The prevalence of hepatitis B virus, human T-lymphotropic virus and human immunodeficiency virus in patients receiving blood transfusions in South Africa.

BACKGROUND AND OBJECTIVES: South Africa has a high prevalence of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and to a lesser extent human T-lymphotropic virus (HTLV). Each of these agents is transfusion-transmissible (TT) but deciding whether to implement preventive screening depends upon knowledge of background prevalence in transfused patients. We determined the prevalence of HIV, HBV and HTLV I/II among blood transfusion recipients in South African hospitals. MATERIALS AND METHODS: We obtained identity-unlinked samples used for blood cross-matching at 634 South African hospitals served by the South African National Blood Service (SANBS). The ABBOTT Alinity S® Immunochemiluminescent system measured HIV, HBV and HTLV I/II antibodies. Repeatedly reactive samples were confirmed using the Roche Cobas® 8000. Logistic regression was performed to investigate the determinants of associations for HIV, HBV and HTLV infections. RESULTS: The overall prevalences of HIV, HBV and HTLV were 37.8%, 7.4% and 0.6%, respectively. The HIV prevalence in blood recipients was twice as high as general population estimates. Public hospital patients had a significantly higher prevalence compared with private hospital patients for HIV and HBV. HIV prevalence was significantly higher in females, and HBV prevalence was significantly higher in males, excluding the unknown gender results. CONCLUSION: Patients receiving blood transfusions in South Africa have high rates of HIV and HBV infection that should be taken into consideration when determining donor screening strategies for other viral infections. Measurable prevalence of HTLV indicates endemicity of this infection in South Africa.

Development and validation of HPLC method for the determination of Cyclosporin A and its impurities in Neoral capsules and its generic versions.

Cyclosporin A (CyA) is a cornerstone immunosuppressant for the prophylaxis against allograft rejection after organ transplantation. The most widely prescribed CyA formulation is Neoral soft gelatine capsules (Novartis Pharmaceuticals, Basel, Switzerland). After Novartis patent expiration, several generic formulations have been developed. In this paper, a simple and reliable HPLC method was developed and validated for the evaluation of four CyA degradation products (ID-005-95, CyH, IsoCyH and IsoCyA) and two related compounds (CyB and CyG) aimed for the quality control of Neoral capsules and its generic formulations. In a second step, the validated method was then compared to the USP assay method for capsules, where some of the mentioned impurities were not adequately resolved from the CyA peak. Isocratic elution at a flow rate of 1.0mLmin(-1) was employed on a Lichrospher RP-18 (4mmx250mm; 5microm) analytical column maintained at 75 degrees C with a tetrahydrofuran:phosphoric acid (0.05M) (44:56, v/v) as mobile phase. The chromatograms were recorded using a Hewlett Packard 1100 chromatographic system. The UV detection wavelength was performed at 220nm and 10microL of sample was injected. The developed method was validated in terms of selectivity, linearity, precision, accuracy, limit of detection and limit of quantitation. The validate method was successfully applied to commercial capsules, Neoral and generic versions. Therefore, the proposed method is suitable for the simultaneous determination of CyA as well as its major impurities.

[Mechanisms and treatment of psoriasis]. / Mécanismes et traitements du psoriasis.

Psoriasis is a common dermatosis that affects 3-5% of the European population. Current treatments offer considerable clinical benefits, but their use is limited due to tolerance problems. Recent years have seen the development of new treatments, used separately or in combination to improve the chronic lesions caused by this disease. T cells play an important role in the pathogenesis of psoriasis. Various techniques target the T cells and the immunological mechanisms involved in their activation. In 2005, treatment of psoriasis is directed essentially towards immunological pathways.

Comparison of 15N analysis by optical emission spectrometry and mass spectrometry for clinical studies during total parenteral nutrition.

During total and stable parenteral nutrition, a branched chain amino acid enriched solution containing [15N]leucine was infused into a patient to determine the fate of the nitrogen administered through this formulation. Measurements of 15N isotopic enrichments were performed on the same biological samples (urinary urea, total plasma proteins and albumin) by optical emission spectrometry (OES) and mass spectrometry (MS) to determine if OES with its specific advantages (cost, handling maintenance) constituted even with low enrichments a useful alternative technique to MS considered as the reference method. The average 15N% enrichments are 0.5% for urinary urea, 0.21% for total plasma proteins and 0.14% for albumin. The coefficients of correlation between both series of 15N% enrichment measurements realized by MS and OES vary from 0.999 to 0.998 and 0.988, respectively, for urinary urea, total plasma proteins and albumin. These results show that OES constituted a very useful analytical technique to obtain reliable information in clinical metabolic studies when low 15N enrichments must be determined.

Long-term follow up of ionic plasma fluoride level in patients receiving hemodialysis treatment.

The elimination half-life of fluoride is significantly increased in patients with chronic renal failure. This led us to conduct a study of variations of its plasma levels in 35 patients receiving dialysis treatment. In this population, there is a gaussian distribution of the values before and after the hemodialysis session, with a significant decrease in the averages. Furthermore, there is a highly significant correlation between fluoride levels before and after the dialysis session (P < 0.00001), and also between the amount of time in hemodialysis (in months) and the average fluoride level before dialysis (r = 0.624; P = 0.008). The presence of a group of patients consuming fluoride waters such as Vichy St-Yorre Water was easily identified by their excessive fluoride levels (above 100 micrograms/l), which could have a tendency to increase the risks of this group.

Investigation of fluoride elimination during a dialysis session.

We have conducted a study of the elimination kinetics of fluoride ions by a log linear regression analysis of plasma levels obtained during a bicarbonate hemodialysis session, with a dialyzer in polymercaprin for six patients with chronic renal failure. Using plasma fluoride levels of 35 patients studied for 20 months, we have validated these kinetics for hemodialysis with sodium bicarbonate, acetate-free biofiltration, hemodiafiltration with low flow rate and other dialyzers. Our results show that the decrease in plasma fluoride levels is statistically significant only after the first hour, and the fall reaches approximately 30% after a 4 h dialysis session. We propose that post-dialysis measurements of plasma fluoride are now not necessary if levels before dialysis are known.

Protein synthesis measurement in cancer patients with 13C valine.

The flooding dose technique is a method that uses tracer amino acids to measure the rate of protein synthesis in tissues in vivo. This technique involves the injection of a large amount of unlabelled amino acid together with the tracer to minimize difference in isotopic enrichment of the free amino acid in plasma and tissue compartments which represent the precursor pool of protein synthesis. Seven patients with localized colorectal carcinoma received a total parenteral nutrition before surgery and protein synthesis was measured in tumour and colon after administration of a large dose of valine (20% atom percent excess). The enrichment of free valine in plasma and tissues was measured by GCMS and the enrichment of protein-bound valine into tumour and colon by IRMS. The fractional synthesis rate in tumours was 13.44 +/- 6.9%/day compared to a value of 10.9 +/- 8.1%/day in healthy colon. The lack of significant difference probably relates to the low number of patients and the variability of protein synthesis rate in tumours.

Hyperkalemia risks in hemodialysed patients consuming fluoride-rich water.

In order to observe the consequences of chronic ingestion of high fluoride-rich water on plasma potassium levels of hemodialysed subjects, we have conducted a retrospective study on 25 patients with chronic renal failure, treated with a substitute method, six of whom (consumers group, group C) were drinkers of a bicarbonate (about 4500 mg/l) and fluoride-rich (9 mg/l) mineral water, the Vichy Saint-Yorre water. With respect to sodium polystyrene sulfonate consumption (n = 17), there was no significant difference between group C and NC (non-consumers group). A significant correlation between plasma fluoride and potassium levels was observed only before dialysis (P < 1 x 10(-7)) but not after dialysis. A group by group analysis revealed that this correlation was linked to group C (P < 5 x 10(-6)), in which kalemia before dialysis was higher than that observed in group NC (P < 0.005). Moreover, it appeared that the higher fluoride levels were, the higher the kalemia was inclined to be. Thus, the risks of hyperkalemia in dialysed patients, who also drink Vichy St-Yorre water or other fluoride-rich waters, are more important, while not forgetting the risk of fluorosis. The mechanisms by which chronically administered fluoride could increase kalemia are also discussed.

Splanchnic acid-base status and urea metabolism in uremic rats.

Acidosis may alter hepato-splanchnic amino acid metabolism during uremia.26 uremic rats and 30 controls were studied for portal and arterial acid-base balance and urea synthesis during enteral nutrition. Uremic rats exhibited increased (p < 0.05) portal H(+) (47.20 +/- 0.018 vs 43.05 +/- 0.49 nmol/I) and decreased HCO(3)(-) (19.45 +/- 0.69 vs 23.01 +/- 0.57 mmol/l) without significant change in arterial H(+) (45.29 +/- 1.13 vs 43.15 +/- 0.49) and HCO(3)(-) (18.41 +/- 0.64 vs 19.59 +/- 0.49). Porto-arterial difference showed an intestinal HCO(3)(-) release in controls only (3.53 +/- 0.64 mmol/l). Urea synthesis rate was significantly enhanced by enteral nutrition in controls only: 54.33 +/- 17.3 vs -11.8 +/- 20 micromol/min 100g body mass. Thus, during uremia, portal acidosis was associated with a decrease in enteral nutrition-induced urea synthesis.

Effect of chronic renal failure with metabolic acidosis on alanine metabolism in isolated liver cells.

BACKGROUND & AIMS: Decreased ureagenesis and gluconeogenesis from alanine have been reported during chronic renal failure in rat. This study addressed the respective roles of plasma-membrane transport and intracellular metabolism in these abnormalities of alanine pathways. METHODS: In hepatocytes isolated from uremic and control rats, we investigated: (1) the influence of uremia on gluconeogenesis and ureagenesis during incubations with alanine; (2) the kinetics of alanine plasma-membrane transport; (3) the relationships between intracellular alanine concentrations and its metabolism. Plasma-membrane alanine transport was assessed after addition of alanine (2 mM) by measuring its intracellular accumulation from 0 to 10 min, in the presence of a transaminase inhibitor. Alanine metabolism was studied in perifused hepatocytes by measuring intracellular alanine concentration together with urea, glucose and lactate production in the presence of increasing concentrations of alanine (0-8 mM). RESULTS: Uremic rats showed decreased plasma bicarbonate. Uremia induced (P<0.05) a decrease in both gluconeogenesis (36%) and ureagenesis (22%). Alanine plasma-membrane transport decreased by 20% during uremia. During perifusions, uremia induced a 30-40% decrease in urea, glucose, and lactate production without modifying intracellular alanine concentration. CONCLUSIONS: In uremic rats with acidosis, hepatocyte alanine utilization was impaired at both plasma-membrane transport and intracellular transamination steps.

Experimental approach to prevention of catheter-related central venous thrombosis.

The role of catheter material in the formation of deep venous thrombosis during parenteral nutrition has been widely emphasized. Systematic venograms show central venous thrombosis in 20 to 33% of cases with polyethylene catheters and in 4% of cases with silicone catheters. Heparin infusion through the catheter diminishes but does not totally eliminate the risk of thrombosis. The aim of this study was to define the conditions under which the risk of thrombophlebitis was minimal. Four series of experiments were carried out, each on five rabbits. Catheters were inserted into the vena cava and, after 10 days, venograms were performed. The animals were then sacrificed, and the vena cava was macroscopically and microscopically studied. Plastic catheters were used in the first series, heparin-Benzalkonium-bonded plastic catheters in the second, silicone catheters in the third, and heparin-Benzalkonium-bonded silicone catheters in the fourth. The results revealed thrombosis of the vena cava and a fibrin sleeve around the catheters in series 1; thrombosis of the vena cava in series 2; a fibrin sleeve around the catheters in series 3; and neither thrombosis nor a fibrin sleeve in series 4. In conclusion, heparin-Benzalkonium-bonded silicone catheters appear to provide the best protection against thrombophlebitis by reducing the damage caused to the intima by the catheters and by slowing down platelet-aggregation around them.

A continuous hemofiltration system using sorbents for hemofiltrate regeneration.

Plasma ultrafiltrate obtained by glomerular filtration undergoes tubular modification which leads to the elimination of toxic substances, excess water and electrolytes, and consequently maintains homeostasis. Using normal urine and the substances it contains as a reference, we have developed a wearable device capable of replacing both the renal excretion function and maintaining fluid and electrolyte equilibrium in uremics within acceptable biological limits. Our device includes a hemofilter allowing continuous plasma ultrafiltration and sorbents obtained from a Redy sorbent cartridge to treat 85% of the ultrafiltrate, whereas 15% of this UF is rejected untreated. After calculating the quantity of ultrafiltrate (about 13 l) containing an amount of waste products of metabolism equivalent to 24-h urine elimination, we determined in vitro the amount of sorbent required to eliminate these waste products from the ultrafiltrate (e.g., 20 g of urea/day) and we have evaluated the quantities of other substances which must be replaced using a tailored diet. This extra-corporeal detoxification process was used in a uremic patient who had been on traditional hemodialysis for the past two years. The continuous treatment permitted maintenance of fluid and electrolyte equilibrium at the desired level and allowed rapid improvement of patient clinical status: elimination uf nausea, vomiting, diarrhea and edema, which had previously reappeared during the interdialytic periods, as well as a rapid decrease in heart size as ascites disappeared. In addition, the patient regained sexual drive and the ability to have an erection. In conclusion, traditional hemodialysis and hemofiltration techniques allow intermittent elimination of products retained by the body and reestablish nearly normal fluid and electrolyte balance.(ABSTRACT TRUNCATED AT 250 WORDS)

The preparation of orally disintegrating tablets using a hydrophilic waxy binder.

The demand for rapidly disintegrating tablets (RDT) has been growing during the last decade especially for elderly and children who have swallowing difficulties. The problem of certain RDT is their low physical resistance and high friability. This work describes a new approach to prepare RDT with sufficient mechanical integrity, involving the use of a hydrophilic waxy binder (Superpolystate, PEG-6-stearate). Superpolystate is a waxy material with a melting point of 33-37 degrees C and an HLB value of 9. So it will not only act as a binder and increase the physical resistance of tablets but will also help the disintegration of the tablets as it melts in the mouth and solublises rapidly leaving no residues. The incorporation of Superpolystate in the formulation of RDT was realised by means of two different granulation methods: wet granulation by using an emulsion of this waxy binder as granulating liquid and melt granulation where the molten form of the binder was used. Granule size distributions of both wet and melt granules of crystallised Paracetamol and D-mannitol were compared using laser light diffractometer. Scanning electron microscopy (SEM) was used to examine their morphological characteristics. The potential of the intragranular addition of croscarmellose sodium as a disintegrating agent was also evaluated. The subsequent step encompassed the preparation and the evaluation of the tablets, including the effect of the extragranular introduction of croscarmellose sodium. An improvement in tablet hardness and friability was observed with both granulation methods where we were able to obtain RDT with a disintegration time of 40 +/- 2 s and a hardness of 47.9 +/- 2.5N.

Using ultrapure water in hemodialysis delays carpal tunnel syndrome.

Since 1977, our patients have undergone chronic HD with ultra-pure dialysate (UPD), defined as having endotoxin levels below 0.008 ng/ml and less than 1 bacteria/ml of dialysate. We evaluated the incidence of carpal tunnel syndrome (CTS) in three groups of patients. Group I (GI), 84 patients, dialysed for 6.1 +/- 3.2 years (mean +/- SD) with UPD only; Group II (GII), 39 patients, first dialysed for 3.7 +/- 2.3 years with non-UPD and afterwards for 8.4 +/- 2.1 years with UPD; Group III (G III), 103 patients treated for 6 +/- 5.9 years exclusively with non-UPD. All patients were dialysed with cuprophan or cellulose acetate membranes. Results, expressed by Kaplan-Meier actuarial survival curves as the percent of patients without CTS, show that CTS occurred significantly less in GI than in GIII. This may be due to less stimulation of monocytes resulting from the absence of bacteria, endotoxins and pyrogens in the dialysate, which would reduce the stimulation of cytokines release, interleukin 1 and 6, and tumor necrosis factor, known to stimulate beta 2 microglobulin synthesis.

Kron's biliary prosthetic bypass in the treatment of neoplastic jaundice.

After experimental study in the dog, which showed the material to be highly reliable, an original method of biliary bypass using a silicone prosthesis in the treatment of neoplastic jaundice is introduced. This prosthesis allows the bile duct to be bypassed regardless of the location of the obstacle. This method was used in 150 patients; recession was sufficiently good in 84 of them to confirm good tolerance and the excellence of the results. In fact, good results were recorded in 95% of cases of cancer of the hilum, which is all the more remarkable in consideration of the difficulties involved in these operations. The main postoperative complications are bile fistulas which resolve spontaneously if the precaution of extensively draining the zones of intubation is taken; postoperative comfort is excellent; no constraint is necessary and the operative risk is moderate, this is particularly desirable in patients in a poor general condition. A short prosthesis makes transtumoral intubation possible, and a long prosthesis allows implantation in the digestive tract: stomach, duodenum or first intestinal loop. Postoperative persistence of jaundice is rare if a prosthesis of sufficient diameter is used and if no major bile duct or part of the liver is excluded. Cholangitis is exceptional and indicative of an excluded biliary area.

Benign breast disease and cancer.

We report the necessity for thoroughly understanding the physiopathology of benign breast lesions in order to treat each type of lesion adequately. Three groups of women are outlined as a practical approach to this problem. Subadipose mastectomy is proposed to treat heteronodular mastopathy. This operation is compared with the subcutaneous mastectomy proposed by plastic surgeons.

An experimental and clinical study of immunocompetence and immunostimulation in breast cancer.

Two hundred and seven patients aged from 37 to 65 years with noninflammatory breast cancer treated by surgery without radiation were studied over a ten year period with a view to forecasting the prognosis on the basis of the immune status and treatment. The immunocompetence or immune status was studied in 121 patients by in vitro and in vivo pre and post-surgical skin tests. The immunostimulation or restoration of the immune status was conducted by the P 40 immunomodulator from the Pasteur Institute: in an experimental study whose results are based on modified Huggins model and take in to account the survival rate and the evaluation of tumor growth; in a subgroup of 86 patients, demonstrating that immunostimulation is effective in low-scores, improves tolerance to chemotherapy and increases the six year survival rate in high risk low-score patients. The results are encouraging enough to propose improving the survival rate in a prospective clinical study of early breast cancer treated by local and regional means using a protocol incorporating an immunostimulation based on the existing immunocompetence with interferon-induced reconversion of the target cells in the hope of specific stimulation.

Immunological investigation and immunotherapy in patients operated on for breast carcinoma.

The tumor-host relationship is an essential factor in the onset, development, and recovery from malignancies. A basic consideration in the treatment of cancer patients must therefore be to understand this relationship and attempt to modify it in order to favor the host. We here discuss the results of a study of the immunologic status of 91 breast cancer patients. The use of a battery of tests with five subcutaneous hypersensitivity antigens allowed us to detect some differences in the immunological profiles of patients with or without lymph node involvement. The effect of an immunostimulant fraction prepared from Corynebacterium granulosum, P40 is also analyzed. This fraction significantly modifies tumoral recurrence in DMBA-induced mammary cancers in the Sprague Dawley rat, causes regression of mammary permeation nodules following in situ injection and modifies the cutaneous reactions of one-half of the anergic breast cancer patients although regular re-challenge is still necessary.

[Plasma and intra-erythrocytic concentrations of copper and zinc in uremic patients treated by periodic hemodialysis]. / Concentrations de cuivre et de zinc plasmatiques et intra-érythrocytaires chez les sujets urémiques traités par hémodialyse périodique.

In this report, the authors have studied the plasma and red blood cell concentrations of both zinc and copper in 90 uremic patients treated by intermittent hemodialysis. They found that plasmatic and erythrocytic levels of zinc together with the copper red blood cell concentrations determined before and after the hemodialysis are not significantly different from these recorded on normal subjects. However, the plasmatic copper concentrations are markedly increased, although no relevant correlation between the determined values and those measured in the dialysis bath can be drawn. Plasmatic copper levels fluctuations have been followed on 5 patients during an hemodialysis period ranging from 4 to 36 months, and did not reveal any relevant increase of copper levels. The etiology of the plasmatic copper concentration still be remain to be determined.

[The bioavailability of natural progesterone given by mouth. Measurement of steroid concentrations in plasma, endometrium and breast tissue]. / Biodisponibilité de la progestérone naturelle administrée par voie orale. Mesure des concentrations du stéroïde dans le plasma, l'endomètre et le tissu mammaire.

The effects of two galenic processes (micronisation and addition of oil) on the bioavailability of progesterone administrated orally were studied. After ingestion of progesterone (200 mg), mean plasma progesterone rapidly rises up to the 2nd hour and reaches levels of the normal luteal phase (12.6 +/- 2.6 ng/mg). It then decreases progressively up to the 8th hour. Daily administration of progesterone (300 mg) for 8 days significantly increases the endometrial concentration of the steroid (18.3 +/- 2.9 ng/ml) and efficiently corrects the tissular hormone deficiency. The breast tissue uptakes and concentrates equally progesterone. After oral administration of the natural hormone, progesterone concentrations are considerably increased in the three tissue compartments studied (normal glands: 25.0 +/- 9.7 ng/g; benign tumor: 38.0 +/- 9.1 ng/g; adipose tissue: 160.2 +/- 65.4 ng/g). These pharmaco-kinetic results correspond to the requirements of general substitutive hormone therapy. They justify the use of natural oral progesterone therapy, providing the amount given is modified according to immediate clinical tolerance.