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Biomedical subjects

J Stone

Publications and source records attributed to J Stone.

At least 145 records · Page 8Linked to original sources
PubMed1997

Tissue oxygen during a critical developmental period controls the death and survival of photoreceptors.

PURPOSE: To study the death of photoreceptors in normally developing and dystrophic retina and to test the role of hypoxia in causing that death. METHODS: Death of photoreceptors was detected in the albino, hooded, and Royal College of Surgeons (RCS) strains of rat, and in the rabbit and cat, using the TUNEL technique. Retinas of selected ages from animals raised normally and those from rat pups raised for periods in hyperoxia (75% oxygen) or hypoxia (10% oxygen) were studied. RESULTS: In all species and strains examined, a naturally occurring wave of photoreceptor death was detected during the last stages of retinal development. In the albino rat, this wave, which began approximately at postnatal day 15 (P15) and peaked at P22, was reduced by hyperoxia and was intensified by hypoxia, producing a "hypoxic dystrophy" of photoreceptors. In the RCS rat, photoreceptor death also commenced at approximately P15 and then proceeded to exhaustion. This degeneration was greatly reduced by hyperoxia. In the RCS rat, hyperoxia was effective in photoreceptor rescue only during a discrete period, from P16 to P22. In the albino rat, the effectiveness of hypoxia in inducing photoreceptor death was much greater between P15 and P21 than at earlier ages, or in the adult. CONCLUSIONS: During a critical period extending approximately from P15 to P22, tissue oxygen levels strongly influence photoreceptor death and survival in dystrophic and normally developing strains of rat. This period is evident in normal development as a period of naturally occurring photoreceptor death and is evident experimentally as a period during which hyperoxia is effective in rescuing dying photoreceptors and during which hypoxia is effective in inducing death of otherwise viable photoreceptors.

Animals↗
PubMed1996

Fate of DNA from retinal cells dying during development: uptake by microglia and macroglia (Müller cells).

The tunel technique of labelling fragmenting dna was used to examine cell death in the developing retina of the rabbit, rat and cat. TUNEL-labelled structures included the still-intact nuclei of retinal cells and smaller, strongly labelled bodies interpreted as fragments of disintegrating nuclei (apoptotic or pyknotic bodies). With confocal microscopy, the cytoplasm around labelled nuclei was observed to be labelled, suggesting that DNA fragments spread into the cytoplasm of the dying cell. Also observed were cells whose nuclei were TUNEL-but whose cytoplasm was TUNEL+, so that their morphology could be discerned. Evidence is presented that these are phagocytes, their cytoplasmic labelling resulting from the ingestion of the fragmenting DNA of a dying neighbour. Results suggest that in developing retina fragmenting DNA is phagocytosed principally by microglia and Müller cells, with a few neurones and no astrocytes active as phagocytes. In the postnatal material studied, microglia are the predominant phagocytes for cells dying in the ganglion cell and inner nuclear layers. Müller cells appear able to phagocytose cells dying in any retinal layer and, since microglia do not normally enter the outer nuclear layer, may be important for the phagocytosis of dying photoreceptors.

Animals↗
PubMed1996

Preterm delivery after selective termination in twin pregnancies.

OBJECTIVE: To determine the effect of selective termination of an abnormal twin on the rate of preterm delivery. METHODS: The study group consisted of 69 patients with twin pregnancies who underwent selective termination between 1987-1994. The comparison groups consisted of singleton (n = 42,362) and twin pregnancies (n = 825) delivered at our institution during the same period. The data were analyzed by Chi2 and Fisher exact test, as appropriate. P < .05 was considered significant. Adjusted odds ratios(OR) and 95% confidence intervals (CI) were calculated by multiple logistic regression. RESULTS: Terminating the presenting twin was associated with a significantly higher risk of delivery before 37 weeks (adjusted OR 4.1, 95% CI 1.4-12.3) and low birth weight (adjusted OR 3.8, 95% CI 1.3-11.4) compared with terminating the nonpresenting twin. When the termination was performed at or after 20 weeks' gestation, only the risk of preterm premature rupture of the membranes or preterm labor was significantly increased (adjusted OR 3.7, 95% CI 1.2-11.5). Selective termination patients had a lower rate of preterm delivery than twin pregnancies (40 versus 58%, P < .005) but higher than singleton pregnancies (40 versus 10%,P < .001). CONCLUSION: Selective termination of the presenting twin at 20 weeks or later was associated with a worse perinatal outcome than terminating the nonpresenting twin or performing the procedure before 20 weeks.

Adult↗
PubMed1996

Pregnancy outcome at age 40 and older.

OBJECTIVE: To examine pregnancy outcome among women age 40 years and older. METHODS: A retrospective cohort study, including 1404 pregnant women at least 40 years of age and 6978 controls age 20-29 years, was conducted. The two groups were stratified, according to parity, to facilitate separate analysis. Associations between maternal age and pregnancy outcomes were assessed with the contingency chi 2 or two-tailed Fisher exact test. Multiple logistic regression was used to evaluate these associations and allowed for calculation of adjusted odds ratios (OR). RESULTS: Older gravidas were more likely to develop gestational diabetes (nulliparas: OR 2.7, 95% confidence interval [CI] 1.9-3.7; multiparas: OR 3.8, 95% CI 2.7-5.4), preeclampsia (nulliparas: OR 1.8, 95% CI 1.3-2.6; multiparas: OR 1.9, 95% CI 1.2-2.9), and placenta previa (nulliparas: OR 13.0, 95% CI 4.8-35.0; multiparas: OR 6.4, 95% CI 2.6-15.6). Older women were also at increased risk for cesarean delivery (nulliparas: OR 3.1, 95% CI 2.6-3.7; multiparas: OR 3.3, 95% CI 2.6-4.1), operative vaginal delivery (nulliparas: OR 2.4, 95% CI 1.9-2.9; multiparas: OR 1.5, 95% CI 1.2-1.9), and induction of labor (nulliparas: OR 1.5, 95% CI 1.2-1.8; multiparas: OR 1.4, 95% CI 1.1-1.7). Older nulliparas had an increased incidence of abnormal labor patterns (OR 1.4, 95% CI 1.2-1.7), neonatal intensive care unit admissions (OR 1.6, 95% CI 1.2-2.2), and low 1-minute Apgar scores (OR 2.3, 95% CI 1.1-4.9). Older multiparas were more likely to experience fetal distress (OR 2.0, 95% CI 1.4-2.8), antepartum vaginal bleeding (OR 1.8, 95% CI 1.1-3.1), and preterm premature rupture of membranes (OR 1.7, 95% CI 1.1-2.9). CONCLUSION: Although maternal morbidity was increased in the older gravidas, the overall neonatal outcome did not appear to be affected.

Adult↗
PubMed1996

Unexplained elevated maternal serum alpha-fetoprotein levels and pregnancy outcome in twins.

OBJECTIVE: To evaluate whether elevated maternal serum alpha-fetoprotein (MSAFP) levels in uncomplicated twin gestations are associated with an increased risk for pregnancy complications and adverse outcomes. METHODS: A retrospective data-base analysis was conducted of 267 women with twin pregnancies delivered between January 1988 and October 1994, of whom 42 had elevated MSAFP levels and 225 had normal levels. We evaluated rates of preterm delivery (defined as gestational age less than 34 weeks at delivery), birth weight less than 1500 g, twin-to-twin birth weight discordance, small for gestational age (SGA) infants (defined as birth weight below the tenth percentile for gestational age), and fetal malformations. Also assessed were potentially confounding variables such as obstetric and medical histories as well as sociodemographic factors. RESULTS: Among nulliparous women, an unexplained elevation in MSAFP levels was associated with a statistically significant increased risk for preterm delivery. Among multiparous women, this association is suggested by the data, but not significantly so. An unexplained elevation in MSAFP level was also associated with a significantly increased risk for birth weight less than 1500 g, but this was related to the increased rate of preterm births. No appreciably increased risk was apparent for SGA infants, fetal malformations (other than neural tube defects and abdominal wall defects), or twin-to-twin birth weight discordance. CONCLUSION: In twin pregnancies, an unexplained elevation in MSAFP level may increase the risk for preterm delivery but not other adverse pregnancy outcomes.

Adult↗
PubMed1996

The current status of multifetal pregnancy reduction.

The number of women conceiving three or more fetuses has increased dramatically as a result of successful infertility therapy with ovulation-inducing agents and assisted reproductive technology. Higher-order multiple gestations have an increased risk of premature delivery and its attendant sequelae of increased neonatal mortality or irreversible morbidity. Multifetal pregnancy reduction is a procedure designed to decrease the increased propensity to deliver very prematurely in these patients by reducing the number of live fetuses they are carrying. The procedure has proved to be both safe and effective, and pregnancies reduced to twins proceed as if that were the number of fetuses originally conceived. Nevertheless, this invasive procedure does have the potential to result in loss of the entire pregnancy and causes considerable emotional distress for some couples who view it as their "least bad" alternative. The medical benefits of performing multifetal pregnancy reduction in women with four or more fetuses seem fairly well established, but this is less true for triplets. Serious attention should be paid to reducing the number of higher-order multiple pregnancies resulting from infertility therapy. In the meantime, when three or more fetuses have been conceived, multifetal pregnancy reduction offers a reasonable option to patients whose only choices in the past were either to accept the risk of delivering extremely prematurely or to terminate the entire pregnancy.

Ethics↗
PubMed1996

High response rates with short infusional 2-chlorodeoxyadenosine in de novo and relapsed low-grade lymphoma. Australian and New Zealand Lymphoma Study Group.

Thirty-five patients (eight de novo, 27 relapsed disease) with low-grade non-Hodgkin's lymphoma (diffuse small lymphocytic, follicular small cleaved cell, follicular mixed cell, and lymphoplasmacytoid) were treated with 2-chlorodeoxyadenosine (2CdA) at a daily dose of 0.14 mg/kg for 5d (2 h infusion) for an average of three cycles. Minor treatment delays, generally due to haematological toxicities, occurred in nine of 105 cycles. Major toxicities were lymphopenia, neutropenia and thrombocytopenia. Opportunistic infections occurred in seven patients. Overall response rate was 69% (five complete, 19 partial) reaching 88% for de novo patients (two complete, five partial). Elevated beta 2-microglobulin level was negatively predictive of response (P = 0.0014). Eight of 24 responders relapsed, with a median follow-up of 13 months. 2CdA administered as an intermittent infusion shows considerable single-agent activity in low-grade lymphomas achieving high response rates of prolonged duration. Consideration of schedules where 2CdA is alternatively administered with combination chemotherapy appears warranted.

Adult↗
PubMed1996

The clinical outcome of preterm premature rupture of membranes in twin versus singleton pregnancies.

The purpose of this study was to determine the clinical outcome of preterm premature rupture of the membranes (PPROM) in twin versus singleton pregnancies at less than or equal to 36 weeks' gestation. A retrospective cohort study was conducted in 116 twin pregnancies with PPROM at less than or equal to 36 weeks' gestational age and 116 matched singleton pregnancies. The two groups were analyzed for differences in maternal demographics and perinatal and neonatal outcome. Perinatal and neonatal outcomes were similar in the two groups. The median latency period, however, was significantly decreased in the twin group (11.4 hours, Inter Quartile Range: 6.3-26.4) versus the singleton group (19.5 hours, Inter Quartile Range: 10.2-49.3, p < 0.05). The latency period in each group was notably longer when PPROM occurred at less than 30 weeks' gestation, but was still shorter in the twin pregnancies (27.6 hours, Inter Quartile Range: 20-307 versus 75.1 hours, Inter Quartile Range: 15-189, p < 0.05). Twin pregnancies with PPROM at less than or equal to 36 weeks' gestational age have a decreased latency period when compared to matched singletons. The perinatal and neonatal outcomes, however, are similar.

Adult↗
PubMed1996

Biomonitoring human exposure to environmental carcinogenic chemicals.

A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of second biological effects (mutation and cytogenetic damage). Adduct detection at the level of DNA or protein (haemoglobin) was carried out by 32P-postlabelling, immunochemical, HPLC or mass spectrometric methods. Urinary excretion products resulting from DNA damage were also estimated (immunochemical assay, mass spectrometry). The measurement of adducts was focused on those from genotoxicants that result from petrochemical combustion or processing, e.g. low-molecular-weight alkylating agents, PAHs and compounds that cause oxidative DNA damage. Cytogenetic analysis of lymphocytes was undertaken (micronuclei, chromosome aberrations and sister chromatid exchanges) and mutation frequency was estimated at a number of loci including the hprt gene and genes involving in cancer development. Blood and urine samples from individuals exposed to urban pollution were collected. Populations exposed through occupational or medical sources to larger amounts of some of the genotoxic compounds present in the environmental samples were used as positive controls for the environmentally exposed population. Samples from rural areas were used as negative controls. The project has led to new, more sensitive and more selective approaches for detecting carcinogen-induced damage to DNA and proteins, and subsequent biological effects. These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in workers in a coke oven plant, garage workers exposed to diesel exhaust and workers exposed to ethylene oxide in a sterilization plant. Dose reponse and adduct repair were studied for methylated adducts in patients treated with methylating cytostatic drugs. The biomonitoring methods have also demonstrated their potential for detecting environmental exposure to genotoxic compounds in nine groups of non-smoking individuals, 32P-postlabelling of DNA adducts being shown to have the greatest sensitivity.

Antineoplastic Agents, Alkylating↗
PubMed1996

Productive persistent infection of hematopoietic cells by human foamy virus.

Human foamy virus can establish persistent infections in human hematopoietic cell lines, such as H92.1.7 (erythroblastoid cells), Jurkat (CD4+ T cells), and U937 (myeloid-monocytic cells). The infection is characterized by constant production of infectious viruses (for > 2 1/2 years) with no cytopathic effects on the host cells. Electron microscopy of the infected cells showed a viral morphology similar to that observed for particles produced after acute infection. We have detected, in addition to the full-length form of bel1, a previously described deletion in the bel1 gene of the proviral DNA in these cells. RNA containing this 301-bp deletion, which mapped to the splice donor and acceptor sites of the intron of the bet gene, was also found in encapsidated virion RNA. However, the presence of this defective provirus harboring the deletion in bel1 does not prevent productive persistence in these chronically infected cells, since the virus titer does not decrease during cultivation.

Base Sequence↗
PubMed1996

Adaptive responses of hypertrophying skeletal muscle to endurance training.

We determined the effects of 6 wk of endurance running on citrate synthase (CS) activity and myosin heavy chain (MHC) expression in bilateral surgical-overloaded rodent fast-twitch plantaris and slow-twitch soleus muscles. The overload induced significant hypertrophy in both muscle types, and this response was enhanced by endurance training. The overload-induced compensatory hypertrophy was accompanied by a proportional increase in muscle CS content. Although endurance training produced significant increases in CS concentration in either muscle type of the normal-trained groups (P < 0.05), it was not effective in causing similar changes in the overloaded trained muscles. Also, overload of either the sedentary or trained groups produced an increase in slower MHC isoforms (i.e., type I in the soleus and types I and IIa in the plantaris) and a concomitant decrease in the faster MHC isoforms (type IIa in the soleus and IIb in the plantaris; P < 0.05), whereas endurance training alone produced the opposite effect, especially in the plantaris. Collectively, these data suggest that 1) increments in muscle oxidative enzyme content due to endurance training are compromised when a hypertrophying process is occurring concomitantly; and 2) the relative loading state imposed on the muscle during repetitive locomotor activity is critical in regulating the pattern of MHC plasticity.

Adaptation, Physiological↗
PubMed1996

Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity.

PURPOSE: To assess the role of vascular endothelial growth factor (VEGF) in the feline model of retinopathy of prematurity (ROP). METHODS: Retinopathy of prematurity was induced in neonatal cats by raising them in an oxygen-enriched (70% to 80%) atmosphere for 4 days to suppress vessel formation and then returning them to room air for 3 to 27 days. In situ hybridization was used to detect the expression of VEGF and its high-affinity receptor, flk-1, in the retina of neonatal cats, and glial fibrillary acidic protein immunocytochemistry was used to assess astrocyte status. RESULTS: The expression of VEGF in the innermost layers of retina fell in hyperoxia and increased on return to room air. Vascular endothelial growth factor expression was transient; it was maximal where vessels were about to form, and it rapidly downregulated after vessels had formed. During the proliferative vasculopathy of ROP, VEGF expression was stronger than in the normally developing retina, and the astrocytes that normally express VEGF degenerated. After the degeneration of astrocytes, VEGF was expressed by neurones of the ganglion cell layer. flk-1 was expressed by intraretinal and preretinal vessels. Supplemental oxygen therapy reduced or eliminated the overexpression of VEGF expression, astrocyte degeneration, and formation of preretinal vessels. CONCLUSIONS: Regulation of VEGF by tissue oxygen mediates the inhibition of vessel growth during hyperoxia and the subsequent proliferative vasculopathy. Degeneration of retinal astrocytes creates conditions for the growth of preretinal vessels.

Animals↗
PubMed1995

Evaluation of a point-of-care testing product for drugs of abuse; testing site is a key variable.

We evaluated the EZ-SCREEN Test Kit (Editek, Inc., Burlington, NC), a point-of-care screening test for the presence of cocaine metabolite (benzoylecgonine; BE), cannabinoids (tetrahydrocannabinol; THC) and opiates in urine. Patient specimens (n = 34) were tested in the laboratory using both Abbott Laboratories ADx (ADx) and EZ-SCREEN (EZS-LAB), and by the nursing staff of an inpatient substance abuse treatment program using the EZ-SCREEN (EZS-RN). We found comparable analytical efficiency between methods used in the laboratory (> 95% for all three analytes with EZS-LAB and ADx) but lower efficiency for THC and BE with point-of-care testing (approximately 82% for EZS-RN). Efficiency for EZS-RN opiates was 100%. We conclude that the EZ-SCREEN Test Kit may not be suitable for use in a busy clinical setting, unless specific measures are taken to insure the accuracy of point-of-care testing (e.g., minimal interruption or distraction, careful training). We recommend that prior to routine use of point-of-care testing products they be evaluated under normal working conditions with personnel who will eventually be required to perform routine testing.

Cocaine↗
PubMed1995

Ankle arthroscopy in industrial injuries of the ankle.

Industry-related injuries to the foot and ankle are not uncommon. These cases are often difficult to evaluate with respect to degree of damage and even more difficult to quantitate with regard to functional impairment. This article represents an attempt to determine the role of ankle arthroscopy in the evaluation of ankle injuries that involve compensation or liability. A retrospective review was conducted. The study group consisted of 40 patients who underwent a total of 42 arthroscopic procedures. The patients were evaluated with regard to the mechanism of injury and clinical manifestations. Pain and swelling were the most common preoperative symptoms. The majority of patients had pain localized to the lateral and anterolateral ankle. There were a high percentage of positive bone scans that correlated well with bone pathology but poorly with soft-tissue pathology. Computed tomography (CT) scans were equivalent to tomograms in the demonstration of bone pathology. Follow-up was obtained in 24 patients. At least 50% of the patients had some improvement in their symptoms. Thirty-three percent believed there was no change, and 17% said they were worse. Over 70% of the patients were able to return to work, although 20% had to change their occupation. Fifteen percent were considered disabled. In patients without a specific diagnosis, ankle arthroscopy was helpful in establishing a diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Occupational↗