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Biomedical subjects

R H Straub

Publications and source records attributed to R H Straub.

At least 19 recordsLinked to original sources
PubMed1999

In vitro superfusion method to study nerve-immune cell interactions in human synovial membrane in long-standing rheumatoid arthritis or osteoarthritis.

Reports on patients with hemiparalysis indicate the importance of the nervous system for the pathophysiology of rheumatoid arthritis (RA) or osteoarthritis (OA). Norepinephrine (NE) and opioids seem to be more antiinflammatory neurotransmitters whereas substance P is proinflammatory. The study aimed to investigate the direct noradrenergic nerve-immune cell interaction in human synovial membrane. We used a recently developed superfusion technique with electrical stimulation of synovial membrane to elicit local NE from synovial membrane slices. The readout parameter of synovial immune cells was interleukin-6 (IL-6). IL-6 was spontaneously secreted from RA and OA synovial membranes. Electrical field stimulation intensively reduced IL-6 secretion. In patients with OA or RA, this electrically induced reduction of IL-6 secretion was not significantly changed by alpha- or beta-adrenergic antagonists. The study demonstrates that local endogenous NE seem to play a minor role, which may be due to a depletion of NE or loss of noradrenergic fibers during chronic RA and OA.

Aged↗
PubMed1999

[A 63-year-old patient with worsening general condition, bone demineralization, hypocalcemia and excess parathyroid hormone: late manifestations of pseudohypohyperparathyroidism].

HISTORY AND CLINICAL FINDINGS: A 63-year-old man was hospitalized because of his worsening general condition and weight loss. Physical examination revealed marked thoracic kyphosis with impaired mobility of his back and restricted walking because of pain in the right hip. He also had other bone pains. INVESTIGATIONS: Serum calcium was reduced (1.60 mmol/l) and there was generalized bone demineralization. Subsequently an increased parathormone (PTH) level was noted (499.0 ng/l) as well as markedly increased activity of enzymes involved in bone metabolism, decreased renal excretion of phosphates (4.76 mmol/24 h) and multiple pathological fractures. TREATMENT AND COURSE: The listed abnormalities indicated the diagnosis of pseudohypoparathyroidism (PHP), type 1 b. After treatment had been started with vitamin D (calcitriol 2 x 0.25 micrograms/d) and calcium (calcium gluconate, 3 x 500 mg/d), the levels of calcium, PTH and enzymes in bone metabolism gradually became normal. A cataract operation had to be performed because of calcification of the lens. CONCLUSION: The level of PTH should be determined in patients with extensive bone demineralization and hypocalcaemia. If PTH is raised, PHP should be included in the differential diagnosis. Normalization of serum calcium by calcium substitution and vitamin D administration will normalize PTH and improve mineralization of the skeleton. In this way the debilitating effects of osteodystrophia cystica generalisata (OCG) (Engel von Recklinghausen syndrome) can be prevented. Also, the consequences of extraosseous calcification, such as extrapyramidal symptoms of calcification of the brain-stem ganglia can be avoided if treated in time.

Bone Demineralization, Pathologic↗
PubMed1999

Relation between dehydroepiandrosterone sulfate and blood pressure levels in a population-based sample.

Endogenous dehydroepiandrosterone sulfate (DHEAS) levels have been reported to be positively related to blood pressure levels. To further analyze this association, we quantified DHEAS in middle-aged subjects (mean age +/-SEM: 57.8+/-0.1 years) of a population-based sample (n = 646). DHEAS levels were higher in hypertensive as compared with normotensive individuals (1.26+/-0.04 v. 1.09+/-0.03 microg/mL, P = .01). After adjustment for age, gender, and body mass index, DHEAS levels were significantly related to systolic blood pressure (P = .01). In addition, in a subgroup of individuals without antihypertensive medication adjusted DHEAS levels were significantly related to systolic and diastolic blood pressure (n = 461; P<.05, both). DHEAS levels were also related to aldosterone (r = 0.15; P = .002) and androstenedione (its main metabolite; r = 0.66; P<.001) but not to renin levels. Like DHEAS, aldosterone, but not androstenedione, was significantly related to blood pressure levels and hypertension status. In a regression analysis that accounted for aldosterone and renin levels, both DHEAS and aldosterone kept their significant relationships with systolic blood pressure levels. Taken together, we observed a consistent positive association between endogenous DHEAS and systolic blood pressure levels that was independent of other, similarly regulated, adrenal steroids.

Aged↗
PubMed1999

Favorable role of interleukin 10 in patients with polymyalgia rheumatica.

OBJECTIVE: To determine the relationship between the antiinflammatory molecule interleukin 10 (IL-10) and disease symptoms, IL-1beta, tumor necrosis factor (TNF), and IL-1 receptor antagonist (IL-1ra) in patients with polymyalgia rheumatica (PMR). METHODS: In 102 patients with PMR, we determined the severity of the disease by the presence of typical clinical symptoms (symptom score with a maximum of 10 points). IL-10, IL-1beta, TNF, and IL-1ra were measured in all patients and 31 age matched healthy controls by enzyme immunometric assays. RESULTS: Compared to patients with elevated serum levels, patients with normal serum levels of IL-10 (below the mean + 3 SD of controls, 7.79 pg/ml) more often had adynamia (p = 0.045), bilateral muscular pain in shoulders, upper arms or neck (p = 0.045), bilateral muscular pain in the pelvic girdle (p < 0.001), headache (p = 0.014), morning stiffness (p < 0.001), symptoms of depression (p = 0.013), and initial weight loss (p = 0.011), and had a higher symptom score (5.5+/-0.4 vs 3.7+/-0.3; p < 0.001). The overall symptom score correlated negatively with IL-10 serum levels (Rrank = -0.421, p < 0.001). IL-10 correlated negatively with IL-1beta (p = 0.013) and TNF-alpha (p = 0.039). The association between elevated serum levels of IL-10 and low serum levels of IL-1beta and TNF was observed only in patients with corticosteroid treatment. In these patients, elevated serum levels of IL-10 were positively associated with an increased ratio of IL-1ra to IL-1beta. CONCLUSION: Elevated serum levels of IL-10 were associated with a more mild form of PMR. This study indicates a favorable role of IL-10 in patients with PMR.

Aged↗
PubMed1998

Centrally applied NPY mimics immunoactivation induced by non-analgesic doses of met-enkephalin.

Neuropeptide Y (NPY) and endogenous opioids (EOPs) such as methionine-enkephalin (Met-enk) regulate similar physiological responses, but it is not known whether nociceptive and immune responses also show analogy after intracerebroventricular (i.c.v.) application. Dose-response studies show that Met-enk stimulates the blood granulocyte and splenic natural killer (NK) cell function of Lewis rats at a low dose (10(2) ng/kg, i.c.v.), whereas a high dose (10(5) ng/kg) causes suppression of innate immune functions associated with analgesia in the hot-plate test. At 15 min, 1 h and 24 h after i.c.v. application, both Met-enk (10(2) ng/kg) and NPY (1 ng/kg) produced similar effects: An initial suppression of innate immune function was followed by a long lasting stimulatory action on cell functions and serum interleukin-6 (sIL-6) levels. Thus, central NPY application resembles Met-enk-induced immunostimulation at doses not affecting nociception, suggesting an involvement of both peptides in shaping stress-induced immunomodulation of the non-analgetic form, possibly via activation of a common immunomodulatory effector mechanism.

Adjuvants, Immunologic↗
PubMed1998

Regeneration of implanted splenic tissue in the rat: re-innervation is host age-dependent and necessary for tissue development.

The loss of spleen may lead to fatal bacterial infections. To prevent this, splenic autotransplantation has been performed in humans and experimental animals. However, there is still controversy about the protective function of this procedure. Since innervation plays an important role in splenic function, we investigated whether splenic regenerates are re-innervated, and whether this depends on the donor and host age. Splenic tissue (30 mg) was implanted into the greater omentum of either young (2 days) or old (12 months) rats, from either young or old syngeneic animals. After 3 months of regeneration, the weight of the regenerates was determined, PGP+ nerve fibers were revealed by immunohistology, and subdivided into nerve fibers of sympathetic (TH+, NPY+) or sensory (SP+, CGRP+) origin. In addition, proliferating (Ki-67 proliferation antigen+) and apoptotic cells (TUNEL technique+) were likewise investigated. No innervation of splenic regenerates was observed after implantation into old hosts, correlating with poorly developed splenic compartments. In contrast, almost normal re-innervation occurred in young hosts after implantation of both young and old splenic tissue. These regenerates showed well-developed splenic compartments and a normal number and tissue distribution of proliferating and apoptotic cells. However, after the implantation of young tissue, the final size of splenic regenerates was three times larger (140 +/- 30 vs. 40 +/- 10 mg). Thus, re-innervation of splenic implants is necessary for their subsequent development. It is determined by host age, whereas the final size of the splenic regenerates is regulated by donor age-dependent factors. This model is useful for studying both the process leading to initial innervation and the consequences of this innervation.

Aging↗
PubMed1998

Association of pupillary parasympathetic hyperreflexia and systemic inflammation in patients with systemic lupus erythematosus.

In chronic inflammatory diseases, cytokines stimulate the hypothalamus pituitary adrenal axis and the hypothalamus autonomic nervous system (HANS) axis. The present study was performed to find autonomic nervous function parameters in patients with systemic lupus erythematosus (SLE) which are suitable to demonstrate the activation of the HANS axis during systemic inflammation. Thirty-four patients with SLE (age 35.3 +/- 1.9 yr) were investigated by seven standardized autonomic nervous function tests. The SLEDAI and laboratory parameters of systemic inflammation were assessed by standard techniques. Pupillary latency time hyperreflexia was found in 29.4%, whereas maximal pupillary area was hyperresponsive in only 2.9%. A total of 12% had overall cardiovascular autonomic nervous hyperreflexia. Patients with latency time hyperreflexia had more severe systemic inflammation [erythrocyte sedimentation rate (ESR): P < 0.001; C-reactive protein (CRP): P = 0.0094; fibrinogen: P < 0.001; albumin: P = 0.003; antinuclear antibodies: P = 0.020]. The longitudinal study of 13 patients during 4 yr demonstrated a parallel increase and decrease in latency time percentile and ESR. SLE patients with increased systemic inflammation had an activated HANS axis which can be measured by a parasympathetic pupillary reflex test.

Adult↗
PubMed1998

Air oesophagogram: a frequent, but not a specific sign of oesophageal involvement in connective tissue diseases.

OBJECTIVE: This study investigates the role of the air oesophagogram in conventional chest X-rays for the diagnosis of oesophageal dysmotility in patients with connective tissue diseases. METHODS: Fifty-one patients with connective tissue diseases were studied by oesophageal manometry and lateral and posterior-anterior chest X-rays. The presence or absence of oesophageal air on chest X-rays were evaluated separately in the upper, middle and distal segment of the oesophagus. Forty-seven chest X-rays of patients without connective tissue diseases, who had undergone manometry for the evaluation of oesophagus-related symptoms and who had normal oesophageal function, were analysed as a control. RESULTS: A total of 23/51 patients with connective tissue diseases showed oesophageal dysfunction in manometry; 16/51 patients (31%) had air in two or more oesophageal segments on the lateral chest X-ray. There was a significant association of manometrically proven oesophageal dysmotility and air in two or three oesophageal segments (P < 0.05; sensitivity 48%, specificity 82%). However, the prevalence of an air oesophagogram showed no significant difference between patients with connective tissue diseases and the control group (10/47; 21%). CONCLUSION: The radiological sign of an air oesophagogram is neither sensitive nor specific enough to omit oesophageal motility studies in patients with connective tissue diseases.

Air↗
PubMed1998

Association of esophageal dysfunction and pulmonary function impairment in systemic sclerosis.

OBJECTIVE: The aim of this study was to investigate the relationship between esophageal dysfunction and pulmonary involvement in patients with systemic sclerosis (SSc). METHODS: Pulmonary function parameters were compared between groups of patients with and without manometric evidence for SSc-induced esophageal dysmotility. RESULTS: Twenty-six of 43 patients (60.5%) exhibited a marked hypo- or aperistalsis of the smooth muscle portion of the esophagus. Total lung capacity, inspiratory vital capacity, and forced vital capacity were significantly lower in patients with esophageal dysfunction compared with those with normal esophageal peristalsis (p < 0.001). Patients with the diffuse form of SSc (n = 20) had significantly lower values for total lung capacity and inspiratory vital capacity compared with patients with the limited type of SSc (n = 23; p < 0.05). CONCLUSION: There is a significant association of esophageal dysmotility with reduced lung volumes in SSc. Possible explanations for these findings are pulmonary damage due to increased gastroesophageal reflux and, more likely, simultaneous involvement of the lungs and the esophagus in the disease process.

Esophageal Motility Disorders↗
PubMed1998

Association of humoral markers of inflammation and dehydroepiandrosterone sulfate or cortisol serum levels in patients with chronic inflammatory bowel disease.

OBJECTIVES: Dehydroepiandrosterone sulfate (DHEAS) and cortisol are multifunctional adrenal hormones with immunomodulating properties. DHEAS levels were found to be very low in chronic inflammatory diseases. This study aimed to shed more light on the interrelation between DHEAS and cortisol (and humoral markers of inflammation) in chronic inflammatory bowel disease. METHODS: DHEAS and cortisol serum levels were measured by ELISA in the serum of 66 normal subjects, 115 patients with Crohn's disease (CD) and 64 patients with ulcerative colitis (UC). Humoral markers of inflammation and disease activity scores were assessed by standard techniques. RESULTS: DHEAS was lower in patients with CD (p < 0.005) and UC (p < 0.005) than in controls, which was, in part, dependent on previous corticosteroid treatment (p < 0.01). In CD patients, z-normalized DHEAS was inversely correlated with blood sedimentation rate (p = 0.017). Z-normalized DHEAS was negatively correlated with interleukin-6 (IL-6) in the form of a trend (p = 0.068), and z-normalized DHEAS was significantly positively correlated with hemoglobin (p = 0.001) but not with the Crohn's disease activity index. Cortisol, however, was positively correlated with blood sedimentation rate (p = 0.034) and C-reactive protein (p = 0.006). In contrast, in UC patients no such correlation of z-normalized DHEAS or cortisol and parameters of humoral inflammatory activity or Rachmilewitz index exist. CONCLUSIONS: DHEAS as a marker of inflammation was low in CD and UC. In CD patients, low DHEAS and high cortisol serum levels were associated with higher humoral inflammatory activity. With respect to humoral inflammatory activity in CD patients, DHEAS and cortisol seem to be inversely regulated, which may have an impact on several immune functions, such as IL-6 secretion.

Adolescent↗
PubMed1998

Tonic neurogenic inhibition of interleukin-6 secretion from murine spleen caused by opioidergic transmission.

The peripheral nervous system and the immune system were shown to have neurohumoral interactions. This study extends observations that demonstrated neuronal modulation of spontaneous interleukin-6 (IL-6) secretion in the spleen by norepinephrine (NE) and beta-endorphin. Spontaneous IL-6 secretion in vivo was markedly reduced by removal of macrophages with the clodronate technique. Furthermore, spontaneous IL-6 secretion was significantly inhibited at physiological concentrations of cortisol (10(-7) M). In the presence of 10(-7) M cortisol, addition of norepinephrine (NE; 10(-5) M) and isoproterenol (10(-6) and 10(-5) M) significantly increased spontaneous IL-6 secretion (+20%; P = 0.0280, P = 0.0005, and P = 0.0050, respectively). In contrast, addition of beta-endorphin significantly inhibited spontaneous IL-6 secretion in the presence of 10(-7) M cortisol (-40%; 10(-11) M, P = 0.0410; 10(-10) M, P = 0.0005). To study the effect of endogenously released transmitters on spontaneous IL-6 secretion, spleen slices were electrically stimulated with 1, 5, 10, 50, and 100 Hz. Spontaneous IL-6 secretion was markedly reduced at a frequency of 10 Hz with 10(-7) M cortisol present (P < 0.0001). This indicates that the combination of nerve firing at 5-10 Hz and physiological cortisol conditions inhibits spontaneous IL-6 secretion. Inhibition of spontaneous IL-6 secretion from spleen macrophages is most probably due to a net inhibitory effect of opioidergic transmission under these conditions.

Animals↗
PubMed1998

Anti-phospholipid-antibodies in patients with relapsing polychondritis.

Relapsing polychondritis (RP) is an extremely rare multisystemic disease thought to be of autoimmune origin. In order to assess if RP is associated with anti-phospholipid antibodies (aPL), clinical data and sera of 21 patients with RP were collected in a multicentre study. Concentration of anti-cardiolipin antibodies (aCL) (IgG-, IgM- and IgA-isotypes), anti-phosphatidylserine-antibodies (aPS) (IgG- and IgM-isotypes) and anti-beta-2-glycoprotein I-antibodies (a beta 2 GPI) were measured by ELISA. In eight patients aCL were found to be elevated. One patient had elevated aPS. No patient had elevated a beta 2 GPI. No patient had clinical signs and symptoms of a aPL syndrome. Interestingly, the two RP patients with the highest aPL had concomitant systemic lupus erythematosus (SLE). Therefore the presence of elevated aPL in RP is probably more closely related to an associated SLE than to RP itself. There is no convincing evidence that aPL are associated with RP.

Adolescent↗
PubMed1998

Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence.

Interleukin-6 (IL-6) is one of the pathogenetic elements in inflammatory and age-related diseases such as rheumatoid arthritis, osteoporosis, atherosclerosis, and late-onset B cell neoplasia. In these diseases or during aging, the decrease in production of sex hormones such as dehydroepiandrosterone (DHEA) is thought to play an important role in IL-6-mediated pathogenetic effects in mice. In humans, we investigated the correlation of serum levels of DHEA, DHEA sulfate (DHEAS), or androstenedione (ASD) and IL-6, tumor necrosis factor-alpha, or IL-2 with age in 120 female and male healthy subjects (15-75 yr of age). Serum DHEA, DHEAS, and ASD levels significantly decreased with age (all P < 0.001), whereas serum IL-6 levels significantly increased with age (P < 0.001). DHEA/DHEAS and IL-6 (but not tumor necrosis factor-alpha or IL-2) were inversely correlated (all patients: r = -0.242/-0.312; P = 0.010/0.001). In female and male subjects, DHEA and ASD concentration dependently inhibited IL-6 production from peripheral blood mononuclear cells (P = 0.001). The concentration-response curve for DHEA was U shaped (maximal effective concentration, 1-5 x 10(-8) mol/L), which may be the optimal range for immunomodulation. In summary, the data indicate a functional link between DHEA or ASD and IL-6. It is concluded that the increase in IL-6 production during the process of aging might be due to diminished DHEA and ASD secretion. Immunosenescence may be directly related to endocrinosenescence, which, in turn, may be a significant cofactor for the manifestation of inflammatory and age-related diseases.

Adolescent↗
PubMed1998

Association of autonomic nervous dysfunction and esophageal dysmotility in systemic sclerosis.

OBJECTIVE: The primary event in the pathogenesis of gastrointestinal involvement in systemic sclerosis (SSc) has been hypothesized to be an early neural lesion. We investigated the association of autonomic nervous dysfunction and esophageal involvement in SSc. METHODS: Thirty-six consecutive patients with SSc were investigated by esophageal manometry and autonomic nervous function tests for cardiovascular and pupillary autonomic dysfunction. RESULTS: In 27 of 36 patients, esophageal manometry showed esophageal dysfunction. Twelve patients had either pupillary (n = 6) or cardiovascular (n = 5) dysfunction or both (n = 1). All patients with autonomic dysfunction had esophageal dysfunction. Patients with autonomic dysfunction had significantly reduced mean distal esophageal contraction amplitudes compared to patients without autonomic nervous dysfunction (p < 0.05). The association of autonomic dysfunction and esophageal dysfunction was significant (p = 0.02). CONCLUSION: Our results support the concept of a role for neurogenic defects in the development of esophageal dysfunction in SSc.

Adolescent↗
PubMed1997

[Cardiovascular and pupillary autonomic and somatosensory neuropathy in chronic diseases with autoimmune phenomena. A comparative study of patients with Crohn disease, ulcerative colitis, systemic lupus erythematosus, progressive systemic sclerosis and type I diabetes mellitus].

BACKGROUND: During the last years, examination of autonomic nervous function and of autonomic neuropathy has attracted attention not only in diabetes mellitus research but also in other areas of internal medicine. However, patients with various chronic diseases with autoimmune phenomenons have never been investigated in a comparative study with standardized examination techniques. Hence, the aim of the study was to examine the prevalence and the severity of autonomic neuropathy in patients with the following chronic diseases. PATIENTS AND METHODS: We investigated 28 patients with Crohn's disease (CD: age: 32.4 +/- 2.0 y), 17 patients with ulcerative colitis (UC: 39.7 +/- 3.6 y), 39 patients with systemic lupus erythematosus (SLE: 34.9 +/- 2.0 y), 38 patients with progressive systemic sclerosis (pSS; 51.5 +/- 2.4 y) and 65 patients with insulin-dependent diabetes mellitus (IDDM: 35.5 +/- 1.6 y). Cardiovascular autonomic (cANP), pupillary autonomic (pANP), and sensorimotor (ssNP) neuropathy were assessed by standardized techniques. RESULTS: Prevalence rates for cANP, pANP and ssNP were found to be 0%, 19%, and 7% in CD, 6%, 25%, and 18% in UC, 5%, 29%, and 10% in SLE, 11%, 16%, and 32% in pSS, and 26%, 66%, and 29% in IDDM, respectively. CONCLUSION: The study demonstrated patients with IDDM to have the highest prevalence rates of cANP and pANP. Patients with other chronic diseases, particularly SLE, pSS and UC, had high prevalence rates of pANP. This may be due to alterations of structures of the central nervous system in these patients. cANP was rare in patients with inflammatory bowel disease and ssNP was found very often in patients with pSS, probably due to local fibrotic lesions. The various disease groups differ in the pattern and severity of autonomic and sensorimotor neuropathy, which indicates that different structures and neuropathogenic mechanisms may be involved.

Adult↗