5-Fluorouracil vs avastin as adjunct to conjunctival autograft in the surgical treatment of pterygium.

BACKGROUND: The use of adjunct antimetabolite therapy along with conjunctiva autograft has been shown to be effective in preventing pterygium recurrence. There has however been fewer reports on the effect of anti-vascular endothelial growth factor on pterygium recurrence. OBJECTIVE: To compare 5-fluorouracil with conjunctival autograft with bevacizumab (avastin) used along with autograft in the surgical treatment of pterygium. METHODS: A randomized controlled prospective study of outcome of pterygium treatment using 5-fluorouracil with conjunctiva autograft as adjuvant treatment compared avastin with conjunctiva autograft. RESULTS: A total of 70 eyes of 70 patients were recruited into the study with a mean age of 51.49 (±14.36) years. Thirty-five patients each were randomized into the 5-fluorouracil treatment group and into the avastin treatment group respectively. The mean follow-up was 18.35 months (18.44 for the 5-FU and 18.26 for the avastin group). Post operative, pterygium recurrence was observed in 1/27 (3.7%) eyes treated with 5-fluorouracil and 1/26 (3.9%) eyes of the avastin group. Both recurrences were observed at 1 year of follow-up and they were both female patients aged 46 and 52 years, respectively. CONCLUSIONS: Both 5-fluorouracil and avastin are comparably effective as adjunct to conjunctival autograft. However, cost, availability, and convenience are other considerations with use of avastin.

Risk factors for pterygium recurrence after surgical excision with combined conjunctival autograft (CAG) and intraoperative antimetabolite use.

BACKGROUND: To identify the determinants of recurrence following primary pterygium excision combined with conjunctival autograft (CAG) and intraoperative use of Mitomycin C (MMC) or 5-Fluorouracil (5-FU). METHODS: A randomized controlled clinical trial comparing 5-FU (50 mg/ml) plus CAG versus MMC (0.01%) plus CAG in preventing recurrence of primary pterygium following excision. RESULTS: A total of 80 eyes of 80 subjects were studied, with 46 eyes in the 5-FU group and 34 eyes in the MMC group. The mean age was 50.7 +/- 13.1 years with a male: female ratio of 0.95:1. Mean follow up period was 35.2 +/- 29.1 weeks. The overall recurrence rate was 10%, with a rate of 8.7% in the 5-FU group and 11.8% in the MMC group. The mean age of the patients who had a recurrence was 38.1 +/- 13.3 years compared to 52.1 +/- 12.4 years in those without a recurrence (p = 0.003). The median size of the pterygium in patients who had a recurrence was 3.2mm, while the median size in patients who did not have a recurrence was 3.0mm (p = 0.8). Five (12.8%) males had a recurrence compared to three (7.3%) females (p = 0.48); while 10.5% of fleshy pterygia recurred compared to none (0%) of the non-fleshy pterygia (p = 1.00). CONCLUSION: Younger age remains a risk factor for recurrence when both CAG and antimetabolites are combined in the treatment of pterygium, while the effect of gender, size and morphology of the pterygium may be diminished by such combination.

Etiology and diagnostic evaluation of macrocytosis.

BACKGROUND: Elevation of mean cell volume (MCV) is a common clinical problem, but the etiologic spectrum and optimal diagnostic evaluation of macrocytosis are not well defined. METHODS: We studied 300 consecutive hospitalized adult patients with MCV values > or = 100 fL. Assessment included complete blood counts, morphologic review, liver function tests, and levels of serum cobalamin (Cbl), methylmalonic acid, and total homocysteine. RESULTS: The most common cause of macrocytosis was drug therapy, followed by alcohol, liver disease, and reticulocytosis. Megaloblastic hematopoiesis accounted for less than 10% of cases. MCV values > 120 fL were usually caused by Cbl deficiency. Anisocytosis, macro-ovalocytosis, and teardrop erythrocytes were most prominent in megaloblastic hematopoiesis. Elevated levels of serum methylmalonic acid and total homocysteine were useful in the diagnosis of Cbl deficiency. CONCLUSIONS: Drugs and alcohol are the most common causes of macrocytosis in hospitalized patients in a New York City teaching hospital. We have formulated tentative guidelines for the evaluation of high MCV values in this setting.

Factors associated with inadequate blood pressure control in hypertensive hemodialysis patients.

Hypertension is common in hemodialysis patients and increases cardiovascular morbidity and mortality. We determined the prevalence of inadequate control of hypertension in 489 patients receiving hemodialysis and identified factors associated with uncontrolled hypertension. We interviewed the patients and abstracted demographic and clinical information from a computerized database. The prevalence of uncontrolled hypertension (average predialysis blood pressure, > or =160/90 mm Hg) was 62%. Ninety-one percent of patients with uncontrolled hypertension were receiving submaximal antihypertensive drug therapy, and 59% withheld their medications before dialysis. Uncontrolled hypertensives had a greater interdialytic weight gain (3.8% v 3.5%, P = 0.07) and a greater excess weight gain (3.1 +/- 1.6 kg v 2.5 +/- 1.4 kg; P < 0.05) compared with controlled hypertensives. Patients with uncontrolled hypertension showed higher interdialytic weight gain (2.7 +/- 0.06 kg v 2.2 +/- 0.13 kg; P < 0.05), were more likely to be black (94% v 81%; P < 0.05), were more likely to have hypertension as the cause of their end-stage renal disease (ESRD) (42% v 24%; P < 0.05), and had been receiving hemodialysis for a shorter time (4.3 +/- 2 yr v 6.1 +/- 0.9 yr; P < 0.05) compared with normotensive patients. There was significant correlation between diastolic blood pressure and both interdialytic weight gain (r = 0.31, P < 0.05) and percent weight gain (r = 0.34, P < 0.05) in the hypertensive but not in the normotensive patients (r = -0.21). Interdialytic weight gain and hypertension as a cause of ESRD were independent predictors of predialysis systolic blood pressure. We conclude that hypertension is uncontrolled in most patients undergoing hemodialysis. Submaximal antihypertensive therapy, excessive interdialytic weight gain, and withholding antihypertensive medication before dialysis are correctable factors potentially contributing to uncontrolled hypertension.

Ovine fetal laryngeal chemoreflex thresholds and respiratory effects.

In newborn infants, laryngeal contact with solutions of low chloride concentration or pH evokes swallowing, laryngeal adduction, and respiratory inhibition (laryngeal chemoreflex). To determine whether the laryngeal chemoreflex is present during fetal life and its effect on fetal respiratory activity, eight time-bred ewes (128 +/- 2 days) were prepared with fetal electrocortical diaphragm and esophageal electrodes and a nasopharyngeal catheter. After a 60-minute control period, increasing volumes (0.1 to 1.0 ml/kg) of 0.15 mol/L NaCl or distilled water (0.05 to 1.0 ml/kg) and decreasing concentrations of NaCl (0.15 to 0.02 mol/L) at a fixed volume (0.3 ml/kg) were sequentially administered through the nasopharyngeal catheter (38 degrees C). The minimum water volume that stimulated swallowing was significantly less than the minimum 0.15 mol/L NaCl volume (0.10 +/- 0.02 vs. 0.70 +/- 0.05 ml/kg). The maximum NaCl concentration that stimulated swallowing was 0.04 +/- 0.01 mol/L During the control period, respiratory activity averaged 14.6 +/- 0.7 breaths/minute and did not change during absent swallow responses or isotonic saline-induced swallows. However, respiratory activity significantly decreased during water (4.7 +/- 0.6 breaths/minute) and hypotonic saline-induced swallow responses (3.7 +/- 0.7 breaths/minute). Fetal electrocortical activity did not change during absent or stimulated swallows. We conclude that laryngeal water or hypotonic saline solution may stimulate fetal swallowing and suppress fetal respiratory activity, similar to the newborn laryngeal chemoreflex. We speculate that an exaggeration of the laryngeal chemoreflex apnea response in the newborn may predispose to sudden infant death syndrome.

Treatment of oligohydramnios with maternal 1-deamino-[8-D-arginine] vasopressin-induced plasma hypoosmolality.

OBJECTIVE: Maternal 1-deamino-[8-D-arginine] vasopressin (a selective antidiuretic agonist) and oral water loading decrease maternal and fetal plasma osmolality and markedly increase fetal urine flow in sheep. We hypothesized that a titrated reduction in maternal plasma osmolality would increase human amniotic fluid volume. STUDY DESIGN: Pregnant women (n = 5) with oligohydramnios at term were administered oral water loading (20 ml/kg) and intravenous 1-deamino-[8-D-arginine] vasopressin (2 micrograms) to induce antidiuresis. Maternal plasma and urine osmolality and urine production were measured hourly, and water replacement was titrated for 8 hours to reduce plasma osmolality by 15 to 20 mOsm/kg. The amniotic fluid index determined by ultrasonography was measured at baseline, 8 hours, and 24 hours. A control group of pregnant women (n = 5) with oligohydramnios at term was observed for 8 hours with maintenance intravenous hydration. RESULTS: In 1-deamino-[8-D-arginine] vasopressin-treated women, maternal urine flow increased with oral water loading, decreased with 1-deamino-[8-D-arginine] vasopressin administration, and remained reduced for 8 hours. Maternal plasma osmolality significantly decreased (285 +/- 4 to 265 +/- 4 mOsm/kg) and the amniotic fluid index significantly increased (4.1 +/- 0.6 to 8.2 +/- 1.5 cm) at 8 hours. Although maternal urine osmolality returned to basal values at 24 hours, plasma osmolality was reduced and the amniotic fluid index remained significantly increased (8.2 +/- 1.3 cm). There was no change in the amniotic fluid index (4.3 +/- 0.4 to 4.7 +/- 0.7 cm) in control patients observed with maintenance intravenous hydration. CONCLUSIONS: Maternal 1-deamino-[8-D-arginine] vasopressin and oral water administration can reduce and stabilize plasma osmolality and increase amniotic fluid volume. 1-Deamino-[8-D-arginine] vasopressin therapy has potential for the prevention and treatment of oligohydramnios.

Ovine fetal swallowing response to intracerebroventricular hypertonic saline.

In the near-term ovine fetus, systemic hyperosmolality stimulates dipsogenic responses. Putative systemic dipsogens (hypertonicity, angiotensin II) may initiate responses by stimulation of select cerebral circumventricular nuclei lacking a blood-brain barrier. To investigate whether central osmotic-dipsogenic mechanisms are functional in utero, fetal swallowing responses to intracerebroventricular (i.c.v.) hypertonic saline were examined. Five pregnant ewes with singleton fetuses (128 +/- 1 days gestation) were prepared with fetal lateral cerebral ventricle and vascular catheters, electrocortical (ECoG) electrodes, and electromyogram wires on the fetal thyrohyoid muscle, nuchal and thoracic esophagus, and diaphragm and studied for a minimum of 5 days postoperatively. After a 2-h basal period, fetuses received an i.c.v. infusion of artificial cerebrospinal fluid followed by successive 30-min infusions of hypertonic NaCl in artificial cerebrospinal fluid (500 and 700 mosmol/kgH2O). In response to the i.c.v. hypertonic NaCl infusions, fetal swallowing significantly increased (1.4 +/- 0.4 to 3.9 +/- 1.4 and 2.9 +/- 0.5 swallows/min low-voltage ECoG, respectively). Plasma arginine vasopressin levels increased, although the change was not statistically significant (9.1 to 24.2 pg/ml; P = 0.07), and there was no change in fetal plasma osmolality, sodium concentration, or ECoG activity. Together with previous studies, these results indicate that both central and systemic osmotic dipsogenic mechanisms are functional in utero.

Central angiotensin II stimulation of ovine fetal swallowing.

In the late-gestation ovine fetus, spontaneous swallowing occurs primarily during fetal low-voltage electrocortical (ECoG) activity in association with fetal breathing movements. Fetal swallowing activity may be stimulated in response to systemic or carotid plasma hyperosmolality, although not to increased plasma angiotensin II (ANG II) levels. In view of the potent dipsogenic effects of central, but not peripheral, ANG II in adult sheep, the present study investigated the effect of intracerebroventricular (ICV) ANG II on fetal swallowing activity. Six ovine fetuses (127 +/- 1 days) were chronically prepared with electromyogram and cortical electrodes and with vascular and lateral ventricle catheters. After a 2-h control period, fetuses received ICV injections of artificial cerebrospinal fluid and increasing concentrations of ANG II (0.1, 1.0, 10, 100, and 500 ng/kg). Fetal ECoG activity did not change, although fetal swallowing activity significantly increased in response to the 100- and 500- ng/kg ANG II doses (1.20 +/- 0.14 to 3.34 +/- 0.59 and 3.46 +/- 0.81 swallows/min of low-voltage ECoG, respectively). In response to the highest ANG II dose, fetal plasma arginine vasopressin levels significantly increased (5.7 +/- 1.2 to 17.2 +/- 4.6 pg/ml). ICV ANG II stimulation of fetal swallowing and arginine vasopressin secretion demonstrates that central ANG II dipsogenic mechanisms are intact by 0.9 of ovine gestation.

Modified suburethral sling procedure for treatment of recurrent or severe stress urinary incontinence.

The most suitable material used to perform suburethral sling procedures for recurrent or severe stress urinary incontinence remains controversial. A comparison was made between two commonly used materials, synthetic Gore-Tex (expanded reinforced polytetrafluoroethylene) and autologous fascia lata. Both groups showed improved urethral pressure profiles postoperatively, but there was no difference in the magnitude of change between groups. The objective cure rate at six months for the Gore-Tex group was 100.0 versus 87.5 percent for the fascia lata group (p = 0.155). While there was no statistical difference between the incidence of de novo detrusor instability or length of postoperative bladder drainage (p = 0.104 and p = 0.978, respectively), there was a trend toward more postoperative complications of urinary obstruction in the Gore-Tex group.