Content of First Prenatal Visits.

Objective The purpose of this study was to examine the content of the first prenatal visit within an academic medical center clinic and to compare the topics discussed to 2014 American College of Obstetrics and Gynecologists guidelines for the initial prenatal visit. Methods Clinical interactions were audio recorded and transcribed (n = 30). A content analysis was used to identify topics discussed during the initial prenatal visit. Topics discussed were then compared to the 2014 ACOG guidelines for adherence. Coded data was queried though the qualitative software and reviewed for accuracy and content. Results First prenatal visits included a physician, nurse practitioner, nurse midwife, medical assistant, medical students, or a combination of these providers. In general, topics that were covered in most visits and closely adhered to ACOG guidelines included vitamin supplementation, laboratory testing, flu vaccinations, and cervical cancer screening. Topics discussed less often included many components of the physical examination, education about pregnancy, and screening for an identification of psychosocial risk. Least number of topics covered included prenatal screening. Conclusions for Practice While the ACOG guidelines may include many components that are traditional in addition to those based on evidence, the guidelines were not closely followed in this study. Identifying new ways to disseminate information during the time constrained initial prenatal visit are needed to ensure improved patient outcomes.

Dry matter intake and feed efficiency profiles of 3 genotypes of Holstein-Friesian within pasture-based systems of milk production.

The primary objective of the study was to quantify the effect of genetic improvement using the Irish total merit index (Economic Breeding Index) on dry matter intake and feed efficiency across lactation and to quantify the variation in performance among alternative definitions of feed efficiency. Three genotypes of Holstein-Friesian dairy cattle were established from within the Moorepark dairy research herd: 1) low Economic Breeding Index North American Holstein-Friesian representative of the Irish national average dairy cow, 2) high genetic merit North American Holstein-Friesian, and 3) high genetic merit New Zealand Holstein-Friesian. Animals from within each genotype were randomly allocated to 1 of 2 possible intensive pasture-based feed systems: 1) the Moorepark pasture system (2.64 cows/ha and 500 kg of concentrate supplement per cow per lactation) and 2) a high output per hectare pasture system (2.85 cows/ha and 1,200 kg of concentrate supplement per cow per lactation). A total of 128 and 140 spring-calving dairy cows were used during the years 2007 and 2008, respectively. Each group had an individual farmlet of 17 paddocks, and all groups were managed similarly throughout the study. The effects of genotype, feed system, and the interaction between genotype and feed system on dry matter intake, milk production, body weight, body condition score, and different definitions of feed efficiency were studied using mixed models with factorial arrangements of genotypes and feed systems accounting for the repeated cow records across years. No significant genotype-by-feed-system interactions were observed for any of the variables measured. Results showed that aggressive selection using the Irish Economic Breeding Index had no effect on dry matter intake across lactation when managed on intensive pasture-based systems of milk production, although the ranking of genotypes for feed efficiency differed depending on the definition of feed efficiency used. Performance of animals grouped on alternative definitions of feed efficiency showed that conventional definitions such as feed conversion efficiency or residual feed intake may be inappropriate measures of efficiency for lactating dairy cows. An alternative definition, residual solids production, is proposed. This definition of feed efficiency identifies animals that produce greater volumes of milk solids at similar levels of feed intake without excessive body tissue mobilization and with improved fertility performance. The results also suggest that although there are differences in feed efficiency between strains of Holstein-Friesian, there is also variation within genotypes so that improvements in feed efficiency can be realized if the appropriate definition of feed efficiency is incorporated into breeding programs.

Loudness predicts prominence: fundamental frequency lends little.

We explored a database covering seven dialects of British and Irish English and three different styles of speech to find acoustic correlates of prominence. We built classifiers, trained the classifiers on human prominence/nonprominence judgments, and then evaluated how well they behaved. The classifiers operate on 452 ms windows centered on syllables, using different acoustic measures. By comparing the performance of classifiers based on different measures, we can learn how prominence is expressed in speech. Contrary to textbooks and common assumption, fundamental frequency (f0) played a minor role in distinguishing prominent syllables from the rest of the utterance. Instead, speakers primarily marked prominence with patterns of loudness and duration. Two other acoustic measures that we examined also played a minor role, comparable to f0. All dialects and speaking styles studied here share a common definition of prominence. The result is robust to differences in labeling practice and the dialect of the labeler.

The management and survival of patients with advanced germ-cell tumours: improving outcome in intermediate and poor prognosis patients.

AIMS: The survival of germ-cell tumours (GCT) was transformed after the introduction of cisplatin-based therapy. Previous trials have indicated BEP (bleomycin, etoposide and cisplatin) as the optimum treatment, although some centres including our own advocate the use of the alternating regimen POMB-ACE (cisplatin, vincristine, methotrexate, bleomycin and dactinomycin, cyclophosphamide and etoposide) for men with intermediate or poor prognosis disease. We analysed the survival and management of GCT patients treated at a specialist cancer centre in relation to internationally recognised prognostic groupings. MATERIALS AND METHODS: We retrieved patient information using the Trent Testicular Tumour Registry and supplemented it with information from patient notes. This included all patients with Royal Marsden Hospital Stage II, III and IV disease and patients with stage I disease at diagnosis with raised markers or subsequent relapse. We compared the efficacy and toxicity of the BEP and POMB-ACE chemotherapy regimens, and assessed relapse-free and overall survival. RESULTS: We identified 178 non-seminomatous germ cell tumours (NSGCT) and 71 seminoma patients. Overall survival was similar to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification for the good (95% vs 92%) and intermediate groups (82% vs 80%). The outcome for the poor prognosis group was better than expected in our series (57% vs 48%). There was a higher proportion of both immediate and late side-effects with POMB-ACE. CONCLUSION: Survival and disease progression rates at this single institution were at least as good as reported by the IGCCCG and somewhat better for the poor-prognosis group. This may reflect use of the POMB-ACE chemotherapy regimen as opposed to standard BEP regimen. However, a randomised comparison of BEP and POMB-ACE would be required to validate this.

Characterization of specific IgE response in vitro against protein and drug allergens using atopic and normal donors.

BACKGROUND: As the incidence of allergy to different compounds increases in society, the need to understand and characterize specific IgE responses becomes obvious. Different cell culture systems have been evaluated for their ability to support such IgE secretion. METHODS: One system employed human peripheral lymphocytes (PBL) from normal donors stimulated with anti-CD3 activated T cells with or without the presence of allergens like benzylpenicillin (BP) and Phlenum pratense (PP). Secretion of IgE was analyzed in ELISA and compared to the IgG response to the nonallergenic antigen tetanus toxoid (TT). Another system employed stimulation of T and B cells with a heterotope, consisting of a T helper cell epitope derived from TT, and a B cell allergen epitope derived from BP. The specific IgE secretion was compared, using lymphocytes from normal as well as BP-allergic donors. RESULTS: Anti-CD3 stimulated T cells supported BP-specific IgE secretion in six of 11 normal donors. This response was inhibited in four donors and enhanced in two donors by the addition of the BP-allergen to the culture. In contrast, addition of the protein allergen (PP) or antigen (TT) to the same culture system inhibited both IgE and IgG synthesis in all experiments. Cells from the majority (10/16) of the BP-allergic donors failed to produce BP-specific IgE in vitro, when cultured in the presence of allergen. CONCLUSIONS: An allergen specific immune response is readily generated in vitro. The differential response against benzylpenicillin between different donor categories most probably reflects the level of pre-exposure to this allergen in vivo.

Integrated case management: the 21st century challenge for HMO case managers: Part I.

As HMOs approach the new millennium, their care and cost management strategies still will be under attack by policy-makers, legislative bodies, the media, American businesses, and the medical professions. The HMO industry will continue to be held accountable for the efficiency of its services, the quality of its care, and the performance and outcome measures that are the results of managing both the care and medical costs of its membership. This first of a two-part series put forward the concept of an integrated CM model to manage the total care of needs of HMO members at the turn of the century. This model consists of three care management approaches commonly used in mature HMOs: demand management, CM, and DM, as illustrated in Figure 1 and defined in Table 1. This article also described the new challenges facing HMOs, physicians, and nurse case managers and how they are navigating the difficult process of mapping demand management and CM approaches to the medical, social, and environmental needs of HMO members. With the costs of chronic conditions consuming 61% of the nation's annual health bill and increased numbers of the elderly joining HMOs, HMOs strongly need to implement DM approaches for economic survival reasons alone. Part two of this series will focus on the newest care management approach: disease state management.

Postnatal cytoarchitecture of the rat medial geniculate body.

The medial geniculate body (MGB) is a thalamic structure that provides vital information flow to the forebrain for complex acoustic processing. The development of cytoarchitectural features of the MGB was examined in rat to identify age-related patterns of growth in major geniculate compartments that have been described previously (Clerici and Coleman [1990] J. Comp. Neurol. 297:14-31; Clerici et al. [1990] J. Comp. Neurol. 297:32-54): the ventral (MGv), dorsal (MGd), and medial (MGm) divisions. Results show that, on the day of parturition, all major nuclei of each division are characterized, including the ovoid (OV) and ventral (LV) nuclei of MGv; the dorsal, deep dorsal (DD), caudodorsal, limitans, and suprageniculate nuclei of MGd; and the MGm. The MGv and MGd, which display comparable areas at birth, show rapid growth to postnatal day 7 (PND7), which then slows until PND11, around the time of ear canal opening; subsequently, MGv accelerates growth to reach larger adult size. From PND11 to PND16, thionin facilitates parcellation by extensive staining of dendritic processes of MGd, MGm, and lateral posterior nucleus neurons but not neurons of the MGv or the dorsal lateral geniculate nucleus. Golgi stains after birth reveal restricted dendritic arborizations in MGv cells and dichotomous branching patterns of MGd neurons. Somal size in MGB increases dramatically subsequent to afferent innervation and again following onset of auditory function. Somal growth occurs between all postnatal age groups tested for OV, LV, and DD nuclei, although LV segments related to high and low frequencies do not differ. Cell packing density predicts the expanse of major MGB divisions better than somal size. These results demonstrate the integrity and growth patterns of MGB nuclei and divisions from nascence and provide a substrate for subsequent study of anatomical and physiological development of the MGB.

Lateral laryngotomy for the removal of Teflon granuloma.

Teflon injection has been used for vocal fold medialization following paralysis. Recently, numerous articles have discussed the complications of Teflon injection, including overinjection, airway obstruction. Teflon granuloma, and an abnormal mass effect creating a decreased vibratory character of the true vocal fold. Multiple techniques for Teflon removal have been described. This report details our experience with complete Teflon granuloma removal via a lateral laryngotomy under local anesthesia. Microscopic dissection of the entire granuloma and the paraglottic space was accomplished in all patients. Due to extensive destruction caused by the granuloma, the vocal ligament was resected in 3 patients; it was partially resected and reanastomosed in 1 case, and spared in 6 patients. Laryngeal reconstruction was accomplished with an inferiorly based sternohyoid muscle rotation flap and arytenoid adduction. Effortful speech secondary to pressed vocal quality resolved in all patients. Near-normal to normal vocal quality was obtained in 4 patients, with the average "voice desirability" improving 60% and the effective glottic width increasing 29%. Factors that contributed to a successful outcome included noninvolvement of the vocal ligament and sparing of the mucosal cover.

Characterization of the physiological requirements for the bactericidal effects of a monoclonal antibody to OspB of Borrelia burgdorferi by confocal microscopy.

A confocal microscopy study was undertaken to characterize the bactericidal effects of the Fab fragments of CB2, an immunoglobulin G1kappa murine monoclonal antibody, to an epitope in the carboxy region of the outer surface protein B (OspB) of Borrelia burgdorferi. Simultaneous direct labeling of both fixed and live spirochetes with fluorochrome-labeled Fab-CB2 and 11G1, and an immunoglobulin Mkappa monoclonal antibody to OspA, showed that OspA and OspB seem to colocalize in dead spirochetes but do not appear to be physically associated when the organisms are alive. A polar bleb composed of a Fab-CB2-OspB complex, followed by incorporation of 11G1-OspA, precedes the formation of a spheroplast. The spheroplasts contain both OspA and OspB and are a terminal stage in the bactericidal process induced by Fab-CB2. Outer membrane destabilization by Fab-CB2, but not cell wall or cytoplasmic membrane alterations, was demonstrated experimentally by the sequential treatment of spirochetes with Fab-CB2 and monoclonal antibodies to flagellin and DnaK. The action of Fab-CB2 is epitope specific, as another monoclonal antibody to an epitope in the amino terminus of OspB was not bactericidal. The bactericidal effect of Fab-CB2 is not dependent on the induction of spirochetal proteases but is dependent on the presence of Ca2+ and Mg2+. Supplementation of Ca2(+)- and Mg2(+)-free medium with these cations restored the bactericidal effects of Fab-CB2. The mechanism by which a Fab fragment of an antibody destroys a bacterium directly may represent a novel form of antibody-organism interaction.

Effects of tectal grafts on sound detection deficits induced by inferior colliculus lesions in hooded rats.

The midbrain inferior colliculus (IC), a major integrating center for auditory processing, provides a model for structural, functional, and behavioral recovery. The present study examined the role of IC in spatial sound detection, and the effects of neural transplantation in sparing of behavioral performance. Hooded rats were presented noise bursts at ambient noise levels and 15 dB above this level randomly at one of eight locations in the horizontal plane, and rats were required to suppress licking upon detecting signal presentations. Following training, rats received bilateral IC lesions, bilateral lesions followed in 1 wk by bilateral tectal grafts (embryonic Day 18), or were sham operated. During repeated testing 15 to 30 days and 40 to 45 days following surgical procedures, rats with lesions showed impaired detection task performance when compared to grafted or sham animals. Detection ratios were statistically higher for grafted rats than for rats with lesions at repeated testing times. Performance of grafted animals was not statistically separable from the sham control group; however, grafted rats never achieved preoperative detection rates nor rates as high as sham rats. Postmortem implantation of diI crystals unilaterally into grafts demonstrated fiber labeling in the ipsilateral IC and lateral lemniscus, and retrograde labeling of neurons in the remaining host IC and dorsal nucleus of lateral lemniscus. Combined with results of previous studies, the results of this study suggest that sparing of detection performance for sounds occurring at random spatial locations may be attributable to partial integration of host-graft pathways.

Development and submission of a nonclinical (pharmacology/toxicology) CANDA.

The experience with the submission of a nonclinical (pharmacology and toxicology) computer-assisted New Drug Application (CANDA) is reviewed. This system consisted of a stand-alone personal computer running several commercial programs in Microsoft Windows to access both text and data. WordPerfect was used as the word processor that contained all the documents and data tables (in read-only format) that were submitted in hard copy, and Andyne GQL was used as a tool to query the data in an Oracle relational database. Microsoft Excel was provided as a spreadsheet for graphics and analysis of data. Documents appeared virtually identical to those in the hard copy NDA submission. Searching the text was facilitated by the use of buttons on the screen, which allowed the NDA to be searched for a particular term. Data could be located either in WordPerfect documents, or in an Oracle database (using Andyne GQL) by querying the data. The data queries could be performed ad hoc, in which the reviewer selected all the parameters for a search, or with predefined query buttons, which retrieved data for principal treatment-related changes. This type of system also could serve as a useful model for both in-house nonclinical review and the submission of INDs and IND amendments.

Isolation and characterisation of a maize cDNA that complements a 1-acyl sn-glycerol-3-phosphate acyltransferase mutant of Escherichia coli and encodes a protein which has similarities to other acyltransferases.

We selected cDNA plasmid clones that corrected the temperature-sensitive phenotype of Escherichia coli strain JC201, which is deficient in 1-acyl-sn-glycerol-3-phosphate acyltransferase activity. A plasmid-based maize endosperm cDNA library was used for complementation and a plasmid that enabled the cells to grow at 44 degrees C on ampicillin was isolated. Addition of this plasmid (pMAT1) to JC201 restored 1-acyl-sn-glycerol-3-phosphate acyltransferase activity to the cells. Total phospholipid labelling showed that the substrate for the enzyme, lysophosphatidic acid, accumulated in JC201 and was further metabolised to phosphatidylethanolamine in complemented cells. Membranes isolated from such cells were able to convert lysophosphatidic acid to phosphatidic acid in acyltransferase assays. The cDNA insert of pMAT1 contains one long open reading frame of 374 amino acids which encodes a protein of relative molecular weight 42,543. The sequence of this protein is most similar to SLC1, which is thought to be able to acylate glycerol at the sn-2 position during synthesis of inositol-containing lipids. Homologies between the SLC1 protein, the 1-acyl-sn-glycerol-3-phosphate acyltransferase of E. coli (PlsC) and the maize ORF were found with blocks of conserved amino acids, whose spacing was conserved between the three proteins, identifiable.

Noise-induced elevations of plasma endothelin (ET-3).

The endothelins (ETs) are a novel family of peptides which participate in hemodynamic homeostasis. Elevated levels of circulating ETs are evident in several stress related conditions and are associated with a variety of vascular pathophysiologies. The purpose of the current study was to test the possibility that plasma concentrations of endothelin increase following noise exposure using radioimmunoassay (RIA). No difference in plasma endothelin was detected in rats subjected to brief noise exposure (30 min of 100 dB SPL broad-band noise) compared to control animals. Statistically significant elevations in plasma endothelin (ET-3) were measured in animals exposed to prolonged noise exposure (90 min and 72 h of 100 dB SPL broad-band noise). These results suggest that hemodynamic alterations, and potential vascular pathophysiologies accompanying prolonged exposure to noise are mediated by endothelin.

Characterization of pea chloroplastic carbonic anhydrase. Expression in Escherichia coli and site-directed mutagenesis.

A cDNA encoding the mature, chloroplast-localized carbonic anhydrase in pea has been expressed in E. coli. The enzyme is fully active and yields of up to 20% of the total soluble protein can be obtained from the bacteria. This expression system was used to monitor the effects of site-directed mutagenesis of seven residues found within conserved regions in the pea carbonic anhydrase amino acid sequence. The effects of these modifications are discussed with respect to the potential of various amino acids to act as sites for zinc coordination or intramolecular proton shuttles.

Micronutrient supplementation in children on continuous cycling peritoneal dialysis (CCPD).

Data on the micronutrient (vitamin and trace mineral) requirements of children on chronic peritoneal dialysis is limited. Few preparations are of suitable content and palatability. In a prospective study we have assessed and compared the serum levels and dietary intakes of micronutrients (vitamins A, E, B12, folate and zinc, copper, iron) in 7 children on CCPD who were receiving either Ketovite tablets (vitamins C, E and B complex) and Cholecalciferol or a more comprehensive supplement, Paediatric Renal Seravit (vitamins A, E, D, C and B complex with trace minerals). All children received nutritional supplements orally or via a gastrostomy button. These supplements contributed significantly to their nutritional intakes. The mean dietary intakes of the studied micronutrients, with the exception of vitamins A, E, B12 and folate, were below RDA (USA) values. The Renal Seravit was tolerated by only 5 of the 7 patients. There was no significant difference in serum levels of the micronutrients while on the Paediatric Renal Seravit compared to Ketovite. Serum iron levels remained low on both supplements. A comprehensive micronutrient supplement may still be required in children on prolonged dialysis.

Drug-protein conjugates--XVII. The effect of storage on the antigenicity and immunogenicity of benzylpenicillin in the rat.

The disposition and immunogenicity of freshly prepared and stored solutions of benzylpenicillin (BP) and benzylpenicillenic acid (BPE), a degradation product of BP, were studied. No IgG anti-benzylpenicilloyl (BPO) antibodies were detected by enzyme-linked immunosorbent assay (ELISA) following daily i.p. or i.m. administration to male Wistar rats of BP (2.7 mmol/kg) freshly dissolved in 0.5% glucose, for 4 consecutive days at 4-week intervals. In contrast, IgG anti-BPO antibodies were detected following both chronic i.p. and i.m. administration of BP (2.7 mmol/kg) stored for 24 hr at room temperature in 0.5% glucose. An IgG anti-BPO response was obtained only after the high dose, following daily i.m. administration of BPE (27 mumol/kg, 2.7 mumol/kg, 0.24 mumol/kg). The specificity of the IgG antibody for the BPO-determinant was confirmed by ELISA inhibition with BPO-amino-caproate. Circulating BPO plasma-protein antigens were detected by a modified ELISA following i.p. and i.m. administration of both stored and fresh BP. Significantly lower BPO-antigen levels were detected in serum following BPE administration. Irreversible binding of BP to 75% rat plasma proteins was of the same magnitude when freshly dissolved in phosphate buffer or in 0.5% glucose (2.63 +/- 0.32% and 2.55 +/- 0.25% bound, respectively after 3 hr incubation at 37 degrees). Irreversible binding was significantly greater (P less than 0.05) when the BP was stored prior to incubation with the protein (3.81 +/- 0.27%). The major degradation product of stored BP was benzylpenicilloic acid; a small amount of BPE (0.2% of incubated BP) was detected in stored but not fresh BP. Thus, the increased immunogenicity of BP stored for 24 hr at room temperature may be due to the formation of reactive degradation products such as BPE in vitro, which can then form immunogenic drug-protein conjugates in vivo. These experiments also show that although BP and BPE form drug-protein conjugates in vivo, circulating levels of antigen do not relate to the immunogenicity of either of the compounds.

Effect of paraquat on lung calcium transport.

The effect of paraquat on lung subcellular calcium transport was studied in male Sprague-Dawley rats. With a high dose of 30 mg/kg given i.p., a significant decrease in the lung mitochondrial and microsomal calcium uptake at 24, 48, and 72 h after paraquat was observed. Trend of recovery was evident at 96 h in the surviving rats. The lung water content and thymidine incorporation into the lung DNA increased significantly after 72 h and 48 h of paraquat administration, respectively. Groups of animals also received a lower dose of paraquat at 10 mg/kg i.p. and were sacrificed at 1, 2, 3, 4, 6, and 8 days. Continuous decrease in the mitochondrial and the microsomal calcium uptake until 4 days followed by a trend of recovery were observed. Thymidine incorporation into the lung DNA increased significantly at all the time periods after day 3 but no significant increases were observed in the lung water content at this dose. The results indicate that paraquat significantly disrupts the lung intracellular calcium uptake even at the doses which do not show any significant increase in the lung water content.

Drug-protein conjugates--XV. A study of the disposition of D-penicillamine in the rat and its relationship to immunogenicity.

The disposition of [14C]D-penicillamine (PA) was investigated in vitro and in vivo with male Wistar rats. Irreversible binding of [14C]PA to isolated rat plasma proteins in vitro reached a maximum of 20.6% of total radioactivity at 6 hr. Irreversibly bound [14C]PA could be dissociated with dithiothreitol, demonstrating that conjugation was via disulphide linkage. Three hours after i.v. administration of [14C]PA (27 mumol/kg) to rats 100% of plasma radioactivity was irreversibly bound, representing approximately 3.5% of the dose. Further studies on the disposition of PA-plasma protein conjugates showed that dissociation occurred readily in vivo: the plasma half-life of the conjugate was approximately 3 hr. Free [14C]PA was the major urinary metabolite after administration of both free and conjugated drug. These studies show that the disposition of PA is similar to that reported for the structurally related sulphydryl drug captopril (CP). Free PA (340 mumol/kg and 3.4 mmol/kg) administered i.p. and i.m. daily for 4 days at one monthly intervals, and also PA-KLH conjugate (100 micrograms/rat) administered by single i.p. injection at monthly intervals with and without Freund's complete adjuvant, failed to induce PA-specific IgG or IgM antibody responses detectable by ELISA. In contrast, CP (270 mumol/kg), administered by the same protocol as free PA, induced a CP-specific IgG antibody response after the third series of monthly injections. These data suggest that the difference in immunogenicity between PA and CP arises from a difference in the intrinsic immunogenicity of the haptens, rather than from their disposition.