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Biomedical subjects

R Linde

Publications and source records attributed to R Linde.

At least 37 records · Page 2Linked to original sources
PubMed1993

Combined therapy in human immunodeficiency virus-infected children--a 4-year experience.

From 1988 to 1991 the long-term efficacy of a combined therapy with a polyvalent immunoglobulin/cytomegalovirus (CMV) hyperimmunoglobulin, oral low dose zidovudine, oral cotrimoxazole or inhaled pentamidine was investigated in three groups of human immunodeficiency virus (HIV)-infected children. Group 1A consisted of three perinatally infected children with a CD4 cell decrease of > 400 cells/microliters per year. Group 1B were 17 perinatally infected children with a CD4 cell decrease of < 400 cells/microliters per year. Group 2 comprised eight haemophilic children infected by clotting factors. Despite combined therapy none of group 1A survived longer than 12 months showing a rapid loss of CD4 cell counts, progressive encephalopathy, wasting syndrome and severe bacterial, fungal and CMV reactivation. Under pure intravenous immunoglobulin (IVIG) therapy severe bacterial infections were seen in 1 of 12 children in group 1B. The majority of these patients showed increases or stabilisation of length and weight percentiles. In this group low dose zidovudine therapy was of benefit in HIV-associated neurological symptoms. Nevertheless combined therapy could not prevent further deterioration of CD4 cell counts. In group 2 severe bacterial infections were not seen under IVIG therapy. In this group a temporary increase (6 months) of CD4 cell counts under IVIG/zidovudine combined therapy occurred. Pneumocystis carinii pneumonia (PCP) prophylaxis with oral cotrimoxazole or inhaled pentamidine successfully prevented PCP in all three groups. Under CMV hyperimmunoglobulin (n = 22), ten out of ten patients did not acquire primary CMV infection, whereas CMV reactivations mainly located in the CNS could not be prevented in 5 of 12 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4-Positive T-Lymphocytes↗
PubMed1993

Cytomegalovirus myelitis in perinatally acquired HIV.

A 7 year old child perinatally infected with HIV who died from progressive muscular paralysis and central nervous respiratory failure is described. Cytomegalovirus (CMV) prophylaxis with a special intravenous CMV hyper-immunoglobulin had been successfully conducted for more than four years. Macroscopic and microscopic immunohistochemical examination of the spinal cord revealed a diffuse CMV infiltration of the entire myelon. CMV infected cells were identified as astrocytes, oligodendrocytes, neurons, macrophages, ependymal, endothelial, and Schwann cells. Other organs had no signs of CMV infection. Central nervous spinal CMV infection was most probably due to insufficient penetration of the blood-brain barrier by the CMV hyper-immunoglobulin. In suspicious cases early spinal magnetic resonance imaging (1.5 tesla) combined with an examination of urine and cerebrospinal fluid for CMV is recommended.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Development of a quasispecies of human immunodeficiency virus type 1 in vivo.

During treatment with one specific batch of blood clotting factor IX, a number of hemophilia B patients in Germany recently became infected with human immunodeficiency virus type 1 (HIV-1). The nucleotide sequences of cloned HIV-1 envelope gene regions including the variable V3 loop and the V4 region derived from short-term virus cultures and directly from peripheral blood cells of these patients were shown to be highly homologous. Based on the assumption that the corresponding consensus sequence (termed HIV-1MBK) was identical to the genotype of the initially infecting virus, we were able to construct phylogenetic trees of the developing quasispecies in two patients studied in detail. True intermediates between input and multiply mutated genotypes were found in individual blood samples. Except for the initially infecting variant HIV-1MBK, variants found at 11 months postinfection had replaced those seen at 5 months postinfection. Variability early after infection was shown to cluster in two small regions located 3' of the V3 loop (i.e., outside the loop) and within the V4 region. This communication therefore describes the evolution of an HIV-1 quasispecies in humans starting from a single genotype.

Amino Acid Sequence↗
PubMed1992

Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs.

The development of factor VIII:C inhibitors remains one of the most serious complications of repeated transfusion in patients with haemophilia A. The proportion of patients affected has been reported to range from 3.6% to 25%, but these figures have been derived mainly from retrospective data and from total numbers of known haemophiliacs instead of number at true risk. The assessment here is based on a prospective study, started in 1976, on the incidence of inhibitor development in haemophiliacs born after 1970 whose FVIII or FIX activity was 5% or less, and who had received replacement therapy at least once. 46 of 63 children with haemophilia A and 13 of 17 with haemophilia B fulfilled the enrollment criteria. Inhibitors developed only in haemophilia A patients who had previously been treated with FVIII products--inhibitor concentrations were high in 12 and low in 3. Inhibitors developed in 24% (15/63) of all haemophilia A patients, and in 52% (14/27) of those with severe disease. The incidence of inhibitor development for all haemophilia patients was 39.1 per 1000 patient-years of observation. All inhibitors were first detected when patients were aged 0.08-5.2 years. The cumulative risk was 33% at age 6 years. The findings indicate that previous reports have underestimated the risk of acquiring FVIII inhibitors. Prospective, standardised studies, especially in children, are needed for the assessment of the true risk of this complication.

Age Factors↗
PubMed1992

[Physiologic blood coagulation studies in idiopathic arterial thrombosis].

QUESTIONING: The prevalence of inherited thrombotic syndromes in the general population appears to be higher than that of inherited bleeding disorders. However, the most important candidates for screening are patients with unexplained thromboembolism at ages of less than 40 years: In 19 children suffering from "idiopathic" arterial thrombosis laboratory screening has been performed. METHODS: PT, PTT, TT, platelet count, spontaneous platelet aggregation, von Willebrand-factor, fibrinogen, plasminogen, antithrombin III, protein C, C1-inactivator, alpha-1-antitrypsin, alpha-1-antichymotrypsin, alpha-2-antiplasmin and alpha-2-macroglobulin have been investigated. RESULTS: Compared to an age matched healthy control group we could demonstrate in children with arterial thrombosis in vitro platelet activation with significant enhanced platelet aggregation, elevated levels of von Willebrand-factor and alpha-1-antichymotrypsin at the onset of disease. Protein C and alpha-2-antiplasmin were significantly decreased. These changes turned back to normal in the following 6 to 9 months. PT, PTT, TT, platelet count, plasminogen, alpha-1-antitrypsin, c1-inactivator and alpha-2-macroglobulin showed no alterations compared to controls. CONCLUSIONS: Platelet activation and alteration of platelet function have been shown in vivo and in vitro to initiate thrombosis. The von Willebrand's VIII molecule is involved in this step. The lowering of protein C levels at the onset of thrombotic diseases is discussed to be due to an increased turnover, whereas the decreased levels of alpha-2-antiplasmin might be a counter-regulation to the thrombotic event, showing an "activated" fibrinolytic system.

Adolescent↗
PubMed1991

Lack of HIV-1 V3 region sequence diversity in two haemophiliac patients infected with a putative biologic clone of HIV-1.

Peripheral blood mononuclear cells (PBMC) from two haemophilia B patients, who presumably became infected with a putative HIV-1 biological clone following treatment with the same suspected batch of commercial factor, were used to clone and sequence the hypervariable V3 region of the HIV-1 envelope protein. In 10 of 12 clones the V3 region was identical and two (one from each patient) had a single non-synonymous point mutation. Viable reisolates (shown to be authentic by sequencing of V3) currently appear to be monocyte tropic. These results strongly indicate that the patients were infected from a common source with a very low number of infectious particles and indicate that variability under these conditions is limited.

Amino Acid Sequence↗
PubMed1989

Digital flashing tomosynthesis (DFTS)--a technique for three-dimensional coronary angiography.

Digital Flashing Tomosynthesis (DFTS) represents a technique for three-dimensional (3D) coronary angiography. Four ECG-gated simultaneously flashed X-ray tubes generate a multiperspective digital substraction image as DFTS multiangiogram for 3D reconstruction and visualization. Computerized morphologic and morphometric quantitative analysis can be performed including videodensitometry. Postmortem coronary angiography of 30 human hearts with suspected coronary artery disease was performed by 35-mm cine technique and by DFTS. The results of angiographic measurements in 50 stenotic arterial segments were compared with the histologic reference and show excellent regression results with correlation coefficients of more than 0.95 (p less than or equal to 0.0001). No significant differences in standard errors of estimates between the techniques were found. DFTS yields an accuracy in depiction of the coronary arteries and angiographic estimation of arterial lumen equivalent to 35-mm cineangiography. DFTS images can be directly used for visual interpretation and for computerized morphologic and morphometric quantitative analysis. DFTS technology reduces the amount of radiation exposure, the amount of contrast medium, and the time of the procedure. DFTS offers the possibility to obtain 3D images of the coronary artery tree.

Aged↗
PubMed1987

Generation of a subtraction mask for digital angiography based on the movement of the coronary arteries.

A synthetic mask technique for angiography of coronary arteries was experimentally studied, using conventional 35 mm film sequences of coronary arteries. The method makes use of the fact that because of the movement of the heart vessels different parts of the background will be hidden. The background is extracted from two or more neighbouring frames by computer assistance and afterwards used for a subtraction mask. The experiments showed that the synthetic masks are of a good accuracy, the background anatomy is markedly reduced and the contrast is increased.

Angiography↗
PubMed1987

Hodgkin's disease with hypercalcemia detected by thallium-201 scintigraphy.

A 53-yr-old man with hypercalcemia was referred after an unsuccessful operative attempt to find a parathyroid adenoma. Metabolic evaluation showed relatively suppressed levels of parathyroid hormone with an elevation of serum 1,25-dihydroxyvitamin D. Thallium-technetium dual isotope imaging revealed localized mediastinal thallium uptake. A vascular mediastinal lesion was then demonstrated by arteriography, with subsequent surgical removal of a mass that proved to be lymphocyte predominant Hodgkin's disease. This case is noteworthy for the finding of isolated lymphocyte predominant Hodgkin's disease in the chest, the association of elevated serum 1,25-dihydroxyvitamin D with hypercalcemia that resolved postoperatively, and the uptake of thallium by the tumor.

Calcitriol↗
PubMed1985

[Selective coronary angiography via flashing tomosynthesis].

To assess the value and significance of short-term tomosynthesis in judging the pathological condition of coronary vessels, the authors examined 34 patients with coronary heart disease. In comparison with 35 mm cinecoronary angiography, all angiographically determined vascular occlusions and stenoses were identified via short-term tomosynthesis. Comparison of the degrees of stenoses yielded good correlation (r = 0.85). Short-term tomosynthesis offers the advantage of employing smaller amounts of contrast medium to be injected; furthermore, the examination period is shorter, and exposure to radiation is also significantly less.

Cineangiography↗
PubMed1985

First clinical results with digital flashing tomosynthesis in coronary angiography.

Digital flashing tomosynthesis (D-FTS) investigations have been performed using a new nonlinear reconstruction algorithm. It is called extreme-value decoding and produces significantly less artefact than back projection used commonly in tomosynthesis. The reduction of artefact allows the use of tomosynthesis based on only four projections in the case of dilute objects, i.e. objects with only a small number of high absorbing voxels. This condition can be realized in angiography by cancelling soft-tissue and bones by subtraction (e.g. DSA technique). The new technique has been carried out in 10 patients with coronary artery disease after investigation with standard 35 mm cineangiography. For the recording step of the D-FTS images we have used a multiple X-ray source. For the digital nonlinear reconstruction step we have used a VAX 11/780 computer. The estimated degree of stenosis found by D-FTS tomograms shows good accordance with the cineangiographic studies. The amount of contrast medium, the X-ray dose, and the investigation time are significantly reduced, because D-FTS requires only a single pre- and post-injection multiple perspective-image for each coronary artery.

Cineangiography↗
PubMed1985

Coronary angiography with flashing tomosynthesis.

Thirty-four patients with coronary artery disease were studied with standard 35 mm coronary cineangiography and flashing tomosynthesis, to assess the value of the latter technique to detect stenotic coronary arteries. All occluded vessels and all coronary stenoses seen by cineangiography were also found by flashing tomosynthesis. A correlation coefficient of r = 0.85 (P less than 0.001) was determined between the degrees of stenosis obtained by the two techniques. With flashing tomosynthesis, less contrast medium was needed, the investigation time was shorter, and the radiation exposure markedly reduced. At present, dynamic events, such as collateral blood flow, cannot be evaluated. We conclude that coronary arterial stenoses and occlusions can be reliably evaluated by flashing tomosynthesis. Further technological developments are necessary for the technique to gain clinical acceptance.

Adult↗
PubMed1985

Effect of a luteinizing hormone releasing hormone agonist given during combination chemotherapy on posttherapy fertility in male patients with lymphoma: preliminary observations.

Six men undergoing potentially curative chemotherapy for advanced lymphomas received daily injections (50 micrograms) of an analogue of luteinizing hormone releasing hormone (LH-RHa) in an attempt to protect posttreatment gonadal function. The median duration of combined LH-RHa-chemotherapy administration was 25 weeks (range, 14 to 31 weeks). During the simultaneous administration of LH-RHa and chemotherapy, plasma testosterone levels decreased to subnormal levels, while both follicle-stimulating hormone (FSH) and luteinizing hormone levels declined to the lower limit of normal. All subjects became oligospermic or azoospermic within eight weeks of starting treatment. Following discontinuation of chemotherapy and LH-RHa, both plasma testosterone and LH promptly increased and stabilized within the normal range. FSH progressively increased to a level well above the normal range. Only one patient has recovered evidence of active spermatogenesis at 84 weeks postcessation of chemotherapy. No untoward side effects due to LH-RHa were experienced. Although LH-RHa can be administered safely during combination chemotherapy, no improvement in posttreatment fertility has yet been demonstrated.

Adolescent↗
PubMed1982

Familial insensitivity of the pituitary and periphery to thyroid hormone: a case report in two generations and a review of the literature.

A clinically euthyroid 2-yr-old girl was found to have diffuse goiter that measured 3 X 5.5 cm with a prominent systolic bruit. Serum free T4 (3.4 ng/dl) and serum T3 (360 ng/dl) remained elevated for the next 10 months even though she remained clinically euthyroid. Elevation of serum free T4 (3.0 ng/dl) and serum T3 (265 ng/dl) was also present in the 24-yr-old nongoitrous mother who had symptoms and signs of hypothyroidism. Following intravenous injection of TRH, basal TSH levels of 2.7 and 2.8 microunits/ml increased to peak values of 17 and 21 microunits/ml at 30 min in the daughter and mother, respectively. Administration of exogenous T3 followed by sequential testing with boluses of TRH revealed retention of TSH responsiveness in both daughter and mother during pretreatment with dosage regimens of T3 below 125 micrograms daily. Maintenance of TSH responsiveness to TRH in the presence of elevated levels of serum free T4 and serum T3 indicates relative pituitary insensitivity to thyroid hormone which could be overridden by increasing the circulating levels of serum T3 three to fivefold over the already elevated basal levels. The absence of clinical signs of thyrotoxicosis indicates peripheral insensitivity to thyroid hormone with elevated circulating concentrations presumptively compensating for the defect. Resistance to thyroid hormone in two generations of the same family suggests genetic inheritance, and is concordant with four earlier reports of familial aggregation in this syndrome.

Adult↗