Dev Maulik

Correlation of Obesity and Osteoporosis: Effect of Fat Mass on the Determination of Osteoporosis

It was previously believed that obesity and osteoporosis were two unrelated diseases, but recent studies have shown that both diseases share several common genetic and environmental factors. Body fat mass, a component of body weight, is one of the most important indices of obesity, and a substantial body of evidence indicates that fat mass may have beneficial effects on bone. Contrasting studies, however, suggest that excessive fat mass may not protect against osteoporosis or osteoporotic fracture. Differences in experimental design, sample structure, and even the selection of covariates may account for some of these inconsistent or contradictory results. Despite the lack of a clear consensus regarding the impact of effects of fat on bone, a number of mechanistic explanations have been proposed to support the observed epidemiologic and physiologic associations between fat and bone. The common precursor stem cell that leads to the differentiation of both adipocytes and osteoblasts, as well the secretion of adipocyte‐derived hormones that affect bone development, may partially explain these associations. Based on our current state of knowledge, it is unclear whether fat has beneficial effects on bone. We anticipate that this will be an active and fruitful focus of research in the coming years.

Emergency peripartum hysterectomy: Experience at a community teaching hospital

OBJECTIVES To estimate the incidence, indications, risk factors, and complications associated with emergency peripartum hysterectomy at a community‐based academic medical center. METHODS We analyzed retrospectively 47 of 48 cases of emergency peripartum hysterectomy performed at Winthrop‐University Hospital from 1991 to 1997. Emergency peripartum hysterectomy was defined as one performed for hemorrhage unresponsive to other treatment less than 24 hours after delivery. Fisher exact test, Wilcoxon rank sum test, and Cochran‐Armitage exact trend test were used for analysis. RESULTS There were 48 emergency peripartum hysterectomies among 34,241 deliveries for a rate of 1.4 per 1000. Most frequent indications were placenta accreta (48.9%, 12 with previa, 11 without previa), uterine atony (29.8%), previa without accreta (8.5%), and uterine laceration (4.3%). Placenta accreta was the most common indication in multiparous women (58.8%, 20 of 34), uterine atony the most common in primiparas (69.2%, nine of 13). Twenty‐two of 23 (95.6%) women with placenta accreta had a previous cesarean delivery or curettage. The number of cesarean deliveries or curettages increased the risk of placenta accreta proportionally. Thirty‐eight (80.9%) of the hysterectomies were subtotal. Postoperative febrile morbidity was 34%; other morbidity was 26.3%. CONCLUSION Placenta accreta has become the most common indication for emergency peripartum hysterectomy.

Fetal growth restriction: the etiology.

Fetal growth restriction (FGR) is etiologically associated with various maternal, fetal and placental factors, although such an association may not be present in many cases. Maternal factors include hypertensive diseases, autoimmune disorders, certain medications, severe malnutrition, and maternal lifestyle including smoking, alcohol and cocaine use. Fetal etiologies include aneuploidy, malformations, syndromes related to abnormal genomic imprinting, perinatal viral or protozoan infections, preterm birth, and multiple gestation. Placental factors may involve many conditions including anatomical, vascular, chromosomal and morphological abnormalities. Better understanding of these etiologic conditions may lead to improved prediction, prevention and management of FGR.

Immediate maternal and neonatal effects of forceps and vacuum-assisted deliveries.

OBJECTIVE: To estimate the differences in immediate maternal and neonatal effects of forceps and vacuum-assisted deliveries. METHODS: We conducted a medical record review of all forceps and vacuum-assisted deliveries that occurred from January 1, 1998, to August 30, 1999, at Winthrop-University Hospital. Maternal demographics and delivery characteristics were recorded. Maternal outcomes, such as use of episiotomy and presence of lacerations, were studied. Neonatal outcomes evaluated were Apgar scores, neonatal intensive care unit admissions, cephalohematomas, instrument marks and bruising, and caput and molding. RESULTS: Of 508 operative vaginal deliveries, 200 were forceps and 308 were vacuum assisted. Forceps were used more often than vacuum for prolonged second stage of labor (P = .001). There was a higher rate of epidural (P = .02) and pudendal (P < .001) anesthesia, episiotomies (P = .01), maternal third- and fourth-degree perineal (P < .001) and vaginal lacerations (P = .004) with the use of forceps, whereas periurethral lacerations were more common in vacuum-assisted (P = .026) deliveries. More instrument marks and bruising (P < .001) were found in the neonates delivered by forceps, whereas there was a greater incidence of cephalohematomas (P = .03) and caput and molding (P < .001) in the neonates delivered with vacuum. Multivariable logistic regression analysis showed that forceps use was associated with an increase in major perineal and vaginal tears (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.27, 2.69; P = .001), an increase in instrument marks and bruising (OR 4.63; 95% CI 2.90, 7.41; P < .001) and a decrease in cephalohematomas (OR 0.49; 95% CI 0.29, 0.83; P = .007) compared with the vacuum. CONCLUSIONS: Maternal injuries are more common with the use of forceps. Neonates delivered with forceps have more facial injuries, whereas neonates delivered with vacuum have more cephalohematomas. LEVEL OF EVIDENCE: II-3

Fetal growth restriction: pathogenic mechanisms.

Complex genetic and environmental mechanisms of maternal, fetal and placental origin regulate fetal growth and may contribute to fetal growth restriction (FGR). The somatotrophic regulatory factors include IGF-I, IGF-II, the IGF binding proteins (IGFBP) 1-6, IGF receptors 1 and 2, and the IGFBP specific proteases. Abnormal remodeling of utero-placental arteries and abnormal fetal-placental angiogenesis has also been implicated in FGR. The underlying molecular mediators include vascular endothelial growth factor (VEGF), placental growth factor (PlGF), VEGF receptors, VEGF binding proteins, and numerous other agents working through multiple pathways many of which still remain unknown. Expression of these major angiogenic factors appears to be regulated by local oxygen partial pressure. Future investigations may resolve many of these issues not only adding to the clarity of our understanding of the mechanisms of growth restriction but also improving clinical management.

Live three-dimensional echocardiography of the human fetus.

The purpose of this study was to investigate the feasibility of using a new three‐dimensional ultrasound system to perform fetal echocardiographic examination in real time. The device consisted of a Philips Sonos 7500 (Andover, MA) ultrasound system and a 4 MHz, 4X matrix transducer. The study was approved by the Institutional Review Board and was performed with the informed consent of the mother. The study population consisted of 12 singleton fetuses with gestational ages of 16–37 weeks. Of these, ten fetuses had normal cardiac anatomy, one had complete atrioventricular septal defect, and the other a thickened tricuspid valve. The system allowed comprehensive visualization of fetal cardiac anatomy and color Doppler flow unattainable by two‐dimensional approaches. This preliminary investigation suggests that live three‐dimensional fetal echocardiography could be a significant tool for prenatal diagnosis and assessment of congenital heart disease in the human fetus. (ECHOCARDIOGRAPHY, Volume 20, November 2003)

Simple Cyst in the Postmenopausal Patient: Detection and Management

The aims of our study were to determine the prevalence of simple ovarian cysts in asymptomatic postmenopausal patients and to investigate the natural history of these cysts by ultrasonographic follow‐up examinations. Three thousand five hundred and eighty‐five women participated in the volunteer pelvic cancer screening program. Entry criteria were as follows: postmenopausal, no clinical symptoms, and no previous gynecologic pathology. An anechoic, small cyst less than 5 cm in greatest diameter was classified as a simple ovarian cyst. A scoring system to determine malignant potential had been established previously. All simple cysts had a score of 2 or less and had a morphology typical of benign lesions. In the case of a positive finding, the patient would be seen at 3 to 6 month intervals. The decision for surgical intervention was made by a private gynecologist or patient or if an interval change was noted. One thousand seven hundred and sixty‐nine postmenopausal women (49.34% of all patients from the screening program) participated in this study. One hundred and sixteen simple cysts were found, with a prevalence of 6.6% in our population. Among those patients, 27 (23.28%) simple cysts resolved spontaneously, 69 (59.48%) have persisted, and 20 (17.24%) have been lost to follow‐up study. Eighteen women (26.09%) with persistent simple ovarian cyst underwent surgery. No malignant ovarian conditions were identified. In conclusion, simple ovarian cysts are more common in postmenopausal women than previously was thought. This condition is very unlikely to be malignant and can be followed conservatively.

Fetal growth compromise: definitions, standards, and classification.

Fetal growth compromise is mostly defined by gestational age specific threshold value of birth weight or ultrasonically estimated fetal weight. The most frequently used threshold is the 10th centile. However, this approach can not differentiate fetal constitutional smallness from fetal growth failure. The most common descriptor terms are fetal growth restriction (FGR), intrauterine growth restriction and small for gestational age. It is recommended to restrict the use of the first two terms to prenatal assessment of growth and the last term to assessment of the birth weight. Growth reference charts are affected by physiological and methodological variables. There is controversy on whether the reference charts should be customized by multiple variables or inclusive of the whole population. Symmetric FGR is more common and has better outcome than asymmetric FGR. However, such a classification may not be clinically relevant.

Oxygen free radical generation during in-utero hypoxia in the fetal guinea pig brain : the effects of maturity and of magnesium sulfate administration

Previous studies have shown, employing direct measurements with electron spin resonance (ESR) spectroscopy, that hypoxia induces an increased production of oxygen free radicals (OFR) in the brain of the guinea pig fetus. The present study using the same approach, investigated the effects of maturity and Mg2+-pretreatment on hypoxia-induced OFR formation in the guinea pig fetal brain. The normoxic and the hypoxic groups were exposed for 60 min to 21% or 7% oxygen, respectively. The control group consisted of term fetuses exposed to normoxia (n=7) and hypoxia (n=7). The experimental groups consisted of the following: (a) for the investigation on maturity effect, preterm fetuses (40 days) exposed to normoxia (n=6) or hypoxia (n=6); and (b) for the Mg2+-pretreatment investigation, term fetuses (60 days) exposed to normoxia (n=6) or hypoxia (n=6) following maternal pretreatment with Mg2+ which consisted of an initial bolus of MgSO4 (600 mg/kg, i.p.) 1 h prior to hypoxia followed by a second dose (300 mg/kg, i.p.). Oxygen free radicals were measured by ESR spectroscopy in the fetal cerebral cortical tissue utilizing phenyl-N-tert-butylnitrone (PBN) spin trapping. Fetal brain tissue hypoxia was documented biochemically by decreased tissue levels of ATP and phosphocreatine. In the control group of term fetuses, the cortical tissue from hypoxic fetuses showed a significant increase in spin adducts (71% increase, p<0.01). In the preterm group, the cortical tissue from hypoxic fetuses showed a 33% increase in spin adducts (p<0.001). The baseline free radical generation during normoxia was 22.5% higher at preterm than at term (41.4+/-3.5 units/g issue vs. 33.8+/-9.3 units/g tissue, p<0.05). In Mg2+-treated groups, spin adduct levels in cortical tissue from hypoxic fetuses did not significantly differ from those of the normoxic group (30.2+/-9.9 units/g tissue, normoxic-Mg2+ vs. 30. 6+/-8.1 units/g tissue, hypoxic-Mg2+). The results indicate that the fetal brain at term may be more susceptible to hypoxia-induced free radical damage than at preterm and that Mg2+ administration significantly decreased the hypoxia-induced increase in oxygen free radical generation in the term fetal guinea pig brain in comparison with non-treated hypoxic group.

Direct measurement of oxygen free radicals during in utero hypoxia in the fetal guinea pig brain

The present study tested the hypothesis that maternal hypoxia induces oxygen free radical generation in the fetal guinea pig brain utilizing techniques of electron spin resonance spectroscopy and alpha-phenyl-tert-butyl nitrone (PBN) spin trapping. Pregnant guinea pigs of 60 days gestation were divided into normoxic and hypoxic groups and exposed to 21% or 7% oxygen for 60 min. Free radical generation was documented by measuring the signal of PBN spin adducts. Fluorescent compounds were determined as an index of lipid peroxidation and the activity of Na+,K+-ATPase was determined as an index of brain cell membrane function. Hypoxic fetal cerebral cortical tissue showed a significant increase in spin adducts (normoxic: 33.8+/-9.3 units/g tissue vs. hypoxic: 57.9+/-9.2 units/g tissue, p<0.01) and fluorescent compounds (normoxic: 0.639+/-0.054 microg quinine sulfate/g brain vs. 0.810+/-0.102 microg quinine sulfate/g brain, p<0.01) and a decrease in Na+,K+-ATPase activity (normoxic: 43.04+/-2.50 micromol Pi/mg protein/h vs. hypoxic: 33. 80+/-3.51 micromol Pi/mg protein/h, p<0.001). These results demonstrate an increased free radical generation during hypoxia in the fetal guinea pig brain. The spectral characteristics of the radicals were consistent with those of alkoxyl radicals. The increased level of fluorescent compounds and decreased activity of Na+,K+-ATPase indicated hypoxia induced brain cell membrane lipid peroxidation and dysfunction, respectively. These results directly demonstrate an increased oxygen free radical generation during hypoxia and suggest that hypoxia-induced increase in lipid peroxidation and decrease in membrane function, as indicated by a decrease in Na+,K+-ATPase activity, are consequences of increased free radicals. The nature of predominantly present alkoxyl radical indicates ongoing lipid peroxidation during hypoxia. The direct demonstration of oxygen free radical generation during hypoxia is the critical missing link in the mechanism of hypoxia-induced brain cell membrane dysfunction and damage.