Medical management of interstitial ectopic pregnancy: a case report and literature review

Recent reports describe successful treatment of interstitial ectopic pregnancies using methotrexate. While the number of reported cases is increasing, no consensus exists regarding the management of this complication of pregnancy. We present the successful use of combined systemic and direct intrasac injection of methotrexate for an interstitial pregnancy with the highest yet reported initial beta-human chorionic gonadotrophin concentration (102,000 mIU/ml). We also describe the use of Doppler ultrasound for monitoring treatment progression. Through a review of the current literature, we propose to facilitate management decisions and increase outcome success by summarizing previously reported treatment regimens and by describing enhanced parameters for patient selection and monitoring.     

Usefulness of electron beam tomography in adolescents and young adults with heterozygous familial hypercholesterolemia

BACKGROUND: Because of the success of secondary prevention of coronary events by intense risk factor modification, a more precise measure of atherosclerosis in youth would have great clinical value both in the design of clinical trials for the demonstration of the usefulness of coronary disease prevention early in life and in guiding therapy. Identification of calcium in coronary arteries by electron beam tomography has been associated with severity of atherosclerosis in adults. METHODS AND RESULTS: Twenty-nine youths 11 to 23 years old with familial hypercholesterolemia (average LDL cholesterol, 5.95 mmol/L) underwent electron beam tomography as well as comprehensive risk factor assessment with measurement of total cholesterol, triglycerides, HDL cholesterol, lipoprotein (a), apolipoprotein E phenotype, blood pressure, body mass index, and history of tobacco use. Significant coronary calcium was identified in 7 of 29 subjects. Increased body mass index was significantly associated with the presence of coronary calcium (25.3 versus 20.6 kg/m2, P<0.03). No other risk factors were associated with the presence of coronary calcium. CONCLUSIONS: Coronary calcium, uncommonly identified before the fourth decade, was found in a significant percentage of adolescents and young adults with familial hypercholesterolemia. Overweight may increase the likelihood of coronary calcium being present in individuals already at high risk.     

Psychopathology among offspring of parents with substance abuse and/or anxiety disorders: a high-risk study

Fas (CD95) and Fas ligand (FasL) play major roles in staphylococcal enterotoxin B (SEB)-induced peripheral deletion of Vbeta8+ T cells. We found that peripheral deletion was defective in radiation chimeras with non-functional tissue FasL, regardless of the FasL status of the bone marrow-derived cells. SEB induced a dramatic upregulation of FasL expression and function in nonlymphoid cells of liver and small intestine. This effect was resistant to inhibition by cyclosporin A, which also failed to inhibit peripheral deletion. In SCID animals nonlymphoid tissues did not express FasL in response to SEB unless transplanted lymphocytes were present. Thus, some immune responses induce FasL in nonlymphoid tissues, which in turn kills activated lymphocytes, leading to peripheral T cell deletion.     

Expression pattern of CD2 locus control region containing retroviral vectors in hemopoietic cells in vitro and in vivo

OBJECTIVE: To determine whether individual surgeon experience is associated with improved short-term clinical and economic outcomes for patients with benign and malignant thyroid disease who underwent thyroid procedures in Maryland between 1991 and 1996. SUMMARY BACKGROUND DATA: There is a prevailing belief that surgeon experience affects patient outcomes in endocrine surgery, but there is a paucity of objective evidence outside of clinical series published by experienced surgeons that supports this view. METHODS: A cross-sectional analysis of all patients who underwent thyroidectomy in Maryland between 1991 and 1996 was conducted using a computerized statewide hospital discharge data base. Surgeons were categorized by volume of thyroidectomies over the 6-year study period: A (1 to 9 cases), B (10 to 29 cases), C (30 to 100 cases), and D (>100 cases). Multivariate regression was used to assess the relation between surgeon caseload and in-hospital complications, length of stay, and total hospital charges, adjusting for case mix and hospital volume. RESULTS: The highest-volume surgeons (group D) performed the greatest proportion of total thyroidectomies among the 5860 discharges, and they were more likely to operate on patients with cancer. After adjusting for case mix and hospital volume, highest-volume surgeons had the shortest length of stay (1.4 days vs. 1.7 days for groups B and C and 1.9 days for group A) and the lowest complication rate (5.1 % vs. 6.1% for groups B and C and 8.6% for group A). Length of stay and complications were more determined by surgeon experience than hospital volume, which had no consistent association with outcomes. CONCLUSIONS: Individual surgeon experience is significantly associated with complication rates and length of stay for thyroidectomy.     

Growth control mechanisms in multiple myeloma

Neo red cells (NRCs) are a blood substitute representing stroma free hemolysate (SFHL) encapsulated in liposomes and containing NAD, glucose, adenine, and inosine, etc. as substrates or coenzymes of the Embden-Meyerhof pathway in RBCs and inositol hexaphosphate (IHP) as an allosteric effector. The oxygen transport efficiency (OTE) of NRCs was increased to > 45% when the oxygen partial pressure in arterial blood increased. We carried out exchange transfusion with NRCs in rats, monitored their functioning as a blood substitute in vivo, and demonstrated that NRCs worked sufficiently. First, we confirmed that the OTE of NRCs was augmented by increasing the oxygen supply to the rats by using oxygen masks. Second, we carried out 70% blood exchange with NRCs (with hemoglobin concentrations of 4, 5, 6, or 7 g/dl), and compared these experimental groups with control groups (RBC and saline). Each sample was contained bovine albumin (final volume of 5% (w/v)). As a result, the NRC groups with hemoglobin concentrations of 5, 6, and 7 g/dl showed stability after the exchange transfusion. On the other hand, the NRC group with hemoglobin concentration of 4 g/dl and the saline group showed respiratory acidosis and a drop of blood pressure and heart rate, and thus did not maintain an adequate oxygen supply. We concluded that a hemoglobin concentration of > 5 g/dl was sufficient in the NRC solution, and demonstrated in an experiment on animals that the OTE of NRCs was increased by using oxygen masks.     

N2- and C8-substituted oligodeoxynucleotides with enhanced thrombin inhibitory activity in vitro and in vivo

2'-Deoxyguanosine (G) analogues carrying various hydrophobic substituents in the N2 and C8 positions were synthesized and introduced through solid-phase synthesis into 15-mer oligodeoxynucleotide, GGTTGGTGTGGTTGG, which forms a chairlike structure consisting of two G-tetrads and is a potent thrombin inhibitor. The effects of the substitutions at N2 and C8 of the G-tetrad-forming G residues on the thrombin inhibitory activity are relatively small, suggesting that these substitutions cause relatively small perturbations on the chairlike structure formed by the oligodeoxynucleotide. Introduction of a benzyl group into N2 of G6 and G11 and naphthylmethyl groups into N2 of G6 increased the thrombin inhibitory activity, whereas other substituents in these positions had almost no effect or decreased the activity. Particularly, the oligodeoxynucleotide carrying a 1-naphthylmethyl group in the N2 position of G6 showed an increase in activity by about 60% both in vitro and in vivo. Substitutions on the N2 position of other G residues had little effect or decreased the activity. Introduction of a relatively small group, such as methyl and propynyl, into the C8 positions of G1, G5, G10, and G14 increased the activity, presumably due to the stabilization of a chairlike structure, whereas introduction of a large substituent group, phenylethynyl, decreased the activity, probably due to the steric hindrance.     

Conformational stability of factor VIIa: biophysical studies of thermal and guanidine hydrochloride-induced denaturation

The binding of the multidomain protein factor VIIa (fVIIa) to tissue factor provides the interprotein communication necessary to make fVIIa an efficient catalyst of the initial event in the extrinsic pathway of blood coagulation. We have investigated the stability of individual domains in fVIIa and the influence of Ca2+ and an irreversible active-site inhibitor (FFR-chloromethyl ketone). Equilibrium guanidine hydrochloride (GuHCl)-induced unfolding monitored by tryptophan fluorescence and far-UV circular dichroism (CD) demonstrated that the gamma-carboxyglutamic acid (Gla) domain unfolds at 0.3 M GuHCl and the serine protease (SP) domain at 3 M GuHCl and that Ca2+ is a prerequisite for the formation of an ordered, compact structure in the Gla domain. The loss of amidolytic activity coincides with the first transition, which is stabilized by the active-site inhibitor, and a change in the environment of the active site is demonstrated using a fluorescent inhibitor (DEGR-chloromethyl ketone). Thermal unfolding monitored by differential scanning calorimetry (DSC) reveals that Ca2+ stabilizes the SP domain slightly, increasing the unfolding temperature by 2.7 degrees C. In addition, Ca2+ is required for a large enthalpy change concomitant with unfolding of the Gla domain, and this unfolding enthalpy is only detectable in the presence of the SP domain, indicating some kind of interaction between these domains. Thermal unfolding measured by CD indicates secondary structural changes at the same temperature as the heat absorption in the DSC but only when both the Gla domain and the SP domain are present together with Ca2+ ions. Taken together, these results indicate a Ca2+-dependent interaction between the Gla domain and the SP domain, implying a high degree of flexibility of the domains in free fVIIa. It is also shown that the epidermal growth factor-like domains are stable at elevated temperatures and high GuHCl concentrations. Moreover, already at physiological temperature, subtle structural changes take place which influence the overall shape of fVIIa and are detrimental to its enzymatic activity.     

Purification of a 5-HT uptake inhibitor from the venom of Cerastes vipera

Heart rate (HR) and heart rate variability (HRV) are risk markers in cardiac disease. HRV is also an index of the sympathovagal modulation of heart rate. Their relations have been rarely analyzed. We aimed to study such relations in normal adult conscious rats by using a novel bradycardic agent, a sinus node inhibitor, S-16257. Placebo-drug crossover designs were used while monitoring HR with telemetry and analyzing HRV in both time and frequency domains. S-16257 (2 mg/kg; n = 10) decreased HR by 29% and markedly increased HRV in parallel. By using various combinations of S-16257, atropine (2 mg/kg), and propranolol (4 mg/kg), a positive relation was shown between RR interval and various indexes of HRV: the slower the HR, the greater the HRV. Nevertheless, there is one exception to this correlation. When S-16257 was associated with both atropine and propranolol, the deep bradycardia was accompanied by a reduction of HRV, which indicates that the physiologic negative correlation between HR and HRV is not an intrinsic property of the pacemaker but is highly dependent on the two components of the autonomic system.     

Complex probes for high-throughput parallel genetic mapping of genomic mouse BAC clones

We investigated the effect of centrally administered pituitary adenylate cyclase activating polypeptide (PACAP) on feeding in rats, and the involvement of hypothalamic neuropeptide gene expression using in situ hybridization. Intracerebroventricular injection of PACAP (1000 pmol/rat) significantly decreased food intake in a dose-dependent manner. In PACAP-treated rats, neuropeptide Y (NPY) mRNA levels in the arcuate nucleus and galanin mRNA levels in the paraventricular nucleus increased, and corticotropin-releasing hormone (CRH) mRNA levels in the paraventricular nucleus decreased. In rats fasted for 72 h, NPY mRNA levels increased, and CRH mRNA levels decreased, but galanin mRNA levels were unchanged. These results indicate that the anorectic function of PACAP is not mediated by NPY or CRH, and that PACAP increases galanin synthesis.