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Biomedical subjects

R J Sokol

Publications and source records attributed to R J Sokol.

At least 19 recordsLinked to original sources
PubMed2006

Alcohol abuse--a persistent preventable risk for congenital anomalies.

OBJECTIVE: To examine whether alcohol abuse (ALC) continued to be a health hazard to pregnant women in the 1990s. STUDY DESIGN: Analysis of a perinatal data base comprising 170,258 women with singleton pregnancies. Univariate cross table analysis and logistic regression were conducted to examine the association between alcohol abuse and congenital malformations coded according to the International Classification of Diseases (ICD). RESULTS: 14,727/170,258 mothers (8.6%) admitted to ALC during pregnancy and 36,705/170,258 (21.6%) to smoking. Anomaly rates for ALC (365/14,092, 4.3%) vs. Non-ALC (6187/149,344, 4.0%) differed significantly (p<0.001). The rates of specific anomalies varied between <0.1% and 1.1%. Odds ratios for 16 ICD 9 anomaly categories were >1 in 14 instances overall (Sign test, p=0.004), in 12 instances in women <30 years (p=0.08), and in 13 instances in women over 30 years (p=0.02). Congenital anomalies of the "respiratory system" (ICD9 748), of "genital organs" (ICD9 752.1), of the "integument" (ICD9 757), and "other anomalies of limbs/other musculoskeletal anomalies" (ICD 755/756) were statistically significantly associated with ALC, especially in women>30 years. CONCLUSION: ALC in pregnancy continued to be an important factor independently associated with an increased incidence of a broader range of congenital anomalies than previously recognized. Risk for anatomic anomalies was increased in offspring of ALC women over age 30, consistent with previous reports of increased risk of neurobehavioral abnormality in offspring of women over 30.

Abnormalities, Drug-Induced↗
PubMed2006

What factors are associated with neonatal injury following shoulder dystocia?

OBJECTIVE: To identify factors associated with the development of neonatal injury in the setting of shoulder dystocia. STUDY DESIGN: Medical record ICD-9 codes and a computerized perinatal database were reviewed to identify cases of shoulder dystocia from January 1996 to January 2001 in a tertiary care center. For confirmation of the diagnosis and collection of data, both maternal and neonatal charts were then reviewed and neonatal injuries categorized as either neurological (brachial plexus injury) or skeletal (clavicular fracture, humeral fracture). Shoulder dystocia cases were divided into groups based on the presence of neonatal injury at delivery or at discharge (with or without Erb's palsy). The group with neonatal injury was compared for demographic and obstetrical factors to the group without injury (control). chi (2) test, Mann-Whitney test and logistic regression were used as appropriate. RESULTS: During this 5-year period, there were 25,995 deliveries and 206 (0.8%) confirmed cases of shoulder dystocia. Of these cases, 36 (17.5%) had neonatal injury diagnosed at delivery and 25 (12%) remained with significant residual injury at discharge. Of these there were 19 cases of Erb's palsy and six cases of clavicular fracture. No association was found between neonatal injury and maternal age, ethnicity, diabetes, operative vaginal delivery or number of obstetrical maneuvers. However, maternal body mass index >30 kg/m2, a second stage of labor >20 min and a birth weight >4500 g were all associated with an increased risk of neonatal injury at delivery and at discharge, including Erb's palsy. After logistic regression analysis, only a second stage of delivery >20 min remained significantly associated with neonatal injury at discharge. CONCLUSION: In our population, maternal obesity was associated with an increased risk of neonatal injury after shoulder dystocia. In addition, a short second stage of labor (<20 min) was associated with a lower rate of neonatal injury.

Adult↗
PubMed2005

Amylopectinosis disease isolated to the heart with normal glycogen branching enzyme activity and gene sequence.

We report a 17-month-old female patient with a rare cause of cardiomyopathy secondary to accumulation of amylopectin-like material (fibrillar glycogen) isolated to the heart. Evidence of amylopectinosis isolated to cardiac myocytes in this patient was demonstrated by histology and electron microscopy. Glycogen content, glycogen branching enzyme (GBE) activity, as well as phosphofructokinase enzyme activities measured in liver, skeletal muscle, fibroblasts and ex-transplanted heart tissue were all in the normal to lower normal ranges. Normal skeletal muscle and liver tissue histology and GBE activity, normal GBE activity in skin fibroblasts, plus normal GBE gene sequence in this patient exclude the classical branching enzyme deficiency (type IV GSD). We believe that this is an as yet uncharacterized and novel phenotype of GSD associated with cardiomyopathy, in which there is an imbalance in the regulation of glycogen metabolism limited to the heart.

1,4-alpha-Glucan Branching Enzyme↗
PubMed2004

The impact of maternal obesity on midtrimester sonographic visualization of fetal cardiac and craniospinal structures.

OBJECTIVE: To examine the impact of maternal obesity on the rate of suboptimal ultrasound visualization (SUV) of fetal anatomy and determine the optimal timing of prenatal ultrasound examination for the obese gravida. METHODS: A computerized ultrasound database was used to identify ultrasound examinations for singleton gestations performed between 14(0/7) and 23(6/7) weeks at a tertiary care, university-based hospital. Patients were divided into four groups and categorized based on body mass index (BMI): nonobese (BMI <30 kg/m2), class I obesity (30< or =BMI<35 kg/m2), class II obesity (35< or =BMI<40 kg/m2), and extreme obesity (BMI > or =40 kg/m2). The rates of SUV for fetal cardiac and craniospinal structures were calculated for each group and compared. RESULTS: A total of 11,019 pregnancies were studied, of which 38.6% of the patients were obese. Overall, the rate of SUV of the fetal structures was higher for obese compared to nonobese women for both cardiac (37.3 [1723/4200] vs 18.7% [1275/6819]; P<0.0001) and craniospinal structures (42.8 [1798/4200] vs 29.5% [2012/6819]; P<0.0001). Increased severity of maternal obesity was associated with SUV rate for both the cardiac (nonobese 18.7% [1275/6819], class I 29.6% [599/2022], class II 39.0% [472/1123], and extreme obesity 49.3% [580/1055]; P<0.0001) and for the craniospinal structures: (nonobese 29.5% [2012/6819], class I 36.8% [744/2022], class II 43.3% [486/1123], and extreme obesity 53.4% [563/1055]; P<0.0001). With increasing gestational age at examination, the rate of SUV decreased for both obese and nonobese women. However, for obese women there was minimal improvement in visualization after 18-20 weeks. Even after adjustment for gestational age and the type of ultrasound machine, obese women (class I, class II, and extreme obesity) were still associated with increased odds for SUV of the fetal cardiac and craniospinal structures compared to nonobese women. CONCLUSION: Maternal obesity increases the rate of SUV for the fetal cardiac structures by 49.8% and for the craniospinal structures by 31%. The optimal gestational age for visualization of fetal cardiac and craniospinal anatomy in obese patients may be after 18-20 weeks.

Body Mass Index↗
PubMed2002

Epstein-Barr virus and post-transplant lymphoproliferative disease.

There is convincing evidence that Epstein-Barr virus (EBV) is associated with post-transplant lymphoproliferative disease (PTLD). Primary EBV infection following transplantation occurs in as many as 90% of cases of PTLD in children and pretransplant EBV seronegativity is a recognized risk factor for developing PTLD. Other risk factors include young age at the time of transplant, the type of transplant that the recipient receives and the type and intensity of immunosuppression. The clinical presentation is often nonspecific and tissue biopsy is necessary to establish the diagnosis. There appears to be a correlation between PTLD and EBV viral load measured by polymerase chain reaction (PCR) of the peripheral blood and quantitative PCR may be a useful guide in the management of PTLD. Antiviral drugs and cytomegalovirus-immunoglobulin G may have a role in preventing PTLD. Because PTLD results from functional over-immunosuppression, the initial treatment is reduction of immunosuppression. Antiviral agents, interferon, immuno-based monoclonal therapy, cell-based therapy and chemotherapy also have a potential role in treating this disorder. At the present time there is no standardized approach to the evaluation and treatment of PTLD.

Child↗
PubMed2002

Successful allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is a rare genetic disorder characterized by pancreatic insufficiency, short stature, skeletal abnormalities and bone marrow dysfunction. Patients with SDS have varying degrees of marrow aplasia, which can be severe or progress to leukemic transformation. While allogeneic hematopoietic stem cell transplantation (HSCT) can be curative for the hematologic disturbances of SDS, a recent review of the literature reveals few survivors. Poor outcome with HSCT is often related to excessive cardiac and other organ toxicity from transplant preparative therapy. We describe two young children with SDS who developed aplastic anemia and subsequently underwent successful allografting using a non-cardiotoxic conditioning regimen. Case 1 received marrow from an HLA-identical sibling while case 2 received partially matched umbilical cord blood from an unrelated donor. Both patients are presently alive and well with sustained donor engraftment and excellent hematopoietic function at 36 and 22 months post-HSCT.

Abnormalities, Multiple↗
PubMed2001

Abnormal cervicovaginal cytology in women with lupus: a retrospective cohort study.

OBJECTIVE: The aim of this study was to review Pap smear reports in women with systemic lupus erythematosus and compare them to a large control population. METHODS: Pap smear results of 29 women with a diagnosis of lupus seen consecutively were compared to those of a control population of 747 women attending the gynecology clinic at the same medical center during the same year. Records of lupus patients were reviewed to obtain clinical data. Fisher's exact test and chi(2) analysis were used to determine statistical significance, as appropriate. RESULTS: Of 29 women with lupus, 1/29 had high-grade squamous intraepithelial lesions (HGSIL) and 6/29 had low-grade squamous intraepithelial lesions (LGSIL). The control population of 747 women had 9/747 with HGSIL and 63/747 with LGSIL. chi(2) and Fisher's exact tests showed that the lupus population had a statistically significant increase in Pap smear reports of dysplasia compared to the control group (P < 0.021 for HGSIL/LGSIL combined, P < 0.036 for LGSIL alone). Examination of serial Pap smear results revealed that 45% of the lupus patients had cervical dysplasia at some time. CONCLUSION: Women with lupus have an increased prevalence of cervical dysplasia. Serial observation revealed dysplastic cytologies in nearly half of the patients, suggesting that this may be a more common problem than previously reported. Serial prospective studies are needed to assess better the risk of premalignant cervical lesions in lupus.

Adult↗
PubMed2001

Bile acid-induced rat hepatocyte apoptosis is inhibited by antioxidants and blockers of the mitochondrial permeability transition.

The accumulation of hydrophobic bile acids plays a role in the induction of apoptosis and necrosis of hepatocytes during cholestasis. The aim of this study was to determine in freshly isolated rat hepatocytes the roles of oxidant stress and the mitochondrial permeability transition (MPT) in bile acid-induced apoptosis. Hepatocytes isolated from adult male Sprague-Dawley rats were incubated for 4 hours in buffer containing the hydrophobic bile acid, glycochenodeoxycholic acid (GCDC, 0-500 micromol/L) or the hydrophilic bile acid, glycocholic acid (GCA), and either the antioxidants, alpha tocopherol, ebselen, or idebenone (a coenzyme Q analogue); or the MPT blockers, cyclosporin A, or bongkrekic acid, or a caspase-8 inhibitor. Apoptosis was assessed hourly by nuclear morphologic changes of fixed cells by DAPI fluorescence microscopy and reactive oxygen species (ROS) generation by dichlorofluorescein fluorescence of hepatocytes. The percent of cells undergoing apoptosis increased in a time- and concentration-dependent manner in cells exposed to GCDC, and to a much lesser extent to GCA. ROS generation preceded the onset of apoptosis. MPT blockers, caspase-8 inhibition, and antioxidants prevented apoptosis and reduced ROS generation by hepatocytes. Flow cytometry analysis showed that MPT occurred within 1 hour of exposure of cells to 100 micromol/L GCDC, prior to onset of significant apoptosis. In conclusion, ROS generation, MPT induction, and cytochrome c release are critical steps in the induction of apoptosis by bile acids. Antioxidants may reduce liver injury caused by low levels of bile acids by preventing the generation of oxidant stress and subsequent stimulation of the MPT and release of cytochrome c from mitochondria.

Animals↗
PubMed2001

Navajo neurohepatopathy: a mitochondrial DNA depletion syndrome?

Navajo neurohepatopathy (NNH) is an autosomal recessive disease of full-blooded Navajo children living in the Navajo Reservation of southwestern United States. Clinical features of NNH include peripheral and central nervous system involvement, acral mutilation, corneal scarring or ulceration, liver failure, and metabolic and immunologic derangement. The cause of NNH is unknown, but the clinical features of NNH are similar to those of patients with mitochondrial DNA (mtDNA) depletion. Therefore, we studied mtDNA concentration in the liver from 2 patients with NNH. Using histochemical, biochemical, and molecular techniques, we found evidence of mtDNA depletion, and we propose that the primary defect in NNH is in the nuclear regulation of mtDNA copy number.

Citrate (si)-Synthase↗
PubMed2001

Cholangiocyte biology and cystic fibrosis liver disease.

Cystic fibrosis (CF) is one of the most common inherited diseases in the white population. The disease results from mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR). How this gene defect leads to the clinical manifestations of the disease, however, is not entirely clear. CFTR functions as a Cl(-) channel in the apical membrane of most secretory epithelia, including biliary epithelial cells, or cholangiocytes. In cholangiocytes, CFTR appears to be an important determinant of biliary secretion and bile flow. Additionally, recent evidence suggests that CFTR regulates other membrane transporters, channels, and proteins. Improving life expectancy has led to an increasing recognition of hepatobiliary complications from CF. The true prevalence of CF liver disease is unknown, but may affect up to 17-25% of CF patients. Clinical manifestations include hepatic steatosis, neonatal cholestasis, focal nodular cirrhosis, multilobular cirrhosis, and biliary tract complications. Why only a subset of CF patients develops severe liver disease and others with the same genotype do not is one of the many scientific curiosities of this disease. This review focuses on the function of CFTR in cholangiocytes with emphasis on ductular bile formation as well as the clinical consequences of abnormal CFTR, namely CF-associated liver disease. Data on the pathogenesis, prevalence, clinical course, and treatment of CF liver disease will be reviewed.

Bile Ducts↗
PubMed2001

Etiopathogenesis of biliary atresia.

Biliary atresia, a progressive sclerosis of the extrahepatic biliary tree that occurs only within the first 3 months of life, is one of the most common causes of neonatal cholestasis and accounts for over half of children who undergo liver transplantation. In biliary atresia, a number of prenatal or perinatal insults to the biliary tree appear to culminate in complete obliteration of the lumen of the extrahepatic biliary tree and continued injury and sclerosis of intrahepatic bile ducts, even after portoenterostomy is successful. A minority of cases of biliary atresia may be caused by defects in morphogenesis of the bile ducts. Potential etiologies for the more common perinatal form of biliary atresia include viral infections, immune-mediated bile duct injury, and autoimmune disease involving the bile ducts. Two viruses, reovirus and rotavirus, have received increasing attention as possible inciters of an immune-mediated injury to the biliary tree. Fas ligand upregulation and apoptosis of bile duct epithelia have been demonstrated in human specimens, as well as T-lymphocyte and macrophage activation in portal tracts. An experimental model using rotavirus infection in newborn mice has been useful in characterizing the mechanisms underlying bile duct injury. It is proposed that virally induced neoantigens displayed on biliary epithelium may play a role in initiating the immune processes involved in destruction of the extrahepatic bile duct and ongoing intrahepatic ductal injury in the perinatal form of biliary atresia. The short window of time after birth during which this disease presents suggests that immaturity of the neonatal immune system and genetic susceptibility also may be key factors. Delineation of the mechanisms underlying bile duct injury will be essential to the development of new potential therapies for this important pediatric disorder.

Animals↗
PubMed2001

Obstetrics and gynecology at the crossroads--again? Still!

It seems, if one can believe presidential addresses, as if our specialty is always at some crossroads or other. In this "opinion piece," uniquely, I don't complain about managed care. I do attempt to identify some of the issues that will be of import for obstetrics and gynecology in the near and not-so-near futures. With regard to research, we await breakthroughs, for example, in the early detection of ovarian cancer, so as to finally be able to improve outcomes. A problem, though, is our failure to focus enough effort on developing a cadre of clinician scientists, who can work out research findings with direct clinical application; this is an issue with which the specialty needs to come to grips. Regarding education, I believe we need to refocus from what type of practitioners we might want to produce to best meet the needs of our patients. The bottom line should be more flexibility in training and emphasis on clinical competence, so that excellent practitioners with competence across the breadth of our specialty are available to provide a full range of appropriate women's health care. The concept of "women's health" is controversial and evolving rapidly. Review of several available sources suggests that reproductive medicine will remain an important component of women's health but that our specialty must now evolve to include other areas, as the major health problems of women change. We need to shift from an organ-based paradigm to a more holistic view, reflecting the woman-centered focus for our specialty. This "paradigm shift" will need to entail continuation of first-rate surgical and obstetrics services but will be expanded to include a full range of services, probably offered by highly trained and competent individuals with specific areas of expertise, practicing in a multi-single-specialty group. Obstetrics and gynecology at the crossroads, indeed!

Humans↗
PubMed2001

Survival after first esophageal variceal hemorrhage in patients with biliary atresia.

OBJECTIVE: To determine the influence of the new onset of esophageal variceal hemorrhage (EVH) on transplant-free survival in children with biliary atresia and to examine variables that predicted survival after the onset of EVH. METHODS: Retrospective chart review of 134 patients with biliary atresia who underwent portoenterostomy between 1973 and 1992 at a single institution; 29% had EVH. RESULTS: The risk of death or need for liver transplantation was 50% at 6 years after the initial episode of EVH. Patients with a serum bilirubin concentration < or =4 mg/dL at the first episode of EVH had transplant-free survival of >80% for 4 years after this episode, those with bilirubin levels >4 to 10 mg/dL had 50% survival at 1 year, and those with bilirubin levels >10 mg/dL had 50% survival at 4 months. The risk of death or transplant for a child with EVH and total serum bilirubin levels >10 mg/dL was 12.0 (95% CI: 6.0, 24.1), 4 to 10 mg/dL was 7.2 (3.1, 16.7), and < or =4 mg/dL was 0.6 (0.1, 3.1) times the risk of a same-aged child who did not have EVH. CONCLUSIONS: Children with biliary atresia and first EVH episode have a variable prognosis related to total serum bilirubin concentration at the time of the episode.

Biliary Atresia↗
PubMed2001

Large-volume paracentesis in the management of ascites in children.

BACKGROUND: Large-volume paracentesis has been evaluated for both therapeutic and diagnostic purposes in the management of ascites in cirrhotic adults. There are no published data relating to the safety, efficacy, or methods of this procedure in children. The objective of this study was to characterize the authors' initial experience with large-volume paracentesis (> 50 ml/kg of ascites) for removal of tense abdominal ascites in the pediatric population. METHODS: Retrospective chart review was performed of 21 large-volume paracentesis sessions in seven children (ages 6 months-18 years) with tense ascites that did not respond to other measures. RESULTS: Mean volume removed was 3,129 +/- 2,966 ml (mean +/- standard deviation) or 118 +/- 56 ml/kg over 2.9 +/- 3.7 hours by a 16-gauge intravascular catheter in 6 sessions, by an 18-gauge intravascular catheter in three sessions, and by a 15-gauge fenestrated, stainless-steel paracentesis needle in 12 sessions. Large-volume paracenteses performed with the paracentesis needle had significantly shorter duration of drainage and faster flow rates than those performed with the intravascular catheter. The only complication encountered was decreased urine output in one session. CONCLUSIONS: Large-volume paracentesis is a safe and effective therapeutic method for managing tense abdominal ascites in children. The use of the paracentesis needle significantly improved the speed and efficiency of large-volume paracentesis compared with the intravascular catheter.

Adolescent↗