Short stature and decreased insulin-like growth factor I (IGF-I)/growth hormone (GH)-ratio in an adult GH-deficient patient pointing to additional partial GH insensitivity due to a R179C mutation of the growth hormone receptor.

OBJECTIVE: Genetic factors play an expanding role in understanding growth hormone (GH) disorders, therefore the German KIMS Pharmacogenetics Study was initiated with the aim of genotyping various GH-/IGF-I-axis-related genes of GH-deficient adult patients to investigate genotype:phenotype relationships and response to GH therapy. PATIENTS AND METHODS: 129 consecutively enrolled GH-deficient adult patients were genotyped for variant 1 (V1) of the alternatively spliced noncoding exons in the 5'-untranslated region and for the nine coding exons of the GH receptor (GHR) gene, which obviously play a striking role in the function of the GH-IGF-I-axis. After detection of a heterozygous, non-synonymous mutation R179C in exon 6 in one single patient with acquired GH-deficiency (GHD) in late adulthood, analysis of her clinical data followed, leading to the diagnosis of mild short stature (-1.5SD). For further endocrine evaluation, five pituitary stimulation tests (arginine) of this patient were statistically compared to stimulation tests (arginine) of ten GH-deficient control patients, retrospectively. RESULTS: The formerly in patients with Laron syndrome and idiopathic short stature reported mutation R179C leads to an amino acid change from an arginine residue (codon CGC) to a cysteine residue (codon TGC) in position 179 of the extracellular domain of the GHR. Statistical analysis revealed significant decreased IGF-I/GH(0) ratio (p=0.004) and IGF-I/GH(max) ratio (p=0.001) of the index patient compared to the control patients, implying growth hormone resistance of the index patient at the level of the GHR, according to the detected R179C mutation. CONCLUSIONS: This study reports on the unusual case of a patient with mild short stature, who acquired GHD in late adulthood due to a non-secreting pituitary adenoma and get additionally diagnosed for pre-existing growth hormone insensitivity due to a formerly in two short statured patients described, single, heterozygous, non-synonymous mutation in the GHR. Our findings support the theory that heterozygous mutations in the GHR gene can have mild phenotypical consequences.

[Endosonographically controlled transluminal fine needle aspiration biopsy: diagnostic quality by cytologic and histopathologic classification]. / Endosonographisch gesteuerte transluminale Feinnadelpunktion: Untersuchung zur diagnostischen Qualität.

BACKGROUND AND OBJECTIVE: EUS-guided fine needle aspiration (EUS-FNA) has emerged as a highly accurate technique for detecting and classifying mediastinal and pancreatic lesions as well as abdominal and recently retroperitoneal masses with a minimum of risk for the patient. PATIENTS AND METHODS: To objectify these statements, we evaluated the quality of 72 EUS-FNA specimens by cytologic and histopathologic classification, investigated their contamination with tissue from the needle pathway and observed puncture-related complications in a retrospective study of 44 EUS-FNA in 41 consecutive patients (56 +/- 14 years, m = 24, f = 17; 13 pancreatic, 9 adrenal, 6 abdominal and 13 mediastinal masses). EUS-FNA was performed using a PENTAX 32 UA endosonoscope (longitudinal 7.5 MHz sector array) in combination with a needle system type "Hancke-Vilmann". RESULTS: 16 vs. 11 of 34 histopathologic and 38 cytologic specimens were classified "excellent", 7 vs. 10 "sufficient", 7 vs. 13 "poor" and 4 vs. 4 "failed". Analysis of contamination with tissue from the needle pathway showed 4 vs. 2 specimens "highly", 3 vs. 14 "clearly", 8 vs. 19 "slightly" and 19 vs. 3 "not" contaminated. Specimens classified "excellent" were less contaminated (p = 0,037). EUS-FNA identified 35 benign and 24 malignant masses. Definite diagnosis failed in 13 specimens. One nonfatal complication occurred. EUS-FNA is an accurate (89 %) and low-risk procedure to examine primary undiagnosed mediastinal, pancreatic, intraabdominal and especially adrenal lesions in most of the cases. Contamination with tissue from the needle pathway seems to be a major predictive factor of poor specimen quality and failed diagnosis. CONCLUSION: EUS-FNA expands the diagnostic approach of mediastinal, abdominal, pancreatic and adrenal masses and provides accurate specimens for reaching new differential-diagnostic competence, especially in endocrinologic cases.

Pitfalls in endosonographic imaging of suspected insulinomas: pancreatic nodules of unknown dignity.

OBJECTIVE: Endosonography enables localization and characterization of gastroenteropancreatic neuroendocrine tumors. We have studied the problem of misleading abnormalities of pancreatic morphology as obtained by endosonographic imaging. DESIGN AND METHODS: A total of 438 endosonographies performed for known or suspected diseases of the adrenal glands and/or the pancreas and/or suspected metastases in the neighboring tissues were analyzed. RESULTS: In the pancreas, nine benign insulinomas, four non-metastatic islet cell carcinomas, and multiple benign neuroendocrine tumors in one patient with multiple-endocrine neoplasia-1 (MEN-1) disease were detected and correctly localized as proven by postoperative histology. In three further patients with genetic diagnosis of MEN-1, asymptomatic tumors were detected and are under observation. However, we also found an 8 x 4 mm hypoechoic tumor in the cauda pancreatis of a patient with severe factitial hypoglycemia (glimepiride). In another patient suffering from severe hypoglycemia, a hypoechoic area of 24 x 10 mm in the processus uncinatus/caput pancreatis was found. Although organic hyperinsulinism was excluded, this patient underwent surgery because of suspected pancreatic carcinoma. There was normal pancreatic tissue in the abnormal region, which was also localized by intraoperative sonography. In a third patient with an adrenal carcinoma, a 6 x 3 mm hypoechoic nodule in the cauda pancreatis did not change its morphology over an observation period of 13 months, its clinical relevance is completely unclear. CONCLUSIONS: Pancreatic nodules of unknown dignity were detected in nearly 1% of our patients and must be considered to be a diagnostic problem. These experiences clearly show, on the one hand, that pancreatic endosonography is a very useful diagnostic support in the management of endocrine tumor patients. However, on the other hand, endosonography of endocrine organs is not a substitute for careful endocrinological examination and testing and must be considered in the context of endocrinological findings.

Changes in cellular proliferation rate of lymphocytes after long-distance flights as a possible risk for patients with HIV-infection.

OBJECTIVES: Several studies showed that long-distance flights can influence cellular immunity. This might be due to a cortisol- and catecholamin- induced change in immunity with an impairment of T-lymphocyte dependent cellular immunity and an enhancement of B-lymphocyte dependent humoral immunity. Similar results can be found in patients with HIV. It is also known that progress of this disease and affection of T-helper-cells by the virus are induced by stimulation of the immune system, a phenomenon that also occurs during long distance flights. Therefore, a possible interaction between long-distance flights and the progression of HIV-infection should be discussed. METHODS: Cell cultures of 22 subjects after long-distance flights with and without rapid time zone shifts and of 16 patients with HIV (stage 2 3) were investigated. Mononuclear blood cells were stimulated with different lectins in culture and proliferation was measured by incorporation of bromodesoxyuridine. Moreover, all cultures were titrated with chromate concentrations between 0 to 700 ng/ml to measure the tolerance of the cells against chromate (VI) in vitro as a marker of the functional efficiency of the cellular part of the immune system. Maximal proliferation rate and tolerance against chromate were compared in both groups. RESULTS: After long distance flights tolerance against chromate decreased significantly during the first 24 h after flight. After 48 h levels were similar to those 1 week after flights. The decrease was similar to the results found in the stage 2 group of HIV-patients, but by far less to the decrease in stage 3 patients. Maximal proliferation rate dropped significantly during the second day after arrival compared to 1-week control values. CONCLUSION: Changes in the cellular immune system in healthy subjects after long-distance flights have been similar to the results of patients with stage 2 of HIV-infection. Mechanisms of changes in both groups are comparable in influencing T-cell-induced immunity. This could point to an additive effect on cellular immunity of HIV-patients by long distance-flights. Rosen neopterin concentrations and increases of apoptotic T-cells in both groups support this assumption. Therefore, further studies are urgently needed to investigate the interactions between HIV-infection and long-distance flights.

Three incidents of human myiasis by rodent Cuterebra (Diptera: Cuterebridae) larvae in a localized region of western Pennsylvania.

Three aberrant incidents of human myiasis by Cuterebra larvae (Diptera: Cuterebridae) are described. All 3 cases were documented in the fall, on a nearly annual basis, and at the same western Pennsylvania hospital. Mature larvae were removed from cutaneous warbles of the neck and torso of a small female child and adult male, respectively. An early 2nd instar was removed from a warble located in the upper anterior quadrant of the left breast of an adult female.