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Biomedical subjects

C Pedersen

Publications and source records attributed to C Pedersen.

At least 91 records · Page 5Linked to original sources
PubMed1997

Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals.

OBJECTIVE: Recently, it has been shown that a homozygous 32 base-pair deletion in the gene encoding CKR-5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1. We have investigated whether HIV-seropositive individuals who were heterozygous for the CKR-5 deletion had a different course of the disease. DESIGN: Thirty-five high-risk HIV-seronegative and 99 HIV-seropositive Danish homosexual men followed form 1985 to 1996 and 37 blood donors were analysed for their CKR-5 genotype by polymerase chain reaction. RESULTS: Two (6%) of the 35 HIV-seropositive subjects at high-risk of infection were homozygous and seven (20%) were heterozygous for the CKR-5 deletion. This was not significantly different from the distribution in normal donors. Twenty-two (22%) of the 99 HIV-seropositive subjects were heterozygous and none was homozygous. Two subgroups of patients who had an opposite course of the HIV disease were identified. Of nine long-term non-progressors, six (66%) were heterozygous for the deletion. This frequency is significantly higher than in nine rapid progressors of whom non was heterozygous. The frequency of heterozygotes in long-term non-progressors was also significantly higher than in the cohort as a whole. A Kaplan-Meier plot of the HIV-seropositive subjects, of whom 57 developed AIDS, showed a significantly better prognosis within the first 7 years of follow-up for those who were heterozygous for the deletion. Heterozygous individuals also had a significantly slower decrease in CD4 T-cell count per year. CONCLUSION: Individuals who are heterozygous for the 32-base-pair deletion in the CKR-5 gene have a slower decrease in their CD4 T-cell count and a longer AIDS-free survival than individuals with the wild-type gene for up to 11 years of follow-up.

CD4 Lymphocyte Count↗
PubMed1997

Physical localization of rRNA genes by two-colour fluorescent in-situ hybridization and sequence analysis of the 5S rRNA gene in Phalaris coerulescens.

The 18S-5.8S-26S rDNA and 5S rDNA loci have been mapped physically by fluorescent in-situ hybridization to the chromosomes of Phalaris coerulescens. The biotin-labelled heterologous 18S-5.8S-26S rRNA probe (pTa71) detected one locus, which corresponded to the secondary constriction (nucleolar organizer) on the long arm of the satellited chromosome II. The homologous 5S rDNA probe (Bam2.12) detected two pairs of 5S rRNA gene clusters which were localized at two different non-satellited chromosomes, one near the telomere on the short arm of the chromosome I, which is the largest chromosome of the complement, and the other about 42% out on the long arm of the chromosome III. A BamHI fragment containing the 5S rRNA gene, has been isolated and characterized. The 5S rDNA repeat unit is 309 bp in length, consisting of 121 bp highly conserved coding region and 188 bp variable spacer region. The karyotype of Phalaris coerulescens is characterized by the similar size of chromosomes within the group 2, group 3, or group 4. This study represents the first step towards the understanding the genome organization of Phalaris coerulescens and provides reliable markers for chromosome identification in this grass, an important species as a model system for the study of self-incompatibility in grasses.

Base Sequence↗
PubMed1997

Cryptococcosis in Denmark: an analysis of 28 cases in 1988-1993.

A total number of 31 events of systemic cryptococcal infection in 28 patients was identified in a nation-wide survey over 6 years from 1988 to the end of 1993. All medical records were reviewed, 24 of the patients were HIV-infected. Meningitis was diagnosed in 25 patients, and fungemia in 8 patients. The most frequent symptom was headache followed by fever. The median duration in days of fever, headache, and other neurological signs/symptoms before diagnosis was 12, 8 and 2 days, respectively, and, after diagnosis and start of treatments 7, 11 and 12 days, respectively. There was a significant correlation between the duration of headache and the duration of neurological signs/symptoms but not between headache and fever. More than 50% of the patients died within 5 months after the diagnosis. In 39% of the cases, the patients were orally treated with various antifungal drugs before the diagnosis. The rate of cryptococcosis (cumulative) in Danish AIDS patients was estimated to be 1.7%. The HIV-positive patients were, at the time of the cryptococcal diseases, profoundly immunocompromised, with a median CD4+ cell count of 18 (range: 0-78)/microliters. From 24 patients at least 1 isolate of Cryptococcus neoformans was typed, all being var. neoformans, identical with serotype A/D.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Influence of age on rates of new AIDS-defining diseases and survival in 6546 AIDS patients.

It has consistently been reported that older AIDS patients have a shortened survival compared with younger patients. The aim of the present study was to investigate whether this difference in survival is caused by differences in the pattern of the complicating diseases. Information on patient follow-up after the AIDS diagnosis was obtained by retrospective case note review. The 6,546 patients were followed from the time of AIDS diagnosis as part of the multicentre AIDS in Europe study, which examined AIDS cases diagnosed at 52 centres in 17 European countries between 1979 and 1989. Occurrence of AIDS-defining events and demographic variables were recorded for all patients, and CD4 lymphocyte count at the time of AIDS diagnosis for approximately half the patients. After adjusting for imbalances in other variables, persons > or = 50 years of age had a significantly higher risk of contracting AIDS wasting syndrome, AIDS dementia complex and oesophageal candidiasis after the initial AIDS diagnosis, compared with age group 30-39 years [relative risk (RR) 95% confidence interval (CI)], 3.23 (2.70-3.75 CI); 2.48 (2.16-2.80 CI); 1.55 (1.26-1.83 CI), respectively]. Shortened survival after the time of AIDS diagnosis was associated with older age. After adjusting for pattern of complicating diseases, the age effect remained unchanged. Older age predisposes to AIDS-related wasting syndrome, AIDS dementia complex and oesophageal candidiasis. Independent of these differences, older age is significantly associated with shortened survival, suggesting that factors such as severity of complicating diseases or the capability of handling serious infections, rather than disease pattern, are responsible for the shortened survival.

AIDS Dementia Complex↗
PubMed1997

Alternating treatment with didanosine and zidovudine versus either drug alone for the treatment of advanced HIV infection. The Alter Study. Nordic HIV Therapy Group.

The efficacy and safety of an alternating regime with zidovudine and didanosine versus treatment with either drug alone were investigated in a randomized, open, controlled trial, 552 patients with advanced HIV infection, 47% of whom had received prior treatment with zidovudine, were enrolled. The patients were randomly assigned to zidovudine 600 mg/day, didanosine 400 mg/day or 4-week alternations with the 2 drugs in the same dose. The study had a median length of follow-up of 88 weeks. In the overall analyses, time to death (p = 0.48) and time to death or new AIDA event (0.80) were equally distributed between the 3 treatment groups. In the subgroup of patients with a CD4 count < 100 x 10(6)/l the survival was longer in the alternating arm (p < 0.005) primarily because of differences among zidovudine naive patients. The alternating regime was better tolerated than the 2 monotherapies, with a longer time to dose reduction or withdrawal owing to side effects (p < 0.001).

Adult↗
PubMed1997

Toxoplasmosis in Danish AIDS patients.

Infection with Toxoplasma gondii was studied in 600 patients with AIDS, diagnosed in the eastern part of Denmark from 1980 up to and including 1990. The median age was 38 years, and 223 (44%) had anti-T. gondii IgG antibodies. Of the patients seropositive to T. gondii 61 (27%) developed toxoplasma encephalitis (TE). Few patients received prophylactic treatment with sulfamethoxazole-trimetoprim. In total, 66 patients were diagnosed with TE. One had no serological test performed, and of the remaining 65, 4 (6%) had no anti-T. gondii IgG antibodies. The predictive value of a negative Sabin-Feldman dye test was 99%. The geometric mean dye test titer was higher in patients with TE than in patients without TE. Of the patients with TE 34% had serological reactivation of their T. gondii infection at the time of TE diagnosis, and 34% had detectable T. gondii-specific antibodies in the cerebrospinal fluid. Specific IgM antibodies were found to have little value in the diagnosis of TE, as only 3% had detectable IgM antibodies. Acute toxoplasmosis was the AIDS-defining diagnosis for 23 (35%) of the patients with TE. The median CD4 count at the time of TE was 30 x 10(6)/l, and the median survival time from diagnosis of TE was 9 months.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Prevalence of antithyroid antibodies in mood disorders.

We examined the prevalence of antimicrosomal and antithyroglobulin antibodies in psychiatric inpatients with unipolar depression (N = 218), bipolar disorder manic (N = 51), bipolar disorder depressed (N = 19), and bipolar disorder mixed (N = 26) in comparison with two control groups: psychiatric inpatients with adjustment disorder (N = 80) and family medicine outpatients without current psychiatric illness (N = 144). A statistical analysis that controlled for age and sex revealed the frequency of positive antibody titers not to be increased in patients with a diagnosis of unipolar depression (6.9%) or bipolar disorder manic (3.9%), when compared with patients with adjustment disorder (2.5%) and non-psychiatric subjects (6.9%). There was a weak trend toward an increased prevalence of antithyroid antibodies in patients with bipolar disorder, mixed (19%) or depressed subtype (16%). The excess occurrence of antibodies in patients with either mixed or depressed bipolar disorder did not appear to be related to lithium exposure, which was similar in all bipolar subgroups. When the intervening influences of age and sex are taken into account, unipolar depression does not appear to be associated with an excessive rate of antithyroid antibodies; however thyroid autoimmunity may be weakly associated with subtypes of bipolar disorder in which depressive symptoms are prominent.

Adult↗
PubMed1996

[Septic infection of hip joint prosthesis with Listeria monocytogenes].

A case of Listeria monocytogenes septicaemia and infection of a prosthetic hip joint is presented in a patient with non-insulin-dependent diabetes mellitus. The patient developed the infection five and a half years after primary alloplastic operation. The prosthesis was removed and a temporary prosthesis with gentamicin was placed ("spacer"). The antibiotic treatment included ampicillin, pivampicillin and sulfamethoxazole-trimetroprim. Six weeks after removal of the prosthesis an un-cemented prosthesis was placed, and the patient had a full functional recovery.

Aged↗
PubMed1996

[Primary HIV infection].

Up to 70% of individuals with primary HIV infection will develop symptoms of an acute illness. The most common symptoms reported are fever, generalized lymphadenopathy, arthralgia and myalgia, headache, pharyngitis, enanthema, skin rash, diarrhoea, and mucocutaneous ulcerations. More rarely, oesophageal candidiasis, meningoencephalitis, rhabdomyolysis and epiglottitis have been reported. The diagnosis of the acute HIV infection syndrome can be established by demonstrating antibodies to HIV or by demonstration of HIV antigen positivity. Detection of virus through culture or PCR may prove to be more sensitive, but are not yet used as routine methods. The course of the primary infection has prognostic importance for the subsequent course of HIV infection. This probably reflects the importance of both the viral phenotype and of the initial immune response to HIV. Primary HIV infection should be considered in any patient with possible exposure to HIV presenting with fever of unknown cause.

HIV Infections↗
PubMed1996

[Primary HIV infection. Case histories].

More than 50% of individuals with primary HIV infection have a symptomatic febrile illness associated with seroconversion. The most common clinical picture is a mononucleosis-like or influenza-like illness but almost any organ system may be involved, and primary HIV infection is often an imitator of other acute diseases. Six cases of symptomatic primary infection are described, one with a characteristic presentation, and five cases respectively presenting with colitis, rhabdomyolysis, epiglottitis, cold agglutination haemolysis and meningitis as marked symptoms.

Adult↗
PubMed1996

Male breast carcinoma: an evaluation of prognostic factors contributing to a poorer outcome.

BACKGROUND: Although breast cancer in men is far less common than breast cancer in women, it is associated with a less favorable prognosis. Conventional histopathologic features and new prognostic markers were evaluated to explain the less favorable survival outcome. METHODS: Forty-six consecutive male breast carcinomas were studied for size, histologic and nuclear grade, histologic subtype, presence of carcinoma in situ, nipple involvement, lymphovascular invasion, hormone receptor status, c-erbB-2 protein overexpression, and p53 protein accumulation. These findings were correlated with survival. RESULTS: Of the 46 carcinomas, 4 were noninvasive and 42 were invasive. In the invasive carcinomas, the median patient age was 64 years, and the median tumor size was 2 cm. The predominant histologic patterns were invasive ductal (45%) and mixed invasive ductal and cribriform (28%). Most tumors were of low histologic and nuclear grades (histologic grades: I, 17%; II, 50%; III, 33%; nuclear grade: I, 12%; II, 44%; III, 44%). Of those surgically staged, 22 patients (60%) were lymph node positive and 15 patients (40%) were node negative. Stage at presentation was higher than in women (0, 10%; 1, 17%; 2, 50%; 3, 13%; 4, 10%). The estrogen and progesterone receptor status was positive in 76% and 83% of tumors, respectively. Lymphatic vessel invasion (63%) and nipple involvement (48%) were also more common than in women. True Paget's disease of the nipple was not seen; all cases with nipple ulceration were the result of direct tumor extension to the epidermis. Of the 17 tumors tested, 41% were c-erbB-2 positive and 29% were p53 positive. Survival analysis was limited by the relatively small cohort size. Five- and 10-year adjusted overall survival rates for invasive tumors were 76 +/- 7% and 42 +/- 9%, respectively. Skin and nipple involvement (P = 0.03) and c-erbB-2-positivity (P = 0.03) were significant predictors of adverse survival. CONCLUSIONS: Male breast carcinoma presents in an advanced stage with less favorable survival, despite low histologic grade, high estrogen receptor content, and small size. Anatomic factors may have been responsible for the poor survival outcome (i.e., paucity of breast tissue and close tumor proximity to skin and nipple, facilitating dermal lymphatic spread and early regional and distant metastasis).

Adenocarcinoma↗
PubMed1996

Epidemiology of AIDS dementia complex in Europe. AIDS in Europe Study Group.

The aim of the study was to describe the epidemiology of AIDS dementia complex (ADC) in Europe and to assess the possible role of zidovudine therapy in preventing or delaying its occurrence. We used an inception cohort, with data collected retrospectively from patients' clinical records from 52 clinical centers in 17 countries across Europe. The subjects were 6,548 adult people with AIDS consecutively diagnosed from 1979 to 1989. The main outcome measures were codiagnosis of ADC at the time of AIDS diagnosis and ADC-free time after AIDS diagnosis. ADC was reported in 295 patients (4.5%) at the time of AIDS diagnosis and during follow-up in a further 402 of the 5,160 patients (7.8%) who were diagnosed with AIDS based on diseases other than ADC. Whether at the time of AIDS diagnosis or later, the occurrence of ADC was significantly associated with age, transmission category, and CD4+ cell counts. The risk was greater in older patients (14 and 19% greater, at AIDS diagnosis and after, respectively, for a 5-year difference in age), in i.v. drug users than in homosexual and bisexual men (89 and 60% greater, at AIDS diagnosis and after, respectively), and for people with lower CD4+ cell counts (14 and 30% greater for a reduction of 1 on the natural log scale). Risk was almost double for women than for men. A significant reduction, of approximately 40%, was found in the risk of developing ADC after AIDS diagnosis for patients receiving zidovudine therapy, but this effect was present only during the first 18 months of treatment, irrespective of whether treatment began before or after AIDS diagnosis. In conclusion, an increase in the risk of developing ADC either at the time of AIDS diagnosis or thereafter is associated with increasing age, i.v. drug use, and decreased CD4+ cell count. Women tend to have a higher risk of ADC at the time of AIDS diagnosis. Zidovudine therapy appears to have a definite, but time-limited, effect of protecting patients against ADC development after AIDS diagnosis.

AIDS Dementia Complex↗
PubMed1996

Factors associated with the CD4+ lymphocyte count at diagnosis of acquired immunodeficiency syndrome. The AIDS IN EUROPE Study Group.

To assess which factors are associated with the CD4+ lymphocyte count at the time of AIDS diagnosis we studied 3046 patients in the AIDS IN EUROPE study who were diagnosed with AIDS in 1 of 17 European countries between 1979 and 1989 and for whom the CD4 count at AIDS diagnosis was known. Data were extracted retrospectively from patient case notes, using a standardized form. There was a wide range of average CD4+ lymphocyte counts at AID diagnosis, according to which diseases were present at diagnosis. The highest geometric mean CD4+ lymphocyte counts at AIDS diagnosis were associated with the diagnosis of extrapulmonary tuberculosis, Kaposi's sarcoma, and non-Hodgkin's lymphoma while the lowest counts were found when histoplasmosis and cytomegalovirus (CMV) retinitis were present. There were no appreciable differences between CD4+ lymphocyte counts at AIDS in patients according to the three major transmission route categories (sex, age, or region of diagnosis) but there was a marked trend (p < 0.005) toward lower CD4+ lymphocyte counts at AIDS diagnosis in more recent years. These associations remained largely unchanged after adjustment for other factors.

AIDS-Related Opportunistic Infections↗
PubMed1996

Tuberculosis among European patients with the acquired immune deficiency syndrome. The AIDS in Europe Study Group.

OBJECTIVES: To describe the characteristics of acquired immune deficiency syndrome (AIDS) patients with tuberculosis in Europe; to assess the incidence and risk factors of tuberculosis after AIDS; to compare survival of AIDS patients with and without extra-pulmonary tuberculosis (EPTB) at the time of AIDS diagnosis. DESIGN: Multicentric retrospective cohort study of 6544 AIDS patients diagnosed in 52 clinical centres and 17 European countries. METHODS: Description of patient characteristics and comparisons of tuberculosis incidence and mortality after AIDS with multivariate Cox proportional hazard models. RESULTS: 14.6% of AIDS patients had tuberculosis and 78% of those with tuberculosis had EPTB. EPTB was the AIDS-defining condition in 8.7% of the patients. Tuberculosis incidence after AIDS was 3.1 per 100 person-years. Age, gender and HIV-transmission category were not significantly associated with an increased risk of tuberculosis and the strongest risk factor for both EPTB and pulmonary tuberculosis (PTB) was the region of origin. The adjusted hazard ratio of EPTB and PTB in Southern Europe compared to Northern Europe were 5.5 (95% confidence interval [CI]: 5.0-6.1) and 2.0 (CI: 1.4-2.7) respectively. The apparent survival advantage of AIDS patients with EPTB compared to patients diagnosed with other conditions (median survival time: 22 vs 16 months) was statistically not significant when confounding variables were adjusted for (Hazard ratio: 0.85; CI: 0.62-1.07). CONCLUSIONS: In Europe, there are large differences in the incidence of tuberculosis among AIDS patients in different countries. They do not seem to be due to differences in age or in the prevalence of injecting drug use and likely reflect differences in the prevalence of tuberculosis infection. The role of recent transmission should also be considered, and national tuberculosis control efforts and Europe-wide surveillance need to be reinforced accordingly.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Longitudinal serum HIV RNA quantification: correlation to viral phenotype at seroconversion and clinical outcome.

OBJECTIVE: To investigate the longitudinal changes in serum HIV RNA, and to clarify whether the viral load early in infection has a predictive value for the clinical outcome; also, to correlate viral phenotype at seroconversion and changes in CD4 cell counts with viral burden. DESIGN: Twenty seroconverters with HIV isolates available at seroconversion had HIV RNA quantified by polymerase chain reaction (PCR) at seroconversion and thereafter every 6 months. Mean follow-up time was 65 months. Patients were classified according to viral phenotype at seroconversion, time to AIDS progression, serum viral load within the first year (less or more than 1.5 x 10(4) copies/ml). RESULTS: High viral load at seroconversion was followed by a significant decline within the first months (P < 0.0005). Decline to < 1.5 x 10(4) copies/ml was correlated with slower progression to AIDS (P < 0.05). A correlation between the rate of CD4 decline and the median viral load during the ensuing viral load plateau phase was also shown (P < 0.05). Subsequent to this phase the viral burden increased. Rapid progressors had higher viral load than slow- or non-progressors; this was particularly pronounced late in infection. Harbouring syncytium-inducing (SI) virus at seroconversion was associated with faster progression to AIDS than non-SI (NSI; P < 0.005). The increased in vitro replication rate of SI over NSI was not translated into significantly higher serum HIV RNA. CONCLUSION: Serum HIV RNA is high around the time of seroconversion. A significant decline within the first months hereafter is followed by a plateau phase, which in turn is followed by an increase in HIV RNA. HIV RNA early in infection has a predictive value for the clinical outcome. The increased virulence of SI over NSI virus did not translate into significantly higher HIV RNA values.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Development of resistance of zidovudine (ZDV) and didanosine (ddI) in HIV from patients in ZDV, ddI and alternating ZDV/ddI therapy.

OBJECTIVE: To study development of phenotypic and genotypic resistance against zidovudine (ZDV) and didanosine (ddI) during 24 months of mono- and monthly alternating therapy. PATIENTS: Forty-six patients, not previously treated with antiretroviral drugs, were included in the study. METHODS: ZDV and ddI sensitivity were determined in a biological assay based on production of HIV antigen in cultures of CD4+ lymphocytes. The ZDV-associated mutations at codon 41 and 215, and the ddI-associated mutation at codon 74 of the reverse transcriptase (RT) gene were analysed using selective polymerase chain reaction on DNA from peripheral blood mononuclear cells. The biological phenotype [syncytium-inducing (SI)/non-SI(NSI)] of the viral isolates was assessed using a MT2 assay. RESULTS: Of the patients, 82% in ZDV therapy and 73% in alternating therapy developed phenotypic resistant HIV [median inhibitory concentration (IC50) > 0.1 microM]. Patients treated for 1 year with ddI (monotherapy or alternating) had significant higher ddI IC50 values than patients in ZDV monotherapy. During ZDV and alternating therapy, 67 and 75% of the patients, respectively, developed mutations in RT codon 41, whereas 83 and 75%, respectively, developed mutations in codon 215. In patients treated with ddI, 60% developed mutations in codon 74, whereas none of the patients in either alternating ZDV/ddI or ZDV therapy developed this mutation. Forty-six per cent of the patients had SI HIV at start of therapy. Four patients switched from SI to NSI during either ZDV, ddI or alternating therapy. Faster development of resistance was associated with the SI phenotype. CONCLUSIONS: No difference in either phenotypic ZDV or ddI resistance, or genotypic ZDV resistance could be demonstrated during monotherapy or monthly alternating ZDV/ddI therapy, whereas genotypic ddI resistance (mutation in RT codon 74) only were detected in patients in ddI monotherapy. In addition, we found that development of phenotypic and genotypic resistance was faster in patients harbouring SI isolates, and that switches from SI to NSI during therapy was independent of the type of therapy.

Anti-HIV Agents↗
PubMed1996

Epidemiology of cryptosporidiosis among European AIDS patients.

OBJECTIVE: To study epidemiology and possible risk factors associated with the development of cryptosporidiosis among European patients with AIDS. METHODS: An inception cohort of 6548 patients with AIDS, consecutively diagnosed from 1979 to 1989, from 52 centres in 17 European countries was studied. Data on all AIDS defining events were collected retrospectively from patients' clinical records. Kaplan-Meier estimates, log rank tests and Cox proportional hazard models were used to examine for possible risk factors associated with cryptosporidiosis. RESULTS: Cryptosporidiosis was diagnosed in 432 (6.6%) patients, 216 at time of the AIDS diagnosis and 216 during follow-up. The probability of being diagnosed with cryptosporidiosis at AIDS diagnosis was significantly lower for intravenous drug users (1.3%) than for homosexual men (4.1%) and for patients belonging to other transmission categories (4.0%) (p < 0.001). The probability was also higher for patients from Central Europe compared with patients from South Europe (4.1% versus 2.5%, p = 0.005). The rate of developing cryptosporidiosis after the diagnosis of AIDS was 3 per 100 patient years of follow-up. The rate was significantly lower for intravenous drug users than for homosexual men (relative risk 0.34, 95% confidence limits 0.22-0.54) and for women compared with men (RR 0.43 (0.21-0.87)). The risk was higher in North Europe than in South and Central Europe. In a multivariate analysis only transmission category remained a significant predictor for the development of cryptosporidiosis. CONCLUSION: The development of cryptosporidiosis in AIDS patients may be associated with sexual risk behaviour.

AIDS-Related Opportunistic Infections↗