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Biomedical subjects

J C Pezzullo

Publications and source records attributed to J C Pezzullo.

At least 19 recordsLinked to original sources

Intrauterine growth restriction in infants of less than thirty-two weeks' gestation: associated placental pathologic features.

OBJECTIVE: Our purpose was to describe placental lesions associated with normal and abnormal fetal growth in infants delivered for obstetric indications at < 32 weeks' gestation. STUDY DESIGN: Maternal and neonatal charts and placental tissues from 420 consecutive nonanomalous live-born singleton infants delivered at < 32 weeks' gestation with accurate gestational dates were retrospectively studied. Excluded were cases with maternal diabetes, chronic hypertension, hydrops fetalis, diagnosed congenital viral infection, and placenta previa, leaving four primary indications for delivery: preeclampsia, preterm labor, premature rupture of membranes, and nonhypertensive abruptio placentae. The presence and severity of placental lesions was scored by a pathologist blinded to clinical data. Birth weight and length percentiles were calculated from published nomograms. Asymmetric intrauterine growth retardation (n = 32) was defined as birth weight < 10th percentile with length > 10th percentile and symmetric intrauterine growth retardation (n = 48) as both weight and length < 10th percentile for gestational age. A "growth restriction index" was developed to express a continuum of growth in both length and weight. Contingency tables, analyses of variance, and multiple regression analysis defined significance as p < 0.05 (with corrections for multiple comparisons). RESULTS: A greater proportion of cases with intrauterine growth retardation had lesions of uteroplacental insufficiency (p < 0.001) or chronic villitis (p < 0.02) than did appropriately grown preterm infants. Cases with asymmetric intrauterine growth retardation tended to have more lesions than did cases with appropriate-for-gestational-age infants. Four multiple regression analyses used the growth restriction index as outcome and the histologic lesion that had significant relationships to fetal growth as independent predictors in univariate analyses. Overall, uteroplacental fibrinoid necrosis, circulating nucleated erythrocytes, avascular terminal villi, and villous infarct were significant independent predictors of fetal growth (adjusted R2 = 0.312). With addition of preeclampsia as a variable, villous fibrosis, avascular villi, infarct, and preeclampsia were independent predictors of fetal growth (adjusted R2 = 0.341). In the 65 preeclampsia cases no histologic lesion was an independent predictor of fetal growth, whereas in the nonpreeclampsia cases, villous fibrosis and avascular villi were independent predictors of fetal growth (adjusted R2 = 0.075). CONCLUSIONS: In nonanomalous preterm infants intrauterine growth retardation is most commonly symmetric and is primarily related to the cumulative number and severity of lesions reflecting abnormal uteroplacental or fetoplacental blood flow. The growth restriction index may contribute to the study of the biologic range of fetal growth. The statistical relationship of most placental lesions to intrauterine growth retardation depends on the presence or absence of preeclampsia.

Analysis of Variance

Relationship between placental histologic features and umbilical cord blood gases in preterm gestations.

OBJECTIVE: Our purpose was to test the hypothesis that placental histologic lesions reflect abnormal placental respiratory function in preterm gestations. STUDY DESIGN: A retrospective study of preterm deliveries from 22 to 32 weeks revealed 431 patients with umbilical venous or arterial blood gas values. Excluded were stillbirth, multiple gestations, placenta previa, maternal medical diseases, and fetal anomalies. Charts were reviewed for principal indication of delivery, diagnosis of labor, and mode of delivery. Blood gases were studied within 10 minutes of delivery on a model 178 automatic pH analyzer (Corning Med, Boston). Placental data included uteroplacental vascular lesions and related villous lesions, lesions of acute inflammation, chronic inflammation, and coagulation. Contingency tables and analysis of variance considered p < 0.05 as significant. RESULTS: Mean +/- SD umbilical vein pH was 7.36 +/- 0.07 (range 6.94 to 7.56) and umbilical artery pH was 7.30 +/- 0.08 (range 6.83 to 7.55). Increasing severity of uteroplacental thrombosis, villous lesions reflective of uteroplacental vascular pathologic mechanisms, avascular villi, histologic evidence of abruptio placentae, chronic villitis, and increased circulating erythrocytes were associated with decrease in umbilical vein and artery pH, increase in umbilical vein and artery PCO2, and decrease in umbilical vein and artery PO2. Histologic evidence of acute infection and villous edema were associated with a higher pH and PO2 and a lower PCO2 in both umbilical vein and artery. Umbilical vein or artery base excess was not related to placental lesions. Labor was not related to blood gas values in this data set, although a subset of cases of extremely preterm premature rupture of membranes and preterm labor who labored and were delivered by cesarean section had significantly poorer umbilical venous and fetal arterial blood gas values (all p < 0.005). Lesions related to poorer blood gas values were significantly more frequent in preterm preeclampsia and nonhypertensive abruptio placentae than in premature rupture of membranes or preterm labor. CONCLUSIONS: Changes in umbilical vein and artery pH, PO2, and PCO2 are significantly related to lesions of uteroplacental vascular pathologic mechanisms and intraplacental thrombosis. Placental lesions may be associated with chronic fetal distress by altering fetal oxygen availability and acid-base status. Placental immaturity resulting from prematurity may be associated with inefficient placental respiratory function and an increased likelihood of cesarean delivery in cases of premature rupture of membranes or preterm labor. Altered fetal acid-base balance plus excess numbers of circulating nucleated erythrocytes suggests that placental respiratory function is functionally abnormal when these lesions are present and leads to fetal tissue hypoxia.

Acidosis

Placental pathologic features of preterm preeclampsia.

OBJECTIVE: Our purpose was to compare the incidence and interrelationships of uteroplacental vasculopathy and chronic inflammatory and placental vasoocclusive lesions in preeclampsia and spontaneous delivery before 32 weeks' gestation. STUDY DESIGN: Review of singleton live-born nonanomalous infants born at 22 to 32 weeks' gestation identified 76 cases of preeclampsia and 353 cases of spontaneous prematurity (spontaneous premature membrane rupture [n = 192], preterm labor, intact membranes [n = 161]). Histologic lesions were considered as belonging to one of five major pathophysiologic groups: (1) uteroplacental vascular lesions and related villous lesions, (2) chronic inflammatory lesions, (3) coagulation-related lesions, (4) acute inflammatory lesions, and (5) unclassified lesions. Contingency table analyses considered p < 0.05 significant. Factor analysis extracted combinations of related variables. RESULTS: More frequent in preeclampsia versus spontaneous prematurity were chronic uteroplacental vasculitis (29% vs 20%, p < 0.05), chronic villitis (20% vs 3%, p < 0.001), avascular villi (39% vs 16%, p < 0.001), and "hemorrhagic endovasculitis" (9% vs 2.5%, p < 0.03). In the preeclampsia cases factor analysis extracted 13 categories of related lesions. Four categories contained uteroplacental vascular lesions. Five categories included lesions related to chronic inflammation, and eight included lesions related to coagulation. Four categories loaded lesions from one major pathophysiologic group only. Three categories loaded lesions from all three pathophysiologic groups. Unclassified lesions loaded into two factor categories that were unrelated to the other lesions. CONCLUSIONS: Chronic inflammatory and placental vasoocclusive lesions are more common in preterm preeclampsia than in spontaneous prematurity. Immunopathologic processes and coagulation may be involved in the pathophysiologic mechanisms of preterm preeclampsia independent of uteroplacental vascular pathologic features.

Acute Disease

A longitudinal study of atlanto-dens relationships in asymptomatic individuals with Down syndrome.

This study was designed to investigate the natural history of atlantoaxial instability in individuals with Down syndrome and to determine whether significant changes in C1-C2 relationship are taking place over time. Although more than 400 patients with Down syndrome who are presently followed at the Child Development Center had cervical spine radiographic examinations in the past, only 141 patients who had serial radiological examinations and whose radiographs were available for reevaluation participated in this study. The results of our investigations revealed that there were only minor changes (1 to 1.5 mm) of atlanto-dens interval measurements over time in 130 (92%) patients with Down syndrome. Eleven patients (8%) had changes of atlanto-dens interval measurements between 2 and 4 mm over time; however, none of these patients had any clinical symptoms. The analyses of data obtained from several subgroups (males and females, various age groups, and patients with and without atlantoaxial instability) did not show any significant changes of atlanto-dens interval measurements of successively obtained radiographs. Our recommendations for and rationale of routine screening for atlantoaxial instability and follow-up examinations are discussed in detail.

Adolescent

Thyroid function in Down syndrome.

The thyroid function of 181 patients with Down syndrome was investigated. When compared with a control group of 163 children we found T4 and FT4 levels to be significantly lower and T3 and TSH levels to be significantly higher in the Down syndrome population. Of the 181 patients with Down syndrome, 29 (16%) showed evidence of either uncompensated or compensated hypothyroidism: 11 (6%) had both low T4 and high TSH levels, 14 (8%) had only high TSH values, and 4 (2%) had only low T4 values. One of the patients with Down syndrome had a significantly elevated T4 level. Studying different age groups, we observed a decline of the mean T4, FT4, T3, FT3, and TBG values with advancing age. T4, T3, and TSH blood levels obtained in 1988 were slightly but not significantly lower when compared with values from 1985. Because thyroid dysfunctions in patients with Down syndrome are more common than in the general population, periodic thyroid hormone function tests should be performed in persons with Down syndrome in particular as they advance in age. Thus, individuals with significantly abnormal results can be identified early before clinical symptoms become manifest. If patients with Down syndrome are found to have a thyroid hormone disorder, appropriate treatment should be forthcoming, which in turn will enhance their quality of life.

Adolescent

Behavioural observations in children with Down's syndrome.

The behavioural characteristics of 40 children with Down's syndrome were studied using the Achenbach Child Behavior Checklist which was completed by both the children's parents and teachers. Statistically significant differences were observed between study and control groups on externalizing and total scores on responses obtained from both parents and teachers, but not on internalizing scores. Further analysis of the data on a subgroup of 28 children between the ages of 6 and 11 years revealed a 'hyperactive' profile pattern for both boys (n = 16) and girls (n = 12). This was primarily due to heavily weighted positive responses to such statements as 'acts too young', 'can't concentrate', 'impulsive', and 'speech problems'. About one half of the boys sometimes exhibited hyperactive behaviours. In addition, scores of children with Down's syndrome were significantly different from control children on the following items: 'trouble sleeping', 'demands a lot of attention', 'clings to adults', 'stubborn', 'prefers playing with younger children', and 'is disobedient at school and home'. In general, however, item analysis revealed that most behaviours of children with Down's syndrome as recorded on the Achenbach Child Behavior Checklist compare well with those of children in the control group.

Adolescent

Gastric adenocarcinoma: prognostic significance of several pathologic parameters and histologic classifications.

Considerable controversy exists about the value of histologic classifications of gastric adenocarcinoma in the prediction of patient survival. Histologic sections of 75 consecutive gastrectomies were used to compare Lauren and Ming classifications with emphasis on clinical stage, size, location of tumor, desmoplasia, inflammatory reaction, and 5-year survival. Both classifications generally correlated and, when combined, proved helpful in defining certain cases. At surgery, about one third of the total cases of intestinal (INT, Lauren) and expanding (ET, Ming) were in early stages, whereas almost all the diffuse (DT, Lauren) and infiltrative (INF, Ming) types were in late stages. When the Lauren classification was applied to preoperative endoscopic biopsies, a 72% diagnostic correlation with the surgical specimens was found. Followup revealed no survivors of the DT and INF and 12 and 11 survivors of INT and ET, respectively, regardless of stage. Inflammatory response was associated with good prognosis. Desmoplasia and size had no prognostic significance. Tumors of the cardia had worse prognoses than those in the body or antrum. Both Lauren and Ming classifications, and especially the degree of inflammation, were significant in predicting survival. Lauren INT and Ming ET should be declared only when they are the sole or predominant features.

Adenocarcinoma

Vitamin A gastrointestinal absorption in persons with Down's syndrome.

The total daily vitamin A intake, physical signs associated with vitamin A deficiency, and the response to a vitamin A challenge were studied in 33 patients with Down's syndrome and in 14 intellectually normal persons (comparison group). The evaluation of detailed dietary histories revealed that the study subjects' mean daily vitamin A intake was similar to the recommended daily allowance for adults and that there was no significant difference of the mean daily vitamin A intake between study and comparison groups (5029 IU and 5706 IU, respectively). Subjects with Down's syndrome had more symptoms usually seen in patients with hypovitaminosis A than the persons in the comparison group. The baseline serum vitamin A levels in the Down's syndrome and comparison groups were within the normal range (106.0 micrograms/dl and 136.5 micrograms/dl, respectively). The vitamin A absorption curve of persons with Down's syndrome paralleled that of normal individuals and no significant difference of vitamin A levels between study and comparison groups was observed except for the 6-h values. Also, the absorption differential (delta = 3-h value + 6-h value/2-O-h value) did not show a significant difference between the two groups. Thus, these investigations do not support previous reports of significantly decreased vitamin A absorption in individuals with Down's syndrome.

Adolescent

Physicians' attitudes toward using deception to resolve difficult ethical problems.

To assess physicians' attitudes toward the use of deception in medicine, we sent a questionnaire to 407 practicing physicians. The questionnaire asked for responses to difficult ethical problems potentially resolvable by deception and asked general questions about attitudes and practices. Two hundred eleven (52%) of the physicians responded. The majority indicated a willingness to misrepresent a screening test as a diagnostic test to secure an insurance payment and to allow the wife of a patient with gonorrhea to be misled about her husband's diagnosis if that were believed necessary to ensure her treatment and preserve a marriage. One third indicated they would offer incomplete or misleading information to a patient's family if a mistake led to a patient's death. Very few physicians would deceive a mother to avoid revealing an adolescent daughter's pregnancy. When forced to make difficult ethical choices, most physicians indicated some willingness to engage in forms of deception. They appear to justify their decisions in terms of the consequences and to place a higher value on their patients' welfare and keeping patients' confidences than truth telling for its own sake.

Adult

Clearance kinetics and fate of macromolecular IgA in patients with IgA nephropathy.

IgA glomerulonephritis is associated with macromolecules of polymeric IgA in the circulation and mesangial deposits. An impairment in the reticulophagocytic function of patients with IgA nephropathy has been postulated as the potential cause for persistence of IgA immune complexes in the circulation and their eventual glomerular deposition. Since the fate and removal mechanisms of circulating macromolecular IgA are unknown in humans, we examined the blood clearance and organ uptake of purified IgA polymers and macromolecules in patients with IgA nephropathy and normal controls. The IgA macromolecules were prepared by covalent cross-linking of purified human polymeric IgA with a heterobifunctional reagent, N-succinimidyl 3-(2-pyridyldithio) propionate. After intravenous injection, large IgA molecules were removed rapidly from the circulation of patients (t1/2 = 3.8 +/- 1.0 minutes) and controls (t1/2 = 4.9 +/- 1.5 minutes). Dynamic gamma camera scintigraphy revealed the liver as the major organ that mediated the removal of the macromolecular IgA with no significant difference in the rate of hepatic uptake for patients (t1/2 = 3.4 +/- 0.6 minutes) and controls (t1/2 = 3.3 +/- 0.9 minutes). No significant amount of radioactivity could be detected in the lungs, kidneys, and spleen. The small polymers had a slower and similar clearance rates for patients (t1/2 = 29.3 +/- 7.9 h) and controls (t1/2 = 29.0 +/- 8.6 h). These findings have general significance in showing the liver as a major organ for removal of macromolecular IgA. In addition, the results have specific importance in showing that patients with IgA nephropathy do not suffer from an IgA removal dysfunction.

Adolescent

Clinical and laboratory features of patients with chronic renal disease at the start of dialysis.

We examined clinical and laboratory features retrospectively in 402 patients at the start of chronic hemodialysis in order to define better the "uremic syndrome" in the dialysis era. The information gathered included demographic data, renal diagnoses, uremic symptoms, biochemical values, and prevalences of hypertension (69%), diabetes mellitus (23%) and ischemic heart disease (16%). Unexpected findings were the wide ranges of serum creatinine levels (3.5 to 35 mg/dl) and blood urea nitrogen levels (35 to 345 mg/dl), and the frequency of hyponatremia (27%), hypoalbuminemia (52%), and anion gaps above 25 mg/dl (5%). There were higher hematocrits in males and diabetics, lower serum creatinine levels in females, diabetics and older patients, and lower blood urea nitrogen levels in blacks. The time interval from diagnosis of diabetes mellitus to initiation of dialysis in patients with diabetic nephropathy due to juvenile-onset diabetes mellitus (20.6 +/- 6.8 years) was twice that in adult onset diabetes mellitus (10.3 +/- 8.3 years).

Acid-Base Equilibrium

Increased body aluminum. An independent risk factor in patients undergoing long-term hemodialysis?

The clinical course and aluminum status of 38 patients who had been receiving dialysis for at least eight years and were still undergoing dialysis in 1985 were evaluated. Twenty-nine had evidence of increased aluminum burden, although only three had evidence of overt aluminum toxicity, and nine did not have evidence of increased aluminum burden. The patients in both the high- and low-aluminum group were similar with regard to age, the cause of their renal failure, presence of hypertension or coronary artery disease, previous parathyroidectomy, and a number of biochemical parameters, along with the amount of prescribed aluminum. All patients were followed up for the next two years or until they died. The amount of ingested aluminum was reduced, and in selected patients, treatment with intermittent infusions of deferoxamine mesylate was instituted. There were no deaths in the low-aluminum group, but ten of 29 died in the high-aluminum group: seven of vascular disease and three of infection. In addition, morbidity as defined by hospitalization for coronary or cerebral vascular disease or infection occurred in only two of the nine patients in the low-aluminum group and in 19 of the 29 patients in the high-aluminum group. These observations imply that the occurrence of increased body aluminum, as suggested by aluminum blood levels or by results of bone biopsies in some patients, has an adverse effect on morbidity and mortality and should be considered as a possible independent risk factor in patients who are receiving long-term hemodialysis.

Adult

Radiation dose from radiopharmaceuticals contaminated with molybdenum-99.

Sixteen patients undergoing routine nuclear imaging procedures were injected with 99mTc-labeled radiopharmaceuticals containing 99Mo which exceeded the recommended limit of 1 microCi of 99mMo per mCi of 99mTc. The kinetics of the resulting 99Mo distribution in 14 of these patients were studied over a period of several weeks. The mean biologic half-life [T 1/2b] ranged from about 19.3 days to 11.2 days depending on the model used. Similarly, the mean radiation dose to the liver ranged from approximately 0.02 rad/microCi of 99Mo to 0.05 microCi of 99Mo.

Humans

Circulating heavy IgM in IgM nephropathy.

IgM nephropathy (IgMN) causes nephrotic syndrome and is characterized by IgM mesangial deposits. It is speculated that these deposits are derived from circulating IgM aggregates or immune complexes, either of which would have a molecular weight heavier than that of normal IgM. To test this hypothesis the sera of 11 patients with IgMN, five patients with nephrotic syndrome of other etiologies, and 13 normal controls were analysed for such heavy IgM. The serum samples were passed over a Biogel A5M molecular sieve column and the fractions were tested for IgM concentration by enzyme linked immunosorbent assay (ELISA). The column effluent from the void volume to the IgM peak was divided into four equal regions, and the average IgM concentrations in each region were compared. The IgMN group had significantly higher IgM concentrations than normal controls in the heaviest region (0.81 +/- 0.84 vs. 0.32 +/- 0.17 micrograms/ml; P = 0.01) and in the lightest region (95.8 +/- 59.5 vs. 46.3 +/- 41.2 micrograms/ml; P = 0.02). Although the IgMN group appeared to have about double the IgM levels of the nephrotic control group in all four regions, this was only significant in the lightest (19S) region. In serum samples from two IgMN patient methods known to break antigen antibody bonds eliminated the heavy IgM; in one case we used gel filtration in potassium thiocyanate and in another ultracentrifugation at pH 2.8. In addition, the heavy IgM in this second patient exhibited complement fixation activity in a sandwich ELISA for IgM-C3 complexes. We conclude that IgMN patients have circulating heavy IgM, which by preliminary studies probably consists of complement fixing IgM immune complexes.

Adolescent

Inflammation and/or necrosis of tumors cannot account for fever in most febrile patients with Hodgkin's disease.

Inflammation and/or necrosis (I/N) of the tumor are generally believed to be a cause of fever in patients with Hodgkin's disease. However, there have been few studies in the literature which can corroborate this common belief. Inflammation and/or necrosis were studied in biopsy specimens of 140 untreated patients with Hodgkin's disease (57 febrile and 83 afebrile). In 37 of the 140 tumors I/N were readily observed; 18 were from febrile patients, and 19 from afebrile. Thus, it is evident that I/N cannot account for fever in the majority of febrile patients, necessitating an alternative explanation. Among the patients with I/N of their tumor, fever occurred most often in male patients and in virtually all patients who had histologic types other than nodular sclerosis. However, it was peculiarly absent in the great majority of patients whose tumors were of the nodular sclerosis type. This paradoxic inverse correlation of fever with I/N of tumors in patients with the nodular sclerosing histologic type has not been described previously.

Biopsy

Cognitive and learning processes in children with Down syndrome.

The primary purpose of this investigation was to study cognitive and learning processes in children with Down syndrome using a recently developed instrument, the Kaufman Assessment Battery for Children (K-ABC). The results obtained from 20 children with Down syndrome were compared with those of 20 younger brothers and sisters of children in the experimental group and 20 mental age-matched nonretarded children. As predicted both the siblings (corrected for mental age) and the nonretarded children performed significantly better on both the Sequential and the Simultaneous Processing Scales of the K-ABC. However, there was no significant difference when the results of the Sequential Processing Scale were contrasted with those of the Simultaneous Processing Scale in all three groups. When subtests that use auditory-vocal (Number Recall) and auditory-motor (Word Order) channels of communication were compared with subtests that employ visual-vocal (Gestalt Closure) and visual-motor (Hand Movement) channels of communication, children with Down syndrome performed significantly better on the latter two tests than on the former two tests. The implications of these results as they relate to designing appropriate educational strategies for children with Down syndrome are discussed.

Analysis of Variance

Atlantoaxial instability in Down syndrome: roentgenographic, neurologic, and somatosensory evoked potential studies.

To identify patients with Down syndrome and asymptomatic atlantoaxial instability who are at increased risk for developing neurologic symptoms, we studied 27 patients with this skeletal disorder and compared them with an age- and sex-matched group of 27 patients with Down syndrome without atlantoaxial instability. A third group of six patients had symptomatic atlantoaxial instability. The mean atlanto-dens intervals and the mean spinal canal widths among the three groups were significantly different. There were no significant differences in mean composite neurologic scores and somatosensory evoked responses between patients in the asymptomatic group and those in the control group. However, when a subsample of patients with high and low latencies (greater than 1 SD below and above the mean) was formed and comparisons were made with roentgenographic findings, there was a high correspondence between somatosensory evoked potential latencies and atlanto-dens interval measurements. We conclude that no single assessment technique, but a combined approach using roentgenographic, CT scan, neurologic, and neurophysiologic investigations, will provide information of the risk status of patients with Down syndrome and atlantoaxial instability.

Adolescent