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Biomedical subjects

P Goldschmidt

Publications and source records attributed to P Goldschmidt.

At least 19 recordsLinked to original sources

Detection by broad-range real-time PCR assay of Chlamydia species infecting human and animals.

BACKGROUND: Tests available for molecular diagnosis of chlamydial infections detect Chlamydiatrachomatis, but do not find other Chlamydia species associated with genital, ophthalmic, cardiovascular, respiratory or neurological diseases. The routine detection of all Chlamydia species would improve the prognosis of infected people and guide therapeutic choices. AIM: To design and validate a sensitive, specific, reproducible, inexpensive and easy-to-perform assay to quantify most Chlamydia species. METHODS: Primers and probe were selected using the gene coding for the 16S rRNA. The detection limits were assessed for suspensions of Chlamydia trachomatis, Chlamydia psittaci and Chlamydia pneumoniae. The performance of this test was compared with that of two commercial kits (Amplicor-Roche and Artus) on 100 samples obtained from children with trachoma. RESULTS: The detection capacities for Chlamydia trachomatis of the broad-range real-time polymerase chain reaction (PCR) were similar or slightly better than those obtained with commercial kits (0.2 copies of DNA/microl). Only the broad-range PCR identified specimens containing Chlamydia psittaci and Chlamydia pneumoniae. The commercial kits and the broad-range assay detected Chlamydia species in 5% and in 11%, respectively, of samples from children with trachoma. CONCLUSIONS: This new real-time PCR offers a sensitive, reproducible assay that produces results in <3 h. With panels of quantified Chlamydia species, this real-time PCR can be run with all real-time PCR equipment. Larger trials are needed to confirm the utility of this test in diagnosis and for therapeutic follow-up.

Animals↗

Effects of topical anaesthetics and fluorescein on the real-time PCR used for the diagnosis of Herpesviruses and Acanthamoeba keratitis.

BACKGROUND: The early microbiological diagnosis of corneal infections may prevent the condition from worsening. AIM: To study the potential interferences of oxybuprocain and fluorescein solutions used by ophthalmologists on the performances of the real-time polymerase chain reaction (PCR) carried out as routine test for diagnosis of keratitis. METHODS: Quantified suspensions of Herpes simplex virus (HSV1), Varicella zoster virus (VZV), Cytomegalovirus (CMV) and Acanthamoeba with and without oxybuprocain or fluorescein added before DNA extraction were tested by real-time PCR. RESULTS: The capacities of the real-time PCR to detect HSV, VZV, CMV and Acanthamoeba were reduced by oxybuprocain and fluorescein. Both products diluted to 1/16 reduced the PCR detection capacities for more than 2 logs (DNA copies/sample). CONCLUSIONS: The simultaneous introduction of fluorescein or topical anaesthetics into the tubes containing the specimens to be tested by PCR may lead to false negative results. Because corneal specimens for microbiological diagnosis of keratitis are obtained after topical administration of anaesthetics and corneal staining with fluorescein, ophthalmologists should be aware to rinse the eye surface intensively with appropriate eye solutions to minimise the risks of misdiagnosis.

Acanthamoeba↗

[In vitro effects of antiallergic eyedrops on complement activation induced by particulate matter].

BACKGROUND: Recent decades have been marked by an increasing number of patients suffering from ocular allergic-like symptoms without being associated with an increase in IgE levels. These symptoms include heaviness of the lid, foreign body sensation, burning, stinging and photophobia. Both epidemiological studies and controlled human exposure clinical studies have shown cause-effect relationships between allergic-like symptoms and environmental factors such as outdoor air pollutants or poor indoor air quality. An ocular surface subclinical inflammation is thought to be responsible for pseudoallergic, pollution-related conjunctivitis. The complement system is considered as one of the major effector mechanisms involved in initiation of the subclinical inflammation that leads to IgE-independent eye irritation. PURPOSE: To study the capability of nine antiallergic eyedrops commonly used in the treatment of allergic conjunctivitis to inhibit complement activation induced in vitro by pollutants. METHODS: Normal human serum obtained from healthy individuals was used as a source of complement. Activation of complement was assessed using the complement hemolytic 50% (CH50) assay, in the absence or the presence of antiallergic eyedrops and in the absence or the presence of various stimuli, including sand, common house dust, eye mascara, and Dactylis glomerata pollen extract. Zymosan was used as a standardized complement activator. The following eyedrops were studied: Naabak (4.9% N-acetyl aspartic acid-glutamic acid, NAAGA, sodium salt), Almide (lodoxamide 0.1%), Levophta (0.05% levocabastine), Emadine (0.05% emedastine), Tilavist (2% nedocromil), Allergodil (0.05% azelastine), Patanol (olopatadine), and Zaditen (0.025% ketotifen). Effects of preservative-free lodoxamide and ketotifen were also assessed and compared to those of the preserved formulations. A solution of 0.01% benzalkonium chloride (BAC), the most widely used preservative in topical eyedrops, was also tested. RESULTS: Zymosan-induced activation of complement (30+/-6%) was significantly lowered by preincubation of serum with unpreserved NAAGA (16.6+/-4%, p=0.0026) or benzalkonium-preserved nedocromil (20+/-2%, p=0.022). Preserved levocabastine, emedastine, olopatadine and ketotifen did not interfere with zymosan-induced complement activation, whereas preserved azelastine, lodoxamide and benzalkonium chloride significantly aggravated complement activation induced by zymosan. Similar results were obtained when complement activation was triggered by sand, common house dust, mascara, or by an allergenic extract of Dactylis glomerata pollen. In the absence of complement activator, none of the antiallergic eyedrops induced a significant change in CH50 titer, indicating that the deleterious pro-inflammatory effect of preserved azelastine and lodoxamide may occur only once complement activation has been initiated, i.e., on an inflamed ocular surface. CONCLUSION: Among the antiallergic eyedrops tested in this study, only Naabak and Tilavist were found to significantly inhibit complement activation triggered by particulate matters or pollen allergenic extract. Such an anticomplement activity confers these two molecules a potential in the therapeutic management of pollution-related pseudoallergic conjunctivitis.

Air Pollutants↗

[N acetyl-aspartyl glutamic acid (NAAGA) inhibits the adhesion of leukocytes to activated endothelial cells and down-modulates the cytokine-induced expression of adhesion molecules].

BACKGROUND: Cell adhesion plays a pivotal role in most ocular surface inflammatory diseases. Adhesion molecules mediate cell-to-cell and cell-to-matrix adhesion. Their expression is up-regulated by pro-inflammatory stimuli such as cytokines, histamine or complement-derived anaphylatoxins. The dipeptide N acetyl-aspartyl glutamic acid (NAAGA) is used as unpreserved topical eyedrops in the treatment of allergic conjunctivitis. NAAGA is known to inhibit leukotriene synthesis, histamine release by mast cells, and complement-derived anaphylatoxin production. PURPOSE: To investigate the potential capability of NAAGA to interfere with leukocyte adhesion to endothelial cells and modulate cytokine-induced expression of adhesion molecules. METHODS: Human blood-derived leukocytes were co-cultured with human umbilical vein endothelial cells (HUVECs) in the absence or the presence of 1000 UI/mL human recombinant TNFalpha, 10(-4) M histamine di-hydrochloride or 5x10(-6) M human recombinant C5a, and in the absence or presence of NAAGA (final concentration 2.45%). Adhesion of leukocytes to HUVECs was calculated by subtracting the number of nonadherent leukocytes from the total number of leukocytes. Expression of adhesion molecules was assessed by flow cytometry using anti-CD11b, anti-CD49d, anti-ICAM-1 (CD54), anti-ICAM-2 (CD102), anti-VCAM-1 (CD106) and anti-ELAM-1 (CD62E) monoclonal antibodies. RESULTS: NAAGA was found to totally inhibit adhesion of unstimulated leukocytes, or leukocytes activated with C5a, TNFalpha, or histamine, to TNFalpha-stimulated HUVECs (P=0.0001). Adhesion of leukocytes to unstimulated HUVECs was not modified by NAAGA. Similar results were obtained with endothelial cells stimulated by histamine or C5a. Taken together, these data indicate that NAAGA totally abrogates cell adhesion under inflammatory conditions, without interfering with the physiological adhesion of leukocytes to normal endothelium. At the molecular level, NAAGA inhibited histamine-induced expression of CD11b (P=0.0004) and CD49d (P=0.0045) on granulocytes. On TNFalpha-activated HUVECs, NAAGA induced a significant decrease in the VCAM-1 expression level (P<0.0001) and totally reversed TNFalpha-induced overexpression of ICAM-1 (P=0.0069), ICAM-2 and ELAM-1 (P<0.0001), without interfering with baseline expression of these molecules. CONCLUSION: These results show that the antiallergic compound NAAGA directly inhibits leukocyte adhesion to endothelial cells induced by pro-inflammatory stimuli, and abrogates TNFalpha-induced expression of adhesion molecules on granulocytes and endothelial cells. This capacity to block overexpression of selectins and integrins induced by pro-inflammatory stimuli confers to NAAGA a potential as an anti-inflammatory drug, since interfering with adhesion molecule expression is probably one of the most efficient ways to curb leukocyte recruitment to inflammatory sites.

Antigens, CD↗

Optimization of the resistance of arterial allografts to infection: comparative study with synthetic prostheses.

Arterial allografts can be used for in situ treatment of prosthetic graft infection. The purpose of this in vitro study was to compare the resistance of allografts and synthetic prostheses to infection by five strains of bacteria and to study antibiotic treatments designed to reduce allograft infection. Fresh and cryopreserved allografts were compared with synthetic prostheses made of various biomaterials including PTFE, plain Dacron, gelatine-sealed Dacron, and gelatine-sealed, rifampicine-bonded Dacron. Allografts were used with or without treatment using an antibiotic containing gentamycine, lincomycine, and vancomycine. The bacterial strains tested were Escherichia coli, Staphylococcus aureus, slime-producing Staphylococcus epidermidis, non-slime-producing Staphylococcus epidermidis, and Pseudomonas aeruginosa. Infection was evaluated by counting the number of adherent bacteria on the allograft or synthetic material after rinsing and ultrasonication. Statistical analysis was achieved using nonparametric Mann-Whitney tests. Results showed that allografts not treated with antibiotics were highly susceptible to bacterial infection. Antibiotic treatment decreased infection. Application of antibiotic after thawing cryopreserved allografts led to a significant decrease. None of the biomaterials tested provided sufficient protection against bacteria resistant to the antibiotics used.

Anti-Bacterial Agents↗

Cyanoside chloride and chromocarbe diethylamine are more effective than vitamin C against exercise-induced oxidative stress.

Exercise generates free radicals only when it is exhaustive. Free radicals are involved in tissue damage caused by exercise. Antioxidant vitamins (vitamin C and E) and other antioxidants such as coenzyme Q, and N-acetyl cysteine prevent muscle damage and decrease muscle fatigue. The main aim of this paper was to test the possible protective effect of two new antioxidants, cyanoside chloride and chromocarbe diethylamine, on the oxidative stress generated by exhaustive exercise. The antioxidants were given to rats daily (50 mg/kg) in drinking water for 30 days. Blood oxidized glutathione/ reduced glutathione ratio, and plasma malondialdehyde levels were determined as indexes of oxidative stress. Plasma creatine kinase, alanine-aminotransferase and lactate dehydrogenase activities were used as markers of muscle damage. Both cyanoside chloride and chromocarbe diethylamine were more effective than vitamin C in the prevention of glutathione oxidation in blood. Furthermore, cyanoside chloride and chromocarbe diethylamine partially prevented muscle damage. Chromocarbe diethylamine was the most effective compound in the prevention of exercise-induced lipid peroxidation (malondialdehyde) in plasma.

Alanine Transaminase↗

New anionic polyelectrolyte hydrogel for corneal surgery.

A new high-water-content (78%) anionic polyelectrolyte hydrogel was obtained by phase inversion (demixion) of a polymer solution containing 9.0% poly(acrylonitrile sodium methallylsulphonate), 85.0% dimethylformamide, and 6.0% saline solution (0.9% NaCl). The hydrogel is permeable to water, saline, urea, creatinine, glucose, human albumin, and saline-dissolved oxygen. Investigation of the interactions between human serum and surfaces prepared with the new yielded hydrogel, compared to serum interaction with silica-free silicone (RTV), regenerated cellulose (Cuprophan), MMA/PVP copolymer (Lidofilcon), PMMA (Perspex), FIFE (Gore-Tex), and poly(acrylonitrile sodium methallylsulphonate) hemodialysis membrane (AN-69), showed the hydrogel and hemodialysis membrane (both prepared with AN-69 copolymer) to be the only materials devoid of complement (C')-activating ability.

Biocompatible Materials↗

Effects of non-steroidal antiallergic eyedrops on the complement-mediated histamine release from human cells.

Leukocytes from ten allergic patients (five allergic to dust-mites and five allergic to pollen) were treated with N-acetyl aspartyl glutamic acid (NAAGA) 4.9%, disodium cromoglycate (DSCG) 2%, lodoxamide (LODO) 1%, and levocabastine (LEVO) 0.5% (concentrations representing the pharmaceutical eyedrop preparations) for 20 minutes. Degranulation was then induced with Complement (rHu5Ca). Histamine was measured in the supernatant with ELISA. LODO and LEVO were inactive in blocking histamine released from human cells, and paradoxical unexpected effects were found with these two agents. They both induced significant histamine release in almost 100% of the samples. DSCG was able to block histamine release in seven patients out of nine (ranging between 5 and 34%). NAAGA was the most active agent on human cells and was able to block basophil degranulation in nine patients out of nine (inhibition ranging between 4 and 66% of total histamine pool).

Allergens↗

What is proper cancer care in the era of managed care?

Managed care and proper cancer care need not be mutually exclusive entities. Managed-care organizations (MCOs) that are committed to patients and society should have the following characteristics: accountability for results, cost containment, measurement of outcomes, health promotion and disease prevention programs, resource consumption management, emphasis on primary care, and continuous quality improvement. Whether these commitments are upheld depends on when and with whom the MCO contracts to provide care and which medical and quality assurance protocols it follows. If proper cancer care is to become a reality in the managed-care era, the oncology community must take a proactive stance. Oncologists must provide the market with an appropriate, efficient disease management plan for cancer. In concert with MCOs, the oncology community must define and, through partnerships, promote the seamless integration of proper cancer care. Patients and advocates should insist that MCOs' quest for efficiency allows for flexibility to address individual patients' circumstances.

Case Management↗

Randomised trial of ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis: a multicentre study.

AIMS: This study was designed to assess the relative efficacy of topical ganciclovir 0.15% gel and acyclovir 3% ointment in the treatment of herpes simplex dendritic keratitis. METHODS: Both treatment modalities were administered on a five times daily basis to patients suffering from herpes simplex keratitis. Patients were assigned randomly to one of the two treatment groups for the purpose of the trial. They were then examined on days 2, 7, 10, and 14 to assess the rate of healing of the dendritic ulceration. RESULTS: There was no statistically significant difference detected in the rate of healing between the two treatment groups over the course of the trial. CONCLUSIONS: Review of the relative efficacy of topical ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis showed that both treatment modalities were equally effective in their ability to heal the viral induced corneal ulceration. There were no significant side effects or adverse effects reported for either treatment modality.

Acyclovir↗

Effects of lodoxamide (LOD), disodium cromoglycate (DSCG) and N-acetyl-aspartyl-glutamate sodium salt (NAAGA) on ocular active anaphylaxis.

LOD, DSCG and NAAGA eye-drops were evaluated on experimentally-induced ocular active anaphylaxis in guinea pigs. Twelve animals per group were sensitized with egg albumin i.p. and challenged on the surface of the eye 14 days later. Two days before challenge, animals were treated with LOD, DSCG or NAAGA 4 times a day. Permeability indexes were calculated after intracardiac injection of Evans Blue. No effect on ocular active anaphylaxis was found with LOD nor with DSCG. NAAGA was able to significantly reduce blood-eye permeability indexes.

Anaphylaxis↗

Ultrasound for the early diagnosis of fracture healing after interlocking nailing of the tibia without reaming.

Fourteen fractures (8 open, 6 closed) were treated with small-diameter interlocking tibial nails and observed for at least 1 year. Radiographs were obtained to monitor the maintenance of reduction and fracture healing. The treating orthopaedic surgeon was blinded to the results of ultrasound studies, which were obtained at 2-week intervals for 10 weeks postoperatively and read by a radiologist who was blinded to the clinical and radiographic progress. Ultrasound correctly predicted fracture healing in all 9 fractures that subsequently progressed to fracture union. Of the 5 fractures that did not heal and required secondary procedures, ultrasound predicted delayed healing in 4 fractures. Overall, ultrasound was able to predict fracture healing before it was radiographically evident. Ultrasound may provide important prognostic information concerning tibial fracture healing after treatment using interlocking nails without reaming. Additional study is warranted.

Adolescent↗

[Bilateral acute retinal necrosis in a patient with acquired immunodeficiency syndrome].

A case of bilateral progressive outer retinal necrosis occurred after herpes zoster ophthalmicus in a patient with acquired immunodeficiency syndrome. This case does not correspond to the classical picture of progressive outer retinal necrosis. The disease led to blindness despite intravenous therapy with acyclovir and foscarnet. PCR could not identify any virus in the aqueous humour, but VZV is evidenced in cerebrospinal fluid. Acute retinal necrosis is now clearly defined by the American Uveitis Society, which should allow to determine its incidence and risk factors. Herpes zoster usually precedes the acute outer retinal necrosis. The infectious theory (VZV, HSV, CMV) widely prevails over the immune theory. We prefer the virus genome identification in the aqueous humor or in the vitreous by PCR to confirm diagnosis rather than the specific antibody titration. Therapy consists in acyclovir, foscarnet and ganciclovir. But whatever the treatment, the visual prognosis is poor.

Acquired Immunodeficiency Syndrome↗

Ganciclovir ophthalmic gel in herpes simplex virus rabbit keratitis: intraocular penetration and efficacy.

A chronic administration of three ganciclovir gels (0.2%, 0.05%, 0.0125%) was compared with a placebo gel and a 3% acyclovir ophthalmic ointment in the treatment of HSV-1 rabbit keratitis. All the ganciclovir gels showed a clinical efficacy: a significant reduction of the corneal ulcer area, clouding and vascularization (p < 0.05) and a fast inhibition of HSV isolates into tear film with the 0.2% and 0.05% ganciclovir gels. However the efficacy was slower than using acyclovir ointment. No significant difference could be shown between the 0.2% and 0.05% ganciclovir gels or the 0.05% ganciclovir gel and the acyclovir treatment on viral isolation, when it was performed on pooled samples. The distribution of ganciclovir and acyclovir into the rabbit eyes (HPLC methods), were similar but markedly higher in solid tissues than ocular fluids. It might explain the recovery from tissue damages. The mean corneal ganciclovir concentrations were largely higher than ED 50 of ganciclovir for HSV-1. No toxicity was expected, due to very limited systemic availability. This study suggests a comparable activity on HSV-1 superficial keratitis between 0.05%, 0.2% ganciclovir gels and 3% acyclovir ointment. Higher concentration of ganciclovir gels are probably necessary in order to treat the HSV-1 kerato-uveitis.

Acyclovir↗

Hemostatic effects of stress hormone infusion.

BACKGROUND: Surgery causes changes in hemostasis, leading to a hypercoagulable state. This postoperative increase in hemostatic function is attenuated in patients receiving regional anesthesia compared with those receiving general anesthesia. Regional anesthesia also decreases the neuroendocrine response to surgery compared with general anesthesia, and this effect is hypothesized to be responsible for the differences in hemostatis. To test the hypothesis that neuroendocrine hormones cause changes in hemostasis, we infused stress hormones into normal volunteers and measured hemostatic function. METHODS: After drug screening, 12 normal volunteers were studied. On two admissions, volunteers randomly received either stress hormone (epinephrine, cortisol, or glucagon) or placebo infusion for 24 h. During infusion, patients remained at bed rest and received controlled meals. Blood was obtained from indwelling venous catheters before infusion and 2, 8, and 24 h after the start of infusion. Blood was analyzed for neuroendocrine hormone concentrations, glucose, complete blood count, coagulation proteins, platelet reactivity, and activity of the fibrinolytic system. RESULTS: In the stress hormone group, concentrations of epinephrine, norepinephrine, cortisol, glucagon, and insulin were increased during the infusion period compared with those in the placebo group. Glucose concentrations and white blood cell counts were increased in the stress hormone group compared with those in the placebo group. Circulating fibrinogen concentrations increased 30% and ex vivo collagen-induced platelet reactivity increased 123% (aggregation) and 103% (dense granule release) in the stress hormone infusion group, whereas there was no change in the placebo group. Fibrinolytic proteins were similar in both groups, demonstrating a decrease in plasminogen activator inhibitor-1 activity at 8 and 24 h (196% in the hormone group vs. 199% in the placebo group). CONCLUSIONS: Infusion of stress hormones to concentrations found during surgery is safely tolerated and causes metabolic changes observed with surgery. Stress hormone infusion increases ex vivo platelet reactivity and fibrinogen concentrations that resemble changes seen postoperatively but does not recreate the postoperative decrease in fibrinolytic activity. Differences in neuroendocrine response between types of anesthesia may explain some postoperative changes in platelet function and acute phase reactivity, but additional uncharacterized factors are responsible for the differences in fibrinolysis.

Adolescent↗

[Evaluation of a new rapid ELISA technique for detecting human cytomegalovirus antibodies (CMV). Applications in emergency blood transfusion and in organ transplantation].

Immunocubes can detect very low HCMV IgG levels with at least the same sensitivity as the reference technique: ELISA. Samples containing bacteria showed no particular interference on the test, and results for non-infected material were in agreement with those of ELISA. The rapid test did not give any false positive reactions even with samples from patients with very high antiherpes immunoglobulins levels. Samples from transplant patients at the beginning of seroconversion or diluted to IgG titers corresponding to ELISA cut-off values were always detected as positive by immunocubes. In view of the rapidity of the test, its high specificity, its ability to detect levels corresponding to extremely low IgG signals in ELISA, and the possibility of conserving objective proof of the test, we conclude that this rapid immunocube technique is of great interest for current serologic screening in an emergency context, especially for transfusion and organ transplantation.

Antibodies, Bacterial↗