Biomedical subjects
Publications and source records attributed to L Meyer.
The results of this case-control study show a significant statistical link between idiopathic arterial ischemic strokes in children and varicella-zoster virus infection.
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BACKGROUND: Little is known about the termination of the T-cell driven inflammation found in patients with allergic asthma. OBJECTIVE: Because signals delivered through Fas/Fas ligand can lead to T-cell apoptosis, we investigated the expression of Fas and Fas ligand on peripheral blood- and bronchoalveolar lavage fluid (BALF)-derived T cells and the percentage of apoptotic BALF cells in asthma. METHODS: Nine atopic subjects with mild asthma and 9 control subjects underwent segmental sham and allergen challenge. Flow cytometry was used to determine the T-cell expression of Fas and Fas ligand, and the terminal dUTP nick end labeled technique was applied to detect apoptotic BALF cells. RESULTS: In asthmatic and control subjects almost all T cells in the BALF expressed Fas antigen without changes after saline or allergen challenge. A small percentage of T cells in BALF expressed the Fas ligand. In asthmatic subjects, but not in control subjects, there was a significant increase in Fas ligand after allergen challenge (CD3: 0.8% +/- 0.6% [baseline] vs 3.2% +/- 1.2% [allergen challenge]; CD4: 1.8% +/- 0.0% vs 4.3% +/- 1.8%; CD8: 2.8% +/- 2.4% vs 9.1% +/- 4.8%) but not after saline challenge, with a significant correlation to the percentage of BALF eosinophils. Apoptotic BALF cells were localized exclusively in macrophages at a very low frequency (0.03% to 0.15%) and without changes after saline or allergen challenge in both groups. CONCLUSION: In asthma there is an upregulation of Fas ligand on T cells in BALF after allergen challenge. Because there is no evidence for increased apoptosis, this phenomenon may reflect antigen-induced T-cell activation rather than apoptosis.
OBJECTIVE: To develop a screening strategy for Chlamydia trachomatis in private gynecology practices. STUDY DESIGN: Forty-six gynecologists in the greater Paris area systematically screened all consecutive female attenders during one week. Endocervical swabs were tested by enzyme immunoassay, and, if positive, was further confirmed by direct fluorescent antibody test. RESULTS: Overall (out of 1893 women tested), the chlamydia prevalence was 0.8% (95% confidence interval: 0.32-1.2%). Among women younger than 21 years, the prevalence was 5.2% (95%, CI 0.8-9.6). Having had a new sexual partner in the last year was associated with chlamydial infection, independent of age. However, half of the infected women had not had a new partner. CONCLUSION: Even in this low risk population, the prevalence was high among young women. Most of these infections would probably not have been detected. We developed a strategy which would have detected 81% of chlamydia positive women by testing only one third of the patients.
The present study investigated: (1) perception of genetic risk and, (2) the psychological effects of genetic counselling in women with a family history of breast cancer. Using a prospective design, with assessment pre- and post-genetic counselling at clinics and by postal follow-up at 1, 6 and 12 months, attenders at four South London genetic clinics were assessed. Participants included 282 women with a family history of breast cancer. Outcome was measured in terms of mental health, cancer-specific distress and risk perception. High levels of cancer-specific distress were found pre-genetic counselling, with 28% of participants reporting that they worried about breast cancer 'frequently or constantly' and 18% that worry about breast cancer was 'a severe or definite problem'. Following genetic counselling, levels of cancer-specific distress were unchanged. General mental health remained unchanged over time (33% psychiatric cases detected pre-genetic counselling, 27% at 12 months after genetic counselling). Prior to their genetics consultation, participants showed poor knowledge of their lifetime risk of breast cancer since there was no association between their perceived lifetime risk (when they were asked to express this as a 1 in x odds ratio) and their actual risk, when the latter was calculated by the geneticist at the clinic using the CASH model. In contrast, women were more accurate about their risk of breast cancer pre-genetic counselling when this was assessed in broad categorical terms (i.e. very much lower/very much higher than the average woman) with a significant association between this rating and the subsequently calculated CASH risk figure (P = 0.001). Genetic counselling produced a modest shift in the accuracy of perceived lifetime risk, expressed as an odds ratio, which was maintained at 12 months' follow-up. A significant minority failed to benefit from genetic counselling; 77 women continued to over-estimate their risk and maintain high levels of cancer-related worry. Most clinic attenders were inaccurate in their estimates of the population risk of breast cancer with only 24% able to give the correct figure prior to genetic counselling and 36% over-estimating this risk. There was some improvement following genetic counselling with 62% able to give the correct figure, but this information was poorly retained and this figure had dropped to 34% by the 1-year follow-up. The study showed that women attending for genetic counselling are worried about breast cancer, with 34% indicating that they had initiated the referral to the genetic clinic themselves. This anxiety is not alleviated by genetic counselling, although women reported that it was less of a problem at follow-up. Women who continue to over-estimate their risk and worry about breast cancer are likely to go on seeking unnecessary screening if they are not reassured.
One hundred and sixteen patients with locally advanced or metastatic breast cancer were randomized to receive CMF (cyclophosphamide 600 mg m(-2) day 1 and 8 i.v., 5-fluorouracil 600 mg m(-2) day 1 and 8 i.v., methotrexate 40 mg m(-2) day 1 and 8 i.v., monthly for 6 cycles) or MM (methotrexate 30 mg m(-2), mitoxantrone 6.5 mg m(-2), both i.v. day 1 3-weekly for 8 cycles) as first line treatment with chemotherapy. Objective responses occurred in 17 patients out of 58 (29%) who received CMF and nine out of 58 (15%) who received MM; 95% confidence interval for difference in response rates (-1%-29%), P = 0.07. No statistically significant differences were seen in overall survival or time to progression between the two regimes although a tendency towards a shorter progression time on the MM regime must be acknowledged. There was, however, significantly reduced haematological toxicity (P < 0.001) and alopecia (P < 0.001) and fewer dose reductions and delays in patients randomized to MM. No statistically significant differences were seen between the two regimes in terms of quality of life (QOL). However, some association between QOL and toxicity was apparent overall with pooled QOL estimates tending to indicate a worsening in psychological state with increasing maximum toxicity over treatment. Despite the fact that results surrounding response rates and time to progression did not reach statistical significance, their possible compatibility with an improved outcome on CMF treatment must be borne in mind. However, MM is a well-tolerated regimen with fewer side-effects than CMF, which with careful patient management and follow-up, therefore, may merit consideration as a first-line treatment to palliate patients with metastatic breast cancer who are infirm or elderly.
The aim of this present study was to compare the use by smokers and non-smokers of pamphlets about smoking as delivered from different settings. The study was a nation-wide cross-sectional survey of 1924 randomly selected, Danish men and women, aged 14-77 y, who had answered a mailed questionnaire in 1994. Of these 71% also participated in a telephone interview enquiring about the use of health education material, smoking status and socio-demographic variables, 39% of readers of household-delivered anti-smoking pamphlets reported having gained information from them and 22% reported having made changes in their own smoking behaviour such as avoiding smoking in the presence of non-smokers. In general practice settings, these percentages were higher among smokers. Smokers who were thinking of stopping smoking in the near future were in addition more likely to take and to read smoking related health education materials from other places. Non-smokers received (3 49%) and read pamphlets about smoking as frequently as did smokers who did not intend to quit. In conclusion, written health education material was well received by readers, but, when distributed in a more open setting it needs to be targeted towards smokers who are considering stopping smoking. In general practice, smokers not thinking of stopping were open to health education, and pamphlets used in this setting should also target this group. Non-smokers contribute indirectly to smokers quitting by providing support to smokers and pamphlets for non-smokers need to be more targeted towards this social role.
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This study attempted to determine whether the CCR5 Delta32 deletion affected progression to certain first AIDS-defining illnesses in human immunodeficiency virus type 1-infected patients enrolled in the French SEROCO/HEMOCO/SEROGEST cohorts. Toxoplasmosis onset as a first AIDS-defining illness was significantly delayed in 253 heterozygous patients, compared with 1404 wild type patients. The relative risk of toxoplasmosis associated with heterozygosity was 0. 39 (95% confidence interval, 0.16-0.96) after adjustment for age, CD4 cell count, and primary specific prophylaxis. A nonsignificant protective trend was observed with regard to the onset of mycobacterial, cytomegalovirus, and herpesvirus diseases, but these events were less frequent than toxoplasmosis. Progression to other conditions (e.g., wasting, non-Hodgkin's lymphoma, Kaposi's sarcoma) was similar in the 2 groups as was the frequency of toxoplasmosis as a subsequent AIDS-defining illness. As chemokines are involved in numerous infectious processes, the Delta32 deletion could delay progression to certain opportunistic infections such as toxoplasmosis.
The incidence of cerebral and extracerebral toxoplasmosis among 1,699 HIV-infected patients followed in the SEROCO and HEMOCO cohorts (1988-1995) was studied. It increased from 0.7 per 100 person-years in 1988 to 2.1 per 100 person-years in 1992, as a result of the increasing prevalence of patients with CD4 cell counts below 200/microL. It decreased thereafter to 0.2 per 100 person-years in 1995, while the proportion of patients receiving specific prophylaxis was increasing. A Toxoplasma antibody titer of >150 IU/mL was an important predictor of toxoplasmosis (adjusted relative risk [aRR], 3.6 [95% confidence interval, 2.1-6.0]), independent of a CD4+ cell count of <200/microL (aRR, 20.8) and specific prophylaxis (aRR, 0.2 [0.1-0.3]). The median CD4+ cell count was 389/microL at the time the antibody titer was first noted to be >150 IU/mL, while the median CD4 cell count at onset of toxoplasmosis was 58/microL. Thus, disease was diagnosed 10 days to 74 months after the rise in Toxoplasma antibody titers. While the risk factors for development of toxoplasmosis remain incompletely defined, the importance of specific prophylaxis for patients with low CD4 cell counts and high Toxoplasma antibody titers is supported by these findings.
The oral fat load tests (OFLT) used to study postprandial lipemia are generally conducted during the day. A nocturnal fat load test could be convenient and physiologically more appropriate. We have therefore compared the lipemic responses of 9 normolipidemic young men to OFLT given at 2200 h (nocturnal) and at 0700 h (diurnal). Triglyceride and retinyl palmitate concentrations were measured for 10 h. Peak plasma concentrations or areas under curves (AUC) for triglyceride after the diurnal and nocturnal tests were not significantly different [2.17 +/- 0.78 (diurnal) vs. 2.04 +/- 0.87 mmol/L (nocturnal) and 13.12 +/- 4.45 (diurnal) vs. 13.74 +/- 5.79 mmol/(L. h) (nocturnal)]. Peak plasma concentrations and AUC retinyl palmitate for the two tests were not different [1.71 +/- 0.69 (diurnal) vs. 1.42 +/- 0.66 mg/L (nocturnal) and 7.17 +/- 3.98 (diurnal) vs. 6.63 +/- 4.23 mg/(L. h) (nocturnal)]. The diurnal triglyceride peak occurred significantly earlier (4.3 +/- 1.2 h) than the nocturnal peak (5.8 +/- 1.7 h, P < 0.05). We have developed a model using only three sample time points to predict AUC [triglyceride at 0 h, triglyceride at average peak-time (4 h for diurnal and 6 h for nocturnal tests), and triglyceride at 10 h], thus reducing the number of blood samples. The predicted AUC was well correlated with the total AUC after nocturnal OFLT (r = 0.98, P < 0.0001). The nocturnal test appeared to be well tolerated by the subjects. The three-point simplified protocol may well be suitable for studies on large groups of subjects.
HIV-specific CD8(+) T cells play a major role in the control of virus during HIV primary infection (PI) but do not completely prevent viral replication. We used IFN-gamma enzyme-linked immunospot assay and intracellular staining to characterize the ex vivo CD8(+) T-cell responses to a large variety of HIV epitopic peptides in 24 subjects with early HIV PI. We observed HIV-specific responses in 71% of subjects. Gag and Nef peptides were more frequently recognized than Env and Pol peptides. The number of peptides recognized was low (median 2, range 0-6). In contrast, a much broader response was observed in 30 asymptomatic subjects with chronic infection: all were responders with a median of 5 peptides recognized (range 1-13). The frequency of HIV-specific CD8(+) T cells among PBMC for a given peptide was of the same order of magnitude in both groups. The proportion of HIV-specific CD8(+)CD28(-) terminally differentiated T cells was much lower in PI than at the chronic stage of infection. The weakness of the immune response during HIV PI could partially account for the failure to control HIV. These findings have potential importance for defining immunotherapeutic strategies and establishing the goals for effective vaccination.
An interruption of continuous sc insulin infusion (CSII) of the insulin analog lispro should result in a more rapid metabolic deterioration of type 1 diabetic patients because of its pharmacokinetic characteristics. We analyzed the metabolic changes occurring during a 5-h interruption of CSII and the 5 h after restarting the pump in 10 type 1 diabetic patients. The study was a randomized, cross-over, open label design comparing insulin analog [Lispro (LP)] and regular insulin [Velosuline (VE)]. Plasma glucose, free insulin, glucagon, betahydroxybutyrate (beta-OHB), and nonesterified fatty acids (NEFA) were measured every hour from 0700 h (time zero) to 1700 h (600 min). After stopping CSII, the plasma glucose level was significantly higher in the LP group than in the VE group (P < 0.05-0.01). The plasma free insulin level decreased significantly with the two treatments, but was significantly lower with LP than with VE (P < 0.05-0.01). Plasma NEFA increased more rapidly and was significantly higher in the LP group than in the VE group (P < 0.01-0.05). Plasma beta-OHB increased earlier with LP, but was not statistically different between the treatments. After restarting the pump, plasma glucose decreased with LP, but continued to increase with VE, and the plasma free insulin peak occurred earlier and was greater with LP than with VE (P < 0.05). Plasma NEFA and beta-OHB levels decreased significantly with the two treatments, but more dramatically with LP treatment. Thus, a short interruption of Lispro in CSII is associated with an earlier, greater metabolic deterioration, but Lispro corrected this metabolic deterioration more effectively.
Supplying adequate iron (Fe) to neonatal pigs to support normal growth and hematological and antioxidant status, while preventing iron toxicity, is a challenge for producers. Three experiments were conducted to determine the effect of frequency and route of Fe administration with or without vitamin E (E) and selenium (Se) on growth, Fe, and antioxidant status of neonatal pigs. In Exp. 1, 12 pigs from dams with reduced E status were fed a semipurified diet without added Fe from d 3 to d 14 of age. At d 6 of age, pigs received the following i.m. injections: 1) FE, 1 mL containing 200 mg of Fe (iron dextran); 2) FEE, treatment FE plus 1 mL containing 300 IU of vitamin E (d-alpha tocopherol); or 3) FESEE, 1.03 mL containing 200 mg of Fe (iron dextran), .15 mg of Se (sodium selenite), and 15 IU of vitamin E (d-alpha tocopherol). Pigs were weighed daily and blood was collected at 3, 7, and 14 d of age. From d 8 to 14, growth was depressed (P < .05) in pigs injected with FESEE. At 14 d of age, pigs injected with FE or FEE had increased (P < .05) hemoglobin (Hb) concentration. Ceruloplasmin activity (CP) was greater (P < .05) at d 7 of age than at d 3 or 14 regardless of treatment. In Exp. 2, 3-d-old pigs (n = 94) received the following: 1) FE, 200 mg Fe (iron dextran) i.m.; (2) FEE, treatment FE plus 300 IU vitamin E i.m.; 3) EFE, 300 IU vitamin E i.m. followed by 200 mg Fe (iron dextran) i.m. 24 h later; or 4) OFE, 100 mg Fe and 10 mg Cu orally. On d 21 of age, one-half of the pigs in each treatment received a second dose of their respective treatment. Blood samples (n = 60) were obtained on d 3 and 21 of age. Pigs injected with FE, FEE, or EFE had greater (P < .05) Hb at d 21 than pigs given OFE. Copper/zinc superoxide dismutase (Cu/ZnSOD) activity was greater (P < .05) at d 21 with OFE than with the other treatments. At 65 d of age, ADG did not differ among treatments. In Exp. 3, pigs (n = 150, in three farrowing groups) were injected with 200 mg of Fe (iron dextran) on d 1 or d 1 and 14. Blood samples were obtained on d 7 and 21 of age. Hemoglobin concentration on d 21 was improved equally by both treatments. Catalase and Cu/ZnSOD activities were increased (P < .05) on d 21 of the experiment compared with d 7 regardless of treatment. Growth was not affected by injection frequency. Results from these experiments indicate that one Fe injection (200 mg) for pigs from sows fed adequate vitamin E will result in adequate growth and hemoglobin concentration with today's improved genetics.
Opto-ciliary shunts are compensatory bypass channels from the retinal venous system to the choroidal veins in case of long standing central retinal vein occlusion. Indocyanine green angiography with the Scanning Laser Ophtalmoscope may be helpful to differentiate acquired optociliary shunts from retinal or choroidal arteriovenous malformations.
OBJECTIVES: The French consensus conference recommended targeted screening for hepatitis C virus infection in patients with a past history of intravenous drug use or transfusion of blood products before 1991. The aim of this study was to determine the feasibility and results of targeted screening by general practitioners. METHODS: For 2 weeks, 58 general practitioners systematically asked all their patients about a past (or current) history of intravenous drug use or transfusion of blood products before 1991. In patients who responded affirmatively, hepatitis C virus screening was proposed if it had not been performed previously. RESULTS: 8,292 patients were included. Blood transfusion and intravenous drug use were present in 383 (4.6%) and 116 (1.4%) patients respectively. Positive hepatitis C virus serology had been identified before the study, in 16 and 63 patients in these groups respectively. Tests were performed in 77% and 50% of patients with a history of blood transfusion and intravenous drug use. Systematic screening showed a positive hepatitis C virus serology in 7 and 4 patients with a history of blood transfusion and intravenous drug use (representing 2% and 15% of the tests performed during the study). Globally, 79 (88%) of the 90 patients with a positive serology had been identified before this systematic screening. CONCLUSIONS: Systematic targeted screening of hepatitis C virus infection only results in a diagnosis in a few cases. In the patients who consulted a general practitioner, 70% and 94% of cases of hepatitis C in patients with a history of blood transfusion or intravenous drug use respectively, were known before systematic screening.
BACKGROUND: We assessed the ability of LDL from 30 type 1 diabetic patients (18 men, 12 women), 65 type 2 diabetic patients (35 men, 30 women), and 35 controls (19 men, 16 women) to generate peroxides. The men and women in the diabetic groups were studied separately and matched for age, body mass index, duration of diabetes, glycohemoglobin, and conventional lipid characteristics according to the presence or absence of hyperlipidemia. METHODS: The ability of LDL to form peroxides was assessed by measuring the thiobarbituric acid-reactive substances corrected for LDL-cholesterol [ratio of malondialdehyde (MDA) to LDL-cholesterol]. LDL particle size was expressed as the ratio of LDL-cholesterol to apolipoprotein B (LDL-cholesterol/apoB). RESULTS: The MDA/LDL-cholesterol ratio was higher in type 1 and type 2 diabetic patients with hyperlipidemia than in controls. The MDA/LDL-cholesterol ratio was also higher in type 2 normolipidemic women than in controls (P <0.01). The LDL-cholesterol/apoB ratio was lower in type 2 diabetic women than in type 2 diabetic men (P <0.05). The MDA/LDL-cholesterol ratio was negatively correlated with the LDL-cholesterol/apoB ratio (r = -0.78, P <0.001) in hyperlipidemic type 1 (not type 2) diabetic patients. In normolipidemic type 2 diabetic patients, the MDA/LDL-cholesterol ratio was also negatively correlated with the LDL-cholesterol/apoB ratio (r = -0.75, P <0.001) because of the highly significant negative correlation in type 2 diabetic women (r = -0.89, P <0.01). CONCLUSIONS: LDL from well-controlled type 2 diabetic women is smaller and more prone to form peroxides. This could explain why diabetic women are at greater risk of cardiovascular disease.
To determine the relationship between plasma Lp(a) concentration and the risk of developing diabetic retinopathy, 341 Type 1 diabetic patients underwent an annual retinal fluorescein angiography and were assigned to one of 3 groups according to the stage of their diabetic retinopathy: no retinopathy (NR), non-proliferative diabetic retinopathy (N-PDR), or proliferative diabetic retinopathy (PDR). One hundred and twenty-three Type 1 diabetic patients had no retinopathy, 188 had N-PDR and 30 had PDR. The ages of the three groups and the duration of diabetes were significantly different. Hypertension, microalbuminuria and diabetic nephropathy were more frequent in PDR than in NR or N-PDR (p < 0.0001). Plasma HbA1c was higher in PDR than in NR or N-PDR (p < 0.01). Type 1 patients who had been diabetic for at least 20 years included 30 NR, 108 N-PDR and 24 PDR. Type 1 diabetic patients with PDR had microalbuminuria and macroproteinuria more frequently than other patients (p < 0.0001 and 0.01, respectively). Type 1 diabetic patients with PDR had the highest median plasma Lp(a) and the highest frequency of Lp(a) above 30 mg/dl (p < 0.05). Multivariate analysis carried out in Type 1 diabetic patients with a duration of diabetes of at least 20 years showed that microproteinuria, HbA1c and Lp(a) accounted significantly for 21% of variance in retinal status. Lp(a) above 30 mg/dl was related to the risk of developing PDR (OR = 8.40, p < 0.05). Lipoprotein(a) appears to be associated with the severity of diabetic retinopathy in Type 1 diabetic patients, and particular attention should be paid to those with Lp(a) above 30 mg/dl and pre-proliferative retinopathy.