Plasma-deposited membranes for controlled release of antibiotic to prevent bacterial adhesion and biofilm formation.

Bacterial infection on implanted medical devices is a significant clinical problem caused by the adhesion of bacteria to the biomaterial surface followed by biofilm formation and recruitment of other cells lines such as blood platelets, leading to potential thrombosis and thromboembolisms. To minimize biofilm formation and potential device-based infections, a polyurethane (Biospan) matrix was developed to release, in a controlled manner, an antibiotic (ciprofloxacin) locally at the implant interface. One material set consisted of the polyetherurethane (PEU) base matrix radiofrequency glow discharge plasma deposited with triethylene glycol dimethyl ether (triglyme); the other set had an additional coating of poly(butyl methyacrylate) (pBMA). Triglyme served as a nonfouling coating, whereas the pBMA served as a controlled porosity release membrane. The pBMA-coated PEU contained and released ciprofloxacin in a controlled manner. The efficacy of the modified PEU polymers against Pseudomonas aeruginosa suspensions was evaluated under flow conditions in a parallel plate flow cell. Bacterial adhesion and colonization, if any, to the test polymers were examined by direct microscopic image analysis and corroborated with destructive sampling, followed by direct cell counting. The rate of initial bacterial cell adhesion to triglyme-coated PEU was 0. 77%, and to the pBMA-coated PEU releasing ciprofloxacin was 6% of the observed adhesion rates for the control PEU. However, the rate of adherent cell accumulation due to cell growth and replication was approximately the same for the triglyme-coated PEU and the PEU controls, but was zero for the pBMA-coated PEU releasing ciprofloxacin.

Plan for compensating full-time physicians involved in medical education.

In response to growing financial pressures, many academic institutions have begun rewarding full-time faculty primarily on the basis of productivity. This formula often overrewards procedure-oriented specialists while poorly compensating primary care physicians. Collections have little to do with clinical effort, and rewarding productivity alone ignores the many other qualities important to the academic mission. We developed a simple, adjustable plan for quantifying and rewarding faculty behavior consistent with the goals of the institution. Eight categories are weighed by the departmental chairperson or committee, including previous year's salary, productivity, patient satisfaction, administration, academic rank, teaching, research, and quality of care. This plan is flexible and rewards behavior consistent with departmental priorities. It also allows for individual members of the department to increase their salaries by adjusting their behavior. As federal funds for training continue to decrease, teaching, research, and other scholarly activities might not be fairly compensated. Unless each institution prospectively develops a program that rewards those activities that the institution values, many important scientific and educational activities will be completely replaced by the more tangible efforts of patient care.

Repeated use of betamethasone in rabbits: effects of treatment variation on adrenal suppression, pulmonary maturation, and pregnancy outcome.

OBJECTIVE: The aim of the study was to determine whether reduced birth weight, adrenal suppression, and lung maturation occur in parallel and are cumulative with increasing courses of betamethasone. STUDY DESIGN: Time-bred rabbits were assigned to a control group or to receive saline solution or 1, 2, or 3 courses of betamethasone (early treatment, beginning day 19). Two additional groups (n = 5 per group) were given 1 or 2 late courses (late treatment). Birth weight, serum cortisol, adrenal 17alpha-hydroxylase (P450c17) messenger ribonucleic acid and fetal lung surfactant proteins A and B were quantified on day 27. RESULTS: Fetal weight was inversely proportional to the number of courses, with late treatment having a greater effect. Maternal cortisol and P450c17 levels were progressively suppressed with each early course, but fetal cortisol and P450c17 levels were only suppressed after 3 courses. A single late treatment profoundly suppressed both maternal and fetal cortisol and P450c17 messenger ribonucleic acid levels. In contrast, fetal lung surfactant proteins A and B increased progressively with betamethasone courses, regardless of timing. CONCLUSIONS: Time from last injection to delivery determined adrenal suppression, whereas total betamethasone courses determined surfactant protein production. Lower birth weight was dependent on the number of courses and was greater with late treatment.

Multiple vs. single betamethasone therapy. Neonatal and maternal effects.

OBJECTIVE: To identify potential neonatal benefits and possible neonatal and maternal complications associated with repeated use of antenatal corticosteroids. STUDY DESIGN: A retrospective chart review was done on all gravidas < 34 weeks who were hospitalized and received antenatal betamethasone at our institution between January 1, 1992 and April 30, 1996. Regression analysis was performed to investigate the relationship between single vs. multiple course of betamethasone and multiple variables. RESULTS: After controlling for significant covariates, multiple courses of betamethasone were associated with a decrease in oxygen use (P < .01). A nonsignificant decline in respiratory distress syndrome and assisted ventilation was noted. No effect on birth weight or maternal or neonatal infection was seen. CONCLUSION: Repeated use of betamethasone is associated with a significant decrease in oxygen use in the preterm neonate. No significant maternal or neonatal complications were found. A prospective, randomized trial is necessary.

Effect of hemodialysis on serum progesterone level in pregnant women.

The objective of this study is to evaluate the effect of chronic hemodialysis on serum progesterone level in pregnancy. Serum progesterone levels were measured predialysis and postdialysis using the radioimmunoassay technique in seven gravid women with renal failure requiring hemodialysis. Uterine contractions were measured before and after hemodialysis using home uterine activity monitoring (HUAM) in two patients. Thirty-three paired serum samples were obtained between 14 and 39 weeks' gestation. The mean change in serum progesterone level postdialysis throughout pregnancy ranged from -52.0% to +8.7% for each individual patient. The change in serum progesterone level was unrelated to gestational age. The woman experiencing the most significant decrease in serum progesterone level with dialysis continued her pregnancy to greater than 39 weeks. No significant increase in uterine contraction frequency was noted on HUAM postdialysis (P = 0.22), although both monitored patients experienced a small increase in serum progesterone levels. In conclusion, serum progesterone values showed a variable patient-specific response when measured predialysis and postdialysis in pregnancies complicated by renal failure. There was no significant increase in uterine activity noted postdialysis. Progesterone withdrawal does not appear to explain the increased frequency of preterm delivery in women after dialysis.

Effect of nifedipine on fetal and maternal hemodynamics and blood gases in the pregnant ewe.

OBJECTIVE: Our purpose was to determine whether the fetal acidosis and hypoxia previously demonstrated in animal models with maternal nifedipine infusion is the result of a decrease in uteroplacental or fetoplacental blood flow and whether this effect is exacerbated by a higher drug concentration and duration of infusion. STUDY DESIGN: Ten chronically instrumented pregnant ewes (gestational age 0.9 term, term = 145 days) received nifedipine infusions (n = 7) or vehicle (95% ethanol/water, 3:7) (n = 3). Three 90-minute periods were evaluated: 5 microg/kg/min infusion (low-dose nifedipine), no infusion, and 10 microg/kg/min (high-dose nifedipine). Paired maternal and fetal blood gases, glucose, lactate, and nifedipine levels were obtained every 30 minutes while hemodynamic parameters were monitored. We determined maternal and fetal blood flows using the radioactive microsphere technique. RESULTS: Although maternal placental blood flows decreased by 25% during low-dose nifedipine (p < 0.05), this was only transient and there were no other decreases in uteroplacental or fetoplacental blood flow. Fetal blood flow increased to the adrenals and diaphragm with high-dose nifedipine (p < 0.05). Maternal and fetal lactate levels increased with both doses (p < 0.05). In addition, fetuses exhibited significant hypoxia (oxygen content fell 0.46 mmol/L) and acidosis (pH fell 0.06 units) throughout the nifedipine infusion and recovery period. Maternal heart rate increased transiently with both doses (p < 0.05); however, there were no changes in either fetal or maternal mean arterial pressure. Infusion of the vehicle alone did not alter maternal or fetal hemodynamics. Maternal and fetal plasma nifedipine levels reached steady-state by 30 minutes, and maternal/fetal ratios were 0.4 to 0.55. The maternal metabolic clearance rates for low- and high-dose nifedipine were 80.0 and 79.8 ml/min/kg, respectively. Maternal half-life calculation revealed a two-compartment model with a calculated half-life of 2.87 +/- 3.15 and 63.57 +/- 154.03 (+/-SD) minutes for the alpha and beta components, respectively. CONCLUSIONS: Maternal nifedipine infusion is associated with hypoxia and acidosis in the sheep fetus, without persistent decreases in uteroplacental or fetoplacental blood flows or blood pressures. These fetal blood gas changes are more severe with high-dose nifedipine and longer duration of infusion and continue to deteriorate even when recovery is allowed. The deterioration of fetal blood gases is out of proportion to the transient decreases in uteroplacental blood flow and demonstrates that another mechanism for this fetal acidosis and hypoxia exists during nifedipine infusion.

Prenatal diagnosis of the two-vessel cord: implications for patient counselling and obstetric management.

The study was designed to investigate the implications of the sonographic diagnosis of the two-vessel umbilical cord for patient counselling and pregnancy management. Retrospective analysis was carried out of prenatal findings and pregnancy outcomes when a two-vessel cord was diagnosed in utero. Eighty-two fetuses each with a single umbilical artery were diagnosed by ultrasound. Ten were aneuploid, including nine with visible structural defects and one with early onset intrauterine growth retardation. Of the remaining 72, 31 had other anomalies diagnosed postnatally; 27 of these had structural defects detected on ultrasound examination. However, in nine of these 27 sonographically abnormal fetuses, one or more major structural defects were missed by ultrasound examination. Among the 45 chromosomally normal fetuses with no visible defects on scan, four had anomalies diagnosed after birth. Among the chromosomally normal singletons, six of 22 with other anomalies seen on scan and seven of 38 with no other visible defects on scan had intrauterine growth retardation. Among chromosomally normal twins, one of two with other anomalies seen and two of five appearing otherwise normal had intrauterine growth retardation; one twin set was delivered at 23 weeks after the demise of both twins. Karyotyping is recommended whenever a two-vessel cord is seen in association with symmetric intrauterine growth retardation or any other defect. The fetus diagnosed with a two-vessel cord and any other anomaly by ultrasound often has additional structural defects not seen on scan. The fetus with an isolated two-vessel cord on scan seldom has unrecognized major anomalies, but is at risk for intrauterine growth retardation.

Trisomy 21, fetal hydrops, and anemia: prenatal diagnosis of transient myeloproliferative disorder?

BACKGROUND: Aneuploidy is frequently cited as an etiology of hydrops fetalis. Traditionally, associated anomalies (specifically cardiovascular abnormalities) have been postulated as the causative factor. CASES: We report two cases of severe anemia associated with hydrops in fetuses that later proved to have Down syndrome. The hematocrit in both fetuses was markedly decreased. The white blood cell count was normal in one but greatly elevated in the other; the latter infant had thrombocytopenia. These findings are consistent with transient myeloproliferative disorder. CONCLUSIONS: Nonimmune fetal hydrops and trisomy 21 may be associated without cardiac or anatomical anomalies. Transient myeloproliferative disorder has been seen in neonates with trisomy 21 and may be a cause of hydrops in some aneuploid fetuses. Chromosomal analysis should not be excluded in the workup of nonimmune hydrops when anemia is found, and therapy may be withheld until karyotyping has been performed.

Amyl nitrite: use as a smooth muscle relaxant in difficult preterm cesarean section.

Amyl nitrite is a smooth muscle relaxant that has been used clinically to facilitate uterine relaxation in difficult deliveries. In this retrospective study, we evaluate the safety of amyl nitrite use during preterm cesarean deliveries, and we assess possible advantageous effects on surgical incision choice. Women who received amyl nitrite cesarean section were compared to a control group matched for gestational age, fetal presentation, and mode of delivery who did not receive amyl nitrite. There were no statistical differences between the groups in the independent variables (maternal age, parity, medical or obstetric history, type of anesthesia, anesthesia or obstetric attending physician, antepartum hematocrit, or neonatal weight). Outcome (dependent) variables (estimated blood loss, Apgar scores, postpartum hematocrit, cord gases, or postpartum complications) were assessed, and there were no significant differences between the groups. Low transverse cesarean section was performed more frequently in the amyl nitrite group (58 of 64) than in the comparison group (48 of 64) (p less than 0.03). Considering the 128 women with and without amyl nitrite together, the decrease in hematocrit observed postpartum was greater after classic section (7%) than after low transverse section (4%) (p less than 0.002). We conclude that the use of amyl nitrite during preterm cesarean section poses no threat to mother or fetus and may facilitate delivery by allowing the performance of a low transverse rather than a classic cesarean section without maternal or neonatal complications.

The impact of alpha-adrenergic stimulation on umbilical blood flow.

This study evaluated the effects of intranasal phenylephrine, an alpha-adrenergic agonist used for respiratory congestion, on uteroplacental blood flow. Twelve subjects were recruited from the Women's Clinic. Inclusion criteria were age greater than 18 years, singleton gestation, absence of medical illness and gestational age of 22-38 weeks. Phenylephrine (0.2 ml of 1% aq. solution) was applied to each nostril. Maternal blood pressure and pulse, umbilical artery velocimetry, and fetal heart rate were recorded prior to drug administration and at 5, 15, 30, 45 and 60 min after administration. There were no significant changes in maternal pulse, blood pressure or fetal heart rate. All subjects had normal baseline umbilical artery Doppler systolic/diastolic ratios. Eleven of 12 subjects demonstrated an elevation of the systolic/diastolic ratio consistent with vasoconstriction following administration. This elevation reached statistical significance at 30 min. Significant individual variation existed with regards to timing of maximal excursion of the systolic/diastolic ratio. The mean maximal change of the systolic/diastolic ratio was 1.57 +/- 1.25 (p < 0.001) ranging from -0.53 to 4.11. The use of over-the-counter alpha-adrenergic agents may result in decreased umbilical artery flow velocities. In high-risk pregnancies these medications may be contraindicated.

Diagnosis of polyhydramnios in early gestation: indication for prenatal diagnosis?

Previously published reports have indicated that idiopathic polyhydramnios may be associated with trisomies 18 and 21 and that chromosomal analysis is indicated. Furthermore, the natural history and fetal outcome of polyhydramnios diagnosed in early gestation have not been well delineated. We identified 138 pregnancies with polyhydramnios prior to 26 weeks' gestation. Of 131 complete cases, 21 were diagnosed as severe, 18 as moderate, and 92 as mild polyhydramnios. Congenital abnormalities were noted in 18 of 21 severe cases (86 per cent). Two of the remaining three cases were twin-to-twin transfusion. Thirteen of 18 cases with moderate polyhydramnios (72 per cent) were associated with anomalies; six of the remaining cases were twin-to-twin transfusion. Sixteen of 92 cases of mild polyhydramnios (17 per cent) were associated with congenital abnormalities. In 69 of 76 cases of mild hydramnios not associated with anomalies (91 per cent), the hydramnios resolved prior to delivery. Only 2 of 16 (13 per cent) associated with anomalies resolved. In 4 of 5 cases (80 per cent) with moderate hydramnios and no anomalies, the amniotic fluid volume was normal on subsequent ultrasound. No case of moderate polyhydramnios associated with anomalies or maternal conditions nor any case of severe polyhydramnios resolved. There were seven cases of chromosomal abnormalities in this series; all were associated with sonographic findings in addition to the presence of polyhydramnios. On the basis of these data, we doubt the benefit of amniocentesis following the early diagnosis of idiopathic polyhydramnios in the absence of other ultrasound findings.

Association of annular pancreas and duodenal obstruction--evidence for Mendelian inheritance?

This report presents a family with two individuals in two successive generations who were affected by annular pancreas and high duodenal obstruction. An argument for autosomal dominant transmission and implications for appropriate team management are discussed.

An algorithm for diagnosis and therapy of management and complications of urolithiasis during pregnancy.

From 1 January 1986 to 30 June 1989, 15 pregnant women were diagnosed as having urolithiasis. Patients presented in the last two trimesters with an infection of the lower part of the urinary tract (60 per cent), flank and abdominal pain (27 per cent) and hematuria (13 per cent). Ultrasonographic findings confirmed the diagnosis in 47 per cent of the patients. Other roentgenologic procedures were required in the remaining patients. Initially, therapy was conservative in all, and in 67 per cent of patients, no further intervention was necessary. Only 33 per cent required invasive measures; cystoscopic passage of an internal ureteral stent was the initial procedure of choice at our institution. Three of five patients who underwent invasive procedures had surgical intervention for relief of ureteral obstruction. Intensive care management was necessary for one of these three patients who had acute hemorrhage occur during the procedure. These data emphasize the need for the accurate diagnosis of urolithiasis during pregnancy. Ultrasonography was a valuable diagnostic technique, but a limited excretory urogram is safe and appropriate when there is uncertainty. Conservative management (hydration, analgesia and antibiotics as indicated) of obstructive uropathy was successful in the majority of instances. A specific clinical algorithm facilitated the successful management of patients necessitating operative intervention. Optimal management requires clinical suspicion and a precise diagnostic and therapeutic plan.

Cystic hygroma colli: perinatal outcome after prenatal diagnosis.

Prenatally diagnosed cystic hygroma colli is associated with Turner syndrome, but has been reported with a variety of other conditions. The association with abnormal karyotypes frequently results in a decision to terminate the pregnancy. Information on the natural history of this malformation is thus limited. We reviewed 34 cases of cystic hygroma colli which were diagnosed by ultrasound at a mean gestational age of 17.3 +/- 3.4 weeks. Pregnancy outcome was known for 31 of these cases. The distribution of fetal karyotypes, available for 23 fetuses, was similar to that reported in other series. Only two fetuses, both with an abnormal karyotype, were liveborn at term. Fourteen pregnancies were electively terminated while the remaining 15 cases resulted in spontaneous pregnancy loss. Twenty-six fetuses underwent necropsy which generally confirmed the prenatal ultrasound findings. However, in 9 cases associated anomalies had been missed by the sonogram. Only one fetus with associated anomalies survived to term. Hydrops was common and occurred in most of the spontaneous losses. This series suggests that the prenatal finding of cystic hygroma colli portends an extremely poor prognosis regardless of the karyotype or the presence or nature of associated anomalies. We confirm that karyotypes other than monosomy X are common and that perinatal survival is highly unlikely, especially in the presence of hydrops fetalis.

Oligohydramnios associated with prostaglandin synthetase inhibitors in preterm labour.

The use of prostaglandin synthetase inhibitors (indomethacin and ibuprofen) for greater than 72 h in women with preterm labour (n = 67) was significantly (P less than 0.001) associated with ultrasound-recorded oligohydramnios compared with the use of ritodrine or magnesium sulphate (control group, n = 67). Oligohydramnios developed in 26 of 37 women (70%) treated with indomethacin and 8 of 30 women treated with ibuprofen (27%) (P less than 0.01). Oligohydramnios developed in only two control subjects and one of these pregnancies was associated with intrauterine growth retardation. All 34 cases of oligohydramnios in the treatment group resolved after stopping medication, whereas the two in the control group did not resolve. No instances of renal failure, premature closure of the ductus arteriosus, pulmonary hypertension, or bleeding disorders were noted in any of the treated or control infants.

Doppler umbilical artery waveform indices--normal values from fourteen to forty-two weeks.

Normal values for Doppler waveform indices of the umbilical artery have been reported for gestational ages of 20 to 40 weeks in small numbers of normal patients. We evaluated 590 patients studies performed at 2-week intervals from 14 to 42 weeks' gestation on patients without medical or pregnancy complications. Readings were obtained during fetal quiet times (no fetal breathing or movements). Values for A (systolic) and B (diastolic) pressures were plotted as Pourcelot (A - B/A) and A/B ratios. Mean, SD, and 95% confidence limits were derived, and the skewness, kurtosis, and regression correlations were calculated. No diastolic flow was found in any pregnancy greater than 15 weeks' gestation (n = 25) or in 50% of the gestations between 15 to 17 weeks (n = 25). When diastolic pressure equals zero, the Pourcelot ratio value equals one and the A/B ratio approaches infinity and loses meaning. Recent work by Thompson et al. suggests that the Pourcelot ratio fits a normal distribution from 20 to 40 weeks' gestation and that the A/B ratio (which does not fit a normal curve) may be transformed to a normal distribution by conversion of the A/B ratio to 1/1 - Pourcelot ratio. Our data supports the normality of both indices from 18 to 42 weeks' gestation, but these assumptions are not applicable as the Pourcelot ratio approaches one or as the A/B ratio approaches infinity. Knowledge of normal umbilical flow ratios at gestational ages from 18 weeks may allow early detection and directed management of high-risk pregnancies.

Exencephaly--clinical and ultrasonic correlation to anencephaly.

The antenatal sonographic diagnosis of exencephaly in four gestations is reported. Exencephaly is an uncommon malformation of the cranium that characteristically involves a large, disorganized mass of cerebral tissue. The flat bones of the calvaria are absent, leaving the brain mass uncovered. Secondarily, anencephaly may develop as a result of prolonged exposure of the developing encephalon to amniotic fluid and trauma in utero. As in anencephaly, facial structures and the bony base of the calvarium are often preserved in exencephaly. Sonographically, the outstanding feature of exencephaly is the cerebral mass, with convolutions or "pseudo" sulcal patterns present. These findings correlate well with the pathologic examination and define a clinical entity that is incompatible with human life.

Mild idiopathic lateral cerebral ventricular dilatation in utero: sonographic evaluation.

The authors prospectively studied 20 fetuses with mild dilatation of the lateral cerebral ventricles but no other detectable central nervous system abnormality. One case (5%) occurred in a diabetic pregnancy, and three (15%) involved twin pregnancies. Fifteen (75%) fetuses were male, and one (5%) had trisomy 21. Postnatal follow-up at 15-31 months showed a normal outcome in eight cases (40%), an uncertain prognosis in four cases (20%), and death in eight cases (40%). Serial antenatal sonograms were obtained in 17 cases. Among the eight cases with a normal outcome, seven demonstrated no additional sonographic abnormalities and six showed resolution of the ventricular dilatation antenatally. Conversely, all 12 fetuses with demise or an uncertain prognosis demonstrated additional sonographic abnormalities, and six showed stable or progressive ventricular dilatation on follow-up sonograms. Since mild idiopathic lateral ventricular dilatation has a widely variable prognosis, antenatal detection of this finding warrants search for additional findings and follow-up sonography.

Measurement of fetal shoulder width with computed tomography in diabetic women.

We conducted a feasibility study of the use of computed tomography (CT) to measure the width of the fetal shoulders and to predict large birth weight in infants of diabetic mothers. Computed tomography pelvimetry using low-dose digital radiographs was performed before delivery at term in 22 diabetic women. Shoulder width was estimated by direct electronic measurement on a single axial section through the shoulders of the fetus, and by orthopedic calipers within 48 hours of birth. Shoulder width by CT was 11.4-16.5 cm, and correlated significantly with postnatal measurements (r = 0.66, P = .01). Shoulder width by CT also correlated well with birth weight (r = 0.84, P less than .01), and measured more than 14 cm in all seven infants with birth weights more than 4200 g. Using 14 cm as a positive test and birth weight 4200 g as an abnormal result, the predictive value of a positive test was 78% and the predictive value of a negative test was 100%. This technique deserves further evaluation in assessing the risk of shoulder dystocia in potentially macrosomic infants.