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Biomedical subjects

L Perrin

Publications and source records attributed to L Perrin.

At least 37 records · Page 2Linked to original sources

[Clinical presentation of primary cytomegalovirus infection in a non-immunodepressed adult].

In the immunocompromised patients and during foetal life an acute infection due to the cytomegalovirus (CMV) causes great morbidity. In adults without predisposing factors the acute infection with CMV is rarely symptomatic, but can also provoke fever, fatigue, headache and anorexia for weeks. The peripheral blood smear shows big atypical lymphocytes within a relative lymphocytosis. The suspicion of the CMV infection is confirmed by the serological evidence of IgM anti-CMV antibodies. There is no etiological treatment, the evolution is spontaneously favorable most of the time. Establishing the diagnosis is reassuring for the patient and for the physician and avoids unnecessary analyses and treatments. We describe a series of 11 adults without predisposing factors who contracted an acute cytomegalovirus infection.

Adult

[Primary HIV infection: an often suspected diagnosis but confirmed late].

We report the history and clinical findings in 17 patients with primary HIV infection (PHI) diagnosed in the first 6 months of 1994. 9 of these patients were infected through heterosexual contacts, 5 were women with, as the only risk factor, sexual contacts with infected men. 10 of the 17 patients were symptomatic and the diagnosis of PHI was suspected in 8 of these patients at their first medical visit. However, the laboratory investigations were incomplete since p24 Ag was only requested for one patient and this led to a delay in diagnosis. Sera collected at the time of the first medical visit were available for 4 symptomatic patients, and in all of them p24 Ag was detected in the absence of HIV specific antibodies. These data underline the frequent occurrence of HIV transmission by the heterosexual route and the need to search for both specific antibodies and p24 Ag at the time of PHI.

AIDS Serodiagnosis

Growth-deficient mycobacteria in patients with AIDS: diagnosis by analysis of DNA amplified from blood or tissue.

Amplification and sequencing of mycobacterial ribosomal RNA genes (16S rDNA) may permit the detection of growth-deficient species (i.e., those exhibiting no growth or those whose growth is delayed for more than 12 weeks). Of blood samples from 26 patients with AIDS and a liver sample from one additional AIDS patient, three samples (two of blood and the one of liver) were positive by polymerase chain reaction only; cultures of these three samples remained negative for more than 12 weeks. Analysis of amplified 16S rDNA from blood revealed a sequence characteristic of Mycobacterium genavense in the first case, in which one of many previous blood cultures had also been positive for M. genavense. The sequences found in the second and third cases were characteristic of Mycobacterium avium. The sample from the second patient was a liver biopsy specimen in which acid-fast bacilli were visualized; the culture of this specimen yielded M. avium after 7 months. The third sample was a blood sample from a patient in whom a relapse of treated M. avium infection was suspected. These results indicate that amplification and sequencing of mycobacterial 16S rDNA may permit early diagnosis and provide a rationale for treatment of infections due to growth-deficient mycobacteria.

Acquired Immunodeficiency Syndrome

Foscarnet decreases human immunodeficiency virus RNA.

Foscarnet inhibits human immunodeficiency virus (HIV) replication in vitro and decreases p24 antigenemia in patients with cytomegalovirus (CMV) retinitis. To evaluate the effect of foscarnet on HIV replication, HIV RNA was quantitated in 17 patients before and during foscarnet therapy. Fifteen patients had CMV retinitis, 1 had CMV encephalitis, and 1 had intractable zoster. A decrease in HIV RNA was observed in 16 of 17 patients. Before the introduction of foscarnet, mean HIV RNA was 5.82 +/- 0.24 log RNA/mL and, after a median of 13 days of therapy, mean HIV RNA was 5.30 +/- 0.27 log RNA/mL (P < .001). Among patients with detectable p24 antigen at baseline, a significant decrease was observed (P = .017). This decrease in HIV RNA demonstrates that foscarnet is a potent antiretroviral drug.

AIDS-Related Opportunistic Infections

V3 sequences in primary HIV-1 infection.

OBJECTIVE: To determine HIV-1 genomic RNA and proviral DNA sequences of the third hypervariable region (V3 loop) of the envelope protein in patients with primary HIV-1 infection (PHI), and to compare these sequences with sequences from patients with more advanced HIV-1 infection. METHODS: Sera and peripheral blood mononuclear cells were collected from 24 patients with PHI living in Geneva. V3 sequences were determined using direct solid-phase sequencing on polymerase chain reaction (PCR) products. RESULTS: A 100% homology rate was observed between HIV-1 genomic RNA and proviral DNA paired nucleotide sequences from the V3 region in the 24 patients. Using a limiting dilution approach for three patients, a unique V3 sequence was observed for the genomic RNA. Three out of 24 amino-acid sequences presented the characteristic signature sequence QRGPGR, first described for the HIV-1LAI isolate, which is associated with lymphocytotropism. These three isolates also presented, for the V3 loop, a characteristic elevated charge (8) at physiological pH in comparison with the other isolates (3-5). There was no significant difference in the distribution of amino acids between the 24 V3 loop sequences from patients with PHI and 245 V3 loop sequences of the B subtype determined in patients with more advanced HIV-1 infection. CONCLUSION: The paired sequences recovered from HIV-1 genomic RNA and proviral DNA are identical for each of the 24 patients with PHI. Three isolates had the V3 loop characteristic signature sequence QRGPGR first described for the HIV-1LAI isolate. There is no characteristic V3 loop pattern associated with PHI isolates.

Adult

Laparoscopic assisted vaginal hysterectomy: an audit plus a word of caution.

Laparoscopic assisted vaginal hysterectomy (LAVH) performed in 109 cases has been reviewed. In this series the mean operative time was 89 minutes and mean inpatient hospitalization was 3.7 days. Throughout the review, 6 patients were considered to have major complications and each is discussed. The association of previous caesarean section and bladder damage is noted. LAVH widens the indications available for vaginal hysterectomy in younger women in whom the abdominal approach would previously be indicated, but extra caution is advised when this technique is first introduced to a gynaecological service.

Adult

Response of HIV RNA to didanosine as a predictive marker of survival.

OBJECTIVE: To evaluate whether early changes in viraemia in response to didanosine (ddI) predict death and occurrence of new AIDS-defining events. METHODS: Forty-three patients were followed during ddI treatment with sequential determinations of serum viraemia, mutations associated with drug resistance, CD4 counts and clinical evaluation. Patients were stratified into two groups of equal size, responders and nonresponders, using the median of individual changes in viraemia 1 month after initiation of ddI therapy. RESULTS: After 1 month of ddI, mean viraemia decreased by 0.35 log RNA copies/ml of serum (P < 0.001) in the population. A significant difference in survival (median, 14 and 35 months in nonresponders and responders, respectively; log rank, P = 0.004) and in the delay to the occurrence of new AIDS-defining events (median, 8 and 33 months in nonresponders and responders, respectively; log rank, P = 0.018) was observed. After stratification for presence of AIDS before starting ddI, viraemia response at 1 month remained predictive of both overall and AIDS-defining event-free survival (log rank, P = 0.0006 and P = 0.01). After a similar stratification for initial CD4, viraemia response still predicted overall survival (log rank, P = 0.009), but its predictive value for AIDS-defining event-free survival did not reach statistical significance (P = 0.12). High initial levels of HIV RNA, presence of mutation 215 or previous duration of zidovudine therapy were not predictive of survival. CONCLUSIONS: In patients treated with ddI, changes in viraemia at 1 month predict survival independently of initial AIDS diagnosis and initial CD4 counts.

Acquired Immunodeficiency Syndrome

[Prevention of viral recurrence following liver transplantation for post-hepatitis B and B-delta cirrhosis].

The incidence of recurrence of hepatitis B virus (HBV) following orthotopic liver transplantation (OLT) is as high as 80% when no attempt at prevention has been considered. HBV reinfection is associated with the reappearance of hepatitis B surface antigen (HBsAg) and HBV DNA in serum and, in most cases, with rapid severe graft damage. Immunoprophylaxis using polyclonal anti-HBs immunoglobulins reduces the risk of recurrence but this long-term therapy remains highly expensive. In this report, we use fresh frozen plasma (FFP) with high titers of anti-HBs immunoglobulins in an attempt to reduce HBV recurrence. From July 1987 to September 1993, 11 patients underwent OLT for HBV-related liver disease (18% of our OLT patients). FFP were administered to 6 patients continually for 7 to 46 months. Only one patient, under long-term immunosuppressive treatment before OLT, was reinfected 7 months after OLT. Rapid development of graft failure was observed with histologic manifestations of a fibrosing cholestatic hepatitis, leading to patient death after 12.5 months with concomitant bacterial infection. In this protocol, the rate of reappearance of HBsAg was 17%, a figure which can be favorably compared with other reports. All patients were subsequently tested for HCV and HIV and remained negative. In conclusion, FFP with high titers of anti-HBs immunoglobulins is at least as effective as polyclonal anti-HBs immunoglobulins in reducing the rate of HBV recurrence following OLT. The estimated cost of this new immunoprophylaxis method is less than 10% of the classical prophylaxis based on purified human polyclonal anti-HBs immunoglobulins.

Graft Rejection

The modifier of variegation modulo gene acts downstream of dorsoventral and HOM-C genes and is required for morphogenesis in Drosophila.

Growing evidence involves chromatin structural flexibility in gene regulation during development. modulo is a dominant suppressor of position effect variegation, suggesting the participation of its product in the assembly of higher order chromatin structures. Here we report the patterns of modulo expression and regulation during embryogenesis, analyzed in correlation with phenotypical defects resulting from the amorphic mutation of the gene. Zygotic expression of modulo depends on the activity of genes which pattern the embryo along dorsoventral and anteroposterior axes and specify diversified morphogenesis, dorsal and the mesoderm-specific genes twist and snail direct modulo expression in the presumptive mesoderm. The homeotic genes Sex combs reduced and Ultrabithorax positively regulate the gene in the ectoderm of parasegment 2 and abdominal mesoderm, respectively, modulo mutants exhibit aberrant morphogenesis of tissues originating from those embryonic primordia which normally express the gene, but do not show defect in cell fate specification. We propose that down-stream of pattern-forming genes modulo controls, via chromatin structural changes, genes critical for the process of morphogenesis of several tissue types.

Animals

Hepatitis C virus acute exacerbation during chemotherapy and radiotherapy for oesophageal carcinoma.

AIMS: We report the first case of an hepatitis C virus positive patient presenting with a solid tumor and developing an exacerbation of his hepatitis C after chemotherapy. CASE REPORT: A 56-year-old white male, previously infected with hepatitis C virus and treated for epidermoid carcinoma of the oesophagus, developed hepatitis (alamine aminotransferase 2376 U/l and aspartate aminotransferase 2262 U/l) after chemotherapy with cisplatin and vinblastine. METHODS: Polymerase chain reaction detected hepatitis C virus RNA in the serum during the acute phase, which returned to negative 14 weeks later. DISCUSSION: Viral replication was probably increased during immunosuppression induced by chemotherapy. Enhanced cellular immune response in the recovery phase was the most likely cause of the hepatitis. CONCLUSIONS: More attention should be paid to liver function tests in patients with a previous history of hepatitis C virus infection. Polymerase chain reaction identification of hepatitis C virus RNA can be a very useful tool that permits rapid diagnosis and appropriate management of such cases.

Antineoplastic Combined Chemotherapy Protocols

Chronic destructive lung disease associated with a novel mycobacterium.

A woman born in 1920 has suffered from a chronic destructive lung disease since 1972, with development of a severe combined restrictive and obstructive ventilatory defect. Large quantities of acid-fast microorganisms have been repeatedly observed in her sputum. Multiple courses of antimycobacterial treatment did not stop the progression of the disease. The mycobacterium involved was first identified as Mycobacterium gordonae, and later as Mycobacterium scrofulaceum. Analysis of part of the amplified gene of the 16S rRNA, however, revealed that its sequence differed from that of any established mycobacterial species, although it was observed once before in a German lymph node isolate, for which the name "Mycobacterium interjectum" has been proposed. Retrospective analysis confirmed the presence of this sequence in frozen samples which had been provided by the patient in 1983, 1985, 1989, 1990, and 1993. Our case confirms the value of amplification and sequencing of mycobacterial 16S rRNA for classifying mycobacteria, and suggests that "Mycobacterium interjectum" may be involved in cases of chronic destructive lung disease.

Aged

High levels of circulating RNA in patients with symptomatic HIV-1 infection.

OBJECTIVE: To evaluate the concentration of circulating RNA (viraemia) in patients with symptomatic primary HIV infection and relate it to sero-immunological parameters. METHODS: Semiquantitation of circulating HIV RNA and proviral HIV DNA was performed using the polymerase chain reaction. Circulating HIV RNA concentrations were expressed as virus equivalent (RNA copies/2) per ml serum. RESULTS: The mean CD4+ lymphocyte count for 19 patients with symptomatic primary HIV infection was 583 x 10(6)/l. Fifteen (79%) patients had detectable levels of p24 antigen (median 462 pg/ml). Circulating HIV RNA (median 2.3 x 10(7) virus equivalent/ml serum) and proviral HIV DNA (median 3630 copies/ml blood) were detected in all samples tested. Follow-up data for five patients (200-1600 days) showed a 1-3 log reduction in circulating RNA within 2 months. Later, circulating RNA concentrations were consistently greater than 10(3) virus equivalent/ml serum. Within 10 days no p24 antigen was detectable. Levels of CD4+ cells varied markedly from patient to patient during the follow-up and, in this small group, no evident correlation was observed between circulating RNA levels and CD4+ lymphocyte counts. CONCLUSIONS: High concentrations of circulating RNA (viraemia) were present in 19 patients with symptomatic primary HIV infection. Although a decrease in viraemia was observed during the following 2 months, viraemia persisted in all patients with long-term follow-up. This suggests that active viral replication is a continuous process in HIV-infected patients.

Adult