Increased placental apoptosis in intrauterine growth restriction

OBJECTIVES: Our purpose was to investigate a possible role for apoptosis in the pathophysiologic mechanisms of intrauterine growth restriction. STUDY DESIGN: Placental samples were obtained from 43 uncomplicated third-trimester pregnancies and from 26 pregnancies complicated by intrauterine growth restriction. The definition used to identify cases of intrauterine growth restriction depended on three criteria: clinical evidence of suboptimal growth, ultrasonographic evidence of deviation from an appropriate growth percentile, and individualized birth weight ratios <10th percentile. Light microscopy was used to quantify the incidence of apoptosis. Electron microscopy and TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling) staining were used to confirm the occurrence of apoptosis. RESULTS: Quantification of apoptosis (medians and interquartile ranges) resulted in the following values: normal third trimester (n = 43) 0.14% of cells (0.08% to 0.20%) and intrauterine growth restriction third trimester (n  = 26) 0.24% of cells (0.16% to 0.29%). The incidence of apoptosis was significantly higher in placentas from pregnancies with intrauterine growth restriction compared with normal third-trimester placentas (p < 0.01, Mann Whitney U test). CONCLUSIONS: These results suggest that apoptosis may play a role in the pathophysiologic mechanisms of intrauterine growth restriction.(Am J Obstet Gynecol 1997;177:401)     

Time course and pattern of compensatory ingestive behavioral adjustments to lysine deficiency in rats

We and others have demonstrated that rats deficient in an essential amino acid (EAA) will consume sufficient quantities of the lacking nutrient to produce repletion when it is made available in solution. In the current series of experiments, we made rats deficient in lysine (LYS) by limiting the level of this EAA in the diet. We then examined licking behavior during approximately 23-h two-bottle intake tests over 4 consecutive days. In three separate experiments, rats were presented with the following: 1) 0.1 mol/L LYS and water, 2) 0.2 mol/L threonine (THR) and water and 3) 0.1 mol/L LYS and 0.2 mol/L THR. Lysine-deficient (LYS-DEF) rats drink significantly more LYS than did nondepleted controls (CON) when this amino acid was available. Meal pattern analysis revealed that the enhanced intake of LYS occurred as a function of a greater number of ingestive bouts, not changes in bout size. A cumulative analysis of LYS intake between CON and LYS-DEF rats revealed that a potentiation of intake developed within 30 min of sampling the solution when LYS and water were available and within 90 min when LYS and THR were the contrasting choices. In conclusion, increased LYS intake in the deficient rats occurs relatively rapidly and appears to be at least somewhat specific. Moreover, LYS deficiency does not seem to enhance the palatability of the limiting amino acid as judged by behaviors such as lick rate and bout size. Instead, LYS-DEF rats relieve the deficiency by increasing the number of drinking episodes initiated.     

The intersection of health informatics and evidence-based medicine: computer-based systems to assist clinicians

Evidence-based medicine and health informatics may assist clinicians contend with the current barriers to the integration of evidence-based "best practice" into typical healthcare settings. Computer-based decision support systems can improve the process of care, but whether they improve patient outcomes in a cost-effective manner is uncertain.     

Hepatocyte growth factor levels during normal and intra-uterine growth-restricted pregnancies

Hepatocyte growth factor (HGF), also known as scatter factor, binds the c-met receptor. It has been shown to be involved in mesenchyme-epithelial interactions. HGF is produced by the villous mesenchyme of the placenta throughout pregnancy and its receptor located on the villous cytotrophoblast cells. In this study the levels of the HGF were measured in consecutive samples of plasma taken from pregnant women. Normal pregnancies were compared with intrauterine growth restricted (IUGR) pregnancies (below the third centile). In both groups, the levels of HGF were found to increase significantly as pregnancy progressed and then fall post partum. There was a considerable amount of variation found between individual women but no significant difference (P=0.65) between the normal and IUGR pregnancies.     

Attenuation of Neomycin Ototoxicity by Iron Chelation

Increasing evidence suggests that aminoglycoside ototoxicity is mediated by the formation of an aminoglycoside-iron complex and that the creation of this complex is a preliminary step in generation of free radical species and subsequent hair cell death. In this study we have assessed the ability of the iron chelator deferoxamine to attenuate the hearing loss induced by an ototoxic dose of the aminoglycoside neomycin (100 mg/kg per day for 14 days). Experiments were carried out on pigmented guinea pigs weighing 250 to 300 g. Changes in auditory sensitivity were characterized by monitoring shifts in compound action potential(CAP) thresholds, recorded through indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results show that animals receiving neomycin alone suffered a mean threshold shift exceeding 35 dB at all test frequencies (2.0, 4.0, and 8.0 kHz) 30 days after initiation of treatment. In comparison, all animals receiving cotherapy of neomycin and deferoxamine (150 mg/kg twice daily for 14 days) maintained their CAP threshold, suggesting significant protection from neomycin ototoxicity. A statistical comparison of treatment groups showed that in the animals receiving cotherapy with neomycin and deferoxamine, deferoxamine produced a significant protective effect against neomycin-induced ototoxicity (P < 0.001). These results provide further evidence of the intrinsic role of iron in aminoglycoside ototoxicity and suggest that deferoxamine may have a therapeutic role in attenuating the cytotoxic action of aminoglycoside antibiotics.     

Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children: a randomized controlled trial. Pediatric AIDS Clinical Trials Group 338 Study Team

CONTEXT: Although protease inhibitors are used routinely in adults with human immunodeficiency virus (HIV) infection, the role of these drugs in the treatment of clinically stable HIV-infected children is not clear. OBJECTIVE: To evaluate the safety, tolerance, and virologic response produced by a change in antiretroviral therapy in HIV-infected children who were clinically and immunologically stable while receiving previous therapy. DESIGN: The Pediatric AIDS Clinical Trials Group 338, a multicenter, phase 2, randomized, open-label controlled trial conducted from February 6 to April 30, 1997 (patient entry period); patients were followed up for 48 weeks. SETTING: Pediatric HIV research clinics in the United States and Puerto Rico. PATIENTS: Two hundred ninety-seven antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children aged 2 to 17 years. INTERVENTIONS: Children were randomized to receive zidovudine, 160 mg/m2 3 times per day, plus lamivudine, 4 mg/kg 2 times per day (n = 100); the same regimen plus ritonavir, 350 mg/m2 2 times per day (n = 100); or ritonavir, 350 mg/m2 2 times per day, and stavudine, 4 mg/kg 2 times per day (n = 97). MAIN OUTCOME MEASURE: Plasma HIV-1 RNA levels at study weeks 12 and 48, compared among the 3 treatment groups. RESULTS: At study week 12, 12% of patients in the zidovudine-lamivudine group had undetectable plasma HIV RNA levels (<400 copies/mL) compared with 52% and 54% of patients in the 2- and 3-drug ritonavir-containing groups, respectively (P<.001). Through study week 48, 70% of children continued receiving their ritonavir-containing regimen. At study week 48, 42% of children receiving ritonavir plus 2 nucleosides compared with 27% of those receiving ritonavir and a single nucleoside had undetectable HIV RNA levels (P = .04); however, similar proportions in each group continuing initial therapy had HIV RNA levels of less than 10000 copies/mL (58% vs 48%, respectively; P = .19). CONCLUSIONS: In our study, change in antiretroviral therapy to a ritonavir-containing regimen was associated with superior virologic response at study week 12 compared with change to a dual nucleoside analog regimen. More children receiving ritonavir in combination with 2 compared with 1 nucleoside analog had undetectable HIV RNA levels at study week 48.     

The value of head ultrasound in infants with macrocephaly

Objective. To assess the value of head ultrasound (HUS) in neurologically normal infants with macrocephaly and to develop a rational approach to radiological investigation of macrocephalic infants. Materials and methods. A retrospective analysis of infants with macrocephaly (seen by one pediatric neurologist at this institution) was conducted. Infants with normal neurological examinations, no evidence of raised intracranial pressure and who had undergone a HUS were included. Results. Twenty-seven infants were included in the analysis. Mean age at first assessment was 4.8 months. In 12 of 27 (44 %), HUS was reported as normal. The remaining 15 had clinically insignificant abnormalities on HUS; 7 had prominent ventricles and 7 had increased subarachnoid fluid, with 1 infant having both. Seven infants had CT or MRI in addition to HUS. No clinically significant abnormalities were seen on CT or MRI scans that were not evident on HUS. Four infants had mild developmental abnormalities on initial evaluation. Mean duration of follow-up was 13.1 months. No infant developed neurological abnormalities during the follow-up period. Conclusion. In infants with macrocephaly with a normal neurological examination and no signs of raised intracranial pressure, HUS in conjunction with close neurological follow-up is reliable for the detection or exclusion of relevant intracranial pathology. Received: 22 May 1997 Accepted: 24 October 1997     

Intracranial leiomyosarcoma: A neuro-oncological consequence of acquired immunodeficiency syndrome

We describe a case of glioblastoma treated with chemoradiotherapy that spread to the dura mater with direct invasion of the skull base, protrusion into the homolateral nasal fossa, and penetrated of the frontal sinus, the orbital wall and the ethmoidal sinuses. Only eight cases of glioblastoma showing this development have been described in the literature; one of these, however, had a sarcomatous component which was absent in our case.     

Satisfaction with midwife-managed care in different time periods: a randomised controlled trial of 1299 women.

OBJECTIVE: To compare women's satisfaction with midwife-managed care with 'shared care' over three different time periods. DESIGN: Randomised controlled trial. SETTING: Glasgow Royal Maternity Hospital, Glasgow, UK. PARTICIPANTS: 1299 women experiencing normal pregnancy (consent rate: 82%). Six hundred and forty-eight women were randomised to midwife-managed care and 651 to 'shared care'. METHODS: Three self-report questionnaires were sent to women's homes. The questionnaires examined: satisfaction with antenatal care at 34-35 weeks' gestation, and satisfaction with intrapartum, hospital- and home-based postnatal care at seven weeks postnatally. The third questionnaire reviewed satisfaction with intrapartum care seven months after delivery. FINDINGS: Women in both groups were satisfied. However, women in the midwife-managed group were more highly satisfied in relation to the dimensions examined: relationships with staff, information transfer, choices and decisions, and social support. The differences between the two groups were evident for all time periods (i.e. antenatal, intrapartum and postnatal periods) and were sustained at seven-month follow-up. This is illustrated in the mean scores for relationships with staff, as measured at 34-35 weeks' gestation (possible range -2; very negative attitudes to 2; very positive attitudes). Women in the midwife-managed group scored a mean of 1.22 compared to 0.74 for the 'shared care' group (mean diff: 0.48; 95% CI: 0.42 to 0.55). While women in both groups were more likely to make positive rather than negative comments in open-ended questions, the midwife-managed group were more likely to make positive comments whereas the 'shared care' group were more likely to make negative comments. CONCLUSION: Midwife-managed care for healthy pregnant women which is integrated into existing services improves satisfaction with antenatal, intrapartum and postnatal care.