Biomedical subjects

H H Peter

Publications and source records attributed to H H Peter.

At least 199 records · Page 11Linked to original sources

PubMed1991

Testing for association in SLE families.

Systemic lupus erythematosus (SLE) is a complex disease which is partly determined by genetic factors which influence susceptibility to the disease phenotype. In this association study we try to define the high risk haplotypes which are responsible for this disease, together with other environmental factors. In many other association studies a set of SLE patients is compared to a set of controls. The basic assumption about the underlying population is that the disease and control sample should originate from the same genetic population, which is not always completely satisfied in many studies. Therefore, we analyse our family data by applying the Haplotype Frequency Difference (HFD) Method, which constructs its internal control group from those haplotypes not transmitted to the affected individual. Results partially conform with other studies, showing that the haplotypes B8 DR3 as well as B7 DR2 have a high positive association with SLE. When the DR locus was analyzed alone, we found besides the alleles DR2 and DR3 a negative association for DR1, DR5, and DR6.

Adult↗

PubMed1991

Primary antiphospholipid syndrome (PAPS). Two case reports and therapeutic implications.

Antiphospholipid antibodies (aPL) interfere with the coagulation system and can cause thrombosis and other clotting disorders. The combination of recurrent venous thrombosis, arterial embolism and recurrent fetal loss is nowadays considered to be primary antiphospholipid syndrome (PAPS), provided an underlying systemic lupus erythematosus (SLE) has been excluded and aPL have been detected. We report on two patients with PAPs, and show the course of their IgG- and IgM-anticardiolipin antibody (aCL) titers during immunosuppressive therapy with prednisone and azathioprine or cyclophosphamide. Over a period of 18 months this therapy was effective in preventing relapses of thrombo-embolism and other complications. Therapy with cyclophosphamide resulted in normalization of the aCL titers in one of the two reported cases. Azathioprine treatment reduced the aCL titer in the other patient, without fully normalizing it. Based on our observation, we propose to treat PAPS-associated severe and recurrent thrombo-embolic complications by aggressive immunosuppression, including azathioprine and cyclophosphamide.

Adolescent↗

PubMed1991

Intravascular coagulation necrosis of the skin associated with cryofibrinogenemia, diabetes mellitus, and cardiolipin autoantibodies.

Intravascular coagulation necrosis of the skin is rare and appears as hemorrhagic infiltrates that may develop ulcerating necrosis, mainly on the acral areas. The face, arms, and legs were severely involved in our patient. In this patient intravascular coagulation necrosis was associated with cryofibrinogenemia, diabetes mellitus, and IgM cardiolipin autoantibodies. In addition, rheumatoid factor, elevated polyclonal IgA, and haptoglobin were present as risk factors for the vasculopathy. Skin biopsy specimens showed plugging of dermal venules by thrombi formed of fibrin and erythrocytes. Immunohistologic staining revealed a strong positive reaction for fibrinogen, with some positivity for C3, C4, IgG, IgA, and IgM. Erythrocyte extravasation occurred in late lesions without being accompanied by perivascular leukocytic infiltrates. Detailed clinical examination failed to identify an underlying malignancy. Treatment with heparin and prednisolone produced only a brief remission. However, the combination of chlorambucil (7 mg/day orally) with low-dose oral prednisolone (10 mg/day) for several weeks controlled the disease and greatly reduced the cryofibrinogen. No relapse occurred after discontinuation of treatment.

Aged↗

PubMed1991

Evaluation of desferrithiocin and its synthetic analogues as orally effective iron chelators.

Desferrithiocin, a novel microbial siderophore isolated from cultures of Streptomyces antibioticus DSM 1865, and a number of its derivatives and analogues are evaluated for their ability to promote iron clearance. The compounds have been designed with the objective of identifying the structural features of desferrithiocin which render this ligand an orally effective iron chelator. The desferrithiocin aromatic hydroxyl and the thiazoline ring carboxyl group are shown to be central to desferrithiocin's activity. The ligand's methyl and the aromatic nitrogen play little role in the compound's efficacy. The animal model chosen for this study, the bile duct cannulated rat, provides information regarding both the chelator-induced total iron output and the kinetics of both biliary and urinary iron excretion.

Administration, Oral↗

PubMed1991

[Immunologic defects in the lymphatic system of the intestinal mucosa in common variable immunodeficiency (CVID) syndrome].

The humoral immune system of the intestinal mucosa of patients with common variable immuno deficiency (CVID) syndrome was studied immunohistologically using antibodies against immunoglobulin (Ig) A1-2, M and G1-4, against the J chain and the secretory component. In 9/13 CVID-patients IgA-positive cells were totally absent whereas a total IgM-defect was found only in 3/14 patients. Considerable numbers of J chain-positive cells were present in all CVID-patients irrespective of the extent of the Ig-defect indicating the presence of early B-cells unable to differentiate and to produce Ig. There was a strong expression of the secretory component in the cytoplasm and at the surface of enterocytes even in those CVID-patients who were totally defective in IgA- and IgM-positive cells.

Humans↗

PubMed1991

[Cardiopulmonary risk factors in patients with sleep apnea].

Since the interaction between disorders of the respiratory coordination and cardiovascular or cardiopulmonary regulation is still largely unknown the intention of the present investigation is to point out the coincidence of cardiac arrhythmias, such as premature ventricular capture (PVC) beats and conduction blocks, with obstructive sleep apnea (OSA). For the first time a group of more than 300 patients with suspected OSA is examined concerning risk factors and frequent diagnoses as obesity, hypertension, coronary heart disease (CHD), heart insufficiency, chronic obstructive pulmonary disease (COPD), and daytime hypoxaemia. Summarizing the results of lung function test, blood gas analysis, strain-ECG, Holter-ECG and inductive plethysmography with oxygen partial pressure measurement by ambulatory work-up the following statements can be made: PVC beats occurring markedly during sleep give hints for OSA being the underlying cause, especially if the patients are young and overweight. Hypoxaemia increasing during the apnea episodes should be considered as one possible pathogenetic mechanism. Second- and third degree conduction blocks and sinus arrest coincident very often with OSA. They suggest to be life-limiting factors the more so since they often go along with CHD or heart insufficiency. Systemic arterial hypertension and overweight have the highest prevalence in OSA, signs for heart insufficiency and daytime hypoxaemia are also significantly more frequent than in non-OSA patients. We could find no hints for direct pathogenetic coherence between CHD and OSA or between COPD and OSA, nevertheless pronounced nocturnal changes in blood gases and intrathoracic hemodynamics have important influence on the cardiopulmonary and cardiovascular system, as partly illuminated in other more pathogenetic oriented studies by the present time.

Arrhythmias, Cardiac↗

PubMed1991

Crescentic glomerulonephritis in Wegener's granulomatosis: morphology, therapy, outcome.

Fourteen patients with Wegener's granulomatosis (WG) and severe renal and extrarenal involvement were studied (serum creatinine on admission 5.8 +/- 3.4 mg/dl). Renal histology showed a necrotizing, crescentic glomerulonephritis in all patients. Despite advanced renal disease on admission cyclophosphamide, steroids (in 13 patients) and plasma exchange (in 9 patients) caused a rapid and sustained improvement of renal function. Four patients required intermittent hemodialysis over a period of one week. After 2 weeks of treatment serum creatinine values below 2 mg/dl (n = 4) indicated a nearly complete recovery of renal function in the long-term follow up (mean serum creatinine achieved after 12 months therapy: 1.1 +/- 0.1 mg/dl (n = 4). Therefore serum creatinine values observed after 2 weeks of therapy, appear to be of prognostic value with regard to renal outcome. No relapse of active WG or progressive renal deterioration was observed during follow-up (22 +/- 13 months) except in one patient with persisting renal impairment. Three patients died (staphylococcus sepsis, intracerebral hemorrhage during hypertensive crisis, pulmonary embolism) during the first two months of therapy. The decline of serum creatinine seemed to be a better indicator of successful therapy than the decrease of anticytoplasmatic antibody (ANCA), erythrocyte sedimentation rate (ESR) and hematuria. On admission ANCA titer neither correlated with serum creatinine, the degree of renal involvement, nor was it of prognostic value. ANCA, serum creatinine and hematuria normalized within 2 to 8 months, whereas ESR and proteinuria remained elevated. Our data indicate a good prognosis of WG even with advanced renal involvement and generalized vasculitis provided aggressive treatment is performed early.

Acute Disease↗

PubMed1991

Immunoglobulin allotypes in systemic lupus erythematosus--results of a central European multicenter study. SLE Study Group.

Immunoglobulin heavy chains (G1m, G2m, G3m, A2m) and kappa light chain (Km) allotype and phenotype frequencies were examined in 323 central European Caucasian patients with systemic lupus erythematosus (SLE). No significant differences were found between the different allotype or phenotype frequencies of the SLE patients and a control group of healthy individuals. Our results indicate that Gm, A2m and Km allotypes do not represent susceptibility factors for SLE in Caucasians.

Gene Frequency↗

PubMed1991

[Chronic immunoproliferative syndromes].

Immunoproliferative syndromes are etiologically unclear, rare diseases which involve polyclonal B- and/or T-cell proliferations and frequently develop into malignant non-Hodgkin-lymphoma. Typically, these diseases are characterized by lymphadenopathies, hepatosplenomegaly, general fatigue and autoimmune phenomena. Here we briefly outline 6 syndromes, two of which--the "pluripotential chronic immunoproliferative syndrome" (CPIS) and the "angioimmunoblastic lymphadenopathy" (AILD)--are discussed in more detail. We favor the notion that CPIS is a variant form of AILD clinically dominated by severe autoimmune hemolytic anemia. Both diseases share the high frequency of anti-cytoskeleton autoantibodies.

Chronic Disease↗

PubMed1991

[Gamma-1 heavy chain disease with the demonstration of Bence-Jones proteins].

We describe a 61-year-old patient suffering from gamma-1-heavy-chain disease (gamma 1-HCD) associated with Bence-Jones-lambda proteinemia and proteinuria. The analysis of the patients gamma 1-HCD protein (WIN) shows a deletion of the complete Fd fragment. The N-terminal seven amino-acid residue does not resemble any of the known immunoglobulin-heavy-chain variable regions. Unexpectedly, in PBL-DNA and in DNA from EBV-immortalized cells we found in addition to the expected predominantly rearranged Ig-lambda-light-chain gene a predominant rearrangement of an Ig-kappa gene. These findings show that the gamma-1-heavy-chain disease of the patient involves a defective regulation of Ig-light-chain-gene activation as well.

Amino Acid Sequence↗

PubMed1991

Low dose methotrexate therapy for rheumatoid arthritis complicated by pancytopenia and Pneumocystis carinii pneumonia.

In a patient with rheumatoid arthritis pancytopenia and Pneumocystis carinii pneumonia occurred during low dose methotrexate therapy. This case emphasizes the potential development of opportunistic infections even with low dose methotrexate. Pneumocystis carinii pneumonia resembles methotrexate induced pneumonitis. Therefore opportunistic infections should be considered before a definite diagnosis of methotrexate induced pneumonitis is made.

Adolescent↗

PubMed1991

Sequelae after infection with Trichinella spiralis: a prospective cohort study.

It is still a matter of debate whether or not infection with Trichinella spiralis is followed by long lasting sequelae. A common source epidemic of trichinosis which occurred in Bitburg, FRG, in October 1982 gave us the opportunity of performing a controlled cohort study (171 patients and 51 controls). 145 patients and 44 controls completed the 3 year follow-up. Complaints persisted in 36% of patients aged less than 30 years and in 100% of patients aged greater than 50 years. Complaints in order of frequency were: muscular complaints 84%, ocular complaints 63%, cardiac complaints 48%, cephalgia 43%, neurological complaints 35%, gastrointestinal complaints 18%, m fatigue and weakness 18%, oedema 12% and fever less than 1%. IgG antibodies to T. spiralis were still present in all but 5 patients 3 years after infection. IgM antibodies were either low or absent. In our patients the frequency and pattern of complaints and the correlation to the specific antibody response provide evidence that trichinosis causes long-lasting disease. Yet, from our data we were unable to draw conclusions as to the causative pathophysiological mechanisms.

Adolescent↗

PubMed1991

[Angioneurotic edema in hereditary alpha-1-antitrypsin deficiency].

A young man with angioedema presented with normal concentration and function of C1-esterase inhibitor, but with a hereditary deficiency of alpha-1 antitrypsin (Pi-ZZ type). The pathogenetic relevance of this defect is discussed with respect to the partial deficiency of the complement component C4 (C4BQ0), which was found in addition.

Adult↗

PubMed1990

[Fetal complete heart block with myocarditis and maternal SS-A-/AA-B/antibodies].

We report on a newborn with fetal acquired heart block (CHB). CHB is a rare, irreversible defect, commonly occurring in conjunction with myocarditis in the neonatal lupus syndrome. Development of CHB is strongly associated with maternal anti-SS-A(Ro)/SS-B(La) antibodies. Intrauterine therapy of CHB is not possible. Concomitant myocarditis, however, can be treated effectively with dexamethasone. Mothers with an elevated risk of fetal CHB can be identified by their history (underlying systemic connective tissue disease, previous pregnancies with CHB), an immunogenetic predisposition (HLA-DR3) and analysis of the SS-A/SS-B antibody pattern. In these pregnancies prevention of CHB with plasmapheresis plus dexamethasone during pregnancy may be possible.

Adult↗

PubMed1990

Successful therapy of meningococcal sepsis in acute disseminated lupus erythematosus with plasmapheresis, immunosuppression, and antibiotics.

A 17-year-old female with a 5-year history of disseminated lupus erythematosus has remained without immunosuppressive therapy for the last 3 years. She was admitted to the hospital for acute abdominal pain, generalized edema, and rapidly developing dyspnea and somnolence. Although all symptoms were consistent with active SLE, septicemia was suspected because of leukocytosis (20,000/microliters), greatly elevated C-reactive protein (45 mg/dl), and normal complement values (C3 0.74 g/l, C4 0.21 g/l). Directly after bacterial blood cultures were prepared, a combined treatment was instituted consisting of plasmapheresis (3 x 2.1 l against fresh frozen plasma), antibiotics, prednisolone, and cyclophosphamide following the last plasmapheresis. Within three days cerebral function returned to normal, edema improved, and CRP fell to 0.5 mg/dl. The blood cultures and pericardial effusion displayed meningococcal colonies.

Adolescent↗

PubMed1990

[Lyme borreliosis. The manifestations of the disease from the internal medicine and rheumatology viewpoints].

Lyme disease is an infectious syndrome transmitted by tick bites. Of the multiple manifestations, cardiac and joint involvement are of primary interest for internists and rheumatologists. Up to 10% of patients develop cardiac symptoms, most frequently a disturbance of atrioventricular conduction. The characteristic presentation of the disease, however, are of symptoms of arthritis in one or several large joints. This review summarizes Lyme disease with emphasis on presenting symptoms important to internists and rheumatologists.

Anti-Bacterial Agents↗

PubMed1990

[Paroxysmal nocturnal hemoglobinuria].

Paroxysmal nocturnal hemoglobinuria, first described in the late 19th century, is an acquired disorder characterized by hemoglobinemia and hemoglobinuria. The major clinical manifestation of PNH is chronic intravascular hemolysis of various severity. Patients-mostly young adults - may also present with episodes of abdominal or back pain. Common cause of death is thrombosis especially of the hepatic veins. Granulocytopenia and thrombocytopenia may be the initial manifestation of PNH, indicating that the disorder is a primary bone-marrow disease, affecting not only the erythrocytes but also other peripheral blood cells and the haematopoietic stem cell. The course of the disease is variable. Partial complete recovery was described, but also fatal thrombosis. The major phenotypic expression of PNH is an increased susceptibility of the erythrocytes to the lytic action of complement in vitro. The enhanced complement susceptibility is most probably due to membrane defects: two membrane proteins regulating the complement cascade in PNH cells were missing, the decay-accelerating factor, DAF, inhibiting the activation of the lytic complement complex and the C8 binding protein, C8bp, which interferes with the lytic process. Aside from the lack of the complement regulators also other membrane defects have been described (e.g. of acetylcholinesterase or alkaline phosphatase). The proteins as well as DAF and C8bp are linked to the cell membrane via a phosphatidylinositol (PI) anchor, leading to the speculation that the disease results from a deficiency in the post-translational PI anchoring mechanism. The diagnosis of PNH is based on the Hamtest, but will be extended to the quantitation of the above described membrane proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Complement System Proteins↗

PubMed1990

Type II collagen-specific human T cell lines established from healthy donors.

Four type II collagen-specific T cell lines established from the peripheral blood of a healthy donor were studied in detail. These CD4+ T cell lines with an alpha/beta T cell receptor proliferated in response to native and denatured human and chicken type II collagen and human type I collagen, but not to human type IV collagen or other potentially arthritogenic antigens. The T cell response showed typical dose response characteristics, peaked between 30 and 48 h, was major histocompatibility complex class II restricted and not due to a mitogenic effect. Type II collagen-reactive T cells could hardly be detected in freshly isolated peripheral blood mononuclear cells from healthy donors, as revealed by limiting dilution analysis (frequency less than 1/100,000). By prestimulation in bulk cultures for 10 days, type II collagen-reactive T cells could be approximately 1000-fold enriched. However, in these limiting dilution cultures, collagen-reactive T cells could only be observed in a narrow window of cell concentrations, suggesting that type II collagen-reactive T cells may be controlled by suppressive mechanisms in healthy persons.

Adult↗