An update of lanreotide acetate for treatment of adults with carcinoid syndrome.

Carcinoid tumors are rare and usually slow-growing. Some patients with advanced metastatic disease however can develop symptoms of carcinoid syndrome, which results in debilitating diarrhea and flushing. Many treatments including chemotherapy were tried unsuccessfully in the past to treat this syndrome. The symptoms of carcinoid syndrome are thought to be related to the ability of the tumors to produce serotonin. The discovery that the production of this hormone can be inhibited by somatostatin led to the development of somatostatin analogues octreotide and lanreotide, which differ from native somatostatin in that they have a longer half-life. These compounds have shown dramatic responses in symptom control and reduction of serotonin metabolites including urinary 5-hydroxyindoleacetic acid (5-HIAA) levels. This review researches the origins of carcinoid tumors, the development of lanreotide as a treatment and future directions for the treatment of carcinoid syndrome.

A novel PF/PN motif inhibits nuclear localization and DNA binding activity of the ESX1 homeoprotein.

Despite their significance for mammalian embryogenesis, the molecular mechanisms that regulate placental growth and development have not been well defined. The Esx1 homeobox gene is of particular interest because it is among the few regulatory genes that have specific expression and function in the placenta during murine development. In addition, the ESX1 protein contains several notable features that are not often associated with homeoproteins, including an atypical homeodomain of the paired-like class, a proline-rich region that contains an SH3 binding motif, and a novel repeat region consisting of prolines alternating with phenylalanines or asparagines that we term the PF/PN motif. We have found that the ESX1 protein is expressed in the labyrinth layer of the placenta in vivo, where its subcellular localization is primarily cytoplasmic. Our results suggest that this unexpected subcellular localization is conferred by the PF/PN motif, which inhibits nuclear localization of ESX1 in cell culture, as well as its DNA binding activity in vitro. Finally, we show that the proline-rich region of ESX1 mediates interactions in vitro with the c-abl SH3 domain as well as with certain WW domains. We propose that the PF/PN motif provides a novel mechanism for regulating nuclear entry and that the essential function of ESX1 during placental development is mediated by its ability to couple cytoplasmic signal transduction events with transcriptional regulation in the nucleus.

Effects of beta-adrenergic blockade in acute myocardial infarction: evaluation by radionuclide ventriculography.

In acute myocardial infarction, beta-adrenergic blockade might depress left ventricular contractility or improve contractility by reducing ischemia. Gated equilibrium radionuclide ventriculography and cuff blood pressure were employed in 10 patients to assess the left ventricular systolic pressure/volume (P/V) ratio as an index of contractility before and after intravenous metoprolol 9.3 +/- 2.5 hr after onset of infarction. In 13 normal subjects, the baseline left ventricular PV ratio was 3.5 and the left ventricular ejection fraction (LVEF) was 70%, both greater than the patients with infarction. In the patients after blockade, the systolic blood pressure decreased (p = 0.02), and the left ventricular end-systolic volume increased (p = 0.003), thus decreasing the P/V ratio from 1.7 to 1.4 (p = 0.003), while the ejection fraction (EF) was unchanged (55% versus 52%). The right ventricular ejection fraction (RVEF) decreased from 50% to 43% (p = 0.004). Thus, radionuclide ventriculography demonstrated that left ventricular contractility was reduced in patients with acute myocardial infarction and that beta-adrenergic blockade further decreased left ventricular contractility and right ventricular performance.

Scurvy presenting as painful gait with bruising in a young boy.

A case of scurvy occurred in an apparently well-nourished 5-year-old boy with normal growth parameters. Only after the diagnosis of scurvy was raised on clinical grounds did we discover the peculiar dietary habits that were responsible for his deficiency of ascorbic acid. His case is a reminder to the clinician that nutritionally based disease may occur in any socioeconomic setting and that nutritional screening remains an important part of every child's general health care.

Resolution of hormonal markers of ectopic gestation: a randomized trial comparing single-dose intramuscular methotrexate with salpingostomy.

OBJECTIVE: To evaluate resolution of serum hCG and progesterone in patients with ectopic pregnancy receiving single-dose intramuscular (IM) methotrexate as compared with those undergoing laparoscopic salpingostomy. METHODS: In this prospective randomized clinical trial, 75 hemodynamically stable women with a diagnosis of ectopic pregnancy were randomized to treatment with single-dose IM methotrexate (1 mg/kg) or laparoscopic salpingostomy. All women had initial, day 4, and weekly serum hCG and progesterone measurements taken until hCG levels were less than 15 mIU/mL. Methotrexate therapy was repeated if posttreatment day 7 hCG levels did not decrease by 15%, as compared with day 4 levels. Success rate was defined as ectopic resolution without the need for the alternate mode of therapy. RESULTS: Thirty-eight women were randomized to treatment with methotrexate and 37 to laparoscopic salpingostomy. The mean (+/-standard deviation) time required for serum progesterone concentrations to decrease to less than 1.5 ng/mL was significantly less for laparoscopic salpingostomy than for treatment with methotrexate: 7.8+/-1.7 and 17.6+/-2.2 days, respectively (P < .01). Within each treatment group, serum progesterone levels resolved (less than 1.5 ng/mL) more rapidly than did hCG levels (less than 15 mIU/mL) (P < .01). No further treatment was required once serum progesterone levels had decreased to less than 1.5 ng/mL. Success rates were similar in both groups: 94.7% (36 of 38) for methotrexate and 91.4% (33 of 36) for laparoscopic salpingostomy. Mean time required for hCG concentrations to decrease to less than 15 mIU/mL was significantly less for laparoscopic salpingostomy than for methotrexate therapy: 20.2+/-2.7 and 27.2+/-2.3 days, respectively (P < .05). Additional methotrexate injections were required in 15.8% (6 of 38) of women randomized to methotrexate therapy. Initial serum hCG levels for patients receiving additional methotrexate doses were 4830+/-1588 mIU/mL as compared with 2133+/-393 mIU/mL for women receiving only one dose (P = .07). CONCLUSION: Serum progesterone levels of less than 1.5 ng/mL are a good predictor of ectopic pregnancy resolution regardless of treatment, and because its return to normal values occurs more rapidly than that of hCG levels, serum progesterone may be a better marker for predicting successful treatment. Although laparoscopic salpingostomy leads to faster resolution of hormonal markers of ectopic gestation, methotrexate is equally successful for treating small unruptured ectopic pregnancies. Initial hCG levels may be a marker for women requiring additional doses of methotrexate.

Pelvic examination, tumor marker level, and gray-scale and Doppler sonography in the prediction of pelvic cancer.

OBJECTIVE: To determine the ability of pelvic examination, tumor marker assessment, and transvaginal ultrasonography, with selected use of Doppler ultrasonography, to predict pelvic malignancy. METHODS: Two hundred twenty-six women scheduled for operative removal of a pelvic mass were entered in the study prospectively. Each woman underwent pelvic examination, tumor marker assessment, and transvaginal ultrasonography preoperatively. Women whose gray-scale findings were suspicious for malignancy underwent Doppler ultrasonography. Suspicious findings included masses that were fixed or irregular on pelvic examination; CA 125 level greater than 35 U/mL; elevations in serum lactic dehydrogenase, alpha-fetoprotein, or hCG; and the presence of a substantial solid component on gray-scale ultrasonography. Suspicious Doppler findings included intratumoral color flow, pulsatility index less than 1.0, or resistance index 0.4 or lower. The findings were correlated with the presence of malignancy. RESULTS: If all three indicators (examination, tumor marker assessment, and gray-scale ultrasound findings) were nonsuspicious, 99% of premenopausal women and 100% of postmenopausal women had benign masses. If all three indicators were suspicious, 77% of premenopausal women and 83% of postmenopausal women had malignant tumors. Logistic regression identified ultrasound impression and tumor size to be significant predictors of malignancy in premenopausal women, whereas CA 125 level and ultrasound impression were significant in postmenopausal women. In patients with suspicious gray-scale findings, recategorization based on Doppler findings resulted in inferior diagnostic indices. CONCLUSIONS: Ultrasonographic tumor size and appearance are the best predictors of pelvic malignancy in premenopausal women, whereas CA 125 level and ultrasonographic appearance are the best predictors in postmenopausal women. Neither color nor spectral Doppler is useful in this setting.

Radiologic studies in acute fatty liver of pregnancy. A review of the literature and 19 new cases.

OBJECTIVE: Radiologic findings thought to be characteristic of acute fatty liver of pregnancy have been described in a limited number of cases. We describe wide experience with liver imaging of this disease. STUDY DESIGN: A retrospective review was performed on charts from 1982 to 1994 to identify those patients with acute fatty liver of pregnancy who had radiologic studies. RESULTS: Twenty-eight patients with acute fatty liver of pregnancy were identified, for an incidence of 1/6,692 births. Nineteen patients underwent at least one imaging study, and seven had more than one. Findings consistent with fatty infiltration of the liver are found in 3/11 patients with ultrasound, 5/10 with computed tomography (CT) and 0/5 with magnetic resonance imaging (MRI). Three patients with normal ultrasound scans subsequently had evidence of fatty filtration on CT scan. CONCLUSION: Detection of fat in the liver of patients with acute fatty liver of pregnancy with current imaging techniques is limited and did not contribute to the management of patients in this series. Further studies are necessary to define to role of MRI--in particular, spectroscopy.

The role of electro-encephalography in Third-World psychiatry.

Patients with organic brain disease often present with psychiatric symptoms that closely mimic functional mental illness. This has major implications in Third-World countries where the psychiatric effects of physical disease are particularly widespread. Developing countries lack the advanced radiological investigations and other diagnostic facilities that may help to differentiate between functional and physical complaints. The association between electro-encephalographic (EEG) abnormalities and organic brain disease is well established; the benefit and importance of the EEG in Third-World psychiatry is described.

Seeing red--a student elective in the People's Republic of China.

A student who undertook his 5th-year clinical elective period at the Doctor Sun Yat-Sen University of Medical Sciences, Guangzhou, People's Republic of China, reports that he joined the Department of Surgery and found the clinical training and practice to be of a high standard, although severely compromised by the prevailing political, economic and cultural ideology.

Exposure of an arginine-rich protein at surface of cells in S, G2, and M phases of the cell cycle.

Phenylglyoxal (PG) is shown to be a cell surface probe specific for arginine moieties in protein: (1) It does not enter the cell as evidenced by lack of PG in the cytoplasm. (2) It does not cause excessive cell leakage as measured by release of 51Cr. (3) It reacts with positively-charged groups in proteins at the cell surface but not with those of phospholipids at the surface; since pronase removes PG from the surface, but phospholipase C does not. (4) Under the conditions used in these experiments, it reacts virtually exclusively with arginine moieties in protein (Freedman et al., '68; Takahashi, '68; Werber and Sokolovsky, '72). Synchronized cells were exposed to radioactive PG to assess quantity of arginine moieties in protein at the surface. There is a sharp decrease in arginine at the cell surface at entry into G1 phase from M and a 24-fold increase upon entry into S phase. There is a slight drop in exposed arginine in late S phase followed by an increase to 26 times the G1 level immediately prior to mitosis. Lactoperoxidase-catalyzed iodination of tyrosine moieties in protein at the surface of synchronized cells shows a very gradual increase in protein as the cells move through the cycle and increase in size. Since the increase in arginine moieties in protein at the surface does not reflect a similar increase in total protein at the surface, an arginine-rich protein appears to be exposed at the cell surface during the division-related phases of the cell cycle.

Very low maternal plasma alpha-fetoprotein concentration. An indication for follow-up.

In the course of a screening programme for the detection of fetal neural tube abnormalities by measurement of maternal plasma alpha-fetoprotein (AFP), 57 patients were identified who had plasma AFP levels of less than 7 units/ml at 15-20 weeks gestation. follow-up at the time of screening included requests to confirm that the patient was pregnant and also to repeat the AFP test. Tow patients were lost to follow-up and of the remaining 55, 17 patients (31 per cent) were subsequently shown not to have a live fetus and 31 patients (56 per cent) had incorrect estimates of gestation. No particular reason for the very low plasma AFP could be identified in the other seven patients.

Hemoperitoneum in a newborn secondary to antenatal hemorrhage into a retroperitoneal lymphangioma.

Hemoperitoneum in the newborn is an uncommon event, occurring most often in the setting of traumatic delivery. Hemoperitoneum resulting from antenatal hemorrhage into an abdominal mass is rare. We present a case of neonatal hemoperitoneum secondary to antenatal hemorrhage into a retroperitoneal lymphangioma. The differential diagnosis of neonatal hemoperitoneum is discussed.

Traumatic epididymitis: evaluation with color Doppler sonography.

OBJECTIVE: We performed this study to determine whether scrotal trauma can cause hyperemia of the epididymis. This diagnosis is helpful because traumatic epididymitis can be treated conservatively. MATERIALS AND METHODS: We retrospectively reviewed color Doppler and gray-scale sonograms of five patients who had suffered trauma to the scrotum that resulted in epididymal hyperemia, which we called traumatic epididymitis. We also reviewed the presentation and management of each patient. RESULTS: Color Doppler sonography revealed focal (one patient) and diffuse (four patients) hyperemia. Gray-scale images revealed epididymal enlargement in all patients. These findings were indistinguishable from those of infectious epididymitis by sonography. One patient also had hyperemia of the testis. Four of the five patients were managed conservatively; the other underwent surgical exploration for a coexisting testicular rupture. CONCLUSION: Careful evaluation of the epididymis with both gray-scale and color Doppler sonography should be part of every sonographic survey of the scrotum for blunt trauma. Traumatic epididymitis, which may be noted on color Doppler images, should not be confused with infectious epididymitis. Surgery is not necessary unless another injury requires it.

Color Doppler sonography of adnexal torsion.

The purpose of this study was to describe the color Doppler sonographic findings in adnexal torsion that distinguish viable from nonviable ovaries. We present the color Doppler sonographic features in 13 patients with surgically proved adnexal torsion that help determine whether or not the ovaries were viable or nonviable at the time of surgery. Eleven combined ovarian and tubal torsions and two isolated tubal torsions were studied. In 10 cases the ovaries were considered nonviable at the time of surgery and in three cases they were considered viable. Of the nonviable group, six showed absent arterial and venous flow centrally, but two had low velocity (< 5 cm/s) arterial flow peripherally in the region of the adnexal branch of the uterine artery or in the main ovarian artery, and two demonstrated absent or reversed diastolic arterial flow. None of the nonviable ovaries showed venous flow centrally. In contrast, all of the viable ovaries demonstrated venous flow centrally, and two had peripheral and central arterial flow. Although the CDS findings in adnexal torsion are variable, ovarian viability may be predicted if central venous flow is present.

Atlanto-occipital subluxation in Down syndrome.

Atlanto-occipital subluxation (AOS) in individuals with Down syndrome is discussed using five new cases and nine patients previously presented in the literature. Although AOS is likely due to ligamentous laxity, it was associated with atlantoaxial instability in only two youngsters. Reducible C1-C2 rotary subluxation was present in a third. Posterior movement of the occiput with respect to C1 occurred on extension and reduced on flexion in all but one individual who demonstrated anterior subluxation. Neurological problems are described in only two individuals: one with severe atlantoaxial subluxation (AAS) and the other with multiple cervical spine anomalies. Since AOS is usually detected on films obtained to screen children with Down syndrome for AAS, the atlanto-occipital joint should be carefully studied on these radiographs. The clinical significance of AOS needs to be determined.