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Biomedical subjects

J T Flynn

Publications and source records attributed to J T Flynn.

At least 19 recordsLinked to original sources

A cohort study of transcutaneous oxygen tension and the incidence and severity of retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity is a disease affecting the blood vessels of the retina in premature infants that may result in scarring, retinal detachment, and loss of vision. An association between this condition and the exposure of premature infants to supplemental oxygen has been postulated, but the relation between retinopathy of prematurity and blood oxygen levels has not been defined. The purpose of this study of a cohort of preterm infants was to correlate the incidence and severity of retinopathy of prematurity with the duration of exposure to different ranges of oxygen tension as measured by transcutaneous monitoring (tcPO2). METHODS: One hundred one premature infants (birth weight, 500 to 1300 g) requiring supplemental oxygen had continuous monitoring of tcPO2. The number of hours during which the tcPO2 was 80 mm Hg or higher was tabulated for each infant during the first four weeks of life. RESULTS: There was a significant association between the amount of time that the tcPO2 was greater than or equal to 80 mm Hg and the incidence and severity of retinopathy of prematurity. The odds ratio for each 12-hour period in which the tcPO2 was greater than or equal to 80 mm Hg was 1.9 (95 percent confidence interval, 1.2 to 3.0) after adjustment for the following factors: birth weight less than or equal to 1300 g (odds ratio, 2.3 [95 percent confidence interval, 1.6 to 3.4]), five-minute Apgar score of 7 or less (odds ratio, 7.2 [95 percent confidence interval, 2.5 to 21]), and exposure to inspired oxygen at a concentration greater than or equal to 0.4 (odds ratio, 1.0 [95 percent confidence interval, 0.97 to 1.05]). The association was stronger for tcPO2 values of greater than or equal to 80 mm Hg occurring from the second through the fourth week of life; during this period, the adjusted odds ratio for a 12-hour period of such exposure was 3.1 (95 percent confidence interval, 1.6 to 6.1). CONCLUSIONS: This study supports an association between the incidence and severity of retinopathy of prematurity and the duration of exposure to arterial oxygen levels of 80 mm Hg or higher, measured transcutaneously.

Apgar Score

Treatment of steroid-resistant post-transplant nephrotic syndrome with cyclophosphamide in a child with congenital nephrotic syndrome.

A child with congenital nephrotic syndrome underwent renal transplantation, was treated for acute rejection, and then developed nephrotic syndrome and renal failure. He was felt to have minimal change disease on allograft biopsy, but failed to respond to therapy with corticosteroids. Cyclophosphamide was substituted for cyclosporine and rapidly induced a complete remission of his nephrotic syndrome. We feel that this case not only represents an important example of a useful therapeutic approach to the child with congenital nephrotic syndrome who develops nephrotic syndrome post transplantation, and also raises questions concerning the pathogenesis of congenital nephrotic syndrome.

Cyclophosphamide

Urinary tract infections in children with posterior urethral valves after kidney transplantation.

The records of 14 boys with posterior urethral valves who had renal failure and subsequently underwent renal transplantation were reviewed to determine the postoperative incidence of urinary tract infection relative to that of 29 male transplant children without valves, who served as controls. There were no significant differences between the posterior urethral valve patients and controls with regard to age, donor source, immunosuppression, followup after transplantation or mean calculated creatinine clearance. Vesicoureteral reflux was found in 1 child with posterior urethral valves and 3 of the children in the control group (p not significant). A total of 15 urinary tract infections occurred in 5 children (36%) with posterior urethral valves, for a rate of 1 per 30 patient-months of followup, and 6 urinary tract infections occurred in 2 controls (7%), for a rate of 1 per 216 patient-months of followup (p < 0.05). However, only 1 of 26 controls (4%) without vesicoureteral reflux had urinary tract infection, for a rate 1 per 1,144 patient-months (p < 0.01). Conversely, the rate of urinary tract infections in controls with vesicoureteral reflux was similar to that of children with posterior urethral valves. Of the 5 children with posterior urethral valves 4 had the initial urinary tract infection within 2 months of transplantation and 10 of 15 episodes occurred within the first 4 months. Antimicrobial prophylaxis did not appear to decrease the rate of infection in children with posterior urethral valves. A history of posterior urethral valves increases the frequency of urinary tract infection after renal transplantation but the usefulness of antimicrobial prophylaxis and the relationship to long-term graft function remain to be determined. Urinary tract infection rarely develops in other transplanted boys without vesicoureteral reflux.

Adolescent

Endotoxin enhances arachidonic acid metabolism by cultured rabbit microvascular endothelial cells.

This study demonstrates that bacterial lipopolysaccharide and lipid A exert a significant effect on eicosanoid formation by primary cultures of microvascular endothelial cells (MECs). Qualitative studies using [14C]-arachidonic acid demonstrated that prostaglandin E2 was the primary eicosanoid formed by MECs after 20 h of treatment with either vehicle or lipopolysaccharide. Significant, dose-dependent productions of PGE2 and prostacyclin, beginning at an endotoxin dose of 0.01 ng/ml, were quantified by radioimmunoassay in supernatants of cells treated for 20 h with lipopolysaccharide or lipid A. This eicosanoid production was inhibited by meclofenamate and cycloheximide and occurred without cellular injury. The time course and kinetics of eicosanoid production in response to endotoxin demonstrate a significant, time-related enhancement. Endotoxin-treated MECs responded to exogenous substrate with augmented PGE2 production, suggesting enhanced prostaglandin endoperoxide synthase activity. These results demonstrate a significant interaction of endotoxin with endothelial cells of microvascular origin that results in an enhanced potential for eicosanoid metabolism. This effect may be mediated in part through induction of prostaglandin endoperoxide synthase.

Animals

Pentafraction reduces the lung lymph response after endotoxin administration in the ovine model.

For the past half-century, several high molecular weight compounds have been used for volume expansion during cardiopulmonary resuscitation. However, the effectiveness and side effects of these different expanders are varied. We have compared plasma, pentastarch, and a new product, pentafraction, for effective plasma volume expansion before and after tissue injury with endotoxin administration. In each group, eight range ewes instrumented with a Swan-Ganz, arterial, and venous catheters, and lung and flank lymphatic cannulas were compared. Each group received 15 ml/kg of either 6% pentafraction, 6% pentastarch, or plasma followed two hours later by 1.5 micrograms/kg/0.5 hr E. Coli endotoxin over 30 min. Data were collected for an additional 24 hr after endotoxin administration. Our results indicated a plasma volume expansion in all three groups. However, the prior administration of pentafraction significantly attenuated the increase in the lung lymph flow and early evaluation of systemic vascular resistance noted with endotoxin in comparison to the other two groups.

6-Ketoprostaglandin F1 alpha

Mechanism of immunoreactive atrial natriuretic factor release in an ovine model of endotoxemia.

We have previously reported an increase in plasma levels of atrial natriuretic factor (ANF) in an ovine model of endotoxemia. The purpose of this study was to determine if this IR-ANF release was mediated by the increase of right atrial pressure (RAP) and right heart volumes concomitantly observed following endotoxin (LPS) administration. We studied right ventricular function, renal blood flow (RBF), urinary output (UO), urinary clearance of free water (CH20), urinary osmolality (UOSM), sodium excretion (UENA), and the plasma IR-ANF concentration (radioimmunoassay), following the administration of an E. coli LPS bolus (1 microgram/kg) with (group O, n = 8) and without (group E, n = 10) pretreatment with OKY-046, a selective thromboxane synthetase inhibitor. LPS induced early increases in RAP, right ventricular end-systolic (RVESV) and end-diastolic (RVEDV) volumes, heart rate (HR), and IR-ANF, and delayed increases in RBF, UO, and CH20. OKY-046 prevented the elevation of RAP, RVEDV, and RVESV; however, both groups showed virtually identical increases in IR-ANF (E: 20.03 +/- 3.8 to 192.33 +/- 35.47 pg/ml, O: 17.9 +/- 4.1 to 159.5 +/- 23 pg/ml) as well as an increase of HR, RBF, UO, and CH20. The increase in IR-ANF release noted following the administration of LPS in an ovine model does not appear to be related to the early elevations in right heart volumes or atrial distension.

Animals

Ocular motility complications following intranasal surgery.

The ocular motility problem of two patients following intranasal surgery is examined. The patients were studied by eye movement records and ultrasonography. Surgery in both cases revealed a defect of the medial orbital wall with scar tissue incarcerated in the defect.

Aged

Congenital nystagmus surgery. A quantitative evaluation of the effects.

Nystagmus intensities at various gaze angles were studied both preoperatively and postoperatively, using accurate ocular motility recordings, in three cases of congenital nystagmus. In addition to shifting the nystagmus null, the surgery broadened the null region and resulted in an overall reduction in nystagmus intensity at all gaze angles. Surgical rotation also resulted in improved visual acuity in all cases. The postoperative acuity at 0 degrees was better than the preoperative acuity at both 0 degrees and the patient's preferred gaze angle (ie, the preoperative null angle). This was not only for the two patients who showed an improved preoperative acuity with their head turn but also for the patient whose preoperative acuity did not substantially improve with her preferred head turn. Eye movement recordings have made it possible to accurately determine the amount of surgery required and to predict acuity increases even when undetectable during the preoperative clinical examination.

Adolescent

Prostaglandin E and hypercalcemia in breast carcinoma: only a tumor marker? A need for perspective.

Prostaglandin E concentrations were measured in a patiet with breast carcinoma, hypercalcemia, undetectable parathyroid hormone (PTH) and no evidence of bone metastases. Catheterization of the drainage bed of her tumor documented production of E series prostaglandins. Treatment with the largest recommended doses of indomethacin for 10 days failed to lower her plasma prostaglandin E (PGE) concentrations or to correct the hypercalcemia, but it normalized urinary excretion of PGE. Subsequent chemotherapy reduced prostaglandin concentrations toward normal values concomitant with a reduction of clinically estimated tumor burden. During this period of time, serum calcium concentrations had no consistent relationship to the plasma PGE levels. We suggest that PGE merely reflected the tumor burden of this patient and did not directly contribute to the genesis of her hypercalcemia. The pertinent literature relating PGE and hypercalcemia is reviewed.

Antineoplastic Agents

Influence of the arachidonic acid cascade on the in vitro hepatic response to hypoxia.

Studies were undertaken to determine the effect of arachidonic acid, the precursor of bisenoic prostanoic acid derivatives, on the response of the isolated, perfused rabbit liver to hypoxia. Two and one half hours of severe hypoxia resulted in significant increases in hepatic vascular perfusion pressure, tissue wet weight, and the rates of cellular loss of lactic dehydrogenase, malic dehydrogenase, and acid phosphatase into the perfusing medium. Hypoxia also increased the rate of hepatic PGF2 alpha production by 25% after 2 1/2 hours (p less than 0.05, hypoxia vs sham). The addition of arachidonic acid (0.1 microgram/g/min for 150 minutes) to the perfusion medium of hypoxic livers significantly attenuated the changes in perfusion pressure, tissue wet weight, and loss of cellular enzymes. Arachidonic acid administration increased the rate of PGF2 alpha production by 100% (p less than 0.05, sham vs hypoxia + arachidonic acid) within 30 min after hypoxia and maintained this rate for the duration of the study. These results demonstrate that hypoxia mediated prostaglandin F2 alpha synthesis in the rabbit liver can occur in the absence of neural and blood borne components and that significant activation of the arachidonic acid cascade via the administration of exogenous arachidonic acid has a salutary effect on hepatic hemodynamics and cellular integrity during hypoxia.

Acid Phosphatase

Fluorescein angiography in retrolental fibroplasia: experience from 1969-1977.

Acute proliferative retrolental fibroplasia (RLF) has been studied in premature infants employing a Zeiss fundus camera and fluorescein angiography. A total of 164 angiograms have been performed on 122 infants. At the present time, angiography is reserved for studying infants with peculiar or puzzling fundus pictures. A dose of 0.1-0.4 cc of 10% sodium fluoresceinate is employed, depending on the age and the weight of the baby. Fluorescein clearly outlines the major arteriovenous shunt in the retina, which is the hallmark of acute RLF. The shunt fills with fluorescein and leaks it profusely. On regression, a fine brush border of capillaries is seen in the region where the shunt previously had been located. Study of the population susceptible to RLF reveals it to be the smallest sickest babies in the premature nursery.

Female

The effects of congenital nystagmus surgery.

Anderson-Kestenbaum operations for congenital nystagmus with severe head turn have been employed for the past 25 years. They have been documented as being effective in correcting head turns associated with congenital nystagmus. We have studied a group of patients with congenital nystagmus and head turn, both preoperatively and postoperatively, by means of recordings of eye movements. We have documented the effect of surgery in shifting the null position, in broadening the null position, and in lowering the nystagmus intensity. In some cases, an improvement of the visual acuity has also occurred.

Adolescent

The underestimated hazards of xanthogranulomatous pyelonephritis.

Twenty-eight cases of xanthogranulomatous pyelonephritis were studied in retrospect and difficulties in diagnosis and treatment are described. Awareness of the entity is the most effective safeguard against over-aggressive resection for this benign condition.

Adolescent

The early and aggressive repair of iatrogenic ureteric injuries.

Sixty-two iatrogenic injuries of the ureter in 52 patients have been studied over a 15-year period. A plea is made for early recognition in post-operative urinary fistulae and early operative repair. The results of 41 cases treated by the Boari-Ockerblad method are reported without post-operative obstruction or failure.

Adult

A technique for selecting and concentrating the motile sperm from semen in oligozoospermia.

Using an albumen-filled column, it was possible to separate highly motile sperm from autoagglutinated, dead and immotile sperm, as well as from other seminal debris. Motility was increased from a mean of 45.4 to 74.3% (P less than 0.001), although the sperm density fell from a mean of 28.2 million per ml to 9.7 million per ml (P less than 0.001). When these selected highly concentional AlH had been repeatedly tried without success, 3 pregnancies were achieved in 18 women (16.7%).

Cell Separation

Herpes simplex retinitis.

Fatal encephalitis with accompanying retinitis developed in a previously healthy 18-month-old infant. Clinically the disease appeared as whitish-yellow punctate lesions, perivascular cuffing, and hemorrhage. The antibody titer to herpes simplex rose from 1:8 on the day of admission to 1:256 on the day of death. Postmortem, intranuclear inclusion bodies that were typical of those found with herpesvirus were seen in the brain and retina. Viral particles consistent with those of herpesvirus were found by electron microscopy in the brain and in the inner-nuclear and ganglion-nerve fiber layers of the retina. This demonstrates the direct infectious nature of herpetic retinitis. Hematogenous spread of the virus to the retina is presumed.

Brain Stem