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Objectives: Cocaine administration to near-term pregnant sheep causes fetal hypoxemia, but oxygen delivery to the heart and brain are preserved because of increased blood flow. We hypothesized that cocaine administration during earlier fetal gestation impairs oxygen delivery to the heart and brain.Study Design: Ten pregnant ewes and fetuses at 0.7 term gestation underwent surgical instrumentation. After 48 hours of recovery fetal blood pressure, heart rate, cerebral and myocardial blood flow, and arterial oxygen content were determined before and during cocaine administration to the ewe.Results: Fetal hypoxemia was not noted in these animals. Fetal myocardial blood flow increased from 220 +/- 100 ml per 100 gm per minute to 349 +/- 183 ml per 100 gm per minute (p=0.03), and oxygen delivery increased from 16 +/- 5 ml of oxygen per 100 gm per minute to 22 +/- ml of oxygen per 100 gm per minute (p=0.02). Fetal cerebral blood flow and oxygen delivery remained unchanged.Conclusion: Cerebral and myocardial oxygen delivery are unimpeded by maternal cocaine administration in 0.7 term gestation ovine fetuses. [ABSTRACT FROM AUTHOR]

For centuries, humans occupying arid regions of North America have maintained an intricate relationship with Agave (Agavoideae, Asparagaceae). Today Agave cultivation, primarily for beverage production, provides an economic engine for rural communities throughout Mexico. Among known dryland-farming methods, the use of rock piles and cattle-grazed areas stand out as promising approaches for Agave cultivation. Identifying new cultivation areas to apply these approaches in Arizona, USA and Sonora, Mexico warrants a geographic assessment of areas outside the known ranges of rock piles and grasslands. The objective of this study was to predict areas for dryland-farming of Agave and develop models to identify potential areas for Agave cultivation. We used maximum entropy (MaxEnt) ecological-niche-modeling algorithms to predict suitable areas for Agave dryland farming. The model was parameterized using occurrence records of Hohokam rock piles in Arizona and grassland fields cultivated with Agave in Sonora. Ten environmental-predictor variables were used in the model, downloaded from the WorldClim 2 climate database. The model identified potential locations for using rock piles as dryland-farming methods from south-central Arizona to northwestern Sonora. The Agave-grassland model indicated that regions from central to southern Sonora have the highest potential for cultivation of Agave, particularly for the species Agave angustifolia. Results suggest that there are many suitable areas where rock piles can be used to cultivate Agave in the Sonoran Desert, particularly in the border of southeastern Arizona and northwest Sonora. Likewise, cattle-grazing grasslands provide a viable environment for cultivating Agave in southern Sonora, where the expanding bacanora-beverage industry continues to grow and where different Agave products (e.g., syrups, fructans, saponins, and medicinal compounds) can potentially strengthen local economies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ortiz Cano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial with excellent activity against pathogens associated with intra-abdominal infections. The purpose of this study was to determine the safety and effectiveness of meropenem in young infants with suspected or complicated intra-abdominal infections., Methods: Preterm and term infants <91 days of age with suspected or confirmed intra-abdominal infections hospitalized in 24 neonatal intensive care units were studied in an open-label, multiple-dose study. Adverse events and serious adverse events were collected through 3 and 30 days following the last meropenem dose, respectively. Effectiveness was assessed by 3 criteria: death, bacterial cultures, and presumptive clinical cure score., Results: Of 200 subjects enrolled in the study, 99 (50%) experienced an adverse event, and 34 (17%) had serious adverse events; no adverse events were probably or definitely related to meropenem. The most commonly reported adverse events were sepsis (6%), seizures (5%), elevated conjugated bilirubin (5%), and hypokalemia (5%). Only 2 of the serious adverse events were determined to be possibly related to meropenem (isolated ileal perforation and an episode of fungal sepsis). Effectiveness was evaluable in 192 (96%) subjects, and overall treatment success was 84%., Conclusions: Meropenem was well tolerated in this cohort of critically ill infants, and the majority of infants treated with meropenem met the definition of therapeutic success., Clinical Trials Registration: NCT00621192.

Background: Suspected or complicated intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial agent with excellent activity against pathogens associated with intra-abdominal infections in this population. The purpose of this study was to determine the pharmacokinetics (PK) of meropenem in young infants as a basis for optimizing dosing and minimizing adverse events., Methods: Premature and term infants <91 days old hospitalized in 24 neonatal intensive care units were studied. Limited PK sampling was performed following single and multiple doses of meropenem 20 to 30 mg/kg of body weight every 8 to 12 hours based on postnatal and gestational age at birth. Population and individual patient (Bayesian) PK parameters were estimated using NONMEM., Results: In this study, 200 infants were enrolled and received the study drug. Of them, 188 infants with 780 plasma meropenem concentrations were analyzed. Their median (range) gestational age at birth and postnatal age at PK evaluation were 28 (23-40) weeks and 21 (1-92) days, respectively. In the final PK model, meropenem clearance was strongly associated with serum creatinine and postmenstrual age (clearance [L/h/kg] = 0.12*[(0.5/serum creatinine)**0.27]*[(postmenstrual age/32.7)**1.46]). Meropenem concentrations remained >4 μg/mL for 50% of the dose interval and >2 μg/mL for 75% of the dose interval in 96% and 92% of patients, respectively. The estimated penetration of meropenem into the cerebrospinal fluid was 70% (5-148)., Conclusions: Meropenem dosing strategies based on postnatal and gestational age achieved therapeutic drug exposure in almost all infants.

Objective: To determine if INH-A21, an intravenous immune globulin (IGIV) derived from donors with high titers of antibody to surface adhesins of Staphylococcus epidermidis and S. aureus prevents late-onset sepsis (LOS) in very low birth weight (VLBW) infants., Study Design: In this double-blind, placebo-controlled study, infants with birth weights 500 to 1250 g were randomized to receive up to four doses of INH-A21 (Veronate) or placebo. The primary objective was to determine the safety and efficacy of INH-A21 versus placebo for prevention of S. aureus LOS in VLBW infants., Results: A total of 1983 infants from 95 neonatal intensive care units were randomized, and received at least one dose of study drug. S. aureus LOS developed in 50 of 989 (5%) and 60 of 994 (6%) infants who received placebo or INH-A21, respectively (P = .34). No differences were found in the frequencies of LOS caused by coagulase-negative staphylococci (CoNS), Candida spp, or overall mortality. No adverse events were statistically significantly associated with INH-A21 infusions compared with placebo., Conclusion: INH-A21 failed to reduce the incidence of staphylococcal LOS or candidemia in premature infants.

Autoimmune neutropenia (AIN) has been reported in infants and children, but not in neonates. AIN is caused by antibodies produced by the patient against their own neutrophils; therefore, it differs from the more common alloimmune neonatal neutropenia and the neonatal neutropenia because of a maternal autoimmune disease in which antineutrophil antibodies of maternal origin cross the placenta. We observed 2 cases of congenital AIN in premature neonates. These are the youngest reported cases, and indicate that AIN can have a prenatal onset. Examination of the bone marrow biopsies revealed an increase in B lymphocytes and myeloperoxidase-positive cells with a maturation arrest at the myelocyte stage. Recombinant human granulocyte colony-stimulating factor effectively treated the neutropenia, as it does in infantile AIN. Ten months after the diagnosis, 1 of the patients still requires recombinant human granulocyte colony-stimulating administration.

Formerly vaunted projections about the triumph of managed care over the provider-controlled health services industry now appear overly optimistic as consumer and provider opposition stiffens. Popular dislike of managed care and purchaser disenchantment over its failure to deliver on promises to control health insurance spending have created a strategic opening for rolling back third-party interference in medical practice. Employer frustration over rising premiums, compounded by workers' antagonism toward benefits restrictions and worry over the loss of government protection against managed care litigation, signals a radical overhaul in the way health insurance is offered. For many employers, substituting defined contribution for defined benefit plans and transferring ownership rights and responsibilities to employees is an attractive solution. Along with the growth of consumer-friendly health plans and a relaxation of onerous managed care practices, physicians can look forward to a restored doctor-patient relationship. This article identifies the forces pushing health care purchasers to adopt defined contribution plans and discusses the implications of such a movement on the physician-patient relationship.

The International Guidelines 2000 Conference on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiac Care (ECC) formulated new evidenced-based recommendations for neonatal resuscitation. These guidelines comprehensively update the last recommendations, published in 1992 after the Fifth National Conference on CPR and ECC. As a result of the evidence evaluation process, significant changes occurred in the recommended management routines for: * Meconium-stained amniotic fluid: If the newly born infant has absent or depressed respirations, heart rate <100 beats per minute (bpm), or poor muscle tone, direct tracheal suctioning should be performed to remove meconium from the airway. * Preventing heat loss: Hyperthermia should be avoided. * Oxygenation and ventilation: 100% oxygen is recommended for assisted ventilation; however, if supplemental oxygen is unavailable, positive-pressure ventilation should be initiated with room air. The laryngeal mask airway may serve as an effective alternative for establishing an airway if bag-mask ventilation is ineffective or attempts at intubation have failed. Exhaled CO(2) detection can be useful in the secondary confirmation of endotracheal intubation. * Chest compressions: Compressions should be administered if the heart rate is absent or remains <60 bpm despite adequate assisted ventilation for 30 seconds. The 2-thumb, encircling-hands method of chest compression is preferred, with a depth of compression one third the anterior-posterior diameter of the chest and sufficient to generate a palpable pulse. * Medications, volume expansion, and vascular access: Epinephrine in a dose of 0.01-0.03 mg/kg (0.1-0.3 mL/kg of 1:10,000 solution) should be administered if the heart rate remains <60 bpm after a minimum of 30 seconds of adequate ventilation and chest compressions. Emergency volume expansion may be accomplished with an isotonic crystalloid solution or O-negative red blood cells; albumin-containing solutions are no longer the fluid of choice for initial volume expansion. Intraosseous access can serve as an alternative route for medications/volume expansion if umbilical or other direct venous access is not readily available. * Noninitiation and discontinuation of resuscitation: There are circumstances (relating to gestational age, birth weight, known underlying condition, lack of response to interventions) in which noninitiation or discontinuation of resuscitation in the delivery room may be appropriate.

A transformation of employment-connected health insurance from a defined benefit to defined contribution arrangement is projected based on new economic realities affecting the competitiveness of the business environment. This article discusses those new realities along with the future of employment-based health insurance. The business of American business is profits, but, to the detriment of that goal, for the past half century business has also been in the business of providing health insurance for workers. However, in light of previously unencountered pressures on profits, employers are realizing they cannot afford to continue the practice of paying for and overseeing the provision of healthcare benefits to employees amid increasing premiums, state and federal mandates, the overbearing cost of managing healthcare benefits, and the threat of loss of protection under ERISA. Yet, the political and social pressures on businesses to continue to provide health insurance are formidable, perhaps impregnable, barriers to complete withdrawal of what has come to be thought of as a "right" of employees. Companies are anxious to find alternatives to the status quo, but any feasible alternative must cost less, require less administrative oversight, and ensure that employees still maintain a measure of choice. Two possible solutions for American businesses are adoption of (1) a "medical savings account" system, or (2) a "voucher" system. Either system would result in lower costs and greater fiscal stability for both employers and employees. They would also remove much of the responsibility for healthcare decisions from employers and place it in the hands of the employees. But, perhaps the greatest contribution of either system would be the reduction in moral hazard and its inflationary effect on medical costs.

The ontogeny of ligand binding to N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptors and to the high affinity, sodium-dependent D-aspartate binding site in prenatal and postnatal ovine brains was studied using quantitative in vitro autoradiography. In general, the binding density for each of the excitatory amino acid receptors peaked during late prenatal and early postnatal development. In contrast, binding density for D-aspartate remained low during late prenatal and early postnatal development and peaked in the adult. These data suggest that an excess number of excitatory amino acid receptors and/or a relative deficiency of transporters may make the immature brain more vulnerable to the pathologic effects of glutamate and other related excitatory amino acids.

The American Heart Association has published guidelines for medication use in neonatal resuscitation. These recommendations should not, however, be regarded as standards or as the final word on resuscitation in neonates. Little work has been performed to justify these recommendations directly; therefore, it was necessary to make recommendations by extrapolating from studies not specifically designed to answer questions concerning the neonate. For example, the optimum dose of epinephrine administered either intravenously or endotracheally in a neonate with hemodynamically significant bradycardia is simply not known. The American Heart Association guidelines were made with reasoning based on the information available, even though the information is tangential. Similarly, since no data exist to document the benefit of NaHCO3 and some data would suggest harmful effects, its routine use is discouraged. Fertile areas for research exist to define better the optimum doses of epinephrine required in newborn resuscitation and to further delineate the importance and safety of rapid reversal of acidosis in newborn resuscitation.

Objective: We hypothesized that during a simulated neonatal resuscitation, heart rate determination with the Neonatal Resuscitation Program's (NRP) 6-second method is difficult and results in inaccuracies. We tried to determine whether a simple electronic timing device improves accuracy of heart rate determination., Methods: One-hundred fourteen clinicians determined four heart rates under conditions simulating a resuscitation by three different methods: their own method, NRP's 6-second method, and an electronic timing device method. Responses were scored as correct if they would have resulted in the same intervention as called for by NRP criteria for each specific heart rate tested., Results: Of 1368 total responses, 267 (19.5%) were incorrect, which could have led to either an inappropriate intervention or lack of an appropriate intervention. The electronic timing device resulted in fewer errors (4%) compared with when clinicians used their own methods (32%) and the NRP's 6-second method (22%)., Conclusion: The use of a simple electronic timing device improves accuracy of heart rate determination compared with the NRP's 6-second method or when clinicians use their own methods.

Seventeen fresh-frozen knee specimens from cadavera were instrumented with a load-cell attached to a mechanically isolated cylinder of subchondral bone containing the tibial insertion of the anterior cruciate ligament. The forces in the intact anterior cruciate ligament were recorded as the knee was passively extended from 90 degrees of flexion to 5 degrees of hyperextension without and with several constant tibial loads: 100 newtons of anterior tibial force, ten newton-meters of internal and external tibial torque, and ten newton-meters of varus and valgus moment. The anterior cruciate ligament was resected, and a bone-patellar ligament-bone graft was inserted. The knee was flexed to 30 degrees, and the graft was pre-tensioned to restore normal anterior-posterior laxity. The knee-loading experiments were repeated at this level of pre-tension (laxity-matched pre-tension) and at a level that was forty-five newtons greater than the laxity-matched pre-tension (over-tension). During passive extension of the knee, the forces in the graft were always greater than the corresponding forces in the intact anterior cruciate ligament. Over-tensioning of the graft increased the forces in the graft at all angles of flexion. At full extension, the mean force in the anterior cruciate ligament was fifty-six newtons; the mean force in the graft at laxity-matched pre-tension was 168 newtons, and it was 286 newtons in the over-tensioned graft. Greater pre-tensioning may be required when the knee demonstrates apparent tightening of the graft in flexion. The mean forces in the graft generated during all constant loading tests were greater than those for the intact anterior cruciate ligament over the range of flexion. When the graft was over-tensioned, the forces generated by the anterior tibial force and by varus and valgus moment increased but those generated by internal and external tibial torque did not. There was no significant change in the mean tibial rotation as a function of the angle of flexion of the knee after insertion of the graft; normal tibial rotation of the knee during passive extension (the so-called screw home mechanism) was eliminated.

Nineteen fresh-frozen knee specimens from cadavera were tested for anterior-posterior laxity with 200 newtons of force applied to the tibia. A cylindrical cap of subchondral bone containing the tibial insertion of the anterior cruciate ligament was isolated with a coring cutter and was potted in acrylic. A thin wire was connected to the undersurface of the cap, and relative displacement between the cap and the tibia was measured with an isometer as the knee was extended. The cap of bone was connected to a load-cell that recorded force in the intact ligament during anterior-posterior testing with the tibia locked in neutral, internal rotation, and external rotation. The anterior cruciate ligament was then resected, and a femoral tunnel was drilled at the site where the isometer readings from the wire were the same as those obtained for the intact anterior cruciate ligament. A bone-patellar ligament-bone graft was used to reconstruct the anterior cruciate ligament, and the isometer measurements were repeated with the graft in place. The graft was pre-tensioned at 30 degrees of flexion to restore normal anterior-posterior laxity. Anterior-posterior laxity tests were repeated at this level of pre-tension (laxity-matched pre-tension) as well as at a level that was forty-five newtons greater (over-tension). The moment required to extend the knee was measured before and after insertion of the graft at both levels of pre-tension. When the tibia was locked in positions of internal and external rotation, the anterior-posterior laxities and the forces in the anterior cruciate ligament (generated by an anterior force applied to the tibia) were significantly less than the corresponding values with the tibia in neutral rotation at 20, 30, and 45 degrees of flexion (p < or = 0.05). Isometer readings for the intact anterior cruciate ligament indicated that the cap of bone retracted into the joint a mean and standard deviation of 3.1 +/- 0.8 millimeters as the knee was extended from 30 degrees of flexion to full extension. For each specimen, the isometer measurements for the trial wire and for the graft were within 1.5 millimeters of those for the intact anterior cruciate ligament. At laxity-matched pre-tension (mean, 28.2 +/- 16.8 newtons), the mean anterior-posterior laxities of the reconstructed knees were within 1.0 millimeter of the corresponding means for the intact knees between 0 and 45 degrees of flexion. Over-tensioning of the graft by forty-five newtons decreased the anterior-posterior laxity a mean of 1.2 millimeters at 30 degrees of flexion. Over-tensioning of the graft did not change the moment required to bring the knee to full extension.

Eight time-dated pregnant ewes at 125 days' gestation (145 days = term) underwent surgery for placement of fetal vascular catheters, electrodes for recording fetal behavioural state, and maternal venous catheters. Three days later, fetal cerebral and myocardial blood flow were determined by the coloured microsphere technique under four conditions: (1) during rapid-eye movement (REM) sleep, before fetal cocaine infusion, (2) 30 min after initiation of a cocaine infusion to the fetus at 0.2 mg/kg per min, (3) during REM sleep, before maternal cocaine infusion, and (4) 30 min after initiation of a cocaine infusion to the ewe at 0.3 mg/kg per min. Cocaine infusion directly to the fetal lamb did not cause hypoxaemia or significantly change cerebral or myocardial blood flow or oxygen delivery. Cocaine administered to the ewe led to a drop in fetal oxygen tension from 3.0 +/- 0.5 to 2.5 +/- 0.3 kPa (P < 0.0001) and in fetal oxygen content from 3.8 +/- 0.7 to 2.8 +/- 0.4 mmol O2/L (P < 0.0001). Prior to maternal cocaine administration, fetal cerebral blood flow was 146 +/- 103 mL/100 g per min and during maternal cocaine infusion it went to 184 +/- 147 mL/100 g per min (P = NS) while myocardial blood flow increased from 156 +/- 92 to 333 +/- 178 mL/100 g per min (P < 0.002). This increase in blood flow negated the effects of hypoxaemia so that cerebral oxygen delivery was unaffected while myocardial oxygen delivery increased an average of 67%. It is concluded that cocaine administration to pregnant sheep does not impede fetal cerebral or myocardial oxygen delivery.

A multicenter, randomized, double-blind, placebo-controlled trial of synthetic surfactant therapy for premature infants with respiratory distress syndrome (RDS) and birth weights of 700 to 1350 gm demonstrated a reduction in severity of RDS, morbidity, and neonatal and 1-year mortality. Of the 419 infants who were entered in the study, 80% of the surviving infants in both the air placebo group (122) and the synthetic surfactant group (138) returned for the follow-up evaluation at 1-year adjusted age. The only significant difference observed at follow-up was a reduction in the incidence of mild cerebral palsy in the synthetic surfactant group (air placebo group, 8 of 122 (7%); synthetic surfactant group, 3 of 138 (2%); relative risk 0.306; 95% confidence interval 0.094, 0.999). No differences were observed between the air placebo and synthetic surfactant treatment groups with respect to health status of the infants, including the incidence of retinopathy of prematurity and neurodevelopmental delays. The difference in the overall incidence of impairment among the 1-year survivors in the air placebo group (43 of 122 (35%)) and in the synthetic surfactant group (40 of 138 (29%)) was not statistically significant. The results of this 1-year follow-up study show that rescue treatment with synthetic surfactant in infants weighing 700 to 1300 gm is not associated with adverse developmental consequences despite the improvement in survival.

Objective: Studies on the effects of cocaine in fetal animals have been limited to acute exposures to the drug. We hypothesized that a prolonged infusion of cocaine to the fetal sheep would initially interrupt normal behavioral state cycling but the effects would be short lived as the fetus gained tolerance to the drug., Study Design: The study was performed in a university laboratory on six time-dated pregnant ewes at 125 days' gestation. Fetal sheep, surgically instrumented 3 days before study, were given cocaine hydrochloride 0.6 mg/min for 6 hours. Fetal behavioral state before, during, and after the infusion was compared by repeated-measures analysis of variance., Results: Infusion of cocaine caused a drop in the percentage time that the fetuses spent in both rapid-eye-movement (p < 0.03) and non-rapid-eye movement (p < 0.001) sleep, which was sustained throughout the 6-hour infusion. This was related to a decrease in the number of rapid-eye-movement and non-rapid-eye-movement episodes as opposed to a decrease in the lengths of these behavioral states. With cessation of cocaine infusion, the fetal sheep showed an increase in rapid-eye-movement sleep, with a higher percentage than during control periods (p < 0.02)., Conclusions: Cocaine disrupts fetal rapid-eye-movement sleep without evidence for tolerance to the drug over a 6-hour period. "Catch-up" rapid-eye-movement sleep occurs with cessation of cocaine infusion. Neurobehavioral abnormalities associated with in utero cocaine exposure may be caused by chronic disruption of rapid-eye-movement sleep.

Umbilical artery catheters can accidentally enter branches of the internal iliac artery during attempted placement in the aorta. The three branches likely to be catheterized are the superior gluteal, inferior gluteal, and internal pudendal arteries. If these misplacements are not recognized and promptly corrected, arterial obstruction may lead to ischemia and infarction of the iliac bone, gluteal muscles, sciatic nerve, perineum, and overlying skin. We present three patients who suffered long-term consequences of umbilical artery catheter misplacements and discuss the radiographic verification of catheter placement that is essential before infusing medications.