Sorafenib paradoxically activates the RAS/RAF/ERK pathway in polyclonal human NK cells during expansion and thereby enhances effector functions in a dose- and time-dependent manner.

Natural killer (NK) cells play a major role in host immunity against leukaemia and lymphoma. However, clinical trials applying NK cells have not been as efficient as hoped for. Patients treated with rapidly accelerated fibrosarcoma (RAF) inhibitors exhibit increased tumour infiltration by immune cells, suggesting that a combination of RAF inhibitors with immunotherapy might be beneficial. As mitogen-activated protein kinases (MAPKs) such as raf-1 proto-oncogene, serine/threonine kinase (CRAF) regulate NK cell functions, we performed an in-vitro investigation on the potential of clinically relevant short-acting tyrosine kinase inhibitors (TKIs) as potential adjuvants for NK cell therapy: NK cells from healthy human blood donors were thus treated with sorafenib, sunitinib or the pan-RAF inhibitor ZM336372 during ex-vivo expansion. Functional outcomes assessed after washout of the drugs included cytokine production, degranulation, cytotoxicity, apoptosis induction and signal transduction with/without target cell contact. Paradoxically, sorafenib enhanced NK cell effector functions in a time- and dose-dependent manner by raising the steady-state activation level. Of note, this did not lead to NK cell exhaustion, but enhanced activity against target cells such as K562 or Daudis mediated via the RAS/RAF/extracellular-regulated kinase (ERK) pathway, but not via protein kinase B (AKT). Our data will pave the path to develop a rationale for the considered use of RAF inhibitors such as sorafenib for pre-activation in NK cell-based adoptive immune therapy.

Clinical tests and magnetic resonance imaging have limited diagnostic value for triangular fibrocartilaginous complex lesions.

INTRODUCTION: The diagnostic value of clinical tests and magnetic resonance (MR) imaging for the investigation of triangular fibrocartilaginous complex (TFCC) lesions is not clear due to a lack of clinical data. MATERIALS AND METHODS: We retrospectively analyzed 908 patients who underwent clinical tests and arthroscopy for suspected TFCC lesions at our institution. Further, MR imaging findings concerning the TFCC were gathered. We correlated clinical tests and MR imaging findings with those obtained during arthroscopy, and we calculated sensitivity, specificity, as well as positive and negative predictive values. RESULTS: In the whole cohort, the positive predictive values of all clinical tests were low, ranging from 0.53 to 0.55. The ulna grinding test had the highest sensitivity, but lowest specificity. Sensitivity and specificity of the ulnar fovea sign and magnetic resonance imaging were similar, ranging from 0.73 to 0.76, and from 0.41 to 0.44, respectively. To some degree, the diagnostic value seemed to depend on the Palmer class of TFCC lesion. CONCLUSIONS: According to this study, clinical tests and MR imaging findings are of very limited diagnostic value for the diagnosis of TFCC lesions.

[Mechanisms of action and clinical application of diuretics in intensive care medicine]. / Wirkmechanismen und klinische Anwendung von Diuretika in der Intensivmedizin.

The paired kidneys play a significant role in the human body due to the multitude of physiological tasks. Complex biochemical processes keep the sensitive electrolyte and water balance stable and thus ensure the organism's ability to adapt to exogenous and endogenous factors, which is essential for survival. The drug class of diuretics includes substances with very differing pharmacological characteristics. The functioning of the nephron is therefore indispensable for a deeper understanding of the pharmacodynamics, pharmacokinetics and side effect profile of diuretics. In the treatment of acute heart failure with pulmonary congestion, certain diuretics represent an important therapeutic option to counteract hypervolemia and thus an increase in preload. According to current data, diuretics have no proven benefits in the treatment or prevention of acute kidney injury but they can counteract hypervolemia and under certain conditions even reduce the use of renal replacement procedures.

Influence of urogenital infections and inflammation on semen quality and male fertility.

BACKGROUND: Urogenital infections and inflammation are a significant etiologic factor in male infertility. METHODS: Data for this review were acquired by a systematic search of the medical literature. Relevant cross-references were also taken into account. RESULTS: We address infectious and inflammatory diseases of different compartments of the male genital tract and discuss their andrological sequelae. Chronic urethritis might be responsible for silent genital tract inflammation with negative impact on semen quality. In chronic pelvic pain syndrome, morphological abnormalities of spermatozoa and seminal plasma alterations are detectable. In the majority of men with epididymitis, a transient impairment of semen quality can be found during the acute infection. However, persistent detrimental effects are not uncommon, even after complete bacteriological cure. The relevance of chronic viral infections as an etiologic factor in male infertility is believed to be underestimated. Data concerning the impact of HIV infection on male fertility are of increasing interest as with the improvement in life expectancy, issues of sexuality and procreation gain importance. Moreover, effects of noninfectious systemic inflammation on the male reproductive tract have to be considered in patients with metabolic syndrome, a disorder of growing relevance worldwide. Finally, microbiological and related diagnostic findings in urine and semen samples are reviewed according to their relevance for male infertility. CONCLUSIONS: Available data provide sufficient evidence that in men with alterations of the ejaculate, urogenital infections and inflammation have to be considered.

Antibiotic treatment and prophylaxis of periprosthetic infections: Evaluation of 666 consecutive breast implant removals.

Periprosthetic infections are feared complications in esthetic and reconstructive breast surgery. The purpose of our study is to evaluate our institution's specific culture data and to identify most common organisms and suitable antibiotics for prophylaxis and first-line treatment. We evaluated all patients with a change or removal of breast implants from 01.01.2012 to 31.12.2017 retrospectively. Based on the medical records, the surgical indications were identified and specifically analyzed for signs of infection, reasons for primary and secondary surgery, and all available microbiological data of these interventions. A total of 666 implant removals or exchanges were performed in 431 patients. Microbiological smears were gathered from 291 patients (449 implants). Bacteria were cultured from 63 implants (56 patients). In six additional patients (ten implants), a periprosthetic infection was seen, without bacteria detection. Advanced capsular contracture correlated with a higher proportion of positive swabs (p<0.05). In 11.5% of smears, bacterial contamination was found despite absence of clinical signs of infection. Coagulase-negative staphylococci were the dominant pathogen in clinical inapparent infections, while Staphylococcus aureus was when there was clinical evidence of infection. All pathogens were sensitive to vancomycin. In the majority of cases, bacterial contamination was an incidental finding, which was more common in the presence of advanced capsular contracture. In our institution, cefuroxime and amoxicillin/clavulanic acid have been proven to be reasonable choices for prevention and treatment of periprosthetic infections. In the treatment of fulminant infections and for the prophylaxis during implant replacement due to advanced capsular contracture, vancomycin became our first choice.

[Therapy standards after flexor tendon and nerve injuries of the hand: results from a survey of German centres for hand surgery]. / Therapiestandards nach Beugesehnen- und Nervenverletzungen der Hand : Ergebnisse einer Umfrage zur Immobilisationsdauer unter deutschen handchirurgischen Zentren.

BACKGROUND: There is little evidence for the ideal aftercare of combined nerve and flexor tendon injuries of the hand. The aim of this study was to elicit whether concomitant nerve injuries are changing the individual treatment plans after flexor tendon repair in a survey of German centres for hand surgery. METHODS: A questionnaire about aftercare of isolated and combined nerve and flexor tendon injuries of the hand was distributed to members of three German Societies of hand, trauma and plastic surgery. RESULTS: Isolated flexor tendon injuries in zones II to IV are treated by early mobilization in all centres, whereas isolated digital nerve repair is usually followed by immobilization (10% no immobilization, 22.5% up to 1 week, 52.5% for 2 weeks and 15% for 3 weeks). The duration of immobilization increases with lesions of the median or ulnar nerves by about 1 week. In 55% of cases concomitant nerve injury does not influence the early onset of dynamic splinting and mobilization after flexor tendon injuries. CONCLUSION: There seem to be no uniform treatment guidelines for flexor tendon repair if concomitant nerve injury is present. Against the background of the current literature early controlled mobilization after tendon and nerve repair seems to be justified.

Use of Erythropoietin as adjuvant therapy in nerve reconstruction.

BACKGROUND AND AIMS: Adjuvant therapies may improve the outcome after nerve reconstruction. We analyzed the influence of recombinant human Erythropoietin (rHuEpo), which has proven angiogenic and neuroprotective effects, on the quality of peripheral nerve regeneration. METHODS: Thirty two female Lewis rats underwent nerve reconstruction by means of tubulization (groups I and II) or autologous sciatic nerve grafting (groups III and IV). Groups I and III received daily subcutaneous rHuEpo injections over 2 weeks (1,000 U/kg bw) with normal saline injections as controls (groups II and IV). Data on histology and muscle weight were collected after 7 weeks. Axon count and diameter were assessed by a new method based on digital segmentation. RESULTS: Atrophy of the tibial muscle was less severe in the rHuEpo-treated group compared to controls resulting in significant higher muscle weight quotients (p = 0.006). The same trend was found in the gastrocnemius muscle, but without being statistically significant. No significant differences in axon count or axon diameter were detected in the presence of rHuEpo treatments. CONCLUSION: Our findings give evidence for a positive effect of Erythropoietin on functional recovery after nerve grafting. Muscle recovery benefited from rHuEpo administration despite absence of improved neural morphology. Semi-automated axon detection facilitated accurate morphometrical assessment.

Growth hormone and bone mineral densitiy in HIV-1-infected male subjects.

The aim of this study was to characterize the GH-IGF-I axis of patients with HIV-1-infection without any symptoms of AIDS-associated wasting. A special emphasis was placed on determine bone mineral density (BMD) and biochemical markers of bone metabolism. Therefore 42 male fasting HIV-1-infected outpatients were included and estimation of serum GH, IGF-I, IGFBP-1 and 3, osteocalcin, TNF-alpha, 1,25dihydroxycholecalciferol, and endocrine markers of the gonad function by commercially available RIA's performed. DEXA-measurements of the lumbar spine and the Ward's triangle of the left hip were done. The GH, IGF-1, IGFBP-1 and 3 serum levels were within the normal range Performing Spearman-correlation test, we established significance between IGF-I serum levels and BMD lumbar spine and Ward's triangle (p < 0.01, p < 0.05), CD4 cell-count (p < 0.05), 1,25dihydroxycholecalciferol (p < 0.05), osteocalcin (p < 0.05), TNF-alpha (p < 0.05), body mass index (BMI) (p < 0.05) and total testosterone (p < 0.01). IGFBP-1 correlates both inversely significantly with CD4 cell-count (p < 0.05) and serum-calcium (p < 0.05). The IGFBP-3 correlates with BMI (p < 0.05) and serum osteocalcin (p < 0.05). Correlation both with markers of bone metabolism and vitamin D metabolites showed the important role of GH/IGF-I axis in modulating the availability of calcium in chronic conditions. This axis may be in a part responsible for the manifestation of the HIV-associated osteopenia.

The "bioartificial living nerve graft".

INTRODUCTION: Nerve tubes seeded with cultured Schwann cells have become a promising alternative to nerve autografts. However, the functional results of these bioartificial cellular grafts remain to be improved. To imitate the three-dimensional structure of peripheral nerves, we designed a Schwann cell-seeded intrinsic framework within a semipermeable biodegradable collagen nerve tube (Integra). MATERIAL AND METHODS: In 90 rats a 25 mm gap was created at the sciatic nerve of the right lower limb. In group I, the gap was treated using the "bioartificial nerve graft". In group II, the tube filled with non-seeded filaments was implanted in order to evaluate the influence of the Schwann cells on regeneration. In group III, the gap was bridged using an autologous nerve graft. For evaluation clinical testing, gait analysis, electrophysiological conduction testing, tibialis anterior muscle weight recording and axon counts from the distal nerve stump were used. RESULTS: There was a significant difference between the "bioartificial nerve graft" (group I) and the non-seeded bioartificial nerve graft (group II) indicating the importance of the living Schwann cells. Comparing the results of the "bioartificial nerve graft" (group I) with the autologous nerve grafts (group III), there was a significant difference in all the examinations indicating a still slower regeneration in the artificial graft. CONCLUSIONS: We conclude that the unique three-dimensional net allowed the settlement of Schwann cells onto the biodegradable filaments, which can be used as "artificial Bünger bands". With further refinements of the "artificial Bünger bands" and Schwann cell cultures there should be improved functional and histological results in the "bioartificial nerve graft" group.

Bridging extended nerve defects with an artifcial nerve graft containing Schwann cells pre-seeded on polyglactin filaments.

A 24 mm long bioartificial nerve graft (BNG) was created to bridge extended peripheral nerve defects of the rat sciatic nerve. In our previous studies, an identical graft had demonstrated good results over nerve gaps of up to 15 mm. The BNG device comprised a collagen-I tube filled with ten Schwann-cell-seeded polyglactin filaments and 10(6) isogenic Schwann cells suspended in Matrigel which were implanted in 27 rats (group I). Schwann-cell-free grafts (27 rats) and nerve autografts (18 rats) served as controls. Functional recovery was followed over a period of six months using walking track analysis. Terminal analyses of graft efficacy included neurophysiology, muscle weight, and histological assessment of the implants and the distal nerve stumps. In 17/27 cases, axonal regeneration into the distal nerve stump could be detected across the BNG, but all animals in group I and II failed to regain motor function of the hindlimb upon completion of the experiment. Axon diameter and axonal density in the graft and distal nerve stump were greater in group I than in group II. Although Schwann cells had a significant positive effect on axonal regeneration, either granuloma formation or the amount of the inserted foreign material may have impaired nerve regeneration by acting as a physical impediment to nerve regeneration or negatively effecting cell function.

[Bridging peripheral nerve defects by means of nerve conduits]. / Uberbrückung peripherer Nervendefekte durch den Einsatz von Nervenröhrchen.

BACKGROUND: The nerve autograft is the gold standard for the reconstruction of peripheral nerve defects. In short gaps, nerve repair by means of tubulization has become an alternative. This technique is discussed based on the current literature and our own experience. PATIENTS AND METHODS: Nerve reconstruction by means of tubulization was performed in 11 patients. Nerve gaps in the hand of up to 18 mm were reconstructed. Sensibility was assessed using static and dynamic two point discrimination (s-, d2PD) and monofilament testing 3, 6 and 12 months postoperatively. RESULTS: Three out of 11 patients complained of a temporary foreign body sensation in the area of the implant; this was persistent in one case. Four out of six patients showed excellent results with s2PD of 15 mm, S0), another poor sensibility (s2PD 15 mm, S3). D2PD and monofilament testing confirmed these results. CONCLUSIONS: Nerve reconstruction by means of tubulization seems to be a suitable method for certain indications in the reconstruction of short defects of digital and palmar nerves. Donor site morbidity can be avoided. Similarly to nerve transplantation, the operation requires microsurgical skills.

[Psychological and behavioural impairment following thermal injury in childhood]. / Psychosoziale Aspekte thermischer Verletzungen im Kindes- und Jugendalter.

BACKGROUND: Thermal injuries are a major hazard in the early childhood. The aim of our study was to determine psychological behavioural disorders following burn and scald injuries in the childhood and to estimate their dependence on the formation of scar tissue and the social background of the children. PATIENTS: 83 patients aged 0 to 18 years who had been treated for thermal injuries in our clinic between September 2002 and December 2005 were included in the follow-up study. The standardised questionnaires CBCL/4-18 and TACQOL-PF were used to evaluate psychological behavioural disorders and quality of life. The follow-up examinations also served to gain information about the social status of the patient's parents and the current physical complaints. Scars were assessed by the Vancouver Scar Scale (VSS). RESULTS: 50 out of 83 patients took part in our follow-up examinations. 21 children suffered from physical complaints following thermal injury. Dryness of the skin as well as heat and cold intolerance were named most frequently. Internalising (p < 0.04) and externalising (p < 0.03) behavioural problems correlated significantly with the severity of scar formation defined by the VSS. Quality of life and social status were inferior to the comparison group. CONCLUSION: The incidence of thermal injuries is highest in the first three years of childhood. The risk for burn and scald injuries is augmented by a poor social status. In children who suffered such injuries we observed a higher rate of internalising and externalising behavioural problems which correlated with the extent of scar formation.

[Heterotopic ossifications: a severe complication following extensive burn injury]. / Heterotope Ossifikationen - eine schwerwiegende Komplikation bei ausgedehnten Brandverletzungen.

Heterotopic ossifications in periarticular tissue can appear after severe head injury, spine trauma or local joint trauma. Following extensive burns, heterotopic ossifications are a rare, severe complication with an unclear pathogenesis. We report one case with this kind of complication in a 50-year old male patient who sustained full and partial thickness burn injuries over 60 % of the body. The thermal injury was accompanied by a severe inhalation injury.

[Mesenteric ischemia: a severe complication in burn patient]. / Mesenterialinfarkt - eine schwerwiegende Komplikation bei Schwerbrandverletzten.

Gastrointestinal complications are a common problem in severe burned patients. Reported complications include paralytic ileus, gastrointestinal tract bleeding, gastric ulcers and acute necrotizing cholecystitis. Although there are no exact data concerning the frequency and outcome of acute intestinal necrotizing ischemia in severe burned patients, it is a well known complication in specialized burn centers. The most common reason for acute intestinal ischemia are arterial embolism, arterial thrombosis, venous thrombosis and non-occlusive disease. The overall survival differs between 81 % and 34 %. The therapy aims at arterial re-perfusion of life-threatening intestinal regions and resection of necrotic tissue. A 45-year-old male patient attempted suicide by inflaming himself with gasoline. He sustained partial and full thickness burn injury of the face and the throat. Additional burn injuries were found at the chest region, both arms and the abdominal wall. The total burn surface area (TBSA) was 42 % including an severe inhalation injury trauma. The ABSI-score (Abbreviated burn severity index) was 10. The combination of a thrombus at the aortic valve with an tachycardic dysrhythmia was the cause for an embolisation with acute intestinal ischemia. The necrotic part of the small intestine was resected, the further course was uncomplicated.

[Management of finger-level avulsion injuries]. / Fingeravulsionsverletzungen.

BACKGROUND: In avulsion-type injuries of the fingers recovery of blood circulation is one of the major obstacles. The indication for finger reconstruction is discussed controversely, being influenced by the patient's needs, the degree of damage to the soft tissue and the prospects of success of the healing process. In this study we present our results after reconstruction of avulsion-type injuries of the fingers. Indications for finger reconstruction will be assessed in consideration of the expected outcome. PATIENTS AND METHODS: From 1999 to 2006 we treated 18 patients with finger level avulsion injuries. 15 casualties were caused by rings and three by ropes looped around a digit. The median age at injury was 23 (12 - 66) years. All patients were examined by an independent observer, who did not participate in the operation. Criteria were functional outcome and patient's complaints and satisfaction. Sensibility was evaluated by 2-point discrimination applying the Greulich star. Finger mobility was assessed with the Buck-Gramcko goniometer. RESULTS: According to the classification of Urbaniak as modified by Kay, 2 patients ranked in class II, 3 in class III and 13 suffered from complete avulsion-amputations (class IV). Of the latter, 8 allowed primary reconstruction of the blood circulation. Two fingers required early or late secondary amputation. After finger reconstruction, patients spent a median time of 18 (12 - 32) days in hospital while primary amputation resulted in a shorter stay of 4 (2 - 5) days. Active motion after replantation in the proximal interphalangeal joint was reduced on average to 64 (25 - 100) degrees. The distal interphalangeal joint nearly ankylosed in all patients following replantation except for one case with an active motion of 40 degrees . Good sensibility could be achieved in one case, protective sensibility in three and none in two patients. All patients with preserved fingers would again decide in favour of finger replantation. CONCLUSION: In specialised centres replantation of complete avulsion-type finger amputations can be achieved. The decision for or against replantation should only be made after microsurgical assessment of the severed soft tissue and in consideration of the patient's specific demands. With the right indication for reconstruction, the patient's satisfaction often outweighs even poor functional outcomes.

Transverse soft tissue distraction preceding separation of complex syndactylies.

UNLABELLED: Various surgical techniques are described for separation of syndactylies leading to good results. However, the use of standard techniques is limited in complex syndactylies with extensive bony fusion and tight soft tissues. The aim of this study was to assess the outcomes of a two-stage procedure involving progressive soft tissue distraction prior to syndactyly release. Between 1996 and 2012 we treated 168 complex syndactylies with this technique. The main indications were syndactylies in Apert syndrome. The digits were distracted through an external fixator at 0.5 mm/day. Distraction of 15-25 mm was achieved. Soft tissue distraction provided additional skin, a wider nail matrix and more bone in the form of callus. Thus subsequent modelling of the fingertips was improved, especially if they were closely fused. This technique facilitates treatment of complex cases and improves aesthetic outcome. LEVEL OF EVIDENCE: Therapeutic IV.

Multiparameter flow cytometric analysis of inflammatory cells contained in bronchoalveolar lavage fluid.

Quantitative analysis of surface molecule expression on viable alveolar macrophages (AM) by use of flow cytometry is hampered by non-specific antibody binding to various AM FcIgG receptors as well as extensive and heterogeneous autofluorescence of this cell type. The following approaches were undertaken to circumvent these obstacles. FcIgG receptors were blocked by excess human immunoglobulin. The use of a long wave-emitting dye (phycoerythrin/cyanine-5 tandem conjugate) permitted avoidance of the peak (green) AM autofluorescence range. Moreover, a cell-by-cell compensation for the remaining red autofluorescence background was employed. This was based on two facts: (i) strict correlation between green (F488/530) and red autofluorescence (F488/660) for all AM populations investigated; and (ii) neglectable overlap of the antibody-associated red fluorescence into the 530 nm autofluorescence detection wavelength. A fraction of the green autofluorescence (F488/530; channel 1) was then subtracted from the red fluorescence (F488/660; channel 2) on a cell-by-cell basis using standard two colour fluorescence compensation circuits. The validity of this FACS technique was confirmed by comparison with immunocytochemical staining and a reverse rosetting method. On AM lavaged from carcinoma-bearing but otherwise disease-free human lungs, the pattern of surface antigen expression was assessed with a panel of monoclonal antibodies. When applying to complex mixtures of bronchoalveolar lavage cells, the autofluorescence was employed to separate AM from granulocytes and lymphocytes. In conclusion, the presently described FACS technique allows quantitative immunostaining of surface molecules on AM, even when present in low copy numbers on highly autofluorescent cells originating from smokers.

Comparison of different antisense oligonucleotides against the BCR/ABL junction in chronic myelogenous leukemia.

The activity of the BCR/ABL hybrid gene is associated with a growth advantage of the chronic myelogenous leukemia (CML) stem cell. Suppression of BCR/ABL hybrid gene expression can be a valuable tool for leukemic cell purging. Antisense oligonucleotides (ODNs) have the capacity to specifically downregulate gene expression. Data reported on the effect they have on BCR/ABL hybrid gene expression are controversial. We present data illustrating that prolongation of ODN half-life by means of chemical or sequence modification has only limited specific growth suppressive effect on BCR/ABL-positive clonogenic cells in vitro. Compared to unmodified phosphodiester ODNs (PO-ODNs) spanning the BCR/ABL junctions, modified ODNs with either a 3'-GC-clamp (GC-ODNs) or ODNs with one 3'-inverted nucleotide (3'-3' ODNs) to prevent 3'-exonuclease degradation, showed significantly prolonged extra- and intracellular half lives and different subcellular distributions in CML cell lines. In clonogenic assays from patients with CML, the modified ODNs were to some extent able to reduce colonies expressing BCR/ABL (GC-ODNs >3'-3'-ODNs >PO-ODNs). This difference did not become significant statistically. We demonstrate a substantially diminished hybridization efficacy of the modified antisense ODNs used, which may serve as a possible explanation for the failure to augment the leukemic cell purging efficacy.

Omega-oxidized leukotriene B4 detected in the broncho-alveolar lavage fluid of patients with non-cardiogenic pulmonary edema, but not in those with cardiogenic edema.

Leukotriene (LT) generation has been implicated in the pathogenesis of the acute respiratory distress syndrome, ARDS. In the present study, we analysed broncho-alveolar lavage fluids of patients on mechanical ventilation because of ARDS (17 samples taken from 9 patients) or because of cardiogenic edema (8 samples taken from 6 patients) and of healthy volunteers (10 samples from different donors). LTs were separated as methylated and non-methylated compounds using different HPLC procedures, and were identified by chromatographic mobility, on-line UV-spectrum analysis and post HPLC immunoreactivity. In the lavage samples of the healthy volunteers and the patients with cardiogenic edema, no LTs were detected by these techniques (detection limit congruent to 0.1-0.2 ng/ml lavage fluid). By contrast, in 15 out of 17 samples from patients with ARDS LTB4 or its metabolites 20-OH-LTB4 and 20-COOH-LTB4 were detected. The endproduct of omega-oxidation, 20-COOH-LTB4, represented the quantitatively predominant compound, detected in the range of 0.3-2.6 ng/ml perfusate. We conclude that the chemotactic agent LTB4 may be involved in the amplification of inflammatory events encountered in ARDS, and that the oxidized metabolites of LTB4 are particularly suitable for monitoring lung leukotriene generation under conditions of neutrophil efflux and oxidative stress.

Changes in calciotropic hormones and biochemical markers of bone metabolism in patients with human immunodeficiency virus infection.

Data on the bone metabolism of human immunodeficiency virus (HIV)-infected patients are still extremely rare. To investigate the influence of HIV infection on the calciotropic hormones and markers of bone metabolism, we therefore performed a cross-sectional study on 100 patients (65 males and 35 females) with proven HIV infection. The following criteria were used for exclusion from the study: age less than 20/more than 50 years, confinement to bed, wasting symptoms, treatment with agents containing ketoconazole, renal or hepatic insufficiency, clinical or echographic signs of liver cirrhosis, endocrine diseases, or treatment with medications known to influence bone metabolism. Bone mineral content (BMC) was determined by single-photon absorptiometry on the left forearm. Reduced BMC was found among the male and female HIV-infected patients. Additional long-term use of heroin resulted in a severe loss of mineralization in the respective females. The markers of bone metabolism were determined in urine and serum samples. Significantly lower osteocalcin concentrations were found, indicating a reduced bone formation rate whose severity showed a significant correlation with the progressive loss of CD4 helper cells and was independent of low vitamin D3 levels (1,25-dihydroxycholecalciferol) and alterations of protein metabolism. Increased urinary excretion of cross-links as an expression of enhanced bone resorption was likewise significantly correlated with the loss of CD4 helper cells and independent of the vitamin D concentration and protein metabolism. It is therefore concluded that the changes in bone metabolism are mainly due to mechanisms of the impaired immune defense of HIV-infected patients.