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J W Mulder

Publications and source records attributed to J W Mulder.

At least 127 records · Page 7Linked to original sources
PubMed1992

Anti-neutrophil cytoplasmic autoantibodies in patients with symptomatic HIV infection.

Antibodies against cytoplasmic antigens of neutrophils, producing perinuclear (p-ANCA) as well as cytoplasmic staining with central accentuation (c-ANCA), have been described in non-HIV-infected patients with specific pathology such as glomerulonephritis and vasculitis. Here, we report on a patient with a vasculitis-like syndrome and a positive ANCA-test who appeared to be infected by HIV. Further analysis revealed that ANCA, p-ANCA as well as c-ANCA without central accentuation can be demonstrated in the serum of HIV+ individuals. In a cross-sectional study on individuals in different stages of HIV infection, we found that the occurrence of ANCA was limited to the symptomatic stages of HIV infection: p-ANCA was found in one out of 10 ARC patients and in two out of 11 AIDS patients with malignancies (AIDS-MAL), but not in AIDS patients with opportunistic infections (AIDS-OI). c-ANCA was found in four of the ARC patients, in two of the 14 AIDS-OI patients and in two AIDS-MAL patients. The presence of ANCA was not related to the degree of hypergammaglobulinaemia nor to specific symptomatology. ANCA containing sera from HIV+ individuals did not react with HEp2 cells nor with cytoplasmic antigens of lymphocytes, natural killer (NK) cells or eosinophils. Five out of the 11 (two p-ANCA and three c-ANCA) sera reacted weakly with cytoplasmic antigens of monocytes. All sera reacted with karyoplasts but not with cytoplasts prepared from neutrophils. These results suggest that HIV-ANCA might be directed against myeloid cell-specific granule constituents. However, sandwich-ELISAs with MoAbs against granule antigens that are frequently the target antigens of ANCA in HIV- individuals were negative. Also immunoprecipitation and immunoblotting, using lysates of neutrophil granules, did not allow further identification of the target antigens of HIV-ANCA.

AIDS-Related Complex↗
PubMed1992

[Repair of residual cleft palates in older adult patients].

Residual cleft palates in adult patients are hard to repair. A prosthesis may cause patients to complain of loss of fluid through the nose when they drink. Furthermore, there may be problems with the retention of the prosthesis. In sixteen adult patients the residual cleft palate was successfully closed. In three patients a second surgical procedure was required.

Adult↗
PubMed1992

The relationship of quantitative nuclear morphology to molecular genetic alterations in the adenoma-carcinoma sequence of the large bowel.

The relationship of abnormal nuclear morphology to molecular genetic alterations that are important in colorectal tumorigenesis is unknown. Therefore, Feulgen-stained isolated nuclei from 22 adenomas and 42 carcinomas that had been analyzed for ras gene mutations and allelic deletions on chromosomes 5q, 18q, and 17p were characterized by computerized image analysis. Both nuclear area and the nuclear shape factor representing irregularity correlated with adenoma-carcinoma progression (r = 0.57 and r = 0.52, P < 0.0001), whereas standard nuclear texture, a parameter of chromatin homogeneity, was inversely correlated with progression (r = -0.80, P < 0.0001). The nuclear parameters were strongly interrelated (P < 0.0005). In multivariate analysis, the nuclear parameters were predominantly associated with adenoma-carcinoma progression (P < or = 0.0001) and were not influenced significantly by the individual molecular genetic alterations. Nuclear texture, however, was inversely correlated with fractional allelic loss, a global measure of genetic changes, in carcinomas (r = -0.39, P = 0.011). The findings indicate that nuclear morphology in colorectal neoplasms is strongly related to tumor progression. Nuclear morphology and biologic behavior appear to be influenced by accumulated alterations in cancer-associated genes.

Adenoma↗
PubMed1991

Ethnic differences in the anatomical location of colorectal adenomatous polyps.

The ratio of right- to left-sided colonic cancer is increasing, but data on the distribution of its usual precursor lesion, the colorectal adenoma, are contradictory. Therefore, we investigated the prevalence of right- and left-sided colorectal adenomatous polyps from January 1, 1970, to September 30, 1989, using the study design of "epidemiologic necropsy" and the autopsy files of The Johns Hopkins Hospital. Compared with the decade of the 1970's, the 1980's showed a slight decrease in the overall prevalence of right-sided adenomas (6.4 per 1,000, 95% confidence limits 4.7-8.8 vs. 5.1 per 1,000, 95% CL 3.6-6.5), but a marked decrease occurred in left-sided adenomas (11.8 per 1,000, 95% CL 9.3-14.3 vs. 6.7 per 1,000, 95% CL 4.8-8.6). As a result, the ratio of right-sided to left-sided adenomas increased from 0.55 in the 1970's to 0.77 in the 1980's. This increased ratio occurred in both sexes, although prevalences were lower in females, and in whites. Unexpectedly, blacks had a ratio of right-sided to left-sided adenomas greater than unity in both the 1970's and 1980's (1.19 vs. 1.79) due to a relatively high prevalence of right-sided adenomas (5.8 per 1,000, 95% CL 3.6-8.0 in 1970's; 5.8 per 1,000, 95% CL 3.3-8.3 in 1980's), but low prevalences of left-sided adenomas (4.9 per 1,000, 95% CL 3.0-6.8 in 1970's; 3.2 per 1,000, 95% CL 1.2-5.2 in 1980's). The overall adenoma prevalence in blacks was lower than in whites. We conclude that the right-sided predominance of colorectal adenomas in blacks suggests ethnic differences in the pathogenesis of colorectal adenomas. This observation may have important implications for secondary prevention of colorectal cancer.

Adenoma↗
PubMed1991

Differences in clinical course in zidovudine-treated asymptomatic HIV-infected men associated with T-cell function at intake.

Declining CD4+ T-cell numbers and anti-CD3-induced T-cell responsiveness are prognostic markers for progression of HIV infection. We investigated the effect of long-term (2-year) zidovudine treatment on these immunological markers in a group of nine asymptomatic p24-antigenaemic men, five of whom progressed to AIDS. A group of 10 untreated HIV-infected men, five of whom progressed to AIDS, was studied as a control. At intake, 1 year before the start of treatment, CD4+ T-cell numbers in the groups were not significantly different. However, at that time progressors already exhibited an extremely low anti-CD3-induced T-cell responsiveness compared with non-progressors. In all people T-cell responsiveness and the number of CD4+ T-cells had improved 6 months after the start of zidovudine treatment. However, CD4+ T-cell numbers were not persistently elevated, and restoration of T-cell responsiveness was of only short duration. Our results show that zidovudine treatment in the asymptomatic phase of HIV infection did not result in a sustained improvement in T-cell function. Furthermore, they suggest that differences in clinical course among zidovudine-treated asymptomatics may be caused by heterogeneity of this group with respect to T-cell functional capacity at the start of treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Immunological and virological markers in individuals progressing from seroconversion to AIDS.

Six men were selected from a large cohort of homosexual men participating in a study on HIV infection that was followed from seroconversion to AIDS. The patients were studied retrospectively for immunological functions of T cells, T-cell subset distribution and biological phenotype of HIV. A severe decrease in anti-CD3 monoclonal antibody (MAb)-induced T-cell proliferation at seroconversion was observed in two out of six men. After this acute phase, CD4+ T-cell numbers were in the normal range in the early asymptomatic period; the proliferative response was subnormal, whereas the capacity to generate cytotoxic T cells (CTL) was normal. From seroconversion on, CD4+CD29+ memory T-cell numbers were decreased to approximately 50% of normal values, which may contribute to loss of T-cell reactivity. In the asymptomatic phase only slow-replicating non-syncytium-inducing HIV variants were observed. The T-cell proliferative response further declined with the depletion of naive CD4+ CD45RA+ T cells and CD4+ T-cell numbers started to decline. This second decrease in T-cell function coincided with the emergence of more rapidly replicating, often (four out of six) syncytium-inducing variants. At diagnosis of AIDS, T-cell proliferation and CD4+ T-cell numbers were extremely low in five out of six patients and CTL function had declined in three out of five individuals tested. Circulating CD8+ cells had gradually shifted to an immature CD38+CD28- phenotype. Our findings support the theory that HIV-induced immune dysfunction allows for the emergence of virulent HIV variants associated with CD4+ cell loss and disease.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Serum beta 2-microglobulin levels in asymptomatic HIV-1-infected subjects during long-term zidovudine treatment.

beta 2-microglobulin levels were determined in the serum of 18 initially asymptomatic HIV-1 p24 antigenaemic subjects who were treated with zidovudine (+/- acyclovir) and who were followed for 2 1/2 years. The median serum beta 2-microglobulin level at week 0 was 2.5 mg/l and decreased to 2.3 mg/l after 12 weeks of treatment (p = 0.001). A correlation was found between individual changes in serum beta 2-microglobulin levels and individual changes in serum p24 antigen levels during the first 48 weeks of treatment (p less than 0.05). Six out of 18 subjects progressed to AIDS after 60-126 weeks of treatment. In this group during a period of more than one year before disease progression median serum beta 2-microglobulin levels increased from 2.5 mg/l to 3.3 mg/l (p = 0.03) and median CD4+ cell counts decreased from 0.3 x 10(9)/l to 0.08 x 10(9)/l (p = 0.03), while in that period the pattern of serum p24 antigen levels was inconsistent. Although the variability in serum beta 2-microglobulin levels appeared to make this marker unsuitable for management decisions in individuals, a decline in beta 2-microglobulin levels was found to parallel a decline in p24 antigen levels during the early phase of zidovudine treatment. Moreover, after prolonged treatment, rising beta 2-microglobulin levels--in contrast to p24 antigen levels--were shown to have predictive value for disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Trends in mortality among AIDS patients in Amsterdam, 1982-1988.

In this study we evaluated the survival of 515 AIDS patients diagnosed in Amsterdam between 1982 and 1988 and followed-up until April 1990. Non-resident patients survived for a shorter period than resident patients (median survival time 10 versus 16 months). Residents had a 1-, 2- and 3-year survival of 56.1, 33.0 and 17.2%, respectively. Heterosexual intravenous drug users tended to have a better survival than homosexual men, although this was not significant. The survival time was longer for AIDS patients less than 30 years of age at diagnosis and varied for the different clinical manifestations leading to AIDS diagnosis. We calculated the 1- and 2-year survival probability by year of diagnosis for patients initially presenting with a Pneumocystis carinii pneumonia (PCP). The 1-year survival improved greatly in 1986 and continued to rise in the following years. The 2-year survival was similar in 1986 and 1987 (26.8 versus 28.2%) but increased in 1988 (38.9%). We conclude that besides better clinical experience and diagnostic methods, this improvement in prognosis could be explained by the start of secondary prophylaxis for PCP in 1985 and the introduction of zidovudine therapy in 1987.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Zidovudine sensitivity of human immunodeficiency viruses from high-risk, symptom-free individuals during therapy.

Human immunodeficiency type 1 isolates from 18 initially symptom-free men who were treated with zidovudine for 2 years were investigated for drug sensitivity. At the start all the men had persistent core antigenaemia; the acquired immunodeficiency syndrome developed in 6 during the study. The polymerase chain reaction was used to detect mutations at residue 215 of reverse transcriptase, a mutation associated with reduced drug sensitivity. After 2 years 16/18 isolates were mutant. However, after about 6 months of treatment the mutation was detected in only 7 isolates, 4 from individuals who subsequently had AIDS. Limited direct virus sensitivity data correlated with the genetic data. The rate of appearance of the 215 mutation seemed to correlate with CD4 counts and viral virulence.

CD4 Antigens↗
PubMed1990

[Closing of central palate defects using a temporal muscle flap].

Large defects of the maxilla are hard to repair. In spite of the prosthesis that covers the defect, patients complain of loss of fluid through the nose when they drink or take liquid food. In five patients the maxillary defect was successfully closed by transposing the anterior part of the temporal muscle or the entire temporal muscle. The donor site was covered by transposing the posterior part of the temporal muscle or by an implant.

Adult↗
PubMed1990

Long-term zidovudine treatment of asymptomatic HIV-1-infected subjects.

Eighteen asymptomatic men with persistent human immunodeficiency virus type 1 (HIV-1) p24 antigenemia were treated with zidovudine 250-500 mg (+/- acyclovir 800 mg) 6-hourly for 4-12 weeks, and thereafter with zidovudine 500 mg (+/- acyclovir 1600 mg) 12-hourly for 92 weeks. Six additional HIV-1 p24 antigenemic subjects were treated with zidovudine 500 mg 12-hourly for 76 weeks. Disease progression occurred in 4 subjects, despite sustained reduction of serum HIV-1 p24 antigen levels: Pneumocystis carinii pneumonia was diagnosed after 60, 80, 90 and 93 weeks, respectively. The median CD4+ cell count of these 4 men at study entry was 0.2 x 10(9)/l, and it declined to 0.07 x 10(9)/l at the moment AIDS was diagnosed. In 20 subjects no disease progression occurred. The median CD4+ cell count of these 20 men at study entry was 0.4 x 10(9)/l and it was 0.45 x 10(9)/l at the end of the study period. Median serum HIV-1 p24 antigen levels at the end of the study period were 42% lower than at study entry in these 20 subjects. In 5/20 men, an initial decline was followed by a rise in antigen levels to above pretreatment value. Treatment with zidovudine was well tolerated. Anemia caused symptoms in 3/24 men, but prolonged leucopenia or neutropenia did not occur. None developed clinical or convincing biochemical evidence of zidovudine-associated myopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Autoantibodies against peripheral blood cells appear early in HIV infection and their prevalence increases with disease progression.

The presence of platelet- and neutrophil-bound immunoglobulin (PBIg and NBIg) in thrombocytopenic or neutropenic HIV-infected individuals has led to the concept that in HIV infection thrombocytopenia and neutropenia are mediated by autoimmunity. However, PBIg and NBIg were also demonstrated in non-cytopenic HIV-infected individuals. We determined the prevalence of autoantibodies against neutrophils and platelets by immunofluorescence in randomly chosen persons in different stages of asymptomatic and symptomatic HIV infection. Platelet and neutrophil autoantibodies already appeared in the asymptomatic stage and their prevalence further increased in the symptomatic stages. No correlation was found between the presence of either platelet or neutrophil antibodies and the occurrence of circulating immune complexes in the blood or the serum immunoglobulin level. There was no significant difference in neutrophil counts in HIV-infected persons with or without neutrophil autoantibodies. In addition, no significant difference in neutrophil count was found between HIV-infected and non-HIV-infected persons. HIV-infected individuals with platelet autoantibodies tended to have a lower platelet count than HIV-infected individuals without these antibodies. However, the platelet count in HIV-infected individuals without platelet antibodies was significantly lower than in the non-HIV infected persons. Thus, autoantibodies against platelets and neutrophils occur early in HIV infection and their prevalence is correlated with disease progression. Their presence is associated with cytopenia only in a limited number of persons. Non-immune mechanisms also mediate thrombocytopenia in HIV infection.

Autoantibodies↗
PubMed1990

HIV-1 P24 antigenaemia does not predict time of survival in AIDS patients.

The time of survival in 176 AIDS patients was investigated in relation to the presence or absence of HIV-1 p24 antigenaemia at the moment of diagnosis. The median time of survival in p24 antigen positive patients was 12 months, in p24 antigen negative patients it was 13 months; no difference in survival curves was found. Also no difference was found in survival between patients with high and low p24 antigen levels. The median time of survival in patients for whom a diagnosis of AIDS was made in the period before the introduction of zidovudine treatment was 10 months; in patients diagnosed in the period thereafter it was 18 months (p less than 0.005). However, when each period was analysed separately, no difference in survival between p24 antigen positive and negative patients was found. Separate analysis of patients with a diagnosis of Kaposi's sarcoma alone showed similar results. HIV-1 p24 antigenaemia at the moment of diagnosis of AIDS (both in the period before and in the period after the introduction of zidovudine) is not a predictor for time of survival.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Serum p24 antigen levels in untreated and zidovudine-treated HIV-1 infected subjects.

HIV-1 p24 antigen levels were determined in sequential serum samples from 71 subjects with persistent p24 antigenaemia, obtained over a period of 6-36 months during which no antiretroviral treatment was given. Fifty-six subjects were initially symptom free: 39 remained so during follow-up and 17 developed AIDS. Fifteen subjects were studied from the moment AIDS was diagnosed. Median serum p24 levels rose in all groups. In 50/71 individuals, p24 levels rose with time; in 21 they declined. The mean change in p24 levels was +194%. Twelve of the symptom-free subjects were subsequently treated with 1000 mg zidovudine daily for 12 months, over which period p24 levels declined in all 12 (mean change -56%). The difference in number of subjects with rising and declining p24 antigen levels between the untreated and zidovudine treated group was significant (P less than 0.001). Triton X-100 pretreatment (which presumably enables detection of virion-associated p24 in addition to free p24) of serum samples from 2 subjects who seroconverted for p24 antigen, from 2 AIDS patients who did not receive antiretroviral treatment and from 2 zidovudine-treated symptom-free subjects, did not lead to a substantial increase in p24 levels, except in the case of one of the p24 antigen seroconverters. It is concluded that the decline in serum p24 levels reported to occur during treatment with putative antiretroviral drugs can largely be ascribed to this treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Markers for progression to acquired immune deficiency syndrome and zidovudine treatment of asymptomatic patients.

Eighteen asymptomatic men with persistent human immunodeficiency virus type I (HIV-I) p24 antigenaemia were treated with zidovudine 250-500 mg (+/- acyclovir 800 mg) 6-hourly for 4-12 weeks, and subsequently with zidovudine 500 mg (+/- acyclovir 1600 mg) 12-hourly for 36 weeks. After 24 weeks six additional HIV antigenaemic subjects were entered and treated directly with zidovudine 500 mg 12-hourly. Over the treatment period serum HIV-I p24 (HIV-Ag) levels declined in all 24 subjects; significantly so in 17, and to below cut-off values in five. Mean serum HIV-Ag levels in different treatment groups declined in 68-78%. Initial increases in CD4+ cell counts were not sustained. Over 48 weeks serum HIV-Ag levels rose in three out of five non-treated men with persistent HIV antigenaemia, and they slightly declined in two; the mean serum HIV-Ag level in this group rose 67%. Regression of enlarged lymph nodes was seen in 19 out of 19 of the zidovudine-treated subjects. In the 24 zidovudine-treated subjects no disease progression occurred during follow-up, whereas two out of five non-treated men went on to develop CDC group IV A, and IV C-2 disease, respectively. Adverse reactions to the study drugs were infrequent and mild. Anaemia caused symptoms in two, but serious leucopenia or neutropenia was not observed. An initial positive effect on thrombocyte numbers was not sustained. These data demonstrate that in asymptomatic HIV-infected subjects zidovudine 500 mg 12-hourly is well tolerated and has a persistent inhibitory effect on viral replication.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Appearance of predictors of disease progression in relation to the development of AIDS.

To study the natural history of HIV-1 infection in relation to serological and immunological profiles, 199 asymptomatic HIV-1-antibody (HIV-1-core-antibody)-seropositive and 76 seroconverted homosexual men were followed prospectively for 39 months. AIDS was diagnosed in 38 men. The AIDS attack rate was 20.8% after 39 months. The AIDS attack rate in the HIV-I-core-antibody positives was 12.1, versus 30.1% in the HIV-1-core-antibody negatives (P less than 0.001), and it was 13.3% in the HIV-1-antigen (HIV-1-Ag) negatives versus 53.9% in the HIV-1-Ag positives (P less than 0.001). The AIDS attack rate after 39 months was 10.9% in men with counts greater than or equal to 0.5 x 10(9)/l and 49.9% in those with CD4+ lymphocyte counts less than 0.5 x 10(9)/l. AIDS attack rates after 30 months in the same cohort have been previously reported [1], and were as follows: 6.8% in the core-antibody positives versus 35.7% in the core-antibody negatives. 6.9% in the HIV-1-Ag negatives versus 43.9% in the HIV-1-Ag positives, and 6.1% in those with CD4+ lymphocyte counts greater than or equal to 0.5 versus 51.9% in those with CD4+ lymphocyte counts less than 0.5 x 10(9)/l. The disappearance of core antibody, the appearance of antigen and the occurrence of low CD4+ lymphocyte counts preceded AIDS by a mean (s.d.) of 21.3 (8.9), 17.7 (8.8) and 15.7 (8.9) months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗