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Biomedical subjects

H Burger

Publications and source records attributed to H Burger.

At least 163 records · Page 9Linked to original sources

A survey of vascular access for haemodialysis in The Netherlands.

After nearly 30 years of access surgery for haemodialysis, a survey of vascular access in a large population seemed relevant in order to analyse the state of the art. On 1 January 1988, 2195 patients in 52 centres in The Netherlands (population 14,714,900) were on long-term haemodialysis and 588 on continuous ambulant peritoneal dialysis (CAPD) for renal insufficiency. A questionnaire was mailed out, to which there was 100% response. Of all the patients on long-term haemodialysis, 70% had a Cimino fistula, 22% a graft fistula, and 6% a more proximal arm fistula. The remaining 2% had a Scribner shunt. Of all the graft fistulae, the expanded polytetrafluoroethylene (ePTFE) graft was the one most used (58%), followed by the homologous vein graft (25%), the autologous vein graft (13%), and those made of other materials (4%). Preference for acute access was recorded; catheterisation of the subclavian vein was used almost exclusively in 17 centres, while in 24 centres it was chosen in more than 50% of the cases. The femoral vein was almost always the choice for acute access in 6 centres and it was selected in more than 50% of the cases in 17 centres. Another alternative, the Scribner shunt, was applied in selected cases in 22 of the 52 centres. Percutaneous transluminal angioplasty (PTA), as a method for treating stenoses in vessels used for vascular access, was applied routinely in 5 centres and occasionally in 19 centres.

Adult↗

Treatment of anovulation due to polycystic ovarian syndrome by laparoscopic ovarian electrocautery.

Our experience of ovarian electrocautery for the treatment of polycystic ovarian syndrome (PCOS) in ten women is described. We found that nine responded favourably, either ovulating spontaneously or becoming more responsive to ovulation induction. There was a significant and persistent fall in serum testosterone levels, and a transient fall with subsequent rise in inhibin. We recommend that laparoscopic ovarian electrocautery is considered as an alternative to ovulation induction with gonadotrophins, in women with PCOS who fail to respond to clomiphene citrate.

Adult↗

Species specificity of human interleukin-3 demonstrated by cloning and expression of the homologous rhesus monkey (Macaca mulatta) gene.

To enable preclinical studies on homologous interleukin-3 (IL-3) in primate species, we isolated the gene encoding Rhesus monkey IL-3 (RhIL-3). The nucleotide sequence of the RhIL-3 gene displayed 92.9% homology with that of the human IL-3 (hIL-3) gene. The isolated RhIL-3 gene encodes a 143-amino acid (aa) precursor polypeptide, nine C-terminal residues shorter than the human protein. Protein homology was found to be 89.5% for the signal peptide (19 aa) and 80.5% for the mature protein (124 aa). Comparison of the human and RhIL-3 coding sequences showed that the majority of substitutions had occurred at amino acid replacement sites indicating a rapid evolution of the IL-3 protein. After expression of a genomic fragment in COS cells, RhIL-3 cDNA was constructed, which enabled large-scale production of the RhIL-3 polypeptide, RhIL-3 produced by Bacillus licheniformis and purified to homogeneity appeared to be approximately 100-fold more effective in stimulating Rhesus monkey hematopoietic progenitors than hIL-3, whereas RhIL-3 and hIL-3 showed comparable stimulatory activity on normal as well as malignant human hematopoietic cells. Thus, the rapid evolution of hIL-3 has resulted in a unidirectional species specificity, which most likely restricts the in vivo effects of hIL-3 in Macaca species.

Amino Acid Sequence↗

Highly increased production of bone marrow-derived blood cells by administration of homologous interleukin-3 to rhesus monkeys.

Recombinant rhesus monkey interleukin-3 (IL-3) was administered to normal rhesus monkeys in graded doses ranging from 3 to 30 micrograms/kg/d subcutaneously for 30 consecutive days or given as a continuous intravenous infusion at a dose of 30 micrograms/kg/d for 16 days. After a lag phase of about 1 week, a highly increased, dose-dependent production of bone marrow-derived blood cells was observed, preceded by amplification of bone marrow hematopoietic progenitor cells. Simultaneously, peripheral blood progenitor cells rose. The increase included basophilic, eosinophilic and neutrophilic granulocytes, monocytes, and the erythrocyte and platelet lineages. Characteristically, a T-lymphocyte response was absent. It is concluded that IL-3 in vivo stimulates blood cell production from an immature, multipotent progenitor cell.

Animals↗

Long HIV-1 incubation periods and dynamics of transmission within a family.

The incubation period of human immunodeficiency virus type 1 (HIV-1) infection was studied in a family of five in which vertical and heterosexual transmission occurred from one index case. This investigation documented incubation periods of longer than 12 years in a mother and her daughter; although neither has symptoms, both are definitely infected and have very low CD4(+)-lymphocyte counts. The study confirmed the predictions of incubation periods longer than 10 years in a small proportion of infected individuals. It provides evidence that vertically HIV-1-infected teenagers can be expected to appear in the population.

Acquired Immunodeficiency Syndrome↗

Interleukin-3.

Interleukin-3 (IL-3) is a hemopoietic growth factor involved in the survival, proliferation and differentiation of multipotent hemopoietic cells. In five mammalian species, including man, the gene encoding IL-3 has been isolated and expressed to yield the mature recombinant proteins. The human IL-3 gene encodes a protein of 133 amino acids with two conserved cysteine residues and 2 potential N-linked glycosylation sites; human native IL-3 has not been characterized. Comparison of the IL-3 genes revealed a more rapid evolutionary divergence than has been observed for other hemopoietic growth factors, and, hence, a more pronounced species specificity of the functional proteins was found. In agreement with its stimulatory action on immature multipotent cells, the in vivo actions of homologous recombinant IL-3 in nonhuman primates include a highly increased production of blood cells along the neutrophilic, eosinophilic and basophilic granulocyte as well as the monocyte, red cell and platelet lineages.

Animals↗

Human immunodeficiency virus type 1 expression in the central nervous system correlates directly with extent of disease.

To investigate human immunodeficiency virus type 1 (HIV-1) pathogenesis in infected individuals and examine the correlation of HIV-1 expression with extent of clinical and pathologic disease, we studied spinal cords from acquired immunodeficiency syndrome patients with a wide range of spinal cord pathology. By performing in situ hybridization with HIV-1-specific riboprobes, we detected HIV-1 RNA in all 10 cords from acquired immunodeficiency syndrome patients with a common, characteristic pathologic entity called vacuolar myelopathy but not in 10 control cords from HIV-1-infected and uninfected patients. In the cords from individuals with vacuolar myelopathy, the level of HIV-1 RNA expression correlated directly with extent of spinal cord pathology and clinical findings. These data support a role for HIV-1 in the pathogenesis of tissue damage and related clinical disease in infected individuals.

Acquired Immunodeficiency Syndrome↗

Dose-limiting toxicity of rifabutin in AIDS-related complex: syndrome of arthralgia/arthritis.

We studied the tolerance of humans to rifabutin, a rifamycin with antimycobacterial and in vitro anti-HIV activity. Sixteen subjects with AIDS-related complex were treated for 4-66 weeks with stepwise increasing oral doses of rifabutin from 300 to 2400 mg/day. The highest dose attained was twice that previously reported for humans. Serum and cerebrospinal fluid levels of drug were detected by high-pressure liquid chromatography. A reversible syndrome of arthritis/arthralgia, not previously described, was seen in most (nine out of 10) of those given doses exceeding 1050 mg/day. Uveitis and aphthous stomatitis developed at doses of approximately 1800 mg in two of those with joint manifestations. Typical manifestations of Reiter's syndrome were not seen in any patient. An orange-tan skin pigmentation was almost universal. Other toxicities resembled those previously associated with rifampin. Serum levels did not approach those found to inhibit HIV significantly in vitro. No consistent antiviral or immunological effects were observed; even at the highest doses, rifabutin did not appear to inhibit cellular immunity. Rifabutin was well tolerated at daily doses blow 1 g.

AIDS-Related Complex↗

Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia.

To determine the timing of pubertal development and the frequency of gonadal dysfunction in children who survive acute lymphoblastic leukemia, we assessed pubertal status and the plasma levels of sex steroids, gonadotropin, and inhibin in 45 children (20 girls and 25 boys) who had received combination chemotherapy along with 24 Gy of irradiation to the cranium (modified LSA2L2 protocol). We also reexamined testicular biopsy specimens, obtained at the time of the cessation of chemotherapy, for the presence of germ cells. Germ-cell damage, indicated by marked elevations in the plasma level of follicle-stimulating hormone (P less than 0.001 for the comparison with normal children), was evident in both sexes and was confirmed in the boys by the absence of germ cells in the testicular biopsy specimens and by the small size of the testes for pubic-hair stage. Only 44 percent of the pubertal girls had measurable plasma inhibin levels, as compared with more than 93 percent of normal pubertal girls. Although plasma sex-steroid levels were normal, the secretion of luteinizing hormone in response to stimulation with gonadotropin-releasing hormone was elevated in the pubertal children (P less than 0.01 for the comparison with normal controls)--a finding that suggests compensation for decreased gonadal function. Despite clear evidence of gonadal damage, girls had early menarche at a mean age (+/- SD) of 11.95 +/- 0.91 years, as compared with the Australian standard of 12.98 +/- 1.11 years (P less than 0.01). Thus, in girls, puberty was early despite primary gonadal damage. Thirteen of 23 boys reached puberty at a mean age of 12.36 +/- 0.73 years. We conclude that treatment for acute lymphoblastic leukemia may lead to primary gonadal damage in both sexes, regardless of the age at treatment, but that the secondary characteristics of puberty develop at a normal age or, in girls, relatively early.

Adolescent↗

Oral discomfort at menopause.

The relationship between oral discomfort and menopause was assessed in 149 women who were divided into three groups determined by response to a questionnaire. The groups consisted of 50 premenopausal women (30 to 43 years old), 47 menopausal women not receiving medical treatment for symptoms of menopause (37 to 66 years old), and 52 menopausal women attending a menopause clinic before and during treatment for menopausal symptoms (30 to 63 years old). The last group had a general medical assessment, including psychological and oral examinations with oral smears and cultures, and the following blood tests: full blood examination, follicle-stimulating hormone, oestradiol, folate, vitamin B12, iron, and total iron binding capacity. Of this last group, 33% reported oral discomfort but had no obvious organic abnormalities that could account for this symptom. The prevalence of oral discomfort was found to be significantly higher in perimenopausal and postmenopausal women (43%) than in premenopausal women (6%). The results also showed an association between oral discomfort and psychological symptoms in menopausal women. Approximately two thirds of the menopausal women with oral discomfort, but without oral clinical signs, found that this symptom was relieved after hormone replacement therapy. The results indicated that oral discomfort is a common symptom of menopause, that it often occurs without overt clinical signs, and that it frequently resolves during appropriate hormone replacement therapy.

Adult↗

Human chorionic gonadotrophin-induced suppression of serum inhibin involves reduction in ovarian inhibin alpha-subunit messenger RNA levels in the pregnant mare serum gonadotrophin-primed female rat.

We have investigated the effect of administration of human chorionic gonadotrophin (hCG) to immature female rats pretreated with pregnant mare serum gonadotrophin (PMSG) on ovarian inhibin alpha-subunit mRNA, serum inhibin and circulating gonadotrophin levels. PMSG stimulation alone caused a 5-fold increase in relative inhibin alpha-subunit mRNA levels and a 12-fold increase in serum inhibin by 48 h. However, injection of hCG at 40 h suppressed PMSG-stimulated ovarian inhibin alpha-subunit mRNA and serum inhibin to levels at 48 h not statistically significantly different from controls. Serum follicle-stimulating hormone (FSH) fell after PMSG treatment, but rose after combined PMSG-hCG treatment. Serum luteinizing hormone (LH) was unchanged after PMSG alone but also rose after combined PMSG and hCG therapy. In conclusion, hCG suppresses ovarian inhibin synthesis in PMSG-stimulated immature female rats with preservation of the reciprocal relationship between inhibin and FSH. This immature female rat model therefore provides further insight into the effects of LH or hCG on granulosa cell inhibin production just prior to ovulation.

Animals↗

Human immunodeficiency virus type 1 in spinal cords of acquired immunodeficiency syndrome patients with myelopathy: expression and replication in macrophages.

Spinal cord disease is common in patients infected with human immunodeficiency virus type 1 (HIV-1), and a characteristic vacuolar myelopathy is present at autopsy in approximately one-fourth of acquired immunodeficiency syndrome patients. Pathologic examination of the spinal cord shows vacuolation of white matter and infiltration by macrophages, a process distinct from HIV-1 encephalopathy. To determine the presence and localization of HIV-1 RNA in the spinal cords of acquired immunodeficiency syndrome patients with vacuolar myelopathy, we used the technique of combined in situ hybridization and immunohistochemical staining on the same slide. Spinal cord tissue sections were stained with markers for macrophages, endothelial cells, oligodendroglia, astrocytes, and myelin and then hybridized in situ with HIV-1-specific RNA probes. Combined in situ hybridization and immunohistochemical staining on three spinal cords showed HIV-1 expression in mononuclear and multinucleated macrophages localized mainly to areas of myelopathy in spinal cord white matter. Immunohistochemical staining and electron microscopy showed myelin within macrophages and electron microscopy revealed HIV-1 budding from macrophages. These data suggest a role for HIV-1-infected macrophages locally in the pathogenesis of vacuolar myelopathy and add to the body of evidence that these cells play a role systemically in the development of HIV-1-related disease.

Acquired Immunodeficiency Syndrome↗

Efficacy of rifabutin in the treatment of AIDS-related complex.

We performed a phase 1-2 antiviral dose escalation trial of rifabutin, a rifamycin antibiotic with anti-HIV-1 activity in vitro. We followed 16 men with AIDS-related complex (ARC) for a mean duration of 29 weeks; the maximum toxicity-limited dose of rifabutin was 2400 mg/day, which was achieved in two patients. There was some evidence of anti-HIV-1 activity in two patients, one of whom had an improvement in immune status, but 11 of the 16 patients showed a deterioration in either virologic or immunologic status. The majority of the patients under study remained clinically stable during the trial, but there was clinical deterioration in the three who entered with CD4 cell counts of less than 100 x 10(6)/l. On the basis of this trial, rifabutin as a single antiviral agent does not appear to be beneficial to ARC patients.

AIDS-Related Complex↗

Clomiphene.

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Animals↗