We investigated several indices involved in sphingomyelin metabolism in developing rat lung. The levels of sphingomyelin gradually increased during lung maturation, with highest levels observed postnatally. The content of sphingosine and ceramide, biologically active sphingomyelin degradation products, did not significantly change in microsomes during the prenatal period, but increased to peak levels in neonatal and adult lung, respectively. Sphingosine content increased 6-fold between the fetal (Day 21) and neonatal period. The developmental profiles of two enzymes involved in sphingomyelin synthesis, serine palmitoyltransferase and sphingomyelin synthase, were similar. Serine palmitoyltransferase activity increased progressively from the fetal to neonatal period, and plateaued at high levels in the adult lung. The activity of serine palmitoyltransferase correlated with the levels of endogenous sphingolipid in lung tissue. Sphingomyelin synthase activity also increased during fetal lung development, but attained highest levels at Day 21 gestation; postnatally, enzyme activity was detected at lower levels. The activities of the sphingolipid hydrolases, acid and neutral sphingomyelinase and acid and alkaline ceramidase, were elevated in fetal lung, thereafter declining to low levels after birth. Studies conducted in alveolar macrophages, fibroblasts, and alveolar type II epithelial cells revealed that these developmental changes in enzyme activities in lung tissue were also occuring globally at the cellular level and were not restricted to any specific cell population. These studies suggest that the developmental increase in lung sphingomyelin content is due to coordinate regulation of enzymes involved in the biosynthesis and degradation of sphingomyelin. These observations also suggest a regulatory role for serine palmitoyltransferase in the generation of long chain sphingoid bases.

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Venous access for pectoral pacemaker and defibrillator lead placement can be compromised by venous occlusion due to previous pacing leads, access ports for medications such as chemotherapy, dialysis access, and other causes. On rare occasion, a femoral access is utilized for device placement. We report here a patient without venous access to the heart from either above or below due to retroperitoneal fibrosis. A bi-ventricular pacing-defibrillator was placed using a direct trans-atrial approach with good results. This minimally invasive approach to device placement may be useful in patients with poor venous access and avoids the placement of epicardial hardware.

Multiple endocrine neoplasia type I syndrome (MEN I) results in parathyroid, anterior pituitary, and pancreatic islet tumors. An uncommon tumor in MEN I is the vasoactive intestinal polypeptide-producing tumor (VIPoma), which usually presents with diarrhea and hypokalemia. We describe a case of MEN I and VIPoma presenting with hypercalcemia and hypokalemia but no diarrhea. This 19-year-old woman with a family history of MEN I presented with metabolic acidosis, hypokalemia, hypercalcemia, and intact parathyroid hormone (iPTH) of 11 pg/mL (normal, 8 -48 pg/mL). A computed tomography scan revealed a pancreatic mass. VIP concentration was 249 pg/mL (normal, Ͻ50). The pancreatic mass was resected, stained positive for VIP, and her VIP level normalized. VIPomas usually present with diarrhea, resulting in metabolic acidosis and hypokalemia. This patient demonstrated hypokalemia and hypercalcemia without diarrhea or elevated parathormone. Thus, VIPomas can have biologic actions, such as hypokalemia and hypercalcemia without inducing diarrhea and should be considered in the differential diagnosis of hypercalcemia in MEN I. Key Words: vasoactive intestinal polypeptide, diarrhea, multiple endocrine neoplasia (The Endocrinologist 2005;15: 320 -324) Learning Objectives • Outline the place of vasoactive intestinal polypeptide (VIP)-producing tumors, or VIPomas, in the context of all islet-cell tumors of the pancreas and as a component of multiple endocrine neoplasia type I (MEN I) syndrome. • Describe the ways in which this patient's clinical and biochemical findings were in accord with or differed from those usually found in patients having a VIPoma. • Give examples of how VIP produces the clinical and biological abnormalities found in patients having a VIPoma as part of the MEN I syndrome.M ultiple endocrine neoplasia type I syndrome (MEN I) is a genetic condition in which affected family members can present with tumors of neuroendocrine tissue, including parathyroid glands, the anterior pituitary, and pancreatic islet cells. 1 The islet cell tumors tend to be the most aggressive and often decrease longevity. The most common islet cell tumors in MEN I are gastrinomas and insulinomas, with vasoactive intestinal polypeptide-producing tumors (VIPomas) occurring infrequently. 2 VIPomas usually present with secretory diarrhea, hypochlorhydria, and hypokalemia. 3 We describe a patient with MEN I syndrome and VIPoma with an unusual presentation of hypokalemia and hypercalcemia without diarrhea. CASE REPORTA 19-year-old previously healthy woman presented to her local emergency room with a 1-week history of diffuse abdominal pain, lethargy, nausea, one episode of vomiting, and a decreased appetite. She experienced a 10-pound weight loss during the previous week and had eaten only one meal during that time. She attributed her symptoms to a "nervous stomach" caused by stress from school and interpersonal relationships. She denied loose or watery stools. She was on no medications and denied previous tobacco, alcohol, and drug use or rec...