Background: Recombinant human growth hormone (hGH) therapy has a beneficial effect on catabolism and wound healing after major surgery. Polymorphonuclear neutrophils (PMN) play an important role in this context. In a prospective, double-blind, randomized, placebo-con trolled trial we studied the effect of perioperative hGH treatment on postoperative wound healing and oil changes in superoxide generation and susceptibility to apoptosis of PMN in elderly patients undergoing elective abdominal aortic aneurysm repair.Methods: Seven patients were treated with high-dose hGH (16 U/d) for nine days, seven patients with a placebo. IGF-1 neutrophil count, O-2-production induced by opsonized zymosan and apoptosis of PMN were measured and correlated with clinical outcome.Results: Perioperative hGH treatment more than doubled the O-2(-) production in PMN before and 24 h after surgery (p < 0.01). The long-term capacity of PMN to generate O-2 in vitro was prolonged (p < 0.001) in the hGH group. Spontaneous and Fas-inducible apoptosis was strongly down-regulated in PMN after surgery in all patients p < 0.01). hGH-treatment distinctly reduced apoptosis in PMN before and after surgery (p < 0.01). Clinical outcome was similar in both groups.Conclusion: Perioperative hGH treatment results in an enhanced O-2 production in PMN and in a prolongation of the functional life span of these cells. This may improve immune function and help to overcome the postoperative allergic state of the immune system especially in elderly individuals. (c) 2005 Elsevier Ltd. All rights reserved.

Background. Little is known about the local accumulation and function of immune cells in peritoneal fluid after elective surgery of the upper and lower gastrointestinal tract. Our study was designed to investigate whether systemic immune cell response mirrors the local response. We focused on the cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha and on monocytes, natural killer (NK) cells, and T cells that play an important role in eliciting the innate and adaptive immune response.Methods. Blood samples were taken prospectively from 25 patients 24 It before surgery, as well as 24 h and 48 h afterward. Abdominal drainage fluids were collected intraoperatively 1 h after the abdomen was opened and 24 h and 48 h postoperatively. Apart from the white blood cells, intracellular T-helper-cell (TH1/ TH2) cytokine production (interferon-gamma, IL-2, IL-4, IL-13) and HILA-DR on monocytes were measured by four-color flow cytometry, IL-6, and TNF-alpha with the fast immunoluminescence method.Results. Cells of the innate immune system (NK cells, monocytes, NK-T cells, CD5(+) B cells) rapidly decreased in abdominal fluids (P < 0.05: +24 h; +48 h) after surgery, which was paralleled by a concomitant decline in peripheral blood. The percentage of abdominal interferon-gamma, IL-2, IL-4, and IL-13-producing TH cells increased in a way that distinctly counteracted the decrease of the natural immune cells. HILA-DR expression on monocytes in peripheral blood declined significantly (P < 0.05: +24 h; +48 h). In contrast, monocytes in abdominal fluids had high HLA-DR expression. Furthermore, abdominal fluids contained significantly higher concentrations of TNF-alpha (P < 0.05: +24 h; +48 h) and IL-6 (P < 0.05: +24 h) compared with peripheral blood.Conclusions. Specific immune cell recruitment and cytokine production play an important role in post-trauma events. Measuring distinct local immune cell repertoires and cytokines provides answers as to how the different phases of postoperative immune events proceed. The evaluation of the local response may provide additional criteria for the evaluation of operative trauma. This knowledge may be helpful in detecting postoperative pathological aberrancies. (C) 2005 Elsevier Inc. All rights reserved.

OBJECTIVE:to evaluate local surgical trauma induced by endovascular (TPEG) and conventional infrarenal aortic aneurysm repair (AAA-C), the inflammatory response and changes in cell-mediated and antibody-mediated immunity as illustrated by the type-1/type-2 T-helper (TH1/TH2) cell balance were investigated.DESIGN:prospective study.PATIENTS AND METHODS:sixteen patients were included, eight patients underwent AAA-C and eight TPEG. Venous peripheral blood samples were collected 24h preoperatively and 24, 48, 72h, 5 and 7 days postoperatively. Besides the WBC, intracellular TH1/TH2 cytokines (IFN-gamma/IL-4) and the cell surface markers HLA-DR on monocytes and CD23 on B cells were measured by four colour flow cytometry.RESULTS:statistically significant higher values in the AAA-C group were demonstrated for neutrophiles. The TH1/TH2 immunobalance (expressed by forming the ratio of IFN-(gamma/IL-4 producing T cells as well as by the ratio of HLA-DR(pos) monocytes/CD23(pos) B-cells) showed a significant shift towards TH2 immunity in the AAA-C group whereas TPEG led to a significant lesser shift 24-72h after surgery (p < 0.05).CONCLUSIONS:TPEG leads to a minor distortion of the TH1/TH2 immunobalance. This implies that TPEG is a less stressing procedure, that is especially beneficial in patients whose conditions are considered less suitable for AAA-C due to age and serious comorbidity.

The aim of this study was to investigate the pituitary‘s capacity to release growth hormone (GH) in critically ill patients by stimulation with GH-releasing hormone (GHRH). Thirty-two patients with severe sepsis and 20 critically ill, nonseptic patients after major surgery were studied in the setting of a surgical intensive care unit. Nine healthy individuals without clinical signs of disturbance of the somatotropic hypothalamic-pituitary axis were included for comparison. The pituitary‘s capacity to release GH was tested with an intravenous bolus injection of 1μg per kg body weight GHRH (Ferring, Kiel, Germany). The median basal plasma GH level was comparable in all groups studied. In contrast, the median peak plasma GH level was significantly lower in critically ill, nonseptic patients after major surgery (5.1, range 1.3–131.0ng/ml, n=20) compared to healthy individuals (23.2, range 12.8–35.2 ng/ml, n=9) (p<>;0.01). However, the median peak plasma GH level in patients with severe sepsis (15.3, range 1.6–111.5ng/ml, n=32) was not significantly different compared to healthy individuals (23.2, range 12.8–35.2ng/ml, n=9) (p>>;0.05). The median plasma insulin-like growth factor-I (IGF-I) level was significantly decreased in patients with severe sepsis (32.0, range 32.0–150.0ng/ml, n=32) and in critically, ill, nonseptic patients after major surgery (50.0, range 32.0–144.0ng/ml, n=20) compared to healthy individuals (229.0, range 129.0–503.0ng/ml, n=9) (p<>;0.001). No significant difference was found between patients after major surgery and patients with severe sepsis. In conclusion, a low level of circulating IGF-I was associated with the pituitary‘s low capacity to release GH in critically ill, nonseptic patients after major surgery, whereas patients with severe sepsis had a widespread range of pituitary capacity to release GH associated with low IGF-I levels. The pathophysiological basis for not secreting stored GH during critical illness is at present unclear. The treatment with high doses of human GH has been shown to attenuate the catabolic response to injury, surgery and sepsis, whereas in patients with severe sepsis GH administration bypasses its pituitary storage and may trigger a hyperinflammatory response. However, critically ill nonseptic patients after major surgery may profit from GH treatment since they possess a low pituitary capacity to release GH. Thus, performing a GHRH test might facilitate the decision for treatment with human GH.

Criteria for the non-invasive diagnosis of lymphocytic hypophysitis (LyHy) and the results of the first prospective trial of high dose methylprednisolone pulse therapy (HDMPT) in nine patients are presented. In three patients, the diagnosis was established histologically, and in the others by clinical and endocrinological assessment, MRI, CSF examination, and measurement of thyroglobulin autoantibody concentration. After HDMPT, adenopituitary function improved in four of the nine patients and diabetes insipidus ceased or improved in all four concerned patients. The MRI findings improved in seven patients. LyHy has to be considered in the differential diagnosis of sellar lesions. The presumptive non-invasive diagnosis of LyHy seems possible in a high proportion of patients. HDMPT may result in the improvement of clinical, endocrinological, and MRI findings.

OBJECTIVE Hydrocortisone replacement regimes remain rather empirical and produce serum cortisol profiles very different from normal physiology. We have analysed the effects of different dosages of hydrocortisone (HC) replacement therapy on the health perception and general well-being of patients with secondary hypocortisolism. We also evaluated the effects of these regimens on bone metabolism.DESIGN In a prospective randomized double-blind study, 3 groups of 3 patients were treated with 3 different dosages of HC (15, 20 and 30 mg/day), in different sequences, each sequence for two weeks.PATIENTS Nine adult patients with complete secondary hypocortisolism.MEASUREMENTS Serum cortisol, ACTH, aldosterone, renin, alkaline phosphatase, bone specific alkaline phosphatase, osteocalcin, PTH, C-telopeptides of type-I collagen, sodium, potassium, phosphate; urinary free cortisol, pyridinium cross-links, urine sodium, potassium and phosphate were measured at the beginning and after each week of the study.For quality of life assessment the patients completed three different questionnaires, the Basler Befindlich-keits-Skala (BBS), the Befindlichkeits-Skala (Bf-S), the Beschwerde-Liste (BL) each week.RESULTS With increasing doses of 15, 20 and 30 mg hydrocortisone a significant increase of free urinary cortisol was achieved (298 +/- 26 nmol/day, 454 +/- 43, 819 +/- 59, respectively; P<0.01). The mean scores of the psychological questionnaires did not change significantly during the whole study (BBS 81.8 +/- 3.9; 82.8 +/- 3.9, 83.6 +/- 3.9; Bf-S 15.9 +/- 3.4, 11.3 +/- 2.6, 12.5 +/- 2.8; BL 15.7 +/- 2.3, 14.4 +/- 2.5, 14.8 +/- 2.6, respectively). Osteocalcin decreased significantly (2.3 +/- 0.49, 2.1 +/- 0.42, 1.8 +/- 0.38, P<0.01) with increasing HC doses but remained within the normal range. The other investigated parameters were within or nearly within the normal range in all patients at the beginning and did not change during the study.CONCLUSION Dosages of 15, 20 or 30 mg hydrocortisone/day have equivalent effects on quality of life in patients with secondary hypocortisolism. With 15 or 20 mg hydrocortisone/day the patients feel nearly as well and content as normal healthy individuals. Since long-term treatment with a high replacement dose of glucocorticoids (hydrocortisone 30 mg/day) induces bone loss, this risk can be avoided with a substitution dosage of 20 mg or even 15 mg hydrocortisone/day, without influencing the well-being of the patient.

A case of pituitary apoplexy occurring after Gd-DTPA-administration for contrast enhanced MRI in a patient with an hGH-producing macro-adenoma is presented. Within days the initially increased hGH level fell to the normal range, the oral glucose tolerance test (OGTT) showed a normal suppression of hGH and complete anterior pituitary insufficiency developed. At this time repeated MRI suggested a haemorrhagic infarction of the macroadenoma. Fourteen months later re-examination confirmed spontaneous cure of the acromegaly, improvement of adenopituitary function and shrinkage of the sellar content. The causal linkage between the pituitary adenoma apoplexy and Gd-DTPA-administration is unclear. It might be due to contrast induced blood pressure and endothelial permeability changes, possibly promoted by pre-existing diabetes mellitus associated vasculopathy.

OBJECTIVEThe present study was designed to assess the diagnostic value of different single measurements in comparison to the classic time‐consuming method, the oral glucose tolerance test (OGTT), in acromegaly.DESIGN, PATIENTS AND MEASUREMENTS IGF‐I, free IGF‐I, 24‐hour‐urinary GH (uGH), serum IGFBP‐3 and 24‐hour‐urinary IGFBP‐3 (uIGFBP‐3) were measured in 12 patients with untreated active acromegaly, in 29 patients who had been treated but were not cured, in 13 patients with cured acromegaly and in 14 healthy control subjects, and compared with the results of the OGTT.RESULTSIn all patients with active acromegaly, whether they had been treated or not, nadir GH in OGTT was >3 mU/I, whereas nadir GH was <1.88 mU/I in the cured patients and the control subjects. In patients with untreated active acromegaly IGF‐I, free IGF‐I, uGH and IGFBP‐3, but not uIGFBP‐3, were significantly higher than in healthy individuals (P<0.0001). Only IGF‐I values did not overlap with the control group. In those patients with acromegaly who had been treated but not cured these parameters overlapped with the control group. In patients with acromegaly there was a significant correlation between nadir GH levels in OGTT and IGF‐I (r=0.71), free IGF‐I (r=0.76, IGFBP‐3 (t=0.73) and uGH (r=0.81) (P<0.0001), but no correlation with uIGFBP‐3.CONCLUSIONSOnly be means of the OGTT could patients with active acromegaly be completely distinguished from the control subjects and from cured patients. IGF‐I, free IGF‐I, IGFBP‐3 and uGH were useful in the diagnosis of acromegaly, but of limited value in the follow‐up of acromegalic patients after treatment. The determination of free IGF‐I, which has yet not been investigated in acromegaly, offered no advantage over that of total IGF‐I and IGFBP‐3; uIGFBP‐3 was not useful in the diagnosis of acromegaly.

Die Serumkonzentration der neuronspezifischen Enolase (NSE) wurde bei 126 Patienten mit malignem Melanom (MM, Stadium I / II: n=80; Stadium II:n = 23; Stadium IV:n = 23) radioimmunologisch bestimmt. Erhöhte NSE-Konzentrationen (Schwellenwert: > 12, 5 μ/L) fanden sich bei 12, 5 % der Patienten mit MM im Stadium I / II, 13. 0 % im Stadium II und bei 39, 1 % im Stadium IV. In der Langzeit-Verlaufskontrolle bei 20 Patienten im Stadium II / K zeigte die NSE-Serumkonzentration eine Übereinstimmung mit der Tumoraktivität. Bei 6 Patienten zeigte sich unter der Therapie ein Abfall erhöhter NSE-Werte als Zeichen einer Tumorregression. Das Ausbleiben eines signifikanten Abfalls oder gar ein Anstieg wies in 86, 7 % (13/15) der Fälle auf eine Tumorprogression hin. Ein signifikanter Anstieg von NSE wurde bei 6 Patienten präfinal gesehen. Daraus läßt sich folgern, daß NSE für die Primärdiagnostik des malignen Melanoms aufgrund der niedrigen Sensitivität als Tumormarker ungeeignet ist; jedoch erscheint eine NSE-Bestimmung bei Patienten mit malignem Melanom im Rahmen einer Verlaufskontrolle sinnvoll.