) had neither a rise in ADAMTS13 activity nor a reduction in the inhibitor titer: 3 had recurrent disease and 1 died. Among 17 patients with AD-AMTS13 activity at presentation higher than 25%, 10 died. Mortality rate for idiopathic TTP was 15%, whereas mortality for nonidiopathic TTP was 59% (P <.02). We conclude that assays of ADAMTS13 activity and inhibitors in addition to the clinical categories (idiopathic TTP and nonidiopathic TTP) are predictive of outcome and may be useful to tailor patient treatment.
BACKGROUND: The ratio of plasma aldosterone concentration to plasma renin activity (PRA) is considered the screening test of choice for primary aldosteronism. Uncertainty exists, however, regarding its diagnostic accuracy and the effects of antihypertensive drugs and dietary sodium balance on test characteristics. METHODS: We measured PRA and aldosterone in 118 white adults [71 men and 47 women; mean (SD) age, 51 (7) years] with previously diagnosed essential hypertension. Measurements were made while individuals were on antihypertensive drug therapy, after a 2-week drug-free period, after 4 days of dietary sodium loading, and after acute furosemide diuresis. We measured 24-h urine aldosterone excretion and PRA on the 4th day of dietary sodium loading to establish the diagnosis of primary aldosteronism. ROC curves were constructed for ratios measured under each clinical condition, and likelihood ratios were determined for individuals on or off antihypertensive drug therapy. RESULTS: Fifteen patients [13%; 95% confidence interval (CI), 7-20%] met the reference standard for primary aldosteronism. The mean (SD) areas under the ROC curves did not differ significantly across conditions of measurement [range, 0.80 (0.10) to 0.85 (0.04); P = 0.72]. When measured on and off antihypertensive drug therapy, the 95% CIs for the optimum cutpoint for the ratio overlapped. Point estimates of sensitivity on and off therapy were 73% (95% CI, 50-96%) and 87% (70-100%), respectively, and specificities were 74% (65-83%) and 75% (66-84%). Under either condition, increased ratios were associated with 2.4- to 13-fold increases of posttest odds above pretest odds. CONCLUSIONS: The aldosterone:PRA ratio provides only fair diagnostic accuracy in screening for primary aldosteronism, but concomitant antihypertensive drug therapy or acute variation in dietary sodium balance does not adversely affect test accuracy. Reporting of likelihood ratios associated with ranges of values of the aldosterone:PRA ratio, rather than use of a single "optimum" cutpoint, may enhance the usefulness of the test.
The present study examined the effects of race and age on the redox potential behavior of blood plasma samples. The oxidative stability was studied in the reaction with p-benzoquinone. The investigated animals represented three different cattle races (Limousin, Angus and Hereford), grazed on pasture. The blood samples from clinical healthy heifers (44) and calves (45) were investigated. The following parameters were determined: the start level of redox potential and the level after adding 10, 20, and 30 mg p-benzoquinone to the samples. The analyses of the redox potentials showed the advantage of oxidative stability of heifers compared with calves. The results showed a significant effect of race on the redox potential behavior of blood plasma.
In this paper, polyethylene glycol (PEG) of different molecular weight was grafted on the polyethylene terephthalate (PET, Dacron) films by plasma surface grafting modification. The competitive adsorption relation of plasma (fibrinogen and albumin) adsorbing on materials surface was analyzed in light of surface energy and interface free energy. The results indicated that the PET films grafted PEG long chain molecular possesses the characteristic of preferentially adsorbing albumin and this adsorption tendency of grafted PEG6000 sample is most distinct. The platelet adhesion tests of the PET films whose surfaces were pre-set in contact with fibrinogen and albumin indicated that the surface adsorbing albumin can distinctly inhibit platelet adhesion and aggregation and possess favorable blood compatibility, but the surface adsorbing fibrinogen can enhance platelet adhesion and aggregation.
The use of plasma and factor concentrates for the treatment of coagulation disorders is well established, but many questions remain. The indications for fresh frozen plasma are still not clearly established and excessive use is rampant. The safety of all blood products has not yet been firmly established. Peer review of transfusion practice in a hospital can be achieved by a Hospital Transfusion Committee. The review and analysis of the statistical reports of the transfusion service and strategies for enhancing quality of patient care will be presented.
The use of FFP has increased dramatically in the last few years. In the majority of cases FFP is transfused in order to provide coagulation factors. Many physicians expect to get "better" blood parameters from concomitant FFP and red blood cell (RBC) transfusions. To avoid the risk of diseases transmitted by homologous blood predeposited autologous blood is useful for elective surgical patients. Intraoperative autotransfusion by blood salvage using a Cell Saver only provides autologous RBC without plasma, so predeposited autologous plasma seems to be a necessary supplement. However, according to the literature most patients receiving RBC units do not require concomitant FFP. Guidelines for the use of FFP based on controlled clinical trials are necessary.
In order to evaluate the efficacity of plasma exchanges (PE) in dermatomyositis and polymyositis, the case histories of 38 patients, who had undergone plasma exchanges between 1980 and 1986 in 10 French plasmapheresis centers, were studied. Large volume PE were performed in 34 patients after failure of conventional therapy and were part of the initial regimen for the 4 others. The initial activity of the muscle disease was acute in 27 patients and subacute or chronic in 11 cases. Clinical results were evaluated on a functional scale based on changes in muscle force: 24 patients improved (10 appreciably and 14 moderately) and 14 remained unchanged. PE were well tolerated in 23 patients. But side effects occurred in 15 patients, necessitating treatment withdrawal in 4 cases. PE seem to be more effective when the dermatomyositis is acute and evolutive than when it is chronic and insidious. The encouraging results of this exhaustive retrospective study prompt us to set up a prospective randomized trial.
Thirteen cases of plasma cell leukemia and 13 cases of nonleukemia plasma cell myeloma were compared with respect to the sizes and shapes of tumor cells in marrow smears. It was demonstrated that the leukemia cells were elongated or ovoid and significantly smaller in size, whereas the myeloma cells were generally more nearly round and larger.
Effective renal plasma flow (ERPF) was evaluated, using continuous-infusion p-aminohippurate clearance (CLPAH) and single-injection plasma clearance of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3; CLMAG3) methods. Simultaneous clearance determinations were made in 6 dogs: 2 determinations for each dog before, and 1 determination after renal failure was induced by administration of amphotericin B. Linear regression analysis was used to derive an equation to estimate ERPF from CLMAG3 after the single IV injection. A Student's t-test was used to compare pharmacokinetics between the dogs when they were healthy and when they were in renal failure. An F-test was used to determine the appropriate Student's t-test. Results indicated that CLMAG3 correlated reasonably well (r = 0.83, P < 0.0001) with ERPF obtained from the CLPAH value. The volume of distribution and elimination of 99mTc-MAG3 decreased during renal failure. Although there was minimal binding of 99mTc-MAG3 to erythrocytes, it was significantly (P = 0.0008) lower during renal failure. Protein binding was not significantly different during renal failure. All dogs had signs of nausea and emesis at variable times after injection of 99mTc-MAG3. Determination of CLMAG3 after a single injection provides an adequate means to rapidly assess ERPF in dogs. The technique could easily be performed in dogs with renal disease, thus providing valuable information regarding progression of naturally acquired renal failure.
Plasma exchange (PE) and intravenous polyvalent immunoglobulins (IVIG) offer a new therapeutic approach to polymyositis (PM) and dermatomyositis (DM). Plasma exchange. The largest open study of PE was reported by Herson et al., in 57 patients with inflammatory myopathies (33 DM, 24 PM) who were resistant to classical treatments. The patients were described as having acute (< 6 mois, n = 38) or subacute or chronic (n = 19) disease. There were 41 females and 16 males with a mean age of 40.4 +/- 20.5 years. The mean number of PE was 14.8 +/- 9.2. The score of muscle function improved in 54% of the patients. A significant improvement in the muscle test was only seen in the acute forms, particularly in severe cases with impaired swallowing. The difference was not significant in the subacute and chronic forms. Intravenous immunoglobulins. Several recent publications have emphasized the importance of polyvalent IVIG in the treatment of inflammatory myopathies. In our experience, 30 patients (21 females, 9 males, mean age 44.5 +/- 18) with PM (n = 22) or DM (n = 8) were given IVIG after unsuccessful classical therapies including corticosteroids (n = 29), immunosuppressors (n = 28), PE (n = 8), total body irradiation (n = 1), and lymphopheresis (n = 1). Three to 6 monthly cures of 2 g/kg/cure polyvalent IVIG were given. Clinical improvement was significant as evaluated by muscle tests in 18 of the 30 patients. Global scores for the 30 patients rose from 44.2 +/- 12.7 to 65.3 +/- 17.9 points (for a theoretical maximum of 88 points) after the third cure (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Synchronization is defined as a prescription sequence aimed at obtaining synergic response or potentialization. THEORETICAL BASIS--The concept of synchronization is based on clinical and biological observations such as similar indications and transient effectiveness. Certain mechanisms of action such as reduction of pathological autoantibodies and accelerated elimination of immune complexes are common to both methods. Inversely, long-term effects differ. Plasma exchange cannot control the synthesis (or could aggravate) of autoantibodies while gammaglobulins have a suppressor effect on autoreactive clones. The aim is to obtain a summation effect by eliminating immediately cytotoxic factors. The potentializing effect of gammaglobulin anti-idiotypes on the modification of the immunologic repertory is favoured by prior reduction in the level of circulating pathogenic antibodies. RESULTS--It is difficult to evaluate the efficacy of this therapeutic association. Only a few trials have been conducted in refractory autoimmune thrombopenic purpura (n = 8), in intra-uterine Rhesus disease (n = 3), and HIV associated pathologies. We report our experience in 11 patients in a situation of therapeutic failure including three cases of renal transplantation, two cases each of chronic polyradiculoneuritis and neurological paraneoplastic syndromes, and one case each of Wegener's syndrome, polymyositis, sclerokeratitis, and antiphospholipid antibodies during pregnancy. Immunoglobulins were injected at an initial dose of 2 g/kg following at least 3 plasma exchanges. Consolidation cures were then administered every 3 weeks at a dose of 1 g/kg. Two major complications occurred and required interruption of the treatment: acute regressive oligo-anuric renal failure (Wegener) and exacerbation of sclerokeratitis inflammatory lesions. The disease process was controlled in 7 patients. CONCLUSIONS--Despite these promising preliminary results, the proposed combination therapy is not devoid of complications and its cost is high (cost of PE for 500 mg/kg Ig is about 5,000 FF). The next step should be the study of experimental models and prospective trials on pathologies with well characterized immunological features.
The relationship between propranolol and 4-hydroxypropranolol plasma concentrations and relief of migraine was assessed in 17 patients during treatment with oral racemic propranolol hydrochloride in doses of 40 to 240 mg/day. Propranolol decreased the migraine index more than 70% in 13 patients: five patients at a dosage of 40 mg/day, five patients at a dosage of 120 mg/day, and three patients at a dosage of 240 mg/day. Three patients did not achieve a good improvement of migraine at any of the doses used. The relief of migraine was not directly related to the propranolol and 4-hydroxypropranolol plasma concentrations.
Sequential paired samples of blood and seminal fluid were obtained from a cohort of 54 HIV-1-infected homosexual males. The prevalence of GBV-C/HGV RNA in the cell-free fractions of some of these patients was determined using reverse-transcription polymerase chain reaction (RT-PCR). To assess the effects of HIV-1 and HCV infection upon GBV-C/HGV RNA status, blood CD4 cell counts, HCV RNA status, and HIV-1 proviral DNA and viral RNA titres were also determined. GBV-C/HGV RNA was detected in 8/30 (27%) of the blood plasma samples obtained at the start of the study, and was present at a frequency of 14/64 (22%) in all the blood plasma samples tested. By contrast, GBV-C/HGV RNA was not detected in the 26 seminal fluid samples obtained at the start of the study, including 8 samples obtained from patients for which GBV-C/HGV RNA was detected in the corresponding blood sample. Of the samples tested for the presence of both GBV-C/HGV and HCV RNA, there was no evidence of coinfection. Although GBV-C/HGV RNA detection rates were significantly higher in individuals with blood CD4 cell counts greater than 200 cells per microlitre, there were no significant differences in the median blood CD4 cell counts or HIV-1 proviral DNA or viral RNA titres observed between the GBV-C/HGV-positive and -negative individuals. The failure to detect GBV-C/HGV RNA in seminal fluid samples obtained from this cohort would suggest that further studies need to be carried out to determine the roles of sexual transmission and of seminal fluid in GBV-C/HGV infection.