Central serous retinopathy and severe preeclampsia.
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Journal Article↗
Biomedical subjects
D Sherman
Publications and source records attributed to D Sherman.
Proposed use of two-part interactive modeling as a means to increase functional skills in children with a variety of disabilities.
PURPOSE: Many behavior modification and intervention programs are based on operant procedures developed for animal subjects, but few use modeling procedures in which one student observes interactions between two proficient trainers. We show how such procedures, which successfully trained Grey parrots (Psittacus erithacus) to produce and comprehend elements of human language, can be adapted for use with children with three types of disabilities: (a) autism with limited social and language skills, (b) developmental delay with physical handicaps and lack of language skills, and (c) hyperactivity with impaired cognitive and social skills. SUMMARY: Children were evaluated before entering the program and outcomes were recorded to determine improvement levels. No child reached totally normative (physical age-appropriate) levels, but all significantly improved their social and communication skills and use of contextually appropriate behavior. CONCLUSIONS: A two-trainer modeling system can be a valuable intervention tool for children whose disabilities involve social and communicative skills.
Animals↗
Serum inhibin A levels in pregnant women with systemic lupus erythematosus or antiphospholipid syndrome.
Maternal serum inhibin A levels are increased on average in pregnancies affected by Down syndrome (DS). However, some reports have found increased serum levels in women with pre-eclamptic toxaemia as well. In the current study, maternal serum inhibin A was retrospectively measured in a series of 32 serum samples from pregnant women previously diagnosed as having either systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). For comparison, normal medians were calculated from 57 unaffected control pregnancies together with a total of 854 samples tested at 13-19 weeks of gestation as part of the routine antenatal DS screening. All results were expressed in multiples of the gestation specific normal medians (MoM). A cubic regression formula was fitted, weighting for the number of women tested at each gestation. The median MoM value in the 16 cases of SLE and the 16 cases of primary APS is 0.60 (95% confidence interval 0.40-0.91) and 0.88 (95% confidence interval 0.66-1.17), respectively. For primary APS this was not statistically significant, whereas the SLE patients had a highly statistically significant reduction of serum inhibin A (p<0.002, Wilcoxon Rank sum Test, 2 tailed). Six pregnancies in the SLE group had a complicated obstetric outcome, i.e. missed abortion, placental abruption, exacerbation of the underlying disease which necessitated delivery, and severe postpartum haemorrhage. In 85% of this subgroup, serum inhibin A levels were below the normal 10th centile. The current data suggest that serum inhibin A is decreased on average in SLE patients. Those preliminary results might have various obstetric implications such as antenatal DS screening of SLE patients, identification of pregnant women at risk of developing SLE, who have presented for routine DS screening and for monitoring SLE patients throughout their pregnancy.
Antiphospholipid Syndrome↗
Validation of a new technique to detect malingering of cognitive symptoms: the b Test.
We administered the b Test, a new measure to identify malingering requiring recognition of overlearned information, to 34 suspected malingerers and to 161 subjects in various clinical groups (moderate to severe head injury, elderly depressed, learning disability, schizophrenia, right and left CVA, and elderly normals). Comparisons of groups revealed more commission and omission errors in the suspected malingerers relative to all groups except the right stroke patients. In addition, suspected malingerers took longer to complete the task than all groups except right and left stroke patients and normal elderly. A cutoff of >2 commission errors produced a sensitivity of 76.5% and specificity for all comparison groups combined of 82.6%. Lower sensitivity rates were documented for omissions (58.8 using cutoff of >40) and time (57.6% using cutoff of >12 minutes), but specificity remained high at 85.1% and 83.9%, respectively. Thus, the b Test shows considerable potential as a malingering detection tool.
Journal Article↗
No evidence for association of multiple sclerosis with the complement factors C6 and C7.
Four genome screens in multiple sclerosis have been completed and each has identified evidence for linkage in the pericentromeric region of chromosome 5. This region encodes a number of candidate genes including those for the complement components C6, C7 and C9. We have used a multiplexed oligoligation assay (OLA) to test single nucleotide polymorphisms (SNPs) from the C6 and C7 genes for evidence of association with multiple sclerosis in our sibling pair families. There was no statistically significant difference in the allele frequencies of these polymorphisms in the index cases from our families when compared with locally derived controls. No evidence for transmission distortion was seen with any of the polymorphisms, or with the haplotype built from the three SNPs from the C7 gene. Despite offering themselves as potential candidates these complement genes appear not to confer susceptibility to multiple sclerosis.
Autoimmune Diseases↗
Accentuated apoptosis in normally developing p53 knockout mouse embryos following genotoxic stress.
In order to identify the alternative pathways which may substitute for the p53 function during embryogenesis, we have focused our studies on p53 -/- normally developing mouse embryos that survived a genotoxic stress. We assumed that under these conditions p53-independent pathways, which physiologically control genomic stability, are enhanced. We found that while p53 +/+ mouse embryos elicited, as expected, a p53-dependent apoptosis, p53-/- normally developing mice exhibited an accentuated p53-independent apoptotic response. The p53-dependent apoptosis detected in p53+/+ embryos, was an immediate reaction mostly detected in the brain, whereas the p53-independent apoptosis was a delayed reaction with a prominent pattern observed in epithelial cells of most organs in the p53-deficient mice only. These results suggest that in the absence of p53-dependent apoptosis, which is a fast response to damaged DNA, p53-independent apoptotic pathways, with slower kinetics, are turned on to secure genome stability.
Animals↗
Reduced capacity to inhibit elastase in abdominal aortic aneurysm.
BACKGROUND: Loss of elastin in the aortic wall is an early event in abdominal aortic aneurysm (AAA). An imbalance in the protease-antiprotease system is proposed to be one of the factors that promote connective tissue destruction. We hypothesize that plasma from AAA patients will have a reduced inhibitory capacity in comparison to normal controls. MATERIALS AND METHODS: Using an assay we developed, plasma (10 microliters), collected from AAA patients (n = 14) and normal controls (n = 13), was added to the elastase inhibition assay containing succinylated elastin substrate. The reaction was initiated with 13.9 units porcine pancreatic elastase (PPE). Elastase activity in the presence and absence of plasma was compared. Plasma elastase was also determined using the Merck PMN-elastase kit. RESULTS: The relative activity of exogenous elastase (%) in the presence of AAA plasma (n = 14, mean age 73.4 years +/- 1.7 SEM) was 42.59% +/- 4.3 SEM, while that in the presence of control plasma (n = 13, mean age 73.9 years +/- 2.1 SEM) was 10.23% +/- 2.1 SEM (P < 0.0001). Analysis of plasma elastase (microgram/L) indicated that there was no significant difference between normal (n = 9, 207.33 microgram/L +/- 58.67 SEM) and AAA (n = 9, 145.34 microgram/L +/- 29.54 SEM) (P = 0.359). CONCLUSION: There is a significant reduction in the plasma inhibitory capacity of elastase in AAA patients in comparison to normal controls, though plasma elastase level was not significantly different. The data presented here give experimental evidence to the protease-antiprotease imbalance in AAA patient plasma and may lead to the development of a measurable parameter to monitor AAA.
Aged↗
The relation between inter-twin birth weight discordance and total twin birth weight.
OBJECTIVE: We tested the hypothesis that the frequency of growth discordance among twins is not related to the uterine capacity for carrying twins. METHOD: We counted and compared the frequencies of birth weight discordance of more than 25% in an unlike-sexed twin cohort (n = 1244) and in a population-based twin cohort (n = 7570) across the deciles of the total twin birth weight (twin A + twin B) distribution. The birth order of the heavier twin was noted. RESULTS: Similar frequencies of discordant pairs were found in both cohorts (11% and 12%, respectively; Mantel-Haenszel chi2 test: P = .131, odds ratio (OR) 0.9, 99% confidence interval (CI) 0.67, 1.11; Woolf test for heterogeneity: two-tailed P = .472). In the discordant pairs, twin A was considerably more often the heavier twin in all birth weight deciles (unlike-sexed cohort: P < 10(-8), OR 5.9, 99% CI 3.0, 11.7; population-based cohort: P < 10(-8), OR 3.1, 99% CI 2.3, 4.0), and in both cohorts (inter-cohort difference: P = .109, OR 1.4, 99% CI 0.83, 2.32). Both cohorts showed a similar nonlinear trend: given that X = decile order, discordance decreased as a function of 22.0 - 6.54 ln[X] for the unlike-sexed twins cohort and 23.0 - 8.18 ln[X] for the population-based cohort, with r values of 0.967. CONCLUSION: The more favorable the uterine milieu for carrying twins, the smaller the likelihood of discordant twin growth. Birth order of the heavier twin appears to be an integral part of the discordance phenomenon. The similarity of the cohorts suggests that these conclusions are valid for both like and unlike-sexed twins.
Birth Weight↗
Uterine flora at cesarean and its relationship to postpartum endometritis.
OBJECTIVE: To evaluate the relationship between the presence of microorganisms at the time of cesarean at different sites of the genital tract and the development of postpartum endometritus. METHODS: One-hundred thirty-three healthy women who delivered by cesarean were enrolled in this prospective study. Cultures were obtained during the surgery and on days 3-5 postoperatively. Gram staining of uterine cavity fluid was done on days 3-5. Gram stains were examined under a high-power microscope for the presence of polymorphonuclear leukocytes. RESULTS: Twenty patients (15.0%) met the criteria for postpartum endometritis. Forty-five patients (33.8%) had one or more positive cultures (n = 133) at the time of surgery, resulting in 93 positive cultures and 123 bacterial isolates. Forty-four patients had positive postoperative uterine cavity cultures at days 3-5 postpartum, resulting in 65 isolates. Of 44 patients with a positive postoperative culture, 26 (59.1%) also had Gram stain positive for polymorphonuclear leukocytes in the uterine cavity fluid, whereas only six of 89 patients (6.7%) with negative postoperative culture had a positive Gram stain (P < .05). The relative risk of having a positive culture on postoperative day 3-5 if the culture at surgery was positive at any site was 15.6 (95% confidence interval [CI] 5.9, 42.2), and it was 19.5 (95% CI 6.8, 57.8) if the culture was positive at the lower uterine segment. CONCLUSION: The presence of bacteria in the lower uterine segment at the time of the surgery predicts their presence in the uterine cavity during puerperium. The Gram stain of uterine cavity fluid on postcesarean days 3-5 is another quick tool that can expedite the diagnosis of postpartum endometritis.
Adult↗
Omphalocele delivery enigma: the best mode of delivery still remains dubious.
OBJECTIVE: To determine an optimal route of delivery for fetuses with prenatally diagnosed omphalocele. DATA SOURCE: MEDLINE search of years 1966-1996. RESULTS: Descriptive retrospective analyses do not support the idea that cesarean delivery of fetuses with omphalocele is associated with an improved survival rate. However, most of those studies do not control for confounding variables like type and severity of associated anomalies, omphalocele size, prematurity rate, presence of trial of vaginal delivery, rate of intrapartum sac rupture, tertiary treatment centers accessibility, time and type of surgical correction, and postoperative morbidity. There is no evidence that vaginal delivery is safer than cesarean for fetuses with isolated small omphalocele. Fetuses with giant (>5 cm) omphalocele should be delivered by cesarean section. Vaginal delivery at term is offered for fetuses with coexisting life-threatening anomalies. CONCLUSIONS: We propose that until randomized trial of vaginal and cesarean delivery for fetal omphalocele is available, the preferred mode of delivery would be the vaginal route as that is safer for the mother.
Abnormalities, Multiple↗
An unusual echocardiograph after heart transplantation.
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Adult↗
Neuropsychological patterns in right versus left frontotemporal dementia.
Patients with frontotemporal dementia (FTD) often present with an asymmetric left or right-sided anterior cerebral perfusion abnormality that is associated with differential behavioral symptoms. However, whether patients with primarily right versus left FTD also have unique neuropsychological characteristics has not been previously investigated. Comparisons of 11 patients with right-sided FTD and 11 with left FTD indicated that the 2 patient groups showed relatively distinct cognitive profiles. Patients with right FTD exhibited relatively worse performance on PIQ than VIQ, and on select nonverbal executive tasks relative to their verbal analogs (e.g., design fluency < word generation; Picture Arrangement < word sequencing). In contrast, patients with left FTD showed the opposite pattern. In addition, the 2 patient groups differed on several absolute test scores; patients with right FTD demonstrated more errors and perseverative responses, and worse percent conceptual level responses, on the Wisconsin Card Sorting Test, while the left FTD patients obtained significantly worse scores on the Boston Naming Test, and Stroop word reading and color naming. Verbal and nonverbal memory, mental speed, visual perceptual-constructional skill, and IQ subtest scaled scores did not significantly differ between groups. These data indicate that FTD should not be viewed as a unitary disorder, and that neuropsychological testing holds promise for the differential diagnosis of right versus left FTD.
Dementia↗
Characteristics of normal lochia.
The objective of this paper is to determine the characteristics of each phase of lochia and how these may be influenced by a number of obstetric variables. Thirty-nine healthy women who had spontaneous vaginal delivery following uncomplicated pregnancy volunteered to complete a diary sheet immediately postpartum. The women were instructed to assess the color of their lochia by a color slide with differential gradation from dark red to white. The color was labeled as rubra (red, red-brown), serosa (brown-pink, brown), or alba (yellow, white). The overall duration of lochia was 36.0 +/- 7.5 days (range 17 to 51 days, median 37 days). Three types of lochia color patterns were identified: type 1--rubra-->serosa-->alba sequence (n = 20); type 2-rubra-->serosa-->alba sequence with prolonged rubra phase and short serosa and alba phases (n = 11); and type 3-with two rubra phases (rubra-->serosa/alba-->rubra-->serosa/alba sequence with near-equal duration of each phase) (n = 8). The rubra phase lasts 12.1 +/- 6.7 days in type 1, 24.8 +/- 5.0 days in type 2, and 5.5 +/- 2.5 days (the first rubra) in type 3 pattern (p < 0.05). There was a higher proportion of lactating women among women with type 1 pattern as compared with type 2 (11/20 and 2/11, p < 0.05, respectively). Women with type 2 pattern were of higher parity (2.8 +/- 1.3) as compared with those with type 1 (1.8 +/- 0.8) (p < 0.05). There were no significant differences in infants' birth weight between the various color types (3,276.0 +/- 379.8 g, 3,564.4 +/- 737.9 g, and 3,080.0 +/- 180.0 g for type 1, type 2, and type 3, respectively. There were no significant differences in overall duration of lochia or gestational age at delivery between the various color types. The results confirm the clinical impression that lochia persists longer than classically reported and is of diverse patterns. Three unique types of color patterns were identified. Type 1 is the most prevalent and is associated with prolonged breast feeding and thus can be considered as the classic type. Type 2 is associated with short or no breast feeding and higher parity. Type 3 may be a variant of type 2. We suggest that traditional teaching on lochia characteristics needs reappraisal.
Adult↗
Myocardial injury and left ventricular performance after subarachnoid hemorrhage.
BACKGROUND AND PURPOSE: Electrocardiographic abnormalities and elevations of the creatine kinase myocardial isoenzyme (CK-MB) occur frequently after subarachnoid hemorrhage. In some patients, a reversible and presumably neurogenic form of left ventricular dysfunction is demonstrated by echocardiography. It is not known whether cardiac injury of this type adversely affects cardiovascular hemodynamic performance. METHODS: We retrospectively studied 72 patients admitted to our neuro-ICU for aneurysmal subarachnoid hemorrhage over a 2.5-year period. We selected patients who met the following criteria: (1) CK-MB levels measured within 3 days of onset, (2) pulmonary artery catheter placed, (3) echocardiogram performed, and (4) no history of preexisting cardiac disease. Hemodynamic profiles were recorded on the day after surgery (n=67) or on the day of echocardiography (n=5) if surgery was not performed (mean, 3. 3+/-1.7 days after onset). The severity of cardiac injury was classified as none (peak CK-MB <1%, n=36), mild (peak CK-MB 1% to 2%, n=21), moderate (peak CK-MB >2%, n=6), or severe (abnormal left ventricular wall motion, n=9). RESULTS: Abnormal left ventricular wall motion occurred exclusively in patients with peak CK-MB levels >2% (P<0.0001), poor neurological grade (P=0.002), and female sex (P=0.02). Left ventricular stroke volume index and stroke work index were elevated above the normal range in patients with peak CK-MB levels <1% and fell progressively as the severity of cardiac injury increased, with mean values for patients with abnormal wall motion below normal (both P<0.0001 by ANOVA). Cardiac index followed a similar trend, but the effect was less pronounced (P<0.0001). Using forward stepwise multiple logistic regression, we found that thick subarachnoid clot on the admission CT scan (odds ratio, 1.9; 95% confidence interval [95% CI], 1.0 to 3.4; P=0.04) and depressed cardiac index (odds ratio, 2.1; 95% CI, 1.0 to 4.1; P=0.04) were independent predictors of symptomatic vasospasm. CONCLUSIONS: Myocardial enzyme release and echocardiographic wall motion abnormalities are associated with impaired left ventricular performance after subarachnoid hemorrhage. In severely affected patients, reduction of cardiac output from normally elevated levels may increase the risk of cerebral ischemia related to vasospasm.
Acute Disease↗
Growth arrest and spontaneous differentiation are initiated through an autocrine loop in clonally derived Schwann cells by alpha1-procollagen I C-propeptide.
Schwann cells cloned from rat sciatic nerve survive and display self-induced growth suppression, or undergo spontaneous apoptosis, on long-term serum-free subconfluent culture. Strain SCL4.1/F7 sustained the capacity to growth arrest for up to 40 generations. A soluble activity transmitted between neighbouring cells of this strain suppresses DNA synthesis within three cell cycles. Autocrine Schwann cell growth-inhibitory factor (SGIF) operates during the G1 phase of the cell cycle, overcomes the mitogenic action of Schwann cell/serum-associated (platelet-derived growth factor-BB) and axon-associated (axolemma-enriched fraction) stimuli in serum-free conditions, and suppresses DNA synthesis in sciatic nerve Schwann cell cultures in a stage-specific manner. A 35-kDa protein with N-terminal sequence and approximate molecular mass of the C-propeptide of rat alpha1-procollagen I makes a major contribution to SGIF. Growth suppression in the SCL4.1/F7 strain is mediated by the ras/extracellular signal-regulated kinase pathway, is accompanied by down-regulation of erbB2/erbB3 and of tetraethylammonium-sensitive K+ currents, and is followed by transition of cells within 5-10 days from O4+, p75 nerve growth factor receptor (p75NGF-R)+, glial fibrillary acidic protein (GFAP)+ to O4+, p75NGF-R-, GFAP-, periaxin+ phenotypes. Oct-6/SCIP mRNA is present in both proliferating and growth-arrested SCL4.1/F7 cells. These results demonstrate an autocrine/ paracrine loop for the growth arrest of clonally derived Schwann cells in the absence of axons linked in part to the metabolism of collagen. Schwann cells thus appear to self-regulate growth in a negative as well as a positive direction through characterized molecular mechanisms and signal pathways.
Animals↗
Temporal dynamics of verbal object comprehension.
Knowledge of the stage composition and the temporal dynamics of human cognitive operations is critical for building theories of higher mental activity. This information has been difficult to acquire, even with different combinations of techniques such as refined behavioral testing, electrical recording/interference, and metabolic imaging studies. Verbal object comprehension was studied herein in a single individual, by using three tasks (object naming, auditory word comprehension, and visual word comprehension), two languages (English and Farsi), and four techniques (stimulus manipulation, direct cortical electrical interference, electrocorticography, and a variation of the technique of direct cortical electrical interference to produce time-delimited effects, called timeslicing), in a subject in whom indwelling subdural electrode arrays had been placed for clinical purposes. Electrical interference at a pair of electrodes on the left lateral occipitotemporal gyrus interfered with naming in both languages and with comprehension in the language tested (English). The naming and comprehension deficit resulted from interference with processing of verbal object meaning. Electrocorticography indices of cortical activation at this site during naming started 250-300 msec after visual stimulus presentation. By using the timeslicing technique, which varies the onset of electrical interference relative to the behavioral task, we found that completion of processing for verbal object meaning varied from 450 to 750 msec after current onset. This variability was found to be a function of the subject's familiarity with the objects.
Adult↗
Persephin, a novel neurotrophic factor related to GDNF and neurturin.
A novel neurotrophic factor named Persephin that is approximately 40% identical to glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) has been identified using degenerate PCR. Persephin, like GDNF and NTN, promotes the survival of ventral midbrain dopaminergic neurons in culture and prevents their degeneration after 6-hydroxydopamine treatment in vivo. Persephin also supports the survival of motor neurons in culture and in vivo after sciatic nerve axotomy and, like GDNF, promotes ureteric bud branching. However, in contrast to GDNF and NTN, persephin does not support any of the peripheral neurons that were examined. Fibroblasts transfected with Ret and one of the coreceptors GFRalpha-1 or GFRalpha-2 do not respond to persephin, suggesting that persephin utilizes additional, or different, receptor components than GDNF and NTN.
Animals↗
Placental isoferritin levels in pregnant patients with systemic lupus erythematosus and/or antiphospholipid syndrome.
PROBLEM: Low serum placental isoferritin (PLF), an immunosuppressive cytokine-like protein, was found in women with underlying placento-vascular dysfunction, such as intrauterine growth retardation and preeclamptic toxemia. The possible contribution of this placental product in the assessment of pregnant patients with either systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) was investigated. METHOD OF STUDY: Seventy-five healthy pregnant women used as controls and 25 preselected pregnant patients with either SLE and/or APS were enrolled in the study. Study patients were in remission during conception and all patients agreed to give 5 ml of venous blood at midgestation. The samples were frozen and analyzed retrospectively. After delivery, pregnancy outcomes were gathered from hospital records. RESULTS: Seventeen (68%) women had uneventful pregnancies and deliveries (normal) whereas 8 (32%) showed pathologic obstetric outcomes. Mean midgestational serum PLF levels were similar in the control and normal outcome groups (87 U/ml), whereas significantly lower levels (37 U/ml) were measured in the pathologic outcome group. Using a cutoff level of 10 U/ml, 85% from the normal outcome group and 15% from the pathologic outcome group were above this threshold level, with 60% specificity and 100% sensitivity. CONCLUSIONS: These preliminary data suggest that PLF values may reflect placento-vascular functions. These may represent a predictive biomarker for developing obstetric complications in pregnant women with either SLE and/or APS.
Adult↗