Reliability of the oral glucose tolerance test in the early postoperative assessment of acromegaly remission

OBJECT: The suppression of growth hormone (GH) to less than 1 microg/L during the oral glucose tolerance test (OGTT) is generally considered to be the standard for the assessment of biochemical remission of GH excess following surgery for GH-secreting pituitary adenomas. In this study the authors examine the reliability of the results of the early postoperative OGTT (epOGTT) in indicating remission or persistence of active acromegaly. METHODS: Data from the case files of 67 consecutive patients who underwent surgery for the first time for GH-secreting pituitary adenomas were reviewed retrospectively. Definitive remission of acromegaly was considered to be present if, without adjuvant therapy and at the most recent follow-up examination, GH was suppressed to less than 1 microg/L during the OGTT, the level of insulin-like growth factor-I (IGF-I) was within normal limits, and there was no clinical or magnetic resonance imaging evidence of persisting disease. The results of the epOGTT (obtained during the 2nd postoperative week) and the 3-month-postoperative OGTT (3mpOGTT) were compared with the patient's outcome at the most recent follow-up examination. A highly sensitive (< or = 0.3 microg/L) immunoradiometric assay for GH and a highly sensitive (< or = 32 microg/L) radioimmunoassay for IGF-I were used. Correct epOGTT findings were noted in 83.6% of the patients: correct normal results (definitive remission of acromegaly) in 55.2% and correct pathological results (persisting acromegaly) in 28.3% of the patients. The rate of false findings was 16.4%: false normal results in 1.5% and false pathological results in 14.9% of the patients. The rate of correct 3mpOGTT findings increased to 98.5%: correct normal results in 68.6% and correct pathological ones in 29.8% of the patients. A false (false pathological) 3pmOGTT result occurred in only one patient (1.5%). At the most recent follow-up examinations (median 3.6 years) all OGTT findings were correct: correct normal results in 70.1% and correct pathological results in 29.9% of the patients. An intact adenopituitary function was associated (p = 0.04) with the occurrence of false epOGTT findings. CONCLUSIONS: The high rate of false results, 16.4% for the epOGTT, declined significantly to 1.5% 3 months postoperatively and to 0% at the most recent follow-up examination. The OGTT appears to be more reliable at 3 months postoperatively. Unless there is obvious evidence of persisting disease following surgery for GH-secreting pituitary adenomas, adjuvant therapy should be delayed for 3 months postoperatively to avoid subjecting the patient to superfluous treatment.     

Small volume hypertonic hydroxyethyl starch reduces acute microvascular dysfunction after closed soft-tissue trauma

A major pathway of closed soft-tissue injury is failure of microvascular perfusion combined with a persistently enhanced inflammatory response. We therefore tested the hypothesis that hypertonic hydroxyethyl starch (HS/HES) effectively restores microcirculation and reduces leukocyte adherence after closed soft-tissue injury. We induced closed soft-tissue injury in the hindlimbs of 14 male isoflurane-anaesthetised rats. Seven traumatised animals received 7.5% sodium chloride-6% HS/HES and seven isovolaemic 0.9% saline (NS). Six non-injured animals did not receive any additional fluid and acted as a control group. The microcirculation of the extensor digitorum longus muscle (EDL) was quantitatively analysed two hours after trauma using intravital microscopy and laser Doppler flowmetry, i.e. erythrocyte flux. Oedema was assessed by the wet-to-dry-weight ratio of the EDL. In NS-treated animals closed soft-tissue injury resulted in massive reduction of functional capillary density (FCD) and a marked increase in microvascular permeability and leukocyte-endothelial cell interaction as compared with the control group. By contrast, HS/HES was effective in restoring the FCD to 94% of values found in the control group. In addition, leukocyte rolling decreased almost to control levels and leukocyte adherence was found to be reduced by approximately 50%. Erythrocyte flux in NS-treated animals decreased to 90 +/- 8% (mean SEM), whereas values in the HS/HES group significantly increased to 137 +/- 3% compared with the baseline flux. Oedema in the HS/HES group (1.06 +/- 0.02) was significantly decreased compared with the NS-group (1.12 +/- 0.01). HS/HES effectively restores nutritive perfusion, decreases leukocyte adherence, improves endothelial integrity and attenuates oedema, thereby restricting tissue damage evolving secondary to closed soft-tissue injury. It appears to be an effective intervention, supporting nutritional blood flow by reducing trauma-induced microvascular dysfunction.     

Electrophysiological correlates of semantic processing during encoding of neutral and emotional pictures in patients with ADHD

The current study investigated the relevance of semantic processing and stimulus salience for memory performance in young ADHD patients and healthy control participants. 18 male ADHD patients and 15 healthy control children and adolescents participated in an ERP study during a visual memory paradigm with two different encoding tasks requiring either perceptual or semantic processing of neutral and emotional pictures. ADHD patients and healthy controls both showed a more negative slow-wave in response to task cues signalling semantic as compared to perceptual stimulus processing. In contrast to ADHD patients, healthy control children showed a larger increase in memory performance for deeply processed neutral pictures which was accompanied by a more positive mid-latency ERP component (so-called P300) after stimulus onset. Our results demonstrate that ADHD patients succeeded in allocating neural resources in preparation of different task demands. However, this increase in preparatory activation to the semantic task cue did not suffice to support successful processing and encoding of neutral stimuli to the same extent as in healthy controls. These findings provide evidence that ADHD patients show deficits in translating pre-stimulus mobilization of neural resources to successful memory formation in the absence of salient stimulus material.     

In vivo analysis of microcirculation following closed soft-tissue injury.

Major loss of tissue is an almost invariable consequence of severe closed soft-tissue injury. Clinically, the extent of soft-tissue trauma determines the outcome of complex injuries and significantly influences bone healing. With use of a new animal model, this study quantitatively analyzed microcirculation, i.e., nutritive perfusion and leukocyte-endothelial cell interaction, in skeletal muscle after standardized closed soft-tissue injury. By means of a computer-assisted controlled-impact technique, a severe standardized closed soft-tissue injury was induced in the left hindlimb of 28 rats. The rats were assigned to four experimental groups (n = 7 per group) that differed by time of analysis (1.5, 24, 72, and 120 hours after injury); rats that were not injured served as controls (n = 7). Intramuscular pressure was measured, and microcirculation in the rat extensor digitorum longus muscle was analyzed by in vivo fluorescence microscopy, which allowed assessment of microvascular diameters, functional capillary density, number of rolling and adherent leukocytes in venules, and microvascular permeability. Edema weight gain was quantified by the ratio of wet to dry weight of the extensor digitorum longus muscle. Microvascular perfusion of the skeletal muscle was characterized by a significant reduction in functional capillary density, which was paralleled by an increase in capillary diameter throughout the 120 hours of observation when compared with the controls. Trauma-induced inflammatory response was reflected by a markedly increased rolling and adherence of leukocytes, primarily restricted to the endothelium of postcapillary venules; this was accompanied by increased microvascular permeability, indicative of a substantial loss of endothelial integrity. The microcirculation surrounding the core of the damaged tissue area resembled that of ischemia-reperfusion injury in skeletal muscle, i.e., heterogeneous capillary perfusion, pronounced microvascular leakage, and adherence of leukocytes. Enhanced vascular leakage and leukocyte adherence (24-72 hours after injury) coincided with the maximum intramuscular pressure (which was not indicative of compartment syndrome) and edema formation. These results demonstrate that initial changes, leading to ultimate tissue death, after closed soft-tissue injury are caused on the microcirculatory level. This standardized model provides further insight into microvascular pathophysiology and cellular interactions following closed soft-tissue injury. Thus, it is an adequate tool for testing novel therapeutic interventions.     

Overrepresentation of 3q and 8q material and loss of 18q material are recurrent findings in advanced human ovarian cancer

In order to define the ability of comparative genomic hybridization (CGH) to detect and map genetic imbalances, we investigated 47 malignant ovarian tumors and 2 ovarian tumors of low malignant potential. The most common genetic changes in order of frequency included DNA gains of chromosome arms 8q (53%), 3q (51%), 20q (43%), 1p (32%), 19q (30%), 1q (28%), 12p (28%), 6p (21%), and 2q (19%). The smallest regions of overrepresentation could be defined in 3q26-qter, 8q23-qter, 1p35-pter, 12p12, and 6p21-22, respectively. Losses were detected on 18q (23%), chromosome 4 (23%), 13q (17%), and 16q (17%) with the smallest underrepresented regions on 18q22-qter, 13q21, and 16q23-qter. Also, losses of the X chromosome (19%) were detected, correlating with higher ages of the patients. Therefore, some of these X chromosome losses might be due to a well-known aging phenomenon and in these cases will be more preferably lost during cell division and tumor progression. Our findings show that ovarian carcinomas reveal consistent chromosomal abnormalities. Further detailed studies of these regions with specific molecular genetic techniques may lead to the identification of oncogenes and/or tumor suppressor genes playing an important role in the tumorigenesis of ovarian carcinomas. Genes Chromosom Cancer 16:46–54 (1996). © 1996 Wiley-Liss, Inc.