The ovijector of Ascaris suum: multiple response types revealed by Caenorhabditis elegans FMRFamide-related peptides.

Caenorhabditis elegans possesses 22 FMRFamide-like peptide (flp) genes predicted to encode 60 different FMRFamide-related peptides with a range of C-terminal signatures. Peptides from five flp genes (1, 6, 8, 9 and 14) are known to modulate the ovijector of Ascaris suum in vitro. This study examines the physiological effects of peptides from the remaining 17 flp genes such that the variety of FMRFamide-related peptide-induced ovijector response types can be delineated. Five categories of response were identified according to the pattern of changes in contractile behaviour and baseline tension. Peptides encoded on 16 flp genes (1, 2, 3, 4, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 17 and 20) had qualitatively similar inhibitory (response type 1) actions, with the lowest activity thresholds (1 nM) recorded for peptides with FIRFamide or FLRFamide C-terminal signatures. Peptides encoded on four flp genes (2, 18, 19 and 21), and on the A. suum afp-1 gene, had excitatory actions on the ovijector (response type 2), with PGVLRFamides having the lowest activity threshold (1 nM). An flp-2 peptide (LRGEPIRFamide) induced a transient contraction of the ovijector (activity threshold, 10nM) that was designated response type 3. Response type 4 comprised a transient contraction followed by an extended period of inactivity and was observed with peptides encoded on flp-5 (AGAKFIRFamide, APKPKFIRFamide), flp-8 (KNEFIRFamide) and flp-22 (SPSAKWMRFamide). SPSAKWMRFamide was the most potent peptide tested with an activity threshold of 0.1 nM. A single peptide (AMRNALVRFamide; activity threshold 0.1 microM), encoded on flp-11, induced response type 5, a shortening of the ovijector coupled with an increase in contraction frequency. Although most flp genes encode structurally related peptides that trigger one of the five ovijector response types, flp-2 and flp-11 co-encode FMRFamide-related peptides that induce distinct responses. Within the ovijector of A. suum FaRPs play a complex role involving at least five receptor subtypes or signalling pathways.

Physiological effects of FMRFamide-related peptides and classical transmitters on dispersed muscle fibres of the turbellarian, Procerodes littoralis.

The physiological effects of selected classical transmitters and FMRFamide-related peptides (FaRPs) on dispersed muscle fibres from the marine turbellarian, Procerodes littoralis have been examined. Confocal scanning laser microscopy coupled with fluorescein isothiocyanate (FITC) or tetramethylrhodamine (TRITC)-labelled phalloidin revealed a highly developed body wall muscle system with circular, longitudinal and diagonal layers of muscle fibres. Dispersed muscle fibres contracted when depolarized by exposure to extracellular media with elevated K+ (15-100 mM) in a concentration-dependent manner, with a maximal response of 87% achieved at > or = 75 mM. 5-Hydroxytryptamine (5-HT) induced concentration-dependent muscle contraction between 0.01 and 1000 microM, with 10 microM producing a near maximal contraction response of 75%. Acetylcholine (ACh) had less pronounced excitatory effects (0.01-1000 microM), inducing contraction of only 32% of the fibres at 100 microM. The flatworm FMRFamide-related peptides (FaRPs), GYIRFamide, YIRFamide and GNFFRFamide each had concentration-dependent myocontractile effects, indicating the occurrence of at least 1 FaRP receptor on P. littoralis muscle fibres. At 10 microM peptide, GNFFRFamide induced contractions in < 40% of the muscle fibres examined, whereas YIRFamide and GYIRFamide induced contraction in 70 and 75% of muscle fibres, respectively. The order of potency of the peptides was: GYIRFamide > YIRFamide > GNFFRFamide. Pre-incubation of the muscle fibres in 5 microM 5-HT significantly reduced the responses to GYIRFamide, YIRFamide and 5-HT, while the responses to high K+ remained unaltered. Muscle fibres pre-incubated in GYIRFamide (0.1 microM) were also less responsive to 5-HT but not to ACh and high-K+. The GYIRFamide analogue, GYIRDFamide, did not induce muscle contraction (0.01-100 microM) per se, but when co-applied with the myoactive peptides GYIRFamide, YIRFamide or GNFFRFamide, it significantly blocked their ability to elicit contractions. This suggests that the peptides tested may act via a common muscle-based neuropeptide receptor. GYIRDFamide did not alter the contractile effects of high K+, 5-HT or ACh. Collectively, these results indicate that FaRPs, 5-HT and ACh all have the potential to cause muscle contraction in flatworms and that 5-HT and FaRPs alter muscle sensitivity to each other, but do not influence the ability of flatworm muscle fibres to contract.

Preventive health care for mentally ill women.

Utilization of preventive medical care was compared for two low-income groups--47 women with serious mental illness in an urban mental health center and 17 women patients at a primary care center. Appropriate preventive care was defined as at least one physical examination, a Pap test, and a breast examination in the past five years and a mammogram if the patient was over age 40. Receipt of preventive care by women in both settings was similar. Histories of physical and sexual abuse were prevalent in both groups, and a history of abuse was associated with less frequent receipt of preventive care. Results indicate that procedures to identify and provide services to women with abuse histories should be further developed.

Graduated Compression Hosiery.

Graduated compression hosiery is used for several clinical conditions related to venous insufficiency and lymphoedema. In the management of venous ulceration, graduated compression hosiery is regarded as an essential component of prevention of ulcer recurrence. Occasionally it is used for ulcer healing. It is also used prophylactically in the prevention of deep vein thrombosis1.

Late echocardiographic findings following childhood chemotherapy with normal serial cardiac monitoring.

PURPOSE: Late development of myocardial dysfunction years following successful treatment of childhood malignancy with anthracyclines is well documented. There have been few studies of late cardiac performance in children in whom serial monitoring during treatment suggested normal cardiac performance, and those studies that do exist rely on the results of extensive evaluation. It was our purpose to determine whether findings consistent with known late cardiac changes could be discovered in these patients by echocardiographic monitoring similar to that routinely performed during treatment. PATIENTS AND METHODS: A total 28 consecutive asymptomatic patients who had completed anthracycline therapy at least 3 years previously, had been free of malignant disease since the completion of therapy, and who had had normal serial echocardiographic studies during and at completion of treatment were restudied by echocardiography. Of these 28, 12 had undergone mediastinal radiation as part of their acute treatment. RESULTS: Four patients (14%) of the study group were found to have abnormally low values for left ventricular shortening and ejection fractions. All four had also received mediastinal radiation. The remaining 24 patients, while having values for shortening fraction within the normal range, had, as a group, experienced a significant decrease in echocardiographic left ventricular shortening since completion of treatment. In these patients, left ventricular wall thickness had not increased commensurate with growth in body size and left ventricular cavity dimension. CONCLUSIONS: The known incidence of late asymptomatic cardiac dysfunction is confirmed despite the presence of persistently normal echocardiographic monitoring studies during and at completion of anthracycline treatment. Additionally, as a population, these patients show impaired myocardial growth over time, placing them at risk for future myocardial failure. Normal echocardiographic monitoring studies during antineoplastic treatment in children may not necessarily predict that patients will be free of the development of late cardiac dysfunction. Routine serial echocardiographic monitoring can, however, be helpful in the long-term management of these patients.

Clinical audit and effective change in leg ulcer services.

An audit of clinical leg ulcer services was undertaken in South Bedfordshire and was followed by a process of implementation using research-based methods; a re-audit was conducted 18 months later. Using an adaptation of the Riverside model, patients were referred to community leg ulcer clinics. They were assessed using Doppler ultrasound; those with ABPI >0.8 were treated using a high-compression four-layer bandage system. Those with ABPI 0.6-0.8 were treated using reduced compression, and those with ABPI <0.6 were sent to their GP for referral for specialist opinion. In October 1993, the average cost of consumables for each patient was £8.53, and this rose to £10.14 in May 1995. However, patients treated in community clinics had a reduced cost of consumables of £7.91 compared with £10.78 for patients treated at home. There was also a corresponding reduction in weekly treatments and an overall reduction in nursing time to treat patients. In 111 patients (134 limbs) treated by high compression in the community clinics, cumulative percentage healing was 54% after 12 weeks and 68% after 24 weeks. Although these results were lower than those achieved in the Riverside project, much of the difference can be explained by the different patient populations and ulcer duration. The results support a system of care which offers rationalisation of service, staff training and research-based effective assessment and treatment.

Microglia in the rat neurohypophysis increase expression of class I major histocompatibility antigens following central nervous system injury.

An immunocytochemical study of the expression of major histocompatibility complex (MHC) class I and II antigens by glial cells of the rat neurohypophysis was performed. Numerous cells with the appearance of microglia were found to constitutively express class I MHC antigens, while only rare cells expressed class II (Ia) antigens. Stereological analysis revealed that expression of class I MHC antigens increased significantly within 10 days after a unilateral hypothalamic lesion known to cause axonal degeneration and compensatory collateral axonal sprouting within the neurohypophysis. In addition, however, a brain lesion which did not affect the axonal population of the neurohypophysis also produced a significant increase in microglial expression of class I MHC antigens in this structure. Neither lesion affected the expression of class II MHC antigens in the neurohypophysis. Simultaneous immunofluorescent labeling for MHC I antigens and glial fibrillary acidic protein (GFAP, a pituicyte marker) or for MHC I and the C3bi complement receptor (a microglial marker) confirmed that the MHC class I-reactive cells were microglia. MHC I-positive cells also bound Griffonia simplicifolia B4 isolectin (GSA I-B4), consistent with their identification as microglia. The majority of MHC class I-reactive microglia were located in close apposition to blood vessels. These results indicate that an unusually large proportion of microglia within the neurohypophysis constitutively express MHC I antigens. In addition, neurohypophysial microglia are capable of responding to penetrating brain injury by upregulation of MHC I antigens in the absence of local tissue degeneration, possibly because of the absence of a blood-brain barrier.

Innervation of the rat anterior and neurointermediate pituitary visualized by immunocytochemistry for the growth-associated protein GAP-43.

Immunocytochemical localization of the neuronal growth associated protein GAP-43 revealed a dense axonal plexus throughout the neurointermediate lobe of the rat pituitary. These axons were fine, presumably monoaminergic fibers, whereas magnocellular neurosecretory axons did not appear to contain detectable GAP-43. These experiments also revealed the presence of an extensive nerve plexus within the anterior lobe. Fine beaded fibers were present throughout the parenchyma of the anterior lobe, and punctate staining suggestive of nerve terminals was seen surrounding numerous endocrine cells. Nerve fibers did not appear to cross directly between the intermediate and anterior lobes, but rather entered the anterior lobe directly from its margins or in association with blood vessels. Preabsorption of antisera with GAP-43 purified from neonatal rat brain completely eliminated immunoreactivity. These findings confirm the existence of a direct innervation of the anterior pituitary of the rat; moreover, the presence of GAP-43 in these fibers suggests that they may be capable of growth and terminal reorganization in the adult animal.

A trial of a hydrocolloid dressing in the management of indolent ulceration.

A report of a randomised, controlled trial of a hydrocolloid dressing used in the treatment of leg ulcers that were failing to heal.

Changes in left ventricular diastolic filling patterns by Doppler echocardiography in cystic fibrosis.

The onset of cor pulmonale is a common terminal finding in patients with cystic fibrosis. Since Doppler echocardiography can detect changes in diastolic filling patterns prior to the onset of either systolic dysfunction or clinical symptoms, we utilized this technique to determine whether detectable changes in left ventricular diastolic filling patterns exist in patients with cystic fibrosis. Among 25 patients, the proportion of left ventricular filling attributable to atrial contraction was significantly increased when compared with age-matched control individuals. When filling patterns were compared with severity of pulmonary disease, worsening pulmonary disease was directly correlated to shifts in left ventricular filling patterns. We conclude that changes in left ventricular patterns of relaxation are detectable early in the course of cystic fibrosis and that such changes are probably progressive. Early detection could lead to therapeutic trials designed to improve left ventricular filling and delay the onset of overt cor pulmonale.

Doppler echocardiographic studies of diastolic ventricular filling patterns in premature infants.

Pulsed Doppler echocardiographic studies of both right and left ventricular diastolic inflow patterns were performed in 10 full-term newborn infants and serially during the first month of life in 21 premature (28 to 35 weeks' gestation) infants with no clinical cardiorespiratory disease. Results of studies performed during the first 10 days of life showed no significant difference in transmitral flow velocity or velocity-time integral measurements between full-term and preterm neonates. Values for transtricuspid velocity measurements were slightly lower in preterm infants, but E/A velocity ratio and relative contribution of E and A components to the total velocity-time integral were unchanged. Within the group of preterm infants gestational age did not affect any of the diastolic flow parameters. As preterm infants aged velocity of flow increased, but no changes were noted in the relative contributions of rapid ventricular filling and atrial contraction, either in terms of velocity of flow-velocity integral measurements. Doppler assessment of diastolic ventricular filling can provide an accessible method for serial evaluation of preterm infants. Values noted in "normal" premature infants resemble those found in full-term infants.

Incidence of end-stage renal disease in type 2 (non-insulin-dependent) diabetes mellitus in Pima Indians.

The incidence of end-stage renal disease was determined in the Pima Indians of the Gila River Indian Community in Arizona, a population with a high prevalence of Type 2 (non-insulin-dependent) diabetes mellitus. Between 1975 and 1986, from a study population of 5059 subjects, end-stage renal disease occurred in 80 persons, 76 (95%) of whom had Type 2 diabetes. A review of the cases with end-stage renal disease indicated that among the diabetic subjects only two cases could be attributed to nondiabetic renal disease; all other cases were attributable to diabetic nephropathy. In diabetic Pima Indians the incidence rate of end-stage renal disease did not change during the study period, was similar in men and women, and was not effected by age at diagnosis of diabetes or by attained age, but did increase significantly with hypertension (p less than 0.05). The incidence of end-stage renal disease attributed to diabetic nephropathy increased from 0 cases/1000 person-years at 0-5 years to 40.8 cases/1000 person-years at greater than or equal to 20 years duration of diabetes. In these subjects with Type 2 diabetes, the incidence rate of end-stage renal disease was similar to that in subjects with Type 1 (insulin-dependent) diabetes who were followed at the Joslin Clinic in Boston, Massachusetts when those with similar duration of diabetes were compared.

Serial changes in left ventricular relaxation and chamber stiffness after large myocardial infarction in rats.

To determine the time course of changes in left ventricular diastolic properties after a large myocardial infarction, we serially measured left ventricular relaxation, chamber stiffness, and the ratio of left ventricular cavity to wall volume (V/VW) after coronary artery ligation in rats. Left ventricular relaxation was measured during the occlusion and then both relaxation and chamber stiffness were measured at 3 hr, 24 hr, and 3, 5, and more than 22 days after infarction. Left ventricular pressures and left ventricular dP/dt were recorded with micromanometer-tipped catheters. Left ventricular relaxation was measured by computer digitization of the left ventricular pressure tracings and averaged over 100 to 150 cardiac cycles. Five chamber stiffness constants were calculated from pressure-volume curves that were obtained ex vivo. We found ventricular relaxation prolonged for the first hour after coronary occlusion; relaxation was maximally prolonged at 10 to 15 min after onset of occlusion. After 1 hr relaxation returned to normal. However, by 5 days ventricular relaxation was again prolonged. Left ventricular stiffness constants were increased at 3 and 24 hr, resulting in a shift of the left ventricular pressure-volume relation to the left. At 3 days after coronary artery ligation, all stiffness constants and the pressure-volume relation returned to normal. At more than 22 days the pressure-volume relation was shifted to the right and the stiffness constant for low filling pressures was decreased. V/VW was significantly decreased from 0.603 +/- 0.021 at 3 and 24 hr to 0.379 +/- 0.024 and 0.362 +/- 0.032, respectively. V/VW was significantly increased at more than 22 days (0.921 +/- 0.094).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of sample volume location on pulsed Doppler diastolic flow parameters in newborn infants.

Pulsed Doppler echocardiography was used to measure parameters of left and right ventricular diastolic filling from both the valve annulus and valve leaflet tips in 36 newborn infants. Absolute values for E and A velocities were 13% higher at the mitral leaflet tips and 10%-18% higher at the tricuspid tips than at the respective valve annulus. Similarly, values for diastolic velocity-time integral measurements were 6%-18% higher when sampling was performed at the leaflet tips. With the exception of the transtricuspid velocity ratio, E/A ratio values were not affected by sample volume location. Doppler sample volume location can influence velocity and velocity-time integral measurements in newborn infants. Attention to consistent sample volume location is important in serial or comparative studies.

Atrial natriuretic peptide levels during development of chronic heart failure after myocardial infarction in rats.

Serum levels of atrial natriuretic peptide (ANP) are elevated in chronic heart failure presumably due to dilatation of the left atrium resulting from increases in intracardiac pressures. To define the time course of changes in serum ANP levels and to determine the relationship to left ventricular end-diastolic pressure, rats were subjected to coronary artery ligation to produce myocardial infarction and left ventricular failure. Atrial natriuretic peptide levels were measured weekly for four weeks thereafter. In rats with myocardial infarction and elevation of left ventricular end-diastolic pressure there was no change in ANP levels at 7 and 14 days. However, at day 21 and 28, ANP levels were elevated more than 3 fold. There was a correlation between ANP levels and left ventricular end-diastolic pressures. There was no correlation between ANP levels and right atrial pressures or serum sodium concentrations. We conclude that the chronic elevation of left ventricular end-diastolic pressure is required to produce an increase in ANP after myocardial infarction which results in chronic heart failure.

The effect of ethanol chronically administered to preweanling rats on cerebellar development: a morphological study.

The effects of ethanol on body, brain and cerebellar growth of the postnatal rat have been studied. Vapor inhalation, the procedure used to administer ethanol directly to preweanling (3-20-day-old) rats, produced maximal blood ethanol levels that averaged 239 mg/100 ml. Weight determinations indicated that brain but not body growth was significantly stunted by exposure to ethanol. Moreover, cerebellar growth, which occurred largely but not wholly during the period of ethanol treatment, was inhibited twice as much as the rest of the brain. Arrested brain and cerebellar growth appeared shortly after ethanol treatment was begun and persisted into adulthood following a postweaning rehabilitation period. Ethanol treatment diminished the growth of both the anterior and posterior lobes and of all layers of the cerebellar vermis. However, the effect of ethanol was larger in the anterior lobe than the posterior lobe, and the medullary layer was more retarded than the others. Some compensatory growth occurred in the molecular and granular layers of the experimental rats during a postweaning rehabilitation period. The effects of ethanol on 2 major neuronal populations of the cerebellar cortex -- the large, prenatally-formed Purkinje cells and the small, postnatally-formed granule cells -- were assessed via light microscopy. After 2 days of ethanol treatment the number of Purkinje cells in all 10 vermal lobules was reduced; neither additional exposure to ethanol nor a postweaning rehabilitation period subsequently altered cell number. The possibility that the regional magnitude of the Purkinje cell loss was related to the chronology of lobular development was discussed; Purkinje cells in the latest maturing lobules being least affected. The morphological development of surviving Purkinje cells proceeded normally. An autoradiographic study indicated the pattern of granule cell neurogenesis in cerebella of ethanol-treated rats and of control rats did not differ, although the experimental animals had consistently fewer cells in all stages of development. The ultimate loss of 20-25% of their granule cells was accounted for by an early diminution of the stem cell population of the external germinal layer by about 10%. The results suggest the initial targets of ethanol were the immature Purkinje cells, which were reduced in number before the onset of granule cell formation. A complex age-dependent interaction between blood ethanol levels and vulnerable periods in Purkinje cell development was suggested. Mechanisms for the subsequent correlative reduction in the granule cell population were also discussed.

Abortion counseling and the school counselor.

PIP: The Supreme Court decision of January 22, 1973, legalizing abortion now requires school counselors to examine both their personal and professional positions on abortion information and abortion counseling. To date a review of school counseling literature reveals a failure to deal with abortion as a counseling issue. Also, schools have failed to develop official policies regarding abortion counseling and the distribution of abortion information. The counselors who have provided abortion information to date have done so at the request of a student or parent rather than by making the information generally available. A study in 1973 in Virginia, however, revealed that Virginia counselor educators believed that there was a need for counselors in training to be exposed to abortion information as part of their formal training experience. Generally, today's present exposure to abortion information makes it impossible for counselors to continue to ignore a growing demand for both abortion information and counseling. School counselors must deal with the following questions: 1) What course of action should school counselors take when a pregnant young seeks counseling on alternatives to pregnancy continuation? 2) What is the counselor's professional role in abortion counseling with respect to his or her personal feelings and beliefs? 3) What kind of training if any should school counselors receive regarding abortion counseling? 4) Is there a need for in-service training on abortion counseling for school counselors? 5) Should various professional organizations develop materials that would assist their members in providing abortion counseling? 6) Should institutions such as schools, churches, and community agencies establish policies concerning abortion counseling? Although the answers are not simple, the school counselors and their professional organizations must begin to develop the answers in order to provide good counseling services to young women exercising their right to choose an abortion.^ieng