Intrauterine growth of full-term infants: impact of prenatal cocaine exposure.

OBJECTIVE: The objectives of this study were to estimate the effect of prenatal cocaine exposure on fetal growth and gestational age after controlling for exposure to alcohol, tobacco, and marijuana and other covariates; to evaluate whether prenatal cocaine exposure has a disproportionate adverse effect on head circumference compared with overall somatic growth; and to assess whether the effect of prenatal cocaine exposure on fetal growth is mediated by cocaine's suspected effect on gestational age. METHODS: The study population includes 476 neonates participating in the Miami Prenatal Cocaine Study, a longitudinal follow-up of in utero cocaine exposure. The sample, restricted to full-term neonates born to African-American inner-city mothers, included 253 infants exposed prenatally to cocaine (with or without alcohol, tobacco, or marijuana exposure) and 223 non-cocaine-exposed infants, of whom 147 were drug-free and 76 were exposed to varying combinations of alcohol, tobacco, or marijuana. RESULTS: Evidence based on structural equations and multiple regression models supports a hypothesis of cocaine-associated fetal growth deficits (0.63 standard deviation) and an independent mild effect on gestational age (0.33 standard deviation). There was no evidence of a disproportionate adverse effect on birth head circumference once the impact on overall growth was estimated. There was evidence that some but not all of the cocaine effect on fetal growth was direct and some was indirect, acting via an intermediate influence of cocaine on gestational age. CONCLUSIONS: Cocaine-associated growth deficits, symmetrical and partially mediated by gestational age, were observed in this sample of inner-city African-American full-term infants prospectively enrolled at birth. Long-term implications will be the subject of future reports from this longitudinal investigation.

Influence of prenatal cocaine exposure on full-term infant neurobehavioral functioning.

This study investigated infant neurobehavioral functioning during the newborn period in 334 full-term, African American neonates (187 cocaine exposed, 147 non-cocaine exposed) enrolled prospectively at birth, with documentation of drug exposure status through maternal interview and urine and meconium toxicology assays. Infants were assessed using the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) during the newborn period (0-6 postnatal days). Findings from multivariate profile analyses support a consistent, modest effect of prenatal cocaine exposure on neurobehavioral functioning in full-term neonates. All of the BNBAS cluster scores, with the exception of abnormal reflexes, were similarly affected, sharing a common slope (D=-0.14; 95% CI=-0.27, -0.003; P=.046) representing a -0.14 point difference between cocaine-exposed and non-cocaine-exposed infants after controlling for prenatal exposure to alcohol, tobacco, and marijuana (ATM); maternal age, education, employment, primigravida status, and prenatal care visits; and infant sex and postnatal age in days. Fetal growth was also related to neurobehavioral functioning and, in part, mediated the relationship between cocaine exposure and the BNBAS cluster scores. Cocaine exposure during each trimester similarly influenced infant neurobehavioral profiles, with cocaine-associated deficits most pronounced in infants with exposure in all three trimesters. Results from qualitative and quantitative urine and meconium bioassay indicators further substantiated these results. Findings, while significant, represent modest effect sizes in full-term infants.

Longitudinal investigation of task persistence and sustained attention in children with prenatal cocaine exposure.

The present study estimates the longitudinal effects of prenatal cocaine exposure on indicators of sustained attention processing at 3, 5 and 7 years of age in an urban sample of full-term African-American children (235 cocaine-exposed, 207 noncocaine-exposed). The sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview, urine and meconium toxicology assays. Sustained attention was measured at age 3 years using a standardized measure of task persistence during a challenging task [G.A. Morgan, N.A. Busch-Rossnagel, C.A. Maslin-Cole and R.J. Harmon, Individualized Assessment of Mastery Motivation: Manual for 15-36 Month Old Children, 1992.], and at ages 5 and 7 years using omission error scores from computerized continuous performance tasks (CPT) [L. Greenberg, R. Leark, T. Dupuy, C. Corman, C. Kindschi, M. Cenedela, Test of Variables of Attention (T.O.V.A. and T.O.V.A.-A.), 22, Universal Attention Disorders, Los Alamitos, CA, 1996; C.K. Conners, Conners' Continuous Performance Test (CPT), second ed., Multi-Health Systems, Canada, 1995.]. Findings from longitudinal GLM/GEE analyses of the three measured time points support a stable influence of prenatal cocaine exposure on indicators of sustained attention, after controlling for prenatal exposure to alcohol, marijuana, tobacco and over 20 additional medical and social-demographic covariates drawn from potentially confounding influences assessed at birth and later assessment visits (D=0.21; 95% CI=0.04, 0.38; P=.017). This effect was not mediated by fetal growth or gestational age and remained highly stable with increasing levels of covariate control. Separately, using the age 7 data, a structural equations model (SEM) was constructed combining all available self-report and bioassay data to measure magnitude of cocaine exposure in relationship to attention task performance. Results indicated a gradient of influence, with each standard deviation increase in the level of prenatal cocaine exposure relating to a 16% standard deviation increase in omission error scores at age 7. Overall findings support a stable cocaine-specific effect on indicators of sustained attention processing during the early childhood years. Results are discussed within the context of neurobiological and behavioral research linking prenatal cocaine exposure to long-lasting disruption of the brain systems subserving arousal and attention.

Herniation of the hepatic flexure through the foramen of Winslow: a case report.

Herniation through the foramen of Winslow is among the rarest of internal hernias. Predisposing factors include an enlarged epiploic foramen, a mobile cecum and ascending colon, and an abnormal length of small bowel mesentery. Obstruction, strangulation, and perforation with associated metabolic and septic sequelae are the major complications associated with this disease. We report a case of herniation through the foramen of Winslow in which the diagnosis was established preoperatively.

Preventive care in pregnancy.

Pregnancy provides unique opportunities for the initiation of preventive practices that can have long-standing implications for a pregnant woman, her infant, and the entire family. The physician has an obligation to evaluate the safety and appropriateness of interventions. This article examines routine prenatal care and its rationale.

Operative and long-term results of staged contralateral carotid endarterectomy: a personal series.

The operative risks as well as the proper interval for patients undergoing staged contralateral carotid endarterectomies remain uncertain. The long-term incidence of stroke after bilateral carotid endarterectomy is also poorly documented. In this report the results of staged contralateral carotid endarterectomies performed by one surgeon in a consecutive series of 89 patients are analyzed. No deaths occurred after a first or contralateral carotid endarterectomy. Four (4%) neurologic deficits (three minor and one major) occurred after a first operation, whereas only one (1%) major neurologic deficit occurred after a contralateral carotid endarterectomy. Postendarterectomy hypertension was noted in 33 (37%) patients after a first operation, and in 62 (70%) patients after a contralateral carotid endarterectomy (p less than 0.00001). No correlation existed among the intervals between carotid operations and the incidence or duration of hypertension after a contralateral carotid endarterectomy. From our results we conclude that the staged contralateral carotid endarterectomy can be safely performed with a stroke-mortality rate approaching 1%. Postendarterectomy hypertension, although more frequent after the contralateral operation as compared with the first operation, has no correlation with the interval between procedures. After a staged bilateral carotid endarterectomy, only one (1%) patient experienced transient ischemic attack symptoms, but five (6%) patients suffered late stroke (four fatal).

Chronic pancreatitis: long-term surgical results of pancreatic duct drainage, pancreatic resection, and near-total pancreatectomy and islet autotransplantation.

Severe abdominal pain was the major indication for operation in 85 patients with chronic pancreatitis. Preoperative endoscopic retrograde cholangiopancreatography (50 patients) or intraoperative pancreatic ductograms (44 patients) demonstrated dilated or obstructed major pancreatic ducts in 50 patients (59%), nonvisualization of the distal duct in 10 patients (12%), and normal or small sized ducts in 34 patients (40%). Operative procedures, tailored according to duct morphology, included pancreatic duct drainage (46 patients), subtotal (40% to 80%) pancreatectomy (21 patients), near-total (85% to 95%) pancreatectomy alone (eight patients), and near-total or total pancreatectomy and intrahepatic islet autotransplantation (10 patients). Pancreatic duct drainage resulted in pain relief in 37/46 patients (80%) followed for 6 years. However, 20/46 patients (43%) had continued loss of pancreatic function after duct drainage as measured by the development of insulin-dependent diabetes (16 patients) or steatorrhea (seven patients). Seven years after subtotal pancreatectomy, pain relief was partial in 9/21 patients (43%) and complete in five patients (24%). A higher incidence of hypoglycemic or ketoacidotic complications was noted in patients treated by subtotal pancreatectomy (three patients, 14%) than by duct drainage (one patient, 2%). Near-total pancreatectomy was the most effective surgical procedure in relieving pain, but late sequelae in three patients (38%) included one hypoglycemic death and two ketoacidotic episodes. Five years after near-total pancreatectomy and islet autotransplantation, one patient remained permanently insulin independent; three patients were insulin independent for 4, 5, and 15 months, respectively, but subsequently developed nonketosis-prone diabetes (tested by insulin withdrawal) and require 15 to 30 U of insulin daily; three patients had immediate insulin requirements and currently need 20 to 30 U of insulin per day but are nonketosis prone; and two patients are ketosis prone and require 30 to 60 U of insulin daily. Our analysis suggests that 5-year survival of patients undergoing operation for chronic pancreatitis is similar after treatment by duct drainage, subtotal pancreatectomy, or near-total pancreatectomy, regardless of duct morphology. Five years after duct drainage or subtotal pancreatic resection, a high incidence of diabetes (59% and 48%) and/or continued pain (20%) and (35%) can be expected.(ABSTRACT TRUNCATED AT 400 WORDS)

The postoperative course and quantitative aspects of rat islet and segmental pancreas isografts.

Duct-ligated segmental pancreas transplants with systemic venous drainage were compared to intrahepatic islet grafts for beta-cell mass (proportional to tissue insulin content) and function in diabetic Lewis rats. Rats were serially killed to measure insulin in the segmental pancreas grafts and in the liver of the islet recipients. Segmental pancreas weight was maximum and insulin concentration and content lowest (P less than 0.05) on Day 3 when acute inflammation was present. At 21 days, there was no inflammation, and graft weight had decreased, but not to Day 0 level because of normal growth; insulin concentration was similar on Days 21 and 0. At 3 months, moderate fibrosis of the graft was present, but both total insulin and insulin concentration had increased (P less than 0.05). In the recipients of islet grafts, total insulin in the liver on Day 1 was only 43% of that contained in the original islet preparation, but by 3 months the insulin content in the liver had increased to that transplanted. IVGTT K values were similar in normal rats (-3.5 +/- 0.7%) and in recipients of segmental pancreas (-4.5 +/- 1.6%) and islet (-4.0 +/- 1.5%) grafts at 3 months post transplant. Acute segmental graft pancreatitis resolved, followed by an increase in beta-cell mass. Islet cell damage during transplantation is either reversible or residual viable islets proliferate, and provide metabolic control equivalent to segmental pancreas transplants, even though the final beta-cell mass is less.

Rejection of established mouse pancreatic islet allografts by active immunization requires class I (H-2 K, D) antigen disparities.

In certain donor-recipient mouse strain combinations with class I (H-2 K, D, and K + D) or with classes I and II (H-2 D + I) disparities the incidence of islet allograft rejection is low. Furthermore pancreatic islet allografts transplanted between strains with class II (H-2 Ia) differences alone are rarely acutely rejected. In this experiment the ability of donor strain or third-party allogeneic splenocytes (active immunization) to induce rejection of established (greater than 100 days) islet allografts when the donor and recipient differed only for class I or class II antigens was tested. Class I disparate islet allografts are rejected if challenged with donor or third-party allogeneic splenocytes. The frequency of rejection is similar (80-89%) if the third-party splenocytes share the class I allele with the islet donor strain. In contrast, class II disparate islet allografts are not rejected after challenge with donor splenocytes or third-party splenocytes even when the third-party strain shares the class II disparity with the islet donor strain as well as class I antigens common to the donor and recipient. Furthermore, rejection of class II disparate islets did not occur following passive transfer of recipient strain splenocytes sensitized in vitro to donor strain lymphocytes. These results show that rejection of established islet allografts can only be induced if (1) the islet graft expresses H-2 K or H-2 D gene products that are different than the recipient strain, i.e., only class I antigens can serve as targets; and (2) challenging splenocytes also have class I disparities with the recipient.

Renal allograft survival in patients with positive B cell crossmatch to their donor.

B cell crossmatches were performed at cold (4 C) and warm (22 C and 37 C) temperatures on 193 renal allograft recipients with negative T cell crossmatches to their donor; 152 of the patients were also tested for autoantibody to autologous B cells. Fifty-six (29%) had a positive B cell crossmatch (21 cold, 35 warm); 14 were autoantibody positive, 23 autoantibody negative, and 19 were not tested for autoantibody. There were no differences in HLA-A, B, C, or DR antigen disparity between the B cell positive (14, 0 DR mismatch; 25, 1 DR mismatch; 9, 0 DR mismatch) and the B cell negative group (40, 0 DR mismatch; 57, 1 DR mismatch; 13, 2 DR mismatch). Similarly, age, diabetic status, and number and type of pretransplant blood transfusions were comparable between B cell positive and negative groups. Although there were no hyperacute rejections, 2-year actuarial graft survival was significantly lower in the B cell positive group, regardless of donor source, graft number, or temperature of reaction. Patients with a positive B cell crossmatch, presumably due to demonstrable autoantibody, may have better graft survival rates than patients with a positive B cell crossmatch and no autoantibody.

The effect of mismatching for HLA-DR in recipients of renal allografts sharing one HLA-ABC haplotype with related donors.

The effects of mismatching for DR antigens on renal allograft survival rates have largely been restricted to analyses of cadaver transplant results. Analyses of HLA matching in recipients of transplants from related donors have focused on the number of haplotypes shared between the recipients without regard to DR, or on the total number of HLA antigens mismatched, or on the degree of MLC responsiveness of the recipient to the donor. Most related donor-recipient pairs sharing only one HLA haplotype will be mismatched for DR at the other haplotype, but because there are a limited number of DR alleles, sharing of DR antigens on the mismatched haplotypes occurs relatively frequently. To determine the influence of mismatching for DR on the fate of renal allografts from related donors, we analyzed the results of 172 kidney transplants from related donors who shared one HLA-ABC haplotype with the recipient. There were 156 primary grafts and 16 retransplants; 147 donor-recipient pairs were satisfactory typed for DR antigens. Because genotyping was not usually done, we performed two analyses under two different assumptions. The first assumption was that individuals expressing less than or equal to 1 DR antigen had null antigens, or were homozygous for DR; the alternative assumption was that blanks were true antigens and individuals with blanks were heterozygous. The first assumption is more likely to be correct, and is the assumption used in most analyses of the effect of DR antigen mismatches on the results of cadaveric transplantation. Under the first assumption, of the 147 related donor-recipient pairs in whom DR typing was satisfactory, 33% were mismatched for 0, 64% for 1, and 3% for 2 DR antigens. The one-year absolute graft survival rates in recipients of kidneys from donors with 0 mismatches for DR was 92% (n = 49); in those with one mismatch for DR it was 82% (n = 94); and from those with two mismatches it was 50% (n = 4). The one-year graft survival rate in 25 donor-recipient pairs in which one or both members could not be satisfactorily DR typed was 76%. Differences in graft survival rates between the 0 and 1 and the 1 and 2 DR-mismatched groups were not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)

Lack of donor-specific tolerance in mice with established anti-Ia-treated islet allografts.

Pancreatic islet allografts pretreated in vitro with monoclonal Ia antibody and transplanted beneath the renal capsule result in normoglycemia beyond 100 days in streptozotocin-induced diabetic recipient mice that differ only at H-2 K, H-2 K + I, or H-2 K + I + D from the donors. Mice with established islet allografts are not tolerant of donor-specific skin or islet antigens, but rather reject donor skin grafts in an accelerated fashion. Established anti-Ia antibody pretreated islet allografts continue to express target antigens and remain susceptible to rejection after challenge with donor skin grafts.

Primary gallbladder carcinoma: significance of subserosal lesions and results of aggressive surgical treatment and adjuvant chemotherapy.

Advances in methods to diagnose biliary disease have not improved the dismal survival rates reported for primary gallbladder cancer. We analyzed the results of operation in 112 patients with gallbladder cancer. Tumors limited to the gallbladder wall and those that required aggressive surgical therapy and adjuvant chemotherapy for advanced disease were analyzed separately according to the following staging system: tumors that were localized to the mucosa (stage, I, n = 4); tumors that penetrated the muscularis (stage II, n = 4); subserosal tumors (stage III, n = 3); tumors with cystic node involvement (stage IV, n = 13); and tumors that had spread to adjacent organs (stage V, n = 88). Of the 11 patients (10%) with tumor limited to the gallbladder wall (stages I to III), one of five patients (20%) treated with cholecystectomy alone and four of six patients (60%) treated with cholecystectomy and lymphadenectomy (with hepatic wedge resection in three and pancreaticoduodenectomy in one) were alive and tumor free 3 to 6 years after operation. Three patients treated with cholecystectomy alone died of recurrent cancer at 18, 48, and 60 months after operation. Of the 13 patients with cystic node involvement (stage IV), nine were treated by cholecystectomy alone, three with lymphadenectomy, and one with pancreaticoduodenectomy; the cumulative survival rate was only 37% at 6 months, and all patients were dead within 18 months. Of 14 patients with advanced disease (stage V) treated with aggressive surgical therapy, including lymphadenectomy in six patients, hepatic wedge resection in six patients, and right hepatic lobectomy in two patients, the mean survival rate was only 3 months.

Predictive value of thallium stress testing for coronary and cardiovascular events in uremic diabetic patients before renal transplantation.

Coronary artery disease and the ability of noninvasive exercise perfusion imaging with thallium-201 to predict future coronary and cardiovascular events was prospectively evaluated in a group of 85 insulin-dependent diabetic renal transplantation candidates. Sixty patients received renal allografts (36 living related donors, 24 cadaver donors) after a thallium stress test; the actuarial 2 year patient survival rate after transplantation was 84 percent. Twenty-five patients remained on dialysis, and the 2 year actuarial survival rate from onset of dialysis was 41 percent, significantly lower than the actuarial survival rate of transplanted patients (p less than 0.01). Thirteen transplanted patients had positive thallium stress test results, and 6 (46 percent) had cardiovascular events (two fatal). In contrast, of 47 transplant patients with negative thallium stress test results, only 13 (28 percent) had cardiovascular events (four fatal). Five patients treated by hemodialysis only had positive test results and three (60 percent) had cardiovascular events (two fatal), whereas of 20 hemodialysis patients with negative test results, 9 (45 percent) suffered cardiovascular events (four fatal). In this study, cardiovascular events included arrhythmia, stroke, and pulmonary embolism. Within the total group, 4 of 18 patients (22 percent) with a positive test result (22 percent) had a fatal myocardial infarction, whereas only 3 of 67 patients (4 percent) with a negative result had a fatal myocardial infarction (p less than 0.05). In comparison, 24 of 85 patients had a history or electrocardiographic evidence of preexisting cardiovascular disease, and 13 (54 percent) had subsequent cardiovascular events (5 of 11 patients with positive test results and 8 of 13 patients with negative results). In summary, renal transplant candidates with positive thallium stress test results appear to be at increased risk compared with those with negative results for the development of fatal myocardial infarction, but thallium stress testing is no more predictive for future coronary and cardiovascular events than is a history or an abnormal electrocardiogram.

Differences in susceptibility to rejection of mouse pancreatic islet allografts disparate for class I or class II major histocompatibility antigens.

Pancreatic islet B cells express class I but not class II antigens, and removal of Ia positive passenger cells from H-2 allogeneic islets by anti-Ia serum and complement leads to permanent allograft survival. A test was made of whether the same result can be achieved by genetically removing the Ia stimulus by performing mouse islet allografts in congenic donor-recipient combinations differing at the H-2 K only, D only, or K + D regions. Mice disparate for class I antigens (H-2 K, D, and K + D) alone reject islet allografts, suggesting that Ia positive passenger cells may be involved in presentation of class I disparities. Established islet allografts appear to be sensitive to rejection induced by injection of donor strain splenocytes when donor and recipient differ for class I (H-2 D alone and D + I) but not class II (H-2 I alone) antigens. These results are consistent with the hypothesis that pancreatic islet allografts do not express class II target antigens, but do express class I antigens that in long-established pancreatic islet allografts are capable of acting as targets but not in initiating an immune response.