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Biomedical subjects

S Curtiss

Publications and source records attributed to S Curtiss.

At least 19 recordsLinked to original sources
PubMed2006

Microfracture and bone morphogenetic protein 7 (BMP-7) synergistically stimulate articular cartilage repair.

OBJECTIVE: Microfracture is used to treat articular cartilage injuries, but leads to the formation of fibrocartilage rather than native hyaline articular cartilage. Since bone morphogenetic protein 7 (BMP-7) induces cartilage differentiation, we hypothesized that the addition of the morphogen would improve the repair tissue generated by microfracture. We determined the effects of these two treatments alone and in combination on the quality and quantity of repair tissue formed in a model of full-thickness articular cartilage injury in adolescent rabbits. DESIGN: Full-thickness defects were made in the articular cartilage of the patellar grooves of forty, 15-week-old rabbits. Eight animals were then assigned to (1) no further treatment (control), (2) microfracture, (3) BMP-7, (4) microfracture with BMP-7 in a collagen sponge (combination treatment), and (5) microfracture with a collagen sponge. Animals were sacrificed after 24 weeks at 39 weeks of age. The extent of healing was quantitated by determining the thickness and the surface area of the repair tissue. The quality of the repair tissue was determined by grading specimens using the International Cartilage Repair Society Visual Histological Assessment Scale. RESULTS: Compared to controls, BMP-7 alone increased the amount of repair tissue without affecting the quality of repair tissue. Microfracture improved both the quantity and surface smoothness of repair tissue. Compared to either single treatment, the combination of microfracture and BMP-7 increased both the quality and quantity of repair tissue. CONCLUSIONS: Microfracture and BMP-7 act synergistically to stimulate cartilage repair, leading to larger amounts of repair tissue that more closely resembles native hyaline articular cartilage.

Animals↗
PubMed2004

Cerebral hemispherectomy: hospital course, seizure, developmental, language, and motor outcomes.

OBJECTIVE: To compare hemispherectomy patients with different pathologic substrates for hospital course, seizure, developmental, language, and motor outcomes. METHODS: The authors compared hemispherectomy patients (n = 115) with hemimegalencephaly (HME; n = 16), hemispheric cortical dysplasia (hemi CD; n = 39), Rasmussen encephalitis (RE; n = 21), infarct/ischemia (n = 27), and other/miscellaneous (n = 12) for differences in operative management, postsurgery seizure control, and antiepilepsy drug (AED) usage. In addition, Vineland Adaptive Behavior Scale (VABS) developmental quotients (DQ), language, and motor assessments were performed pre- or postsurgery, or both. RESULTS: Surgically, HME patients had the greatest perioperative blood loss, and the longest surgery time. Fewer HME patients were seizure free or not taking AEDs 1 to 5 years postsurgery, but the differences between pathologic groups were not significant. Postsurgery, 66% of HME patients had little or no language and worse motor scores in the paretic limbs. By contrast, 40 to 50% of hemi CD children showed near normal language and motor assessments, similar to RE and infarct/ischemia cases. VABS DQ scores showed +5 points or more improvement postsurgery in 57% of patients, and hemi CD (+12.7) and HME (+9.1) children showed the most progress compared with RE (+4.6) and infarct/ischemia (-0.6) cases. Postsurgery VABS DQ scores correlated with seizure duration, seizure control, and presurgery DQ scores. CONCLUSIONS: The pathologic substrate predicted pre- and postsurgery differences in outcomes, with hemimegalencephaly (but not hemispheric cortical dysplasia) patients doing worse in several domains. Furthermore, shorter seizure durations, seizure control, and greater presurgery developmental quotients predicted better postsurgery developmental quotients in all patients, irrespective of pathology.

Anticonvulsants↗
PubMed2001

Spoken language outcomes after hemispherectomy: factoring in etiology.

We analyzed postsurgery linguistic outcomes of 43 hemispherectomy patients operated on at UCLA. We rated spoken language (Spoken Language Rank, SLR) on a scale from 0 (no language) to 6 (mature grammar) and examined the effects of side of resection/damage, age at surgery/seizure onset, seizure control postsurgery, and etiology on language development. Etiology was defined as developmental (cortical dysplasia and prenatal stroke) and acquired pathology (Rasmussen's encephalitis and postnatal stroke). We found that clinical variables were predictive of language outcomes only when they were considered within distinct etiology groups. Specifically, children with developmental etiologies had lower SLRs than those with acquired pathologies (p =.0006); age factors correlated positively with higher SLRs only for children with acquired etiologies (p =.0006); right-sided resections led to higher SLRs only for the acquired group (p =.0008); and postsurgery seizure control correlated positively with SLR only for those with developmental etiologies (p =.0047). We argue that the variables considered are not independent predictors of spoken language outcome posthemispherectomy but should be viewed instead as characteristics of etiology.

Adolescent↗
PubMed1999

Age and etiology as predictors of language outcome following hemispherectomy.

We report on the effects of etiology and age on the linguistic outcomes in a large pediatric hemispherectomy population. Four populations were considered separately: cortical dysplasia (multilobar involvement), Rasmussen's encephalitis, infarction as a primary etiology and, fourth, children who failed to develop language, regardless of etiology. We argue against the 'the-earlier-the-better' hypothesis and propose our own hypothesis that weds maturational factors to etiological factors to predict language outcomes following pervasive brain insult. The implications of our 'critical impact point' hypothesis are discussed.

Age of Onset↗
PubMed1998

Hyperosmolarity associated with diabetes insipidus alters hepatocyte structure and function but not survival after orthotopic liver transplantation in rats.

BACKGROUND: This study was designed to evaluate the effect of donor hyperosmolarity secondary to diabetes insipidus, an almost universal occurrence among brain-dead patients, on hepatic function. METHODS: In vitro (isolated liver perfusion) and in vivo (hyaluronic acid and indocyanine green uptake, arterial ketone body ratio, orthotopic liver transplantation) experiments were conducted using Brattleboro rats, with hereditary hypothalamic diabetes insipidus, and Sprague-Dawley rats, with normal pituitary function. ATP content and recovery after cold preservation were measured during the perfusion. RESULTS: Cold-preserved livers from hyperosmolar rats were observed to have elevated hepatic enzyme release and decreased bile production compared with normosmolar controls. Moreover, in these livers, the recovery of ATP after cold preservation was completely absent. Transmission electron microscopy of liver biopsies collected from hyperosmolar rats demonstrated profound ultrastructural changes, particularly in the mitochondria, that were not evident in the biopsies from normosmolar rats. All the experimental groups demonstrated similar hyaluronic acid uptake, whereas indocyanine green uptake was markedly impaired in the hyperosmolar group, suggesting that hepatocyte and not sinusoidal endothelial cell function is adversely affected by hyperosmolarity. The arterial ketone body ratio was profoundly compromised by chronic and, to an even greater degree, by acute hyperosmolarity. Survival after transplantation using hyperosmolar donors was not affected in this study. CONCLUSIONS: These results are an important step toward understanding the mechanism whereby brain death, a complicated pathophysiologic phenomenon, adversely affects the hepatic allograft.

Adenosine Triphosphate↗
PubMed1997

High resolution analysis of chromosome 3p alterations in cervical carcinoma.

Although loss of heterozygosity (LOH) for loci on chromosome 3p is a common event in cervical carcinoma (CC), the frequency and affected regions of 3p are inconsistent among studies. Here we report a comprehensive analysis of LOH on 3p in 66 primary tumors and 16 CC-derived cell lines using a high density of marker loci. Clonal LOH was found in over 70% of primary tumors, and the patterns of loss indicated four to five target regions, with 3p14 being the most frequent. The majority of tumors had complex patterns of allelic imbalance, with regions of subclonal and clonal losses often present in individual tumors. We exploited marker homozygosity in CC-derived cell lines as an indirect measure of LOH and identified four homozygous deletions (HDs) during this analysis at loci located within the 3p14.2 region to which the FHIT gene has been mapped recently. This led to a careful reevaluation of the LOH patterns in primary CCs, which showed apparent retention of heterozygosity for loci in this region indicative of the presence of several additional HDs. To our knowledge, this is the first report of HDs encompassing the FHIT gene region in primary tumor samples and underscores the usefulness of high resolution genetic analysis of tumor genomes in determining the chromosomal aberrations underlying the malignant progression of CC.

Alleles↗
PubMed1997

Differential contribution of graft and recipient to perioperative TNF-alpha, IL-1 beta, IL-6 and IL-8 levels and correlation with early graft function in clinical liver transplantation.

Cytokines, produced by both the recipient and the newly vascularized allograft, are central mediators in the inflammatory response to allografted tissue. This study examines the relationship between pre- and intraoperative levels of TNF, IL-1, IL-6, and IL-8 and hepatic allograft function in the early postoperative period and also determines which cytokines are produced in a significant amount by the newly vascularized allograft. Baseline levels of IL-6 and IL-8 tended to be higher in patients with more advanced disease and showed an increase during the anhepatic period. TNF and IL-1 remained stable from baseline to anhepatic phase. IL-1 showed an increase from portal vein to effluent samples, suggesting that the graft has an important contribution to circulating IL-1 levels. Analysis of the data according to early graft performance revealed extremely high levels of effluent IL-1, IL-6 and IL-8, and the prolonged elevation of the latter two cytokines in patients with poor early graft function. Our findings demonstrate that sequential perioperative measurements of proinflammatory cytokines can be useful in monitoring graft function.

Adult↗
PubMed1996

Plasmapheresis in primary dysfunction of hepatic transplants.

BACKGROUND: Primary dysfunction is a failure of graft function which occurs in approximately 5% of transplanted livers. Retransplantation is often required. The presence of elevated serum cytokines interleukin 6 and tumor necrosis factor with hepatic graft dysfunction, as well as the historical benefit of plasmapheresis in fulminant hepatic failure-associated coma suggest a possible role for plasmapheresis therapy in the management of primary graft dysfunction in liver transplantation. DESIGN AND METHODS: We evaluated the effectiveness of plasmapheresis in the management of primary graft dysfunction in 18 patients who underwent orthotopic liver transplantation in this institution. Patients who were diagnosed with primary dysfunction of hepatic grafts underwent a course of four daily plasma exchange procedures. The clinical outcome, patient and graft survival, was compared to that of historical controls. RESULTS: Graft survival at 10 days was 77.7% and 76.2% and patient survival at 100 days was 83.3% and 85.7% in the plasmapheresed and control groups, respectively. The patients who underwent plasmapheresis had a higher incidence of dialysis intervention, 38% versus 19%, indicating more severe graft dysfunction. In the small number of patients compared for concomitant dialysis therapy, patient survival in the plasmapheresed group was 85.7% versus 50% (control), and graft survival was 57.0% versus 50%. Serum cytokine levels of tumor necrosis factor and interleukin 6 were reduced by 66.0% and 55.2%, respectively, with a single procedure. CONCLUSION: Plasmapheresis did not significantly effect graft survival in patients with primary graft dysfunction. An increase in patient survival in severe graft dysfunction with renal failure was noted but was not significant. Removal of elevated serum cytokines TNF and IL-6 was documented.

Adult↗
PubMed1996

Pediatric Rasmussen encephalitis: social communication, language, PET and pathology before and after hemispherectomy.

This prospective case study examined social communication (i.e., formal thought disorder, cohesion), language, positron emission tomography glucose utilization, and neuropathology in four children with Rasmussen encephalitis who achieved seizure control following right hemispherectomy. Prior to hemispherectomy, all four children had illogical thinking, loose associations, cohesive deficits, and impaired performance on formal language tests. Their postoperative improvement in social communication and language appeared to be related to age of onset, duration of illness, and postsurgical reversibility of hypometabolism in the nonresected prefrontal cortex. These changes were not associated with increase in IQ scores. The variability in the type and extent of pathologic change across subjects reflected the severity and duration of the illness. The study's findings imply that early surgical intervention might have mitigated certain aspects of the social communication and linguistic deficits found in these children.

Adolescent↗
PubMed1993

Conversations with children who are language impaired: asking questions.

Samples of conversational language were elicited with a standardized interview protocol from 24 children, aged 2:6 to 7:8, half with specific language impairment (SLI), half with normally developing language (LN), matched for language level. Samples were analyzed to determine whether there were associations between adult questioning and children's use of ellipsis. For the SLI children, but not the LN children, increased proportions of questions were significantly correlated to increased proportions of ellipsis. This finding has implications for the use of MLU measures in clinical and research practice.

Case-Control Studies↗
PubMed1993

Language, learning, and behavioral disturbances in childhood: a longitudinal perspective.

OBJECTIVE: Investigate longitudinally the course of development of preschool learning impaired (LI) children to better understand the interaction between neurodevelopmental delay, behavioral/emotional disorders, and language development and disorders. METHOD: Relationships between developmental language disorders and emotional problems were investigated in 99 8-year-old specifically language impaired and control children originally assessed at age 4 years using the Achenbach Child Behavior Checklist and the Conners' Parents Questionnaire. RESULTS: LI children received higher behavior problem scores and were more likely to score in the clinical range than were control children. Neither degree of early language impairment nor amount of language improvement predicted 8-year behavioral/emotional status. LI children with the largest drop in IQ between ages 4 and 8 received the highest behavior problem scores. No significant comorbid relationship was seen between LI and attention-deficit hyperactivity disorder. CONCLUSIONS: The enhanced incidence of behavior problems reported heretofore may be related more to lower IQ than to linguistic deficit per se. Care must be taken to differentiate the symptoms of neurodevelopmental delay and emotional disturbance, however, preschool children with scores in the clinical range on such measures should be referred for additional evaluation.

Attention Deficit Disorder with Hyperactivity↗
PubMed1992

Rapid automatized naming and gesture by normal and language-impaired children.

This study investigates whether language-impaired (LI) children show deficits in rapid automatized naming and whether RAN performance is specific to verbal output (or to rapid motor output in general). A total of 67 LI and 54 age-matched control children were tested with the Rapid Automatized Naming (RAN) test (Denckla & Rudel, 1976) and with a manual version of the RAN (RAN-manual) in which subjects were required to provide a nonverbal, pantomime response. Subjects also completed tests of rapid oral and manual sequencing skills and standardized tests of reading ability. Each subject was tested at 4, 6, and 8 years old. The results showed that LI children perform significantly poorer on both versions of the RAN than age-matched controls. Correlations between RAN scores and tests of reading ability were significant for normal and LI subjects and were particularly high for 8-year-old LI children. RAN-manual scores also correlated with 8-year-old LI children's reading scores. Further, RAN and RAN-manual scores for the LI children correlated significantly with these children's manual sequencing abilities, whereas this was not the case for the control subjects. These findings suggest that LI children's rapid sequential processing deficits are not limited to verbal output, but also generalize to other motoric domains.

Child↗
PubMed1992

Delay versus deviance in the language acquisition of language-impaired children.

To investigate the issue of delay versus deviance in the language acquisition of language-impaired (LI) children, the order of acquisition of a set of linguistic structures and the relationship obtaining between one structure and another were examined in comprehension and production over a 5-year period in a group of LI and language-matched normal children. The results demonstrated a marked similarity between groups, both in the point at which mastery of individual structures was achieved and in the overall patterns of acquisition demonstrated. These data suggest that LI children are constructing grammars based on the same rules and principles as those of linguistically normal control subjects, and that their linguistic impairments may be principally processing, not representational, in nature.

Child, Preschool↗
PubMed1991

Phenotypic profiles of language-impaired children based on genetic/family history.

Although etiological influences in developmental language impairment (dysphasia) are not well defined, a significant increase of family aggregation for the disorder has been reported. We report data from a large cohort of language-impaired (LI) children participating in the San Diego longitudinal study in which we examined whether children with or without positive family histories show different phenotypic profiles. Due to the longitudinal design of the study, questions pertaining to change over time are also addressed. Second, a subgroup of the most impaired children were reevaluated to obtain additional information pertaining to family history and phenotypic outcome. Approximately 70% of the LI children met criteria for inclusion as family history positive, with fathers reporting a history of language or learning problems one and a half to two times as frequently as mothers. LI children with or without a positive family history were not significantly different on language skills or IQ. However, subjects having a positive family history for developmental language/learning problems were significantly lower in socioeconomic status and were rated by parents and teachers as having more attention-related behavior problems than their family history negative counterparts. Similarly, family history positive LI children performed more poorly on standardized academic tests as well as on tests of auditory processing and attention.

Child↗
PubMed1990

Selecting language-impaired children for research studies: insights from the San Diego Longitudinal Study.

The need for a standardized approach to the selection of research subjects for studies on language impairment has long been an area of controversy in the literature. The data obtained from the selection of language-impaired and control subjects for the San Diego Longitudinal Study allows one to evaluate the effects a two-stage subject-selection procedure has on the characteristics of the language-impaired and normal subjects selected for research studies. Specifically, what effect do quantitative measures, as compared to clinical judgements and referrals, have on the characteristics of subjects selected for research studies? Explicit and detailed oral and written descriptions of subjects sought for both a language-impaired group and a control group were given to teachers and clinicians. However, only 39 of the first 100 children referred as language-impaired and 29 of the first 60 referred as normal controls were found on standardized testing to meet the study criteria and to be matched on important variables, such as IQ and socioeconomic status. These results demonstrate the importance of establishing quantitative inclusionary as well as exclusionary criteria for selecting and matching subjects in clinical research studies.

Child, Preschool↗
PubMed1989

Unexpected sex-ratios in families of language/learning-impaired children.

There is a well-documented propensity of males affected with developmental language/learning impairment. Results from this study demonstrate, unexpectedly, that this sex-ratio difference of males to females with developmental language/learning disorders was found to occur significantly only in families with a language/learning-impaired mother. In addition, a remarkably aberrant offspring sex-ratio was found in families of language/learning-impaired children who had an affected mother, but not father. Mothers who were developmentally language/learning-impaired had three times as many sons as daughters, and five times as many language/learning-impaired sons as daughters. Genetic and hormonal influences that might affect both sex-ratio and neuroanatomical development and disorders are discussed.

Child, Preschool↗