Hepatitis C/HIV co-infection is associated with higher mortality in hospitalized patients with hepatitis C or HIV.

Up to 10% of all patients with Hepatitis C virus (HCV) infection are co-infected with human immunodeficiency virus (HIV); 25-30% of HIV patients are co-infected with HCV. The aim of this study was to examine the association of HCV/HIV co-infection with outcomes of hospitalized patients compared to those with HCV or HIV monoinfection. Using the 2006 Nationwide Inpatient Sample, patients with HCV or HIV monoinfection or HCV/HIV co-infection were identified using ICD-9-CM codes. We compared liver-related and infection-related admission between the three groups of patients. Multivariate logistic regression was performed to identify independent predictors of in-hospital mortality. A total of 474,843 discharges with HCV monoinfection, 206,758 with HIV monoinfection and 56,304 with HCV/HIV co-infection were included. Liver-related admissions were more common in co-infected patients (15.4%) compared to those with HIV monoinfection (3.3%, P < 0.001). Primary infectious hospitalizations were more common in HIV monoinfection (33.9%) compared to co-infected patients (26%, P < 0.001). HCV/HIV co-infection was associated with higher mortality compared to HCV monoinfection (OR 1.41, 95% CI 1.20-1.65) but not when compared to monoinfected-HIV patients. HCV-associated cirrhosis or complications thereof conferred four times greater mortality risk in patients with HIV (OR 3.96, 95% CI 3.29-4.79). The rate of hospitalization for HCV/HIV co-infected patients (23.5%) was significantly higher than those with HCV (14.8%) or HIV (19.9%) (P < 0.001). HCV/HIV co-infection is associated with significantly higher rates of hospitalization and is a risk factor for in-hospital mortality compared to patients with isolated HCV.

The amnionless gene, essential for mouse gastrulation, encodes a visceral-endoderm-specific protein with an extracellular cysteine-rich domain.

Fate-mapping experiments in the mouse have revealed that the primitive streak can be divided into three functional regions: the proximal region gives rise to germ cells and the extra-embryonic mesoderm of the yolk sac; the distal region generates cardiac mesoderm and node-derived axial mesendoderm; and the middle streak region produces the paraxial, intermediate and lateral plate mesoderm of the trunk. To gain insight into the mechanisms that mediate the assembly of the primitive streak into these functional regions, we have cloned and functionally identified the gene disrupted in the amnionless (amn) mouse, which has a recessive, embryonic lethal mutation that interferes specifically with the formation and/or specification of the middle primitive streak region during gastrulation. Here we report that the gene Amn encodes a novel type I transmembrane protein that is expressed exclusively in the extra-embryonic visceral endoderm layer during gastrulation. The extracellular region of the Amn protein contains a cysteine-rich domain with similarity to bone morphogenetic protein (BMP)-binding cysteine-rich domains in chordin, its Drosophila melanogaster homolog (Short gastrulation) and procollagen IIA (ref. 3). Our findings indicate that Amn may direct the production of trunk mesoderm derived from the middle streak by acting in the underlying visceral endoderm to modulate a BMP signaling pathway.

Prematurity prevention programs: an analysis of successes and failures.

OBJECTIVE: Our purpose was to assess the long-term results of established prematurity prevention programs. STUDY DESIGN: A population cohort of pregnant women from two major urban health care organizations were examined. Rates and cost-benefit analysis of prematurity and patient, system, or physician failures were analyzed. During 1990 1143 pregnant women were prospectively reviewed. RESULTS: A total of 11.8% of the mothers were high risk and responsible for 108 (50.2%) of the preterm deliveries. The preterm birth rate of all enrollees was 4.6%. One percent of the preterm neonates required level III care for complications. The average charge for a 35 week infant was 18 times, and a 36 week infant was five times more costly than a term infant. Patient, physician, and health care system failures occurred at different rates. CONCLUSIONS: This preterm prevention program resulted in low preterm birth rates. Potentially preventable preterm births most often occurred as a result of patient and physician failures.

Survival and follow-up of infants born at 23 to 26 weeks of gestational age: effects of surfactant therapy.

Little information is available regarding the effect of surfactant on outcome for infants born at or before 26 weeks of gestation. We addressed this issue by reviewing records of 310 infants born at gestational ages of 23 through 26 weeks who were admitted to our nursery from 1986, when surfactant was introduced, through 1990. Surfactant was administered to 154 infants (5 during a single-dose prevention study, 25 during a multiple-dose prevention study, 124 while receiving a Food and Drug Administration treatment investigational new drug); 156 infants were not treated with surfactant. Seventy-three percent of the treated infants survived, compared with 55% of the nontreated infants. Increased survival occurred at all gestational ages between 23 and 26 weeks but were greatest in infants born at 23 and 24 weeks. At follow-up, no differences in neurologic outcome were detected between surfactant-treated and nontreated infants. We conclude that surfactant use in extremely premature infants improves survival rates without increasing the proportion of impaired survivors.

New prospective studies of the association of Ureaplasma urealyticum colonization and chronic lung disease.

This study examined the association between Ureaplasma urealyticum colonization and the development of chronic lung disease (CLD) in 93 premature infants who were treated with surfactant and who had birth weights < 1251 g. Nasopharyngeal and tracheal cultures for U. urealyticum were obtained at 2 +/- 1 and at 14 +/- 1 days after birth and were positive in 17 (18%) of 93 patients. Infants born vaginally were 4.5 times more likely to be colonized than were those born by cesarean section. Colonization with U. urealyticum was associated with 1.66 (95% confidence interval, 1.24-2.20, P = .024) times the risk of developing CLD and with a greater incidence of > or = 2+ polymorphonuclear leukocytes in the tracheal aspirate at 2 +/- 1 days of age compared with uncolonized infants (P = .025). We conclude that U. urealyticum colonization is associated with CLD even after surfactant treatment. The presence of U. urealyticum is also associated with inflammatory cells in the tracheal aspirate.

Retrieval of placental blood from the umbilical vein to determine volume, sterility, and presence of clot formation.

From August 1988 to October 1989, 60 specimens of citrate-phosphate-dextrose-adenine anticoagulated blood were retrieved from the placental umbilical veins of newborns from three gestational age groups. The specimens were removed with a needle and syringe apparatus and placed directly into sterile transfusion packs. The specimens were evaluated for the volume obtained, sterility, and presence of macroscopic clots. A blood volume sufficient to provide at least one transfusion (10 mL/kg) for 87% of the premature infants studied was retrieved from the placenta. A greater blood volume per unit of birth weight was recovered from the placentas of the smaller newborns. A 12% positive culture frequency and a 7% frequency of detectable clots were identified. These rates of occurrence suggest the need for further studies to determine the origins of these complicating factors before the adoption of this technique in the clinical setting. These findings support the hypothesis that, with proper patient selection and with specimen culture and filtration, placental blood may be a viable option for the autologous transfusion of sick, premature infants.

Quantitating hemodialysis: a comparison of three kinetic models.

Three urea kinetic analyses were applied to hemodialysis and their conformity assessed. Sixteen patients underwent 50 measurements of dialyzer clearance (K), protein catabolic rate (PCR), and dialysis quantification (Kt/V) using the urea kinetic model (UKM) of Gotch and Sargent, Malchesky's direct dialysis quantification (DDQ), and the graphic technique of urea reduction analysis (URA) devised by Keshaviah. Additionally, the equations proposed by Jindal (percent urea reduction), and Daugirdas were used to calculate Kt/V values for each study. Dialyzer performance determined by whole blood urea clearance consistently exceeded simultaneous dialysate urea removal and was 55% greater than the clearance calculated by DDQ. Despite these variations, dialysis adequacy (Kt/V) and normalized protein catabolic rate (nPCR) were remarkably constant when derived by fixed-volume single-pool analyses (ie, UKM, DDQ, and URA). Application of variable-volume corrections increased Kt/V and nPCR, but caused DDQ values to diverge from those of UKM and URA. During rapid high-efficiency dialysis (RHED), the UKM predicted urea removal in excess of that documented by DDQ. During this trial (low-level RHED with K = 2.98 mL.kg-1 per min), urea dysequilibrium across blood-cell interfaces was sufficient to cause UKM to overestimate protein catabolism by 5%. The basic assumption of single-pool kinetics may be inappropriate during RHED, and further increases in dialyzer clearance will increase the discrepancy between projected and actual urea removal. Future comparisons of RHED prescriptions should employ mass balance data, or redesigned kinetic analyses.

Effect of hematocrit on solute removal during high efficiency hemodialysis.

The effect of changing hematocrit (Hct) on solute removal during high efficiency hemodialysis was evaluated in 12 patients. In five subjects, Hct was raised by recombinant human erythropoietin (rHuEPO) treatment, and in the other seven by blood transfusion. Solute removal was assessed by measuring: (1) whole blood (kb), blood water (kbw) and dialysate (kd) clearances; (2) the amount of solute in the spent dialysate; (3) the fractional decrement of serum solute concentration achieved by hemodialysis; and (4) urea kinetics, including kt/V and protein catabolic rate (PCR). The results showed that increasing the Hct did result in a slight reduction in some solute clearances. The decrement, however, was minor (5 to 8%), whereas the rise in Hct was marked (55 and 65%) in the transfused and EPO-treated groups, respectively. More importantly, linear regression analysis of kd/kb ratios versus Hct indicated that a rise of Hct from 20 to 40% would reduce creatinine and phosphate clearance by 8 and 13%, respectively. By contrast, assessment of the absolute amount of solute removed in the spent dialysate failed to detect differences between the two study periods. Additionally, a rise in Hct also did not affect urea kinetic parameters including kt/V and PCR. Based on these data, it appears prudent to increase hemodialysis prescription by 10 to 15% when Hct is raised to near 40% to avoid excessive retention of molecules with slow transcellular movement.

Multicenter trial of single-dose modified bovine surfactant extract (Survanta) for prevention of respiratory distress syndrome. Ross Collaborative Surfactant Prevention Study Group.

A multicenter, prospective randomized controlled trial was performed comparing the efficacy of a single intratracheal dose of modified bovine surfactant extract (Survanta, 100 mg/kg, Abbott Laboratory, North Chicago, IL) with air placebo in preventing respiratory distress syndrome. Infants were enrolled if they were estimated to be between 24 and 30 weeks' gestation, weighed between 750 and 1250 g, and were intubated and stabilized within 15 minutes after birth. A total of 160 infants were treated (79 with surfactant, 81 with air placebo) between 4 and 37 minutes after birth (median time 12 minutes). Of these, 5 infants were excluded from the final analysis. The 72-hour average values for the arterial-alveolar oxygen ratio, fraction of inspired oxygen, and mean airway pressure were calculated from the area under the curve of scheduled values measured throughout 72 hours. Clinical status was classified using five ordered categories (no supplemental oxygen or assisted ventilation, supplemental oxygen only, continuous positive airway pressure or assisted ventilation with intermittent mandatory ventilation less than or equal to 6 breaths/min, assisted ventilation with intermittent mandatory ventilation greater than 6 breaths/min, death). Chest radiographs at 24 hours were graded for severity of respiratory distress syndrome. Infants receiving Survanta had less severe radiographic changes at 24 hours of age and decreased average fraction of inspired oxygen (31% vs 42%, P = .002) compared with control infants. No differences were noted in the average arterial-alveolar oxygen ratio, mean airway pressure, or clinical status on days 7 and 28. A beneficial effect was noted in the incidence of pneumothorax (P = .057) and an increase was noted in the incidence of necrotizing enterocolitis (P = .052). No differences in incidence of patent ductus arteriosus, intraventricular hemorrhage, sepsis, or bronchopulmonary dysplasia were seen. According to results of a secondary analysis, there was improvement in the fraction of inspired oxygen and a greater number of survivors without bronchopulmonary dysplasia in the subgroup of infants weighing less than 1000 g who were treated with surfactant. It was concluded that a single dose of Survanta given shortly after birth resulted in decreased severity of chest radiographic findings 24 hours after treatment and improved oxygenation during 72 hours after treatment, but did not improve other acute measures of disease severity or clinical status later in the neonatal period. The group at highest risk for respiratory distress syndrome (infants with birth weights between 750 and 999 g) may benefit the most from preventive therapy.

Effect of recombinant human erythropoietin on renal function in humans.

To assess the effect of recombinant human erythropoietin (r-HuEPO) treatment on renal function, the slopes of the regression lines of the reciprocal of serum creatinine versus time were compared in 26 patients with renal insufficiency (serum creatinine ranged from 2.3 to 11.7 mg/dl) followed for a period of 2.7 to 24 months. Ten patients received r-HuEPO and the anemia was corrected (Group I). Sixteen patients did not receive r-HuEPO. Ten of them were anemic (Group II) and six had normal hematocrits (Group III). All study groups were matched for age, diagnosis and degree of renal insufficiency. All cohorts were followed prospectively (Period B, from the first day of the study to the time of data analysis or dialysis and transplantation); renal function was also examined retrospectively (Period A, from the first day of the study to the time of first renal function measurement). Hematocrit was lowest in Group II control patients, 27%, highest in the Group III control subjects, 43%, and intermediate in Group I EPO-treated patients, 36%. Serum creatinine uniformly increased in all three groups of patients. The rate of progression, as measured by the slopes of the reciprocal of serum creatinine versus time, however, was similar in all three groups of subjects and during both periods. The mean slopes for Group I patients before and after r-HuEPO were, respectively, -0.0058 and -0.0054, that of the control cohorts with low and normal hematocrit during period B were -0.0063 and -0.0010, respectively. Thus, it appeared that neither r-HuEPO administration nor a normal hematocrit accelerated the deterioration of renal function in these patients with renal insufficiency.

Effects of exogenous surfactant therapy on dynamic compliance during mechanical breathing in preterm infants with hyaline membrane disease.

In a prospective, randomized, controlled clinical trial, the immediate and the longitudinal effects of exogenous surfactant therapy on pulmonary mechanics were evaluated in extremely premature infants during mechanical respiration. Ninety-four infants weighing between 600 and 1250 gm received either exogenous surfactant or sham (air) therapy in the delivery room and up to three additional doses in the first 48 hours of life if they were ventilator-dependent, had fractional inspiratory oxygen requirements greater than or equal to 0.30, and radiographic findings consistent with hyaline membrane disease. Each infant underwent pulmonary mechanics assessment (dynamic compliance, total pulmonary resistance, tidal volume) immediately before and 1 hour after each dose, and at 24, 48, and 72 hours and 7 days of age. There were no significant differences in dynamic compliance, total pulmonary resistance, and tidal volume in the surfactant (n = 47) and control (n = 47) groups before and 1 hour after each dose. However, dynamic compliance was 50% greater in the surfactant group at 24 hours of age (p less than or equal to 0.009); this difference steadily increased to 94% at 7 days of age (p less than or equal to 0.009). Oxygenation, assessed by the ratio of alveolar to arterial oxygen pressure, was significantly greater in the surfactant group during the first 72 hours of life; the greatest difference was noted at 24 hours (p less than or equal to 0.001). Mean airway pressure requirements in the surfactant group were significantly less than in the control group at all times during the first week. We conclude that exogenous surfactant therapy, administered at birth and during the first 48 hours of life in extremely premature infants with hyaline membrane disease, improves dynamic compliance and gas exchange during mechanical breathing.

The safety and the efficacy of maintenance therapy of recombinant human erythropoietin in patients with renal insufficiency.

Ten anemic predialysis renal patients participated in a study to examine the long-term effects of recombinant human erythropoietin (r-HuEPO) treatment. The drug was initially given intravenously three times a week for 1 to 5 months, then by subcutaneous injections three times each week for 4 to 8 months, and finally by subcutaneous injection once weekly for 3 to 18 months. The duration of follow-up ranged from 11 to 29 months. Anemia was ameliorated in all participants. Mean hematocrit increased from a basal value of 26.8% to 35.1% during the intravenous phase and to 36.7% and 34.6% during the two subcutaneous periods. Mean weekly doses of erythropoietin (EPO) were 276 units/kg during intravenous therapy and 134 and 108 units/kg in the two subcutaneous periods. The differences in the doses were significant only between the intravenous and the two subcutaneous periods. Mean erythrocyte mass increased from a baseline value of 13.6 mL/kg to 20.4 mL/kg 8 months after initiation of treatment. Mean erythrocyte survival half-time was increased from 23 days before to 26 days, 8 months after r-HuEPO treatment, P less than 0.002. Mean blood pressure (mm Hg) was 105 before and 95 after treatment. Mean serum creatinine was 513 mumol/L (5.8 mg/dL) at the beginning of the study. At the time of this writing (11 to 29 months after treatment), seven patients have required dialysis treatment. There were three episodes of transient refractoriness to r-HuEPO documented during periods of infection and surgical procedures. All subjects tolerated the medication well, and no serious side effects attributable to the medication were noted. Furthermore, circulating antibodies against r-HuEPO were consistently negative.

Changing outcome of extremely premature infants (less than or equal to 26 weeks' gestation and less than or equal to 750 gm): survival and follow-up at a tertiary center.

Management of extremely premature infants is controversial because limits of viability are not established. From 1981 to 1987, 175 infants were admitted to the neonatal intensive care unit at Minneapolis Children's Medical Center with gestational ages less than or equal to 26 weeks and birth weights less than or equal to 750 gm. To assess current prognosis and to analyze trends over time, survival data and developmental characteristics of surviving infants were reviewed. During the study period, antenatal obstetric management was assertive, with liberal indications for tocolysis and expectant management for preterm prolonged membrane rupture, with the goal of delivery of infants in a nonasphyxiated condition. Ninety-one percent of infants were inborn and were managed aggressively after birth with full neonatal support. Survival increased from 21% in 1981-1982 to greater than 50% in 1986-1987 and occurred as early as 23 weeks' gestation. Seventy-one percent of all deaths occurred within 48 hours of birth, and late death (greater than 28 days) was uncommon. At follow-up, 23% of survivors were impaired, a proportion that remained relatively constant during the study period. Improvements in survival were not associated with an increased proportion of impaired infants. Survival with good outcome is attainable at gestational ages and birth weights previously considered nonviable. For obstetricians, neonatologists, and parents, knowledge of such current data can play an important role in making appropriate management decisions for both mother and infant.

Recombinant human erythropoietin treatment in pre-dialysis patients. A double-blind placebo-controlled trial.

STUDY OBJECTIVE: To determine the efficacy and safety of recombinant human erythropoietin (r-HuEPO) in predialysis renal patients. DESIGN: Randomized, double-blind, placebo-controlled trial for 8 weeks. SETTING: Inpatient and outpatient facility in the Clinical Research Center of a university-based hospital. PATIENTS: Fourteen adult subjects with renal insufficiency (mean serum creatinine, 473 mumol/L +/- 61 [6.2 +/- 0.8 mg/dL]) and anemia (mean hematocrit, 0.27 +/- 0.01). INTERVENTIONS: Recombinant human erythropoietin, 50, 100, or 150 IU/kg body weight or placebo given intravenously three times per week. MEASUREMENTS AND MAIN RESULTS: Subjects who received active r-HuEPO showed a dose-dependent rise in hematocrit; mean hematocrit increased 41% from 0.27 +/- 0.01 to 0.38 +/- 0.01. At the same time, erythrocyte mass rose 43% from 13.7 +/- 0.6 mL/kg in the baseline state to 19.6 +/- 1.0 mL/kg after treatment. Maximal oxygen consumption during exercise increased 9% from 16.0 mL/min.kg +/- 1.8 to 17.5 mL/min.kg +/- 1.9. CONCLUSIONS: Recombinant human erythropoietin is effective and safe in ameliorating the anemia of pre-dialysis patients.