[Herniation of the middle lobe of the right lung due to a coarsely dislocated sternum fracture]. / Prolaps des rechten Lungenmittellappens über eine grob dislozierte Sternumquerfraktur.

In cases of multiple trauma in patients with an injury severity score (ISS) > or =16 chest injuries, abbreviated injury scale (AIS) > or =3, are also sustained in 57.2% of all patients. Life-threatening complications may occur with lung contusions and rib fractures also in combination with hemothorax/pneumothorax being the most common diagnoses. In addition the lungs can also be functionally impaired by ruptures of the great thoracic vessels or in isolated cases by herniation of lung tissue following tears in the wall of the thorax. A case of multiple trauma in a 44-year-old male (ISS 29) with blunt thoracic trauma resulting in herniation of the middle lobe of the right lung into the subcutaneous tissue due to a coarsely dislocated fracture of the sternum is reported. This still ventilated lung tissue was surgically resituated 4 weeks after the event and the sternum fracture was simultaneously stabilized by plate osteosynthesis. Clinical examination and awareness of the possibility of other injuries (high level of suspicion) are essential. Therefore, standard diagnostic procedures combined with multislice computed tomography during the first examination and reassessment should be included to avoid missed injuries.

Association of autonomic nervous hyperreflexia and systemic inflammation in patients with Crohn's disease and ulcerative colitis.

The autonomic nervous system modulates gastrointestinal motility, secretion and mucosal immunity. Its dysfunction may be of pathogenetic importance in inflammatory bowel disease (IBD). This study aimed at investigating the autonomic nervous function in patients with IBD. Forty-seven patients with IBD, 28 with Crohn's disease (CD) and 19 with ulcerative colitis (UC), were investigated by means of 5 cardiovascular and 2 pupillary standardized autonomic nervous function tests. In CD and UC, cardiovascular autonomic neuropathy was very rare (0%, 5%), whereas pupillary autonomic neuropathy was more prevalent (21%, 21%). In contrast to autonomic neuropathy, overall cardiovascular (CD: 29%, UC: 26%) and pupillary autonomic hyperreflexia (46%, 37%) were found more often. Patients with CD and UC demonstrated elevated percentiles in the respiratory sinus arrhythmia test as compared to controls (RSA: 82.3 +/- 3.9%, 80.0 +/- 5.9%, controls: 50.0% +/- 1.5%, p < 0.0001). CD patients with, as compared to patients without, RSA hyperreflexia had significantly higher CDAIs (p < 0.001), increased erythrocyte sedimentation rates (p < 0.005) and more often extraintestinal disease manifestations (p < 0.001). UC patients with, as compared to patients without, pupillary latency time hyperreflexia had lower hemoglobin (p < 0.05), lower albumin (p < 0.01) and increased erythrocyte sedimentation rates (p < 0.05). Autonomic hyperreflexia was significantly associated with more severe inflammation and systemic disease in IBD. Hyperreflexia may be a response to inflammation or a pathogenetic element that drives mucosal inflammation.

Spontaneous pneumothorax in a patient with systemic sclerosis.

A 28-year-old woman developed spontaneously a right- sided pneumothorax, the leading clinical symptom of an as yet undiagnosed systemic sclerosis. The diagnosis was confirmed by Raynaud's phenomenon, microstomia, arthralgia, distal oesophageal dysfunction and antinuclear antibodies. Initial treatment with pleural suction was followed by thoracoscopy and segmental pulmonary resection. Spontaneous pneumothorax is a rare complication in patients with systemic sclerosis, most likely caused by the rupture of subpleural cysts.

[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]. / Kardiovaskuläre und pupilläre autonome und somatosensible Neuropathie bei chronischen Erkrankungen mit Autoimmunphänomenen. Eine vergleichende Untersuchung bei Patienten mit Morbus Crohn, Colitis ulcerosa, systemischem Lupus erythematodes, progressiver Systemsklerose und Typ-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.

Anorectal function in systemic sclerosis: correlation with esophageal dysfunction?

PURPOSE: This study was designed to compare esophageal and anorectal function parameters in patients with systemic sclerosis and to define the role of anorectal manometry in the diagnosis of gastrointestinal involvement of systemic sclerosis. PATIENTS AND METHODS: Twenty-six consecutive patients (22 females) with systemic sclerosis originally referred for assessment of esophageal function were evaluated by esophageal and anorectal manometry. Anorectal function parameters were compared between patients with normal and those with disturbed esophageal function. RESULTS: A total of 17 of 26 patients (65 percent) had severe esophageal dysfunction with aperistalsis of the lower two-thirds of the esophagus, whereas 9 patients (35 percent) had normal esophageal manometry. Only three patients (11.5 percent) suffered from occasional fecal incontinence. Anorectal function parameters (resting pressure, maximum squeeze pressure, perception threshold) were not significantly different between patients with normal and those with disturbed esophageal motility. Rectoanal inhibitory reflex was excitable in nearly 90 percent of patients. CONCLUSION: In an unselected group of patients with systemic sclerosis, fecal incontinence and abnormal anorectal function are rather rare findings. Anorectal manometry cannot differentiate between patients with and without gastrointestinal involvement of systemic sclerosis.

High prolactin and low dehydroepiandrosterone sulphate serum levels in patients with severe systemic sclerosis.

The aim was to determine serum levels of prolactin (PRL) and dehydroepiandrosterone sulphate (DHEAS), and to demonstrate a link between PRL or DHEAS and soluble immune mediators in patients with systemic sclerosis (SSc) with different degrees of disease-induced organ involvement. Thirty-one patients with SSc were studied to evaluate 18 possible disease manifestations. In the serum, PRL, DHEAS and soluble immune mediators were determined by ELISA. Compared to SSc with <9 disease manifestations, patients with > or =9 disease manifestations had higher PRL (P = 0.044), higher soluble interleukin 2 receptor (sIL-2R, P = 0.004) and vascular cell adhesion molecule (sVCAM, P = 0.044), and lower DHEAS (P = 0.029). PRL (R(Rank) = 0.490, P = 0.003) and DHEAS (R(Rank) = -0.399, P = 0.013) were significantly correlated with the number of disease manifestations. The inverse correlation between PRL and DHEAS showed a trend (P = 0.059). PRL correlated with sIL-2R (R(Rank) = 0.553, P = 0.001) and sVCAM (R(Rank) = 0.520, P = 0.002). The number of disease manifestations and sIL-2R correlated significantly (R(Rank) = 0.463, P = 0.006). Psychometric variables to examine the presence of depression were not measured, but from the general aspect, the patients were not suffering from major depression which may have influenced our results. In conclusion, this study demonstrates the close association between DHEAS and, particularly, PRL and SSc severity and T-lymphocyte mechanisms.

Dehydroepiandrosterone sulfate is positively correlated with soluble interleukin 2 receptor and soluble intercellular adhesion molecule in systemic lupus erythematosus.

OBJECTIVE: To determine whether dehydroepiandrosterone sulfate (DHEAS) is linked with soluble immune mediators in systemic lupus erythematosus (SLE). METHODS: DHEAS and various soluble immune mediators were measured by ELISA in the serum of 35 patients with SLE (26 women, 9 men) and in 41 control subjects. RESULTS: DHEAS was lower in patients with SLE compared to controls (male 1.29 +/- 0.32 vs 3.04 +/- 0.33 micrograms/ml, p < 0.001; female 0.75 +/- 0.12 vs 2.16 +/- 0.18 micrograms/ml, p < 0.001). The DHEAS reduction was in part dependent on prior glucocorticosteroid treatment (p < 0.02). After adjustment for multiple comparisons, there was significant negative correlation between steroid dose and DHEAS (RRank = -0.426, p = 0.005), but with none of the soluble immune mediators. No significant difference in the percentage of steroid treated male and female patients was found (p = 0.220). However, there was positive correlation between DHEAS and soluble interleukin 2 receptor in women, but not in men, with SLE [RRank = 0.747 (n = 26, p < 0.0001) vs RRank = -0.1333( n = 9, p = 0.366)] and between DHEAS and soluble intercellular adhesion molecule in women, but not in men, with SLE [RRank = 0.509 (n = 26, p = 0.005) vs RRank = 0.4833 (n = 9, p = 0.094)]. CONCLUSION: These data demonstrate positive interrelation between DHEAS and soluble immune mediators involved in leukocyte function and leukocyte adhesion only in female patients with SLE.

Relapsing polychondritis: clinical and immunogenetic analysis of 62 patients.

OBJECTIVE: In this study we describe clinical and immunogenetic findings in 62 unselected patients with relapsing polychondritis. METHODS: In a multicenter study, clinical data of 26 (41.9%) female and 36 (58.1%) male patients were collected. HLA-DR specificities were identified in 60, and the frequencies were compared with those in healthy controls. RESULTS: The median age at the time of diagnosis was 46.6 years (range 17 to 86). 58 (93.5%) patients had auricular chondritis, 31 (50.0%) ocular symptoms, 35 (56.5%) nasal involvement. Involvement of joints (53.2%), respiratory system (30.6%), skin (24.2%), cardiovascular system (22.6%), central nervous system (9.7%), and kidneys (6.5%) was found as well. 22 (35.5%) patients had associated diseases such as systemic lupus erythematosus or rheumatoid arthritis. Susceptibility to relapsing polychondritis was significantly associated with HLA-DR4 (p < 0.001). There was no difference in the frequency or distribution of DRB1*04 subtype alleles between patients and healthy controls. The extent of organ involvement was negatively associated with HLA-DR6 (p < 0.011). CONCLUSION: Immunogenetic findings as well as similarities and overlapping clinical symptoms with other autoimmune or rheumatic diseases suggest that immunological mechanisms play a major role in the pathogenesis of relapsing polychondritis.

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.

Gallbladder motility in systemic sclerosis.

In 20 patients with systemic sclerosis (SSc) and 24 healthy controls, gallbladder motility was evaluated by abdominal ultrasonography after stimulation by a standard liquid meal. Results from patients with normal and disturbed oesophageal function were analysed separately in order to investigate the significance of gallbladder motility as a parameter for gastrointestinal involvement in SSc. All patients showed a marked decrease in gallbladder size after stimulation (patients 61 +/- 13%; controls 48 +/- 12%). Patients with oesophageal dysfunction (n = 12) had a slightly lower gallbladder contraction (maximal decrease = 58 +/- 13%) when compared to patients with normal oesophageal function (n = 8; 66 +/- 13%); however, this difference was not statistically significant. Gallbladder motility in patients with SSc was not reduced when compared with healthy controls. SSc-induced oesophageal dysfunction was not associated with impaired gallbladder motility. Thus, measurement of gallbladder emptying is not a helpful tool when looking for gastrointestinal involvement in SSc.

Stimulation of the immune response in outpatients with hepatocellular carcinomas by low doses of cyclophosphamide (LDCY), echinacea purpurea extracts (Echinacin) and thymostimulin.

Outpatients with inoperable far advanced hepato-cellular carcinomas (n = 5) were treated with LDCY--300 mg/m2 i.v. every 28 days-, echinacin--60 mg/m2 i.m.--and thymostimulin--30 mg/m2 i.m., day 3-10 after LDCY, then twice a week. Therapy was well tolerated by all patients. Their Karnofsky' index increased for 10% in the mean. A stable disease for more than 8 weeks was documented by abdominal ultrasonography in one patient. Serum levels of Alpha-Fetoprotein (AFP), Carcinoembryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA) did not increase in 2 patients. Median survival time was 2.5 months. One patient is still alive after 8 months. Absolute numbers of CD8+ cells significantly (p less than 0.02) decreased for 7% 1 day after LDCY, whereas CD4+ cells increased (p less than 0.02) from day 1-7. Numbers of natural killer (NK-) cells increased for 17% (p less than 0.05), their activity for 90% (p less than 0.05). Activities of peripheral polymorphs (p less than 0.05) increased for 27% and of Lymphokine Activated Killer (LAK-) cells for 180% (p less than 0.05).

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.

Nonspecific immunostimulation with low doses of cyclophosphamide (LDCY), thymostimulin, and Echinacea purpurea extracts (echinacin) in patients with far advanced colorectal cancers: preliminary results.

Outpatients (n = 15) with metastasizing far advanced colorectal cancers received immunotherapy consisting of low-dose cyclophosphamide (LDCY) 300 mg/m2 every 28 days i.v., thymostimulin 30 mg/m2, days 3-10 after low-dose cyclophosphamide i.m. once daily, then twice a week, and echinacin 60 mg/m2 together with thymostimulin i.m. All patients had had previous surgery and/or chemotherapy and had progressive disease upon entering the study. Two months after onset of therapy a partial tumor regression was documented in one and a stable disease in 6 other patients by abdominal ultrasonography, decrease of the tumor markers carcinoembryonic antigen (CEA), CA 19-9, CA 15-3, and/or chest roentgenography, which may also be attributed to the natural course of disease. Mean survival time was 4 months, 2 patients survived for more than 8 months. Immunotherapy was well tolerated by all patients without side effects.

Esophageal manometry in systemic sclerosis: screening procedure or confined to symptomatic patients?

The predictive value of esophagus-related symptoms for the diagnosis of esophageal dysmotility induced by systemic sclerosis (SSc) was prospectively evaluated in 50 consecutive patients with SSc. Patients were classified as symptomatic when either dysphagia or repeated episodes of heartburn were present. All patients underwent esophageal manometry; SSc-induced esophageal dysfunction was diagnosed when there was aperistalsis or marked hypocontractility of the distal two-thirds of the esophageal body. Twenty-nine patients (58%) had a history of esophagus-related symptoms, while 21 patients (42%) were asymptomatic. Compared to esophageal manometry, esophagus-related symptoms had a sensitivity of 64%, a specificity of 52%, a negative predictive value of 50% and a positive predictive value of 62% for the diagnosis of SSc-induced esophageal dysfunction. In conclusion, the association of esophagus-related symptoms and esophageal motility pattern is poor. As clinical management strategies depend on proof of esophageal dysfunction, screening examinations are mandatory in all patients with SSc.

Autonomic and sensorimotor neuropathy in patients with systemic lupus erythematosus and systemic sclerosis.

OBJECTIVE: To determine and compare the prevalence and degree of autonomic (ANP) and sensorimotor neuropathy (SNP) in patients with systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). METHODS: Thirty-one patients with SLE and 19 with SSc were investigated. Pupillary ANP was assessed by pupillometry, cardiovascular ANP using a standardized test battery, and SNP by a standardized clinical examination. RESULTS: In patients with SLE (SSc), 26% (10.5%) had a pathological pupillary latency time and 6.5% (13.7%) had an abnormal maximal pupillary area (p for the difference between latency time and maximal pupillary area in SLE = 0.040). Thus, patients with SLE had more often lesions of the pupillary parasympathetic portion of the autonomic nervous system. Overall prevalence of ANP was not different between the 2 groups; 29.0% in SLE and 21.1% in SSc for pupillary ANP and 9.7 and 15.7% for cardiovascular ANP, respectively. Overall prevalence of SNP was 6.5% in SLE and 21.1% in SSc. Disease activity was correlated with ANP (p = 0.008) and SNP (p = 0.020) in SLE. Kidney involvement was associated with more severe ANP in patients with SSc (p = 0.031). Duration of the disease did not correlate with any type of neuropathy. CONCLUSION: ANP and SNP are often present in SLE and SSc. SLE and SSc differ in the pattern of ANP and SNP, which indicates that different structures and neuropathogenic mechanisms may be involved. Patients with SLE had severe pupillary ANP, probably a sign of central nervous system involvement.

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.

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.