Reduced systolic pressure load decreases cell-cycle activity in the fetal sheep heart.

The fetal heart is highly sensitive to changes in mechanical load. We have previously demonstrated that increased cardiac load can stimulate cell cycle activity and maturation of immature cardiomyocytes, but the effects of reduced load are not known. Sixteen fetal sheep were given either continuous intravenous infusion of lactated Ringer solution (LR) or enalaprilat, an angiotensin-converting enzyme inhibitor beginning at 127 days gestational age. After 8 days, fetal arterial pressure in the enalaprilat-infused fetuses (23.8 +/- 2.8 mmHg) was lower than that of control fetuses (47.5 +/- 4.7 mmHg) (P < 0.0001). Although the body weights of the two groups of fetuses were similar, the heart weight-to-body weight ratios of the enalaprilat-infused fetuses were less than those of the LR-infused fetuses (5.6 +/- 0.5 g/kg vs. 7.0 +/- 0.6 g/kg, P < 0.0001). Dimensions of ventricular myocytes were not different between control and enalaprilat-infused fetuses. However, there was a significant decrease in cell cycle activity in both the right ventricle (P < 0.005) and the left ventricle (P < 0.002) of the enalaprilat-infused fetuses. Thus, we conclude a sustained reduction in systolic pressure load decreases hyperplastic growth in the fetal heart.

Persistent changes in arterial blood gases in fetal sheep.

Two anaesthetic protocols were compared using pregnant sheep. In both groups of animals, anaesthesia was induced using an intravenous (i.v.) injection of diazepam and ketamine. The ewes were then intubated for positive pressure ventilation using 0.8 L/min of nitrous oxide and 2 L/min oxygen with 1.1-1.8% halothane. If the ewe showed any signs of awakening, one of two protocols was followed. First, the halothane concentration was increased to 2-3% until the ewe was completely anaesthetized. Second, the halothane concentration was not altered, but the ewe was given doses of i.v. diazepam (0.1 mg/kg) and ketamine (1 mg/kg) until again completely anaesthetized. At the completion of surgery, maternal recovery was rapid and similar between the two groups. However, five days after surgery, the fetal arterial Po(2) and oxygen content of the fetuses receiving additional halothane (1.9 +/- 0.2 kPa and 4.4 +/- 1.0 mL/100 mL) were statistically significantly depressed when compared with the fetuses receiving additional diazepam and ketamine (2.9 +/- 0.1 kPa and 7.0 +/- 0.5 mL/100 mL). These results led us to conclude that certain anaesthetic protocols, in spite of good maternal recovery, can lead to deleterious effects upon the fetus that persist for at least five days after surgery.

Fetal infusions of plasma cause an increase in umbilical vascular resistance in sheep.

Earlier studies suggested that the fetal placental circulation is relatively inert with fetal placental flow increasing or decreasing with perfusion pressure. Subsequent studies have demonstrated that the placenta may not be an unreactive vascular bed. The present study was undertaken to determine if plasma infusion-induced hypertension increased fetal placental flow in proportion to the driving pressure across the fetal placental circulation. Six fetal sheep were operated on at 118-122 days to place intravascular catheters and a flow sensor on the common umbilical artery. Starting 6 days later, the fetuses were infused with adult sheep plasma. During the 7-day-long infusion period, they received a total of 1515+/-217 (SD) ml of fluid and 93.2+/-12.0 g of protein. Fetal plasma protein concentrations increased from 34.2+/-2.3 to 77.0+/-9.7 g/l (P<0.0001). Fetal arterial blood pressures rose from 42+/-3 to 59+/-4 mmHg (P<0.01) and venous pressures rose from 2.2+/-0.5 to 4.8+/-0.8 mmHg (P<0.01). In spite of the large increase in driving pressure, fetal placental blood flow remained (statistically) constant (627+/-299 ml/min and 552+/-221 ml/min) while fetal umbilical resistance increased from 0.077+/-0.038 to 0.115+/-0.053 mmHg min/ml (P<0.01). On day 7, plasma renin activity had fallen from 6.7+/-4.2 ng/(ml/h) at preinfusion control to 0.6+/-0.6 ng/(ml/h) (P<0.05) and plasma angiotensin-II concentration had fallen from 33.2+/-26.6 to 6.2+/-3.9 pg/ml, although this fall was not statistically significant (P=0.07). Fetal placental flow did not increase with increased driving pressure across the fetal placental circulation. The increase in fetal placental resistance may be a response to the increase in arterial pressure since there was no increase in flow.

The relative contribution of mast cell subsets to conjunctival TH2-like cytokines.

PURPOSE: To investigate the distribution of the T-helper (TH)2-like cytokines, interleukin (IL)-4, IL-5, IL-6, and IL-13 between mast cell subsets in conjunctival biopsy specimens from normal subjects and those with seasonal allergic conjunctivitis (SAC) during and outside of the grass pollen season. METHODS: Sequential and double in situ hybridization (ISH) and immunohistochemistry (IHC) were performed on thin sections of human conjunctiva to determine the colocalization of the immunoreactivity of IL-4, IL-5, IL-6, and IL-13 to mast cell subsets in normal subjects and subjects with atopy and to detect IL-4 mRNA in conjunctival mast cells. RESULTS: More than 90% of IL-4+-immunoreactive cells were observed to be mast cells in conjunctival biopsy specimens from all patient groups. The majority of IL-5+, IL-6+, and IL-13+ cells were also noted to be mast cells for each group. IL-4 preferentially colocalized to the tryptase+-chymase+ mast cell phenotype (MC(TC)) with MC(TC) cells comprising 93.3% of cytokine+ mast cells in symptomatic SAC (P = 0.0017), 89.2% in asymptomatic SAC (P = 0.0008), and 77.8% in normal subjects (P = 0.0472). IL-13 appeared to colocalize preferentially to the MC(TC) phenotype and IL-5 and IL-6 to the MC(T) phenotype. ISH showed that 75.8% of mast cells in normal subjects, 78.7% in subjects with symptomatic SAC, and 18.7% in subjects with asymptomatic SAC expressed mRNA for IL-4. CONCLUSIONS: Conjunctival mast cells are an important source of IL-4, IL-5, IL-6, and IL-13 immunoreactivity, with preferential colocalization of IL-4 and IL-13 on the MC(TC) subset and IL-5 and IL-6 to the MC(T) subset. This evidence suggests that differences in protease phenotype may also reflect functional differences evidenced by the different patterns of cytokine distribution.

Adhesion molecules and relationship to leukocyte levels in allergic eye disease.

PURPOSE: To evaluate the conjunctival expression of leukocyte cell adhesion molecules (CAMs) and their relationship to leukocyte patterns on the microvasculature in the different clinical subtypes of allergic eye disease. METHODS: Immunohistochemical analysis, using appropriate monoclonal antibodies, was applied to glycolmethacrylate-embedded biopsies of bulbar and tarsal conjunctival tissue. The proportion of total blood vessels expressing a particular CAM was derived and related to individual cell types identified by cell-specific markers, such as mast cells, eosinophils, neutrophils, T cells, and macrophages. Statistical analysis was used to correlate adhesion molecule expression and, ultimately, cell type. RESULTS: There was a basal expression of intercellular adhesion molecule-1 (ICAM-1) (21% bulbar, 18% tarsal), E-selectin (15% bulbar, 21% tarsal), and vascular cell adhesion molecule-1 (VCAM-1) (13% bulbar and tarsal) in normal controls. In seasonal and perennial (bulbar and tarsal conjunctival) allergic tissue, ICAM-1 and E-selectin were expressed in 40% to 78% of vessels; in chronic disease, they were expressed in 45% to 80% of vessels; and in vernal giant papillae, they were expressed in as many as 90% of vessels. There was also increased expression of endothelial VCAM-1 in all forms of allergic eye disease; the greatest values were found in vernal giant papillae (64%). Biopsies taken in winter from seasonal sufferers demonstrated a marked reduction in levels of all three CAMs compared with those taken in the pollen season. This is almost consistent with values found in normal conjunctiva. Positive correlations were found between the levels of ICAM-1 and E-selectin expression and the degree of granulocyte and lymphocyte infiltration, although VCAM-1 expression correlated most closely with eosinophil numbers. CONCLUSIONS: Increased levels of cell adhesion molecules on the microvasculature and the factors that regulate them are likely to be responsible for the infiltration of cells bearing their ligands and may perpetuate inflammation in the chronic forms of allergic eye disease.

Current topic: water volume of the ovine conceptus; point of view.

The sheep is the only species for which there is sufficient information to justify an overview of maternofetal water transfer. Current information points to the following conclusions: (1) the site of water exchange between mother and conceptus is mainly the placenta; (2) the pressure that initiates transfer to the fetus is the osmotic pressure of solutes that are present in higher concentrations in fetal plasma than in maternal plasma, such as urea, fructose, amino acids, bicarbonate and lactate; (3) maternal ultrafiltrate thus attracted into the conceptus arrives there mostly denuded of electrolytes and is strongly hypotonic; thus it is the transfer of electrolyte that restrains the transfer of water; (4) maternofetal transfer of water is strongly facilitated by angiotensin I in the fetal circulation by a sequence of events that has not yet been elucidated; (5) the net combined osmotic and hydrostatic pressure that drives water across the placenta is of the order of only 20 to 80 mm Hg; (6) it is necessary to make a sharp distinction between transfer from mother to conceptus and transfer from one compartment to another compartment within the conceptus. Finally, the review lists certain precautions to be taken in the further study of water exchange between mother and conceptus.

Angiotensin mediated interaction of fetal kidney and placenta in the control of fetal arterial pressure and its role in hydrops fetalis.

Fetal cardiovascular control is effected by an interaction of the fetal somatic and placental circulations. Three primary regulatory mechanisms are involved: transplacental transfer of extracellular fluid, driven by a difference in hydrostatic and oncotic pressures; modulation of fetal placental and somatic vascular resistances by means of blood pressure controlled production of angiotensin; and somatic autoregulation of flow. A systems analysis incorporates these and other fetal cardiovascular functions and this analysis was modelled for computer simulation. Given physiologically plausible values for known cardiovascular parameters in the fetal sheep, the model reproduced in detail a variety of experimental protocols with known outcomes; these included the normal fetus, the fetus after bilateral nephrectomy, the nephrectomized fetus infused with angiotensin, the intact fetus infused with NaCl solutions, the fetus with lymphatic obstruction and the severely anaemic fetus. The systems analysis demonstrated that fetal cardiac failure constituted the strongest stimulus for the formation of fetal oedema of any tested pathological intervention.

Disproportionate referrals for child academic/behavior problems: replication and extension.

Drabman, Tarnowski, and Kelly (1987) investigated children's month of birth in relation to mental health referrals and found that the younger children in a class were disproportionately referred for services. We conducted a replication and extension of the Drabman et al. investigation. Data were collected on children's (N = 222) cognitive and academic competencies. Results indicated that (a) younger children in a class were disproportionately referred, (b) the referral pattern remained constant across all grades examined, (c) the referral pattern could not be explained by differences in children's competencies, and (d) although the youngest children in the class were referred most frequently, they had the lowest rate of qualification for special services.

A beam intensity monitor for the Loma Linda cancer therapy proton accelerator.

A beam intensity monitor was tested in a 230-MeV proton beam at the Loma Linda Proton Therapy Accelerator during its commissioning at Fermi National Accelerator Laboratory. The intensity monitor was designed to regulate the beam intensity extracted from the proton synchrotron. The proton beam is tunable between 70 and 250 MeV with an adjustable intensity between 10(10) and 10(11) protons per spill. A beam spill is typically 1 s long with a 2-s repetition period. The intensity monitor must be radiation hard, expose minimum mass to the beam, and measure intensity to 1% in 1-ms time intervals. To this end, a 5-cm-thick xenon gas scintillator optically coupled to a photomultiplier tube (PMT) was tested to measure its response to the proton beam. The gas cell was operated at 1.2 atm of pressure and has 12.7-microns-thick titanium entrance and exit foils. The total mass exposed to the beam is 0.14 g/cm2 and is dominated by the titanium windows. This mass corresponds to a range attenuation equal to 1.4 mm of water. The energy lost to the xenon gas is about 70 keV per proton. Each passing proton will produce approximately 2000 photons. With a detection efficiency on the order of 0.05% for this UV light, one would anticipate over 10(10) photoelectrons per second. In a 1-ms time bin there will be approximately 10(7) photoelectrons. This yields a resolution limited by systematics. For unregulated 0.4-s proton spills, we observe a response bandwidth in excess of 10(4) Hz. While signal-to-noise and linearity were not easily measured, we estimate as few as 10(3) protons can be observed suggesting a dynamic range in excess of 10(5) is available.

Amniotic membrane transplantation for partial limbal stem cell deficiency.

AIM: To examine the efficacy, safety, and long term outcomes of amniotic membrane transplantation for corneal surface reconstruction in cases of partial limbal stem cell deficiency. METHODS: 17 eyes of 15 patients with partial limbal stem cell deficiency underwent superficial keratectomy of the conjunctivalised corneal surface followed by amniotic membrane transplantation. Cases were followed up for at least a year. RESULTS: All eyes exhibited a stable, intact corneal epithelial surface after a mean follow up period of 25.8 months with no eyes developing recurrent erosion or persistent epithelial defect. The mean time to re-epithelialisation was 22.8 days. Overall improvement in visual acuity was observed in 92.9% of 14 eyes with visual potential. Of those, five eyes gained six or more lines, two eyes gained between four and five lines, six eyes gained between one and three lines, and one eye lost three lines of Snellen acuity. Pain and photophobia were abolished in 86% of cases and substantially reduced in 14%, with all eyes exhibiting decreased vascularisation and inflammation at final follow up. CONCLUSIONS: Amniotic membrane transplantation appears to be a safe and effective method of restoring a stable corneal epithelium for cases of partial limbal stem cell deficiency and can be considered as an alternative to limbal autograft or allograft.

Correlation of long term phenotypic and clinical outcomes following limbal epithelial transplantation cultivated on amniotic membrane in rabbits.

AIM: To determine the epithelial phenotype in rabbits with total limbal stem cell deficiency (LSCD) after reconstruction with autologous limbal epithelial stem cells ex vivo expanded on rabbit amniotic membrane (AM). METHODS: Left eyes of 52 rabbits were rendered total LSCD, verified by impression cytology. The fibrovascular pannus of each cornea was removed. Group I (n = 10) received rabbit AM transplantation alone, while groups II-IV (n = 42) underwent transplantation of LSC cultured on rabbit AM (LSC-AM) from a small limbal biopsy taken from the right eye. Clinical outcome was graded as "success," "partial success," or "failure" depending on the corneal smoothness and avascularity. Epithelial phenotype was determined by immunostaining and graded as "corneal (K)," "conjunctival (J)," or "mixed (M)" depending on expression of K3 and Muc5AC. RESULTS: After 1 year follow up, group I showed 100% failure and groups II-IV showed 26% success (p<0.001). Clinical failure correlated with J phenotype p = 0.001), while clinical success correlated with K phenotype p = 0.01). When the phenotypic outcome was used for comparison, J phenotype was significantly high in group I (p = 0.003), while K phenotype was significantly high in groups II-IV (p<0.05). CONCLUSION: There is a strong correlation between clinical success and resultant corneal epithelial phenotype. Ex vivo expanded LSC can successfully reconstruct corneal surfaces with unilateral total LSCD.

Predictive factors for the development of rubeosis following proton beam radiotherapy for uveal melanoma.

AIMS/BACKGROUND: Proton beam radiotherapy can effectively treat primary uveal melanomas of any size. Some patients, however, develop adverse late effects following treatment and the purpose of this study was to determine which factors give rise to a poor local outcome. METHODS: The hospital records from a first cohort of 127 patients treated by protons from 1989 to 1992 were reviewed retrospectively. The presence of rubeosis was selected as a measure of significant ocular damage. Split file analysis was performed with 73 cases forming a test group with the remaining 54 cases acting as a validation group. RESULTS: Large tumour size and the presence of retinal detachment were significant, independent risk factors for developing rubeosis for both the test and validation groups. These factors also predicted subsequent enucleation for uncontrolled ocular pain. Patients with tumours too large to plaque and with an associated retinal detachment had a 90% chance of developing rubeosis within 4 years of proton beam radiotherapy. CONCLUSIONS: Patients with a uveal melanoma too large for plaque therapy and an associated retinal detachment run a very high risk of developing rubeosis after proton beam radiotherapy and one third of individuals developing rubeosis required enucleation for pain even if local tumour control was satisfactory.

Amniotic membrane transplantation after the primary surgical management of band keratopathy.

PURPOSE: To determine the safety and efficacy of amniotic membrane transplantation to restore and maintain a stable corneal epithelium and reduce ocular surface pain after surgical removal of band keratopathy arising from ocular causes. METHODS: Fifteen patients (16 eyes) from two centers with band keratopathy secondary to ocular causes underwent amniotic membrane transplantation as a graft after surgical removal of calcific deposits with or without the use of ethylenediaminetetraacetic acid. In a prospective, consecutive, uncontrolled case series, the rate of corneal epithelialization and resultant surface stability were recorded over a mean follow-up period of 14.6 months. RESULTS: Pain from ocular surface instability was the presenting complaint in 14 of 15 (93.3%) patients and resolved in all cases after the procedure even for those who experienced a recurrence of the calcific deposit. Fifteen of 16 eyes (93.7%) achieved epithelialization with a mean time to epithelial healing of 15.2 days. The only eye that failed to heal was subsequently diagnosed with total limbal stem cell deficiency. Visual acuity improved in five of nine (44%) sighted eyes and remained unchanged in four of nine (56%). No patient experienced any major surgical or medical complication after the procedure. CONCLUSION: Amniotic membrane transplantation represents a safe and effective method to restore a stable corneal epithelium in eyes after primary surgical removal of band keratopathy arising from ocular causes.

Excess extrafetal fluid without demonstrable changes in placental concentration gradients after week-long infusions of angiotensin into fetal lambs.

It is known that a week-long infusion of angiotensin into fetal sheep produces polyhydramnios. The purpose of the present experiments was to determine whether an increased osmotic force across the placental barrier could account for the excess transfer of water. Six fetuses with indwelling catheters were infused with angiotensin-I and one with angiotensin-II; all, except one fetus in the first group, developed gross polyhydramnios. None of the transplacental concentration differences of the small plasma solutes Na+, Cl-, HCO3-, K+, urea, or glucose showed a demonstrable change and the same was true of the transplacental difference in freezing point osmolality and for the transplacental difference in plasma protein concentration. It is concluded that the infusion of angiotensin at a low dose rate is a reliable protocol for producing polyhydramnios. However, the present findings lend no support to the hypothesis that a primary change in transplacental osmotic force is the cause of the increased transplacental water transfer in this form of polyhydramnios. Alternative hypotheses are discussed in the light of recent discoveries.

Eating disordered behaviors: a comparison of male and female university students.

This study compared male and female students on measures characteristic of eating disordered behavior. Measures investigated were subscales of the Eating Disorders Inventory and of the Restrained Eating Scale. Results indicated that both males and females reported a fundamental pattern of eating disordered behavior. This pattern consisted of going on and off diets with an accompanying complaint of a lack of confidence in recognizing and identifying sensations of hunger and satiety. Females differed from males in that they reported more anorexic behavior and scored significantly higher on most measures of eating disordered behavior. Although the fundamental pattern of disordered eating leading to bulimia may be similar between the sexes, females appear to be at greater risk to the development of these behaviors.

Non-communication between ophthalmologists and optometrists.

Many patients seen in the British hospital eye service are referred by high-street optometrists; and, if the optometrist is to receive feedback from the ophthalmologist, the patient should consent to disclosure of medical information. On the referral form (revised GOS 18) there is a space for this purpose. We investigated the level of communication by asking optometrists in our hospital catchment area about their use of the GOS 18 form and by examining the medical records of all new patients seen in the eye outpatient department in one month. 79 optometrists (55%) returned the questionnaire. 54 routinely used the GOS 18; and, of these, 10 said they obtained patient consent always, 23 sometimes and 21 never. 158 of 555 sets of medical notes contained an optometrist's referral, 107 of them on the revised GOS 18; and patient consent had been recorded on 17 of these forms. Ophthalmologists responded to the optometrist in 2/17 (12%) cases where consent had been obtained and 15/90 (17%) where it had not. Ophthalmologists could provide much better feedback to optometrists. The GOS 18 form could be used more effectively; and there is no reason why patient consent to disclosure of medical information should not be obtained by ophthalmologists as well as by optometrists.

Direct ophthalmoscopy versus slit lamp biomicroscopy in diagnosis of the acute red eye.

The causes of red eye range from trivial to life-threatening, and many general practitioners are uncertain of their ability to diagnose them with the aid of an ophthalmoscope. We tested the hypothesis that, in the assessment of a patient with red eye, a doctor using a slit lamp biomicroscope would not differ in diagnostic accuracy from a doctor using a direct ophthalmoscope. A cross-over study was conducted in 98 patients newly attending an eye casualty department. 71% of diagnoses agreed exactly, and all potentially sight-threatening lesions were either diagnosed correctly or managed appropriately by doctors using an ophthalmoscope. We conclude that the initial diagnosis and management of patients with an acute red eye is not prejudiced by the lack of a slit lamp biomicroscope.

Development of an exercise identity scale.

This study examined an instrument measuring the salience of an individual's identification with exercise as an integral part of the concept of self. The 9-item Exercise Identity Scale was given to 51 college students. Test-retest reliability (1 wk.) was .93 and Cronbach alpha. 94. Assessment of the relationship between exercise identity scores and other variables related to participation in exercise documents evidence for validity. A measure of exercise identity may help identify persons least likely and most likely to maintain an exercise program and so may assist in the development of effective intervention strategies.

Effects of age and temporal placement of a modeled skill on children's performance on a balance task.

The present investigation explored the effect of age and temporal placement of a modelled skill on performance on a balance task. 60 boys, aged 7 and 9 yr., were randomly assigned to one of three conditions. The model was presented before any trials were attempted, midway, or not at all during 12 trials. A 2 (age) X 3 (model condition) X 12 (trials) repeated-measures design was utilized. Analysis of variance indicated significant effects of age, temporal appearance of the model, and an interaction of model by age for time on-balance. Model affected younger subjects but not older ones. Treatment did not affect off-balance errors. Findings for age and temporal placement are not consistent with some previous research.