brother of rhomboid, a rhomboid-related gene expressed during early Drosophila oogenesis, promotes EGF-R/MAPK signaling.

The Drosophila rhomboid (rho) gene participates in localized activation of EGF-receptor signaling in various developmental settings. The Rhomboid protein has been proposed to promote presentation and/or processing of the membrane-bound Spitz (mSpi) EGF-related ligand to generate an active diffusible form of the ligand. Here, we report on a new rhomboid-related gene identified by sequence similarity searching that we have named brother of rhomboid (brho). In contrast to rho, which is expressed in complex patterns during many stages of development, brho appears to be expressed only during oogenesis. brho transcripts are present in early oocytes and abut posterior follicle cells which exhibit high levels of MAPK activation. brho, like rho, collaborates with Star to promote signaling through the EGF-R/MAPK pathway, and genetic evidence indicates that Brho can activate both the mSpi and the Grk precursor EGF ligands in the wing. We propose that endogenous brho may activate the oocyte-specific Gurken ligand and thereby participate in defining posterior cell fates in the early follicular epithelium.

Safety and acceptability of a baggy latex condom.

A total of 104 couples participated in a randomized crossover trial to compare a new baggy condom with a straight-shaft condom produced by the same manufacturer. Participants completed a coital log after using each condom. All couples used five condoms of each type. Among 102 couples who did not report major deviations from the protocol, the breakage rate was eight of 510 (1.6%) for the baggy condom, and six of 510 (1.2%) for the standard condom (rate difference, RD = 0. 4%, 95% confidence interval of the RD, CI = -1.0%; +1.8%). Slippage was reported in 50 baggy condom logs and in 58 standard condom logs; the slippage rate was 50 of 510 (9.8%) for the baggy condom, and 58 of 510 (11.4%) for the standard condom (RD = -1.6%, 95% CI = -5.4%; +2.2%). Slippage was most often partial (<1 inch) and may not indicate condom failure. Severe slippage rates were 11 of 510 (2.2%) for the baggy condom, and 18 of 510 (3.5%) for the standard condom (RD = -1.4%, 95% CI = -3.4%; +0.7%). The findings support the conclusion that the two condoms are equivalent with respect to breakage and slippage. The participants appeared to prefer the baggy condom, suggesting that the new product may be more acceptable to the public than the traditional straight-shaft condoms, and may be easier to use consistently over long time periods.

Critical pathways.

A critical Pathway (CP) is a clinical management tool that helps medical care providers coordinate the delivery of patient care for a particular case type or condition. As a guide to usual treatment patterns, a CP gives a view of the "big picture." The CP usually recommends a total treatment regimen. Treatment regimens are formulated through the consensus of a multi-disciplinary collaboration of all those involved in a patient's care. If developed and implemented properly, critical paths can lead to desirable outcomes for the patient and improved operating effectiveness/efficiency for the healthcare facility. Components of CPs often include protocols, algorithms, and clinical practice guidelines. Metrics, bench-marks, compliance, and variances become common terms among members of the healthcare team. Although CPs have gained wide acceptance as inpatient management tools, they are rapidly being sought for outpatient settings as well. This article details the CP process and cites examples of two hospitals that have used CPs to reduce length of stay and cut costs.

The Drosophila rhomboid protein is concentrated in patches at the apical cell surface.

Patterned expression of the Drosophila rhomboid (rho) gene is thought to promote signaling by the EGF receptor (EGFR) in specific cell types. In this report we examine the subcellular localization of the Rhomboid protein (Rho) which is predicted to be an integral membrane protein. At the light level, immunocytochemical staining for Rho reveals a small number of large patches (or plaques) at or near the apical cell surface. In some cells Rho plaques colocalize with Armadillo at adherens junctions, while in other cells plaques are only found basal to the adherens junction. Immunoelectron microscopy reveals that Rho plaques are composed of a highly localized patch of plasma membrane and a densely staining underlying structure. Concentration of Rho in distinct plaques depends on a balance of synthesis and membrane recycling since increasing the amount of rho expression or blocking membrane recycling leads to more uniform cell surface labeling. A limiting cellular component also appears to be required for concentrating Rho in plaques. We discuss clustering of Rho in plasma membrane patches with respect to the proposed role of Rho in promoting EGF-R signaling.

scratch, a pan-neural gene encoding a zinc finger protein related to snail, promotes neuronal development.

The Drosophila scratch (scrt) gene is expressed in most or all neuronal precursor cells and encodes a predicted zinc finger transcription factor closely related to the product of the mesoderm determination gene snail (sna). Adult flies homozygous for scrt null alleles have a reduced number of photoreceptors in the eye, and embryos lacking the function of both scrt and the pan-neural gene deadpan (dpn), which encodes a basic helix-loop-helix (bHLH) protein, exhibit a significant loss of neurons. Conversely, ectopic expression of a scrt transgene during embryonic and adult development leads to the production of supernumerary neurons. Consistent with scrt functioning as a transcription factor, various genes are more broadly expressed than normal in scrt null mutants. Reciprocally, these same genes are expressed at reduced levels in response to ectopic scrt expression. We propose that scrt promotes neuronal cell fates by suppressing expression of genes promoting non-neuronal cell fates. We discuss the similarities between the roles of the ancestrally related scrt, sna, and escargot (esc) genes in regulating cell fate choices.

Econotherapeutics.

A program that represents the efforts of a hospital pharmacy management company to control drug costs is described. The program, Econotherapeutics, was developed in response to a changed health care reimbursement system that focused on the costs of products rather than the revenue generated by these products. For antimicrobial agents, a hospital-specific antibiogram is used to encourage cost-effective prescribing. A pharmacist intervention program, medical staff presentations, drug usage evaluation, management systems, and educational programs for pharmacists are all essential parts of the program. Centralized data gathering has allowed cost comparison of specific antimicrobial agents so that differences between variable cost estimates and costs based on actual use can be evaluated. Actual dose and dosage interval were used to calculate average cost per treatment day in a 121-hospital sample. Our cost data support the choice of cefotaxime over ceftriaxone.

The Drosophila rhomboid gene mediates the localized formation of wing veins and interacts genetically with components of the EGF-R signaling pathway.

The rhomboid (rho) gene, which encodes a transmembrane protein, is a member of a small group of genes (ventrolateral genes) required for the differentiation of ventral epidermis in the Drosophila embryo. The ventrolateral genes include spitz, which encodes an EGF-like ligand, and Star. The receptor for spitz may be the gene encoding the Drosophila epidermal growth factor-receptor (Egf-r) because the phenotype resulting from partial loss of function of Egf-r is similar to that of ventrolateral group mutants. Among ventrolateral genes encoding cell-surface or secreted proteins, rho is the only member expressed in a localized pattern corresponding to cells requiring the activity of the ventrolateral pathway. In this paper we provide evidence that spatial localization of rho plays an analogous role in establishing vein pattern in the adult wing. rho is expressed in early wing disc cells likely to be wing vein primordia and later is sharply restricted to developing veins. Flies homozygous for the viable rho(ve) allele have missing veins and rho fails to be expressed in rho(ve) mutant wing discs. Ectopic expression of rho during wing development leads to the formation of extra veins. Gene dosage studies among ventrolateral genes suggest that the rho product (Rho) may facilitate Spi-EGF-R signaling, resulting in activation of RAS. We discuss models for how localized expression of Rho may amplify signaling mediated by ubiquitously distributed ligand and receptor components.

An evaluation of the effect of gonadotropin-releasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: a prospective, randomized, double blind, placebo-controlled, crossover trial.

The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/day) in either the first (protocol A) or last (protocol B) 12-week period along with a 6-month course of the GnRH analog (GnRH-a; leuprolide acetate; 1 mg/day, sc) on uterine and leiomyomata volumes and hormone (estradiol, LH, and FSH) and serum lipid (total cholesterol, triglycerides, and high and low density lipoprotein) levels. Sixteen women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, respectively, and were then crossed over at 12 weeks to placebo or MPA, respectively, for the final 12-week interval of GnRH-a therapy. Total, myoma, and nonmyoma uterine volumes were determined by magnetic resonance imaging, and serum studies were performed at the beginning of the study and at 12 and 24 weeks. In both protocols, LH and estradiol levels declined by 80-90% (P < 0.03) and 55-72% (P < 0.02) of the baseline, respectively, at 12 weeks and remained at this level at 24 weeks. There were no significant changes in the other laboratory tests between protocols or longitudinally over time. Total uterine volume decreased to 73% of the baseline at 12 weeks in protocol B (P < 0.04), but did not change in protocol A. After crossover at 12 weeks, the total uterine volume of women in protocol A decreased to 74% of the baseline (P < 0.02) at 24 weeks. Between-protocol comparisons demonstrated a greater decline in total uterine volume in protocol B than A at 12 weeks, but after cross-over, MPA addition was associated with a significant increase in total uterine volume (protocol B) compared to a decrease in protocol A at 24 weeks (P < 0.005). In contrast, although myoma volume declined in both protocols, no significant changes in myoma volume were detected within or between groups over the treatment period. Nonmyoma volume changes in protocols A and B roughly paralleled total uterine volume changes, with MPA coadministration showing a correlation with a reversal in the GnRH-a-associated decrease in nonmyomatous tissue volume.(ABSTRACT TRUNCATED AT 400 WORDS)

Slowing rate of cost increases in the pharmacy.

As the emergence of new drugs and technology and the growing acuity of patients drive up the cost of hospital pharmaceuticals, hospital administrators can act to slow the rate of increase. The key, writes the author, lies in recognizing that newness in pharmaceuticals does not equal clinical superiority or cost-effectiveness.

Fine-structure mutational analysis of a stage- and tissue-specific promoter element of the Drosophila glue gene Sgs-3.

The Sgs-3 gene of Drosophila melanogaster exhibits a tightly regulated pattern of expression governed by two functionally equivalent elements within 1 kb of the gene, each of which is sufficient to confer third-instar salivary gland-specific transcription. In this report we describe a detailed functional analysis of one of these, the proximal element. To determine the nucleotides responsible for specific expression, we have introduced mutations into the proximal element and then assessed the effects of each alteration on expression in the developing animal. We have identified six particularly important base pairs which are located in two regions separated by nonessential sequences. These base pairs, along with some surrounding sequence, are conserved within the upstream regions of the three glue genes at 68C. Nearly identical groups of base pairs can be found upstream of the other glue genes which have been cloned. This analysis has allowed us to derive a consensus sequence, which we believe contains binding sites for two different factors which interact to direct third-instar salivary gland-specific expression.

Cooperative enhancement at the Drosophila Sgs-3 locus.

The Drosophila glue gene Sgs-3 is specifically expressed in the secretory cells of the salivary glands of third instar larvae. We have assayed the expression of gene fusions to determine the role of cis-acting Sgs-3 sequences in conferring this pattern of expression. These experiments define two regulatory regions required for expression of reporter genes from the Sgs-3 promoter. One region, between 106 and 56 bp upstream of the Sgs-3 mRNA 5' end is sufficient for low but correct tissue- and stage-specific expression. A second region, lying between 629 and 130 bp 5' of the RNA start site is functionally equivalent; that is, it alone will also direct low level, specific expression. These two regions act synergistically to give high level expression. More distant upstream regions function to further increase levels of expression. These two regulatory elements can confer a salivary gland-specific pattern of expression on a heterologous promoter and are also sufficient to drive gene expression in other Drosophila species, implying conservation of regulators.

Ticarcillin/clavulanate in the treatment of pelvic infections.

Ticarcillin/clavulanate was used to treat 130 women with pelvic infections. The 129 who completed an initial course of treatment with ticarcillin/clavulanate were analyzed according to type and clinical severity of infection, and pretreatment and posttreatment endometrial bacteriology. There were 26 cases of pelvic inflammatory disease and 103 puerperal infections, 61 of which occurred in women who had delivered by cesarean section (46 elective with no antibiotic prophylaxis at the time of surgery). Of the 129 patients treated, 124 were clinically cured, and one improved (97%). There were four treatment failures, all of which were among a total of 20 cases classified as clinically severe. All the patients designated as treatment failures required prolonged treatment with other antibacterials to achieve a clinical cure, but a longer duration of treatment with ticarcillin/clavulanate might have effected a clinical resolution even in these cases. In vitro examination of endometrial isolates revealed a significant reduction of the minimum inhibitory concentrations (MICs) of beta-lactamase-producing bacteria with the addition of clavulanate to ticarcillin. The relationship of non-beta-lactamase-producing enterococci having relatively high MICs to clinical failure was examined.

Thyrotoxicosis complicating pregnancy.

During the 12-year period from 1974 through 1985, nearly 120,000 women were delivered of infants at Parkland Hospital, and pregnancy was complicated by overt thyrotoxicosis in 60 of them (1:2000). Initial treatment was based on clinical assessment, and propylthiouracil was usually given in doses of 300 to 800 mg daily. In compliant women seen by midpregnancy, euthyroidism was achieved by a mean of 8 weeks; however, the daily dose was decreased to less than or equal to 150 mg by delivery in only 10%. Metabolic status at delivery correlated directly with pregnancy outcome, and women treated earlier in pregnancy were more likely to be euthyroid at delivery and to have good outcomes. Diagnosis of thyrotoxicosis antecedent to pregnancy was associated with earlier treatment, and 80% of 28 such women were euthyroid by delivery. Conversely, 32 women with a first diagnosis during pregnancy had the preponderance of morbidity, including five of six stillbirths and six of seven cases of heart failure. This group was characterized by a relative delay in gestational age at diagnosis. Preterm delivery, perinatal mortality, and maternal heart failure were more common in women who remained thyrotoxic despite treatment and in those who were never treated. Although we infrequently achieved maintenance doses recommended by most, because there were minimal adverse effects from therapy described here and because uncontrolled thyrotoxicosis caused significant maternal and perinatal morbidity, aggressive medical therapy seems appropriate, especially when pregnancy is advanced.

Transcripts of the Drosophila blastoderm-specific locus, terminus, are concentrated posteriorly and encode a potential DNA-binding finger.

The commitment of cells to specific fates, as well as the transitions in the cell cycle and transcription that occur at the cellular blastoderm stage of Drosophila embryogenesis, suggest that there are genes with unique functions expressed specifically at this stage. In an attempt to identify such genes, we used molecular screening to isolate several loci which encode blastoderm-specific transcripts (Roark et al., (1985). Dev. Biol. 109, 476-488). We report here the complete nucleotide sequence of one of these genes, terminus (ter), which maps to 75C1,2. The predicted ter protein possesses a transcription factor IIIA (TFIIIA)-like putative Zn-binding, DNA-binding finger. The ter RNA, detected by in situ hybridization, is distributed uniformly in the embryo during the syncytial blastoderm stage, and then becomes more concentrated in the posterior during the late cellular blastoderm stage. During gastrulation, the RNA is most concentrated in the amnioproctodeal invagination; it is also found at a lower concentration in the ventral furrow and in the anterodorsal neurogenic region. By the end of germ band extension, ter RNA is no longer detected.

Cervical dilatation and prematurity revisited.

Cervical examination between 26 and 30 weeks' gestation is described as a method for identifying women at risk for delivery before 34 weeks. Blinded cervical examinations were performed in 185 consecutive women, and 15 (8%) were found to have cervixes dilated 2 or 3 cm. The incidence of delivery before 34 weeks' gestation was 27% in such women compared with 2% in those whose cervixes were undilated or 1 cm. Other factors linked to cervical dilatation included parity and prior preterm delivery. However, parous women with cervical dilatation remained at increased risk for delivery before 34 weeks' gestation. We conclude that early third-trimester cervical examination may be an important adjunct in identifying women at risk for preterm delivery.

A prospective comparison of selective and universal electronic fetal monitoring in 34,995 pregnancies.

We investigated the effects of using intrapartum electronic fetal monitoring in all pregnancies, as compared with using it only in cases in which the fetus is judged to be at high risk. Predominant risk factors included oxytocin stimulation of labor, dysfunctional labor, abnormal fetal heart rate, or meconium-stained amniotic fluid. This prospective alternate-month clinical trial took place over a 36-month period during which 34,995 women gave birth. In alternate months, either 7 (for "selective monitoring") or 19 (for "universal monitoring") fetal monitors were made available in the labor and delivery unit. During the "selective" months, 6420 of 17,409 women (37 percent) were electronically monitored, as compared with 13,956 of 17,586 women (79 percent) during the "universal months." Universal monitoring was associated with a small but significant increase in the incidence of delivery by cesarean section because of fetal distress, but perinatal outcomes as assessed by intrapartum stillbirths, low Apgar scores, a need for assisted ventilation of the newborn, admission to the intensive care nursery, or neonatal seizures were not significantly different. We conclude that not all pregnancies, and particularly not those considered at low risk of perinatal complications, need continuous electronic fetal monitoring during labor.

Prenatal care and the low birth weight infant.

In this study the authors assessed human and economic consequences of low birth weight linked to the lack of prenatal care for indigent women. Low birth weight infants were defined as those who weighed between 860 and 2220 g, corresponding to the 50th percentiles at 26 and 34 weeks' gestation. Women seeking prenatal care had a significantly decreased incidence of low birth weight infants compared with those without such care. Concomitantly, low birth weight infants born to women with prenatal care had significantly better perinatal survival as well as less frequent respiratory distress and intraventricular hemorrhage. Because of these factors, infants born to clinic mothers used fewer neonatal intensive care days and had shorter hospitalizations. Hospital costs were reviewed for 175 surviving infants and failure to obtain prenatal care was associated with a 50% increase in costs for each infant. The frequencies of the most common pregnancy complications in women with and without prenatal care, coupled with corresponding obstetric interventions, suggest that such care facilitates identification and management of women at risk for delivery of low birth weight infants. The authors conclude that there are important human and economic advantages of antenatal care for indigent women.

Blastoderm-differential and blastoderm-specific genes of Drosophila melanogaster.

We have isolated, by molecular cloning, genes expressed differentially at the blastoderm stage of Drosophila melanogaster. Two of the blastoderm-differential genes are reexpressed at later stages, and map to single chromosomal loci 95C and 99E. The sequence at 99E is that encoding the myosin light chain 2. Two other blastoderm-differential sequences are members of multigene families (one of which is B104, or roo) and map to multiple dispersed chromosomal loci. A gastrula-differential sequence was found which maps to 71A. Most significantly, we have identified three genes encoding transcripts expressed uniquely at the blastoderm stage; these map to single chromosomal loci: 25D3, 75C, and 99D4-8. At least some of the blastoderm-differential and blastoderm-specific loci appear to be distinct from loci involved in embryonic pattern formation that have been identified in recent genetic "saturation" screens. The procedure of identifying genes specific to the blastoderm stage may thus allow the identification of genes, not previously identified by classical genetic techniques, that are involved in important embryonic processes.