Assessment of psychoeducational outcomes after pediatric liver transplant.

Outcomes research in pediatric liver transplant (LT) has focused on mortality and morbidity but there is a need to also evaluate functional outcomes. Standardized cognitive testing was administered to a cohort of children with infantile chronic liver disease who were transplanted at the University of Alberta during their preschool years. Thirty children had comprehensive assessments with the Bayley Scales of Infant Development or Wechsler testing. Patient variables potentially associated with cognitive delay were analyzed with multiple regression analysis. The mean DQ/IQ score (developmental quotient/intelligence quotient) was 81 +/- 17. Delay (DQ/IQ score < 70), and borderline delay (DQ/IQ 70-84) were each present in 27% of the cohort, with only 46% demonstrating normal cognition. Regression analysis demonstrated that the decreased IQ was associated with pretransplant growth retardation and elevated calcineurin inhibitor levels. Performance IQ had strong correlation with pretransplant growth retardation and elevated serum ammonia, R(2)= 45%, compared to verbal IQ that was associated was elevated calcineurin inhibitor levels, R(2)= 23%. Children post-LT are at high risk for cognitive delay or borderline delay. This is the first study to demonstrate the association calcineurin inhibitors with impaired IQ and also the unique finding of different variables predictive of impaired verbal intelligence quotient (VIQ) versus performance intelligence quotient (PIQ).

Association between small for gestational age and paternally inherited 5' insulin haplotypes.

OBJECTIVE: To test the association between small for gestational age and polymorphisms in the insulin gene in newborns and their mothers, as well as the effect of the parental transmission of haplotypes. SUBJECTS: Pairs of healthy African-American full-term newborns (N=207) and mothers were recruited from Memphis TN and Jackson MS with birth weights ranging from 2210 to 4735 g. METHODS: Six single nucleotide polymorphisms (SNPs) located in the insulin (INS) and insulin-like growth factor 2 (IGF2) genes were genotyped in mothers and newborns. Haplotypes composed of three SNPs in the 5' region of the INS-IGF2 locus were computationally inferred. Odds ratios for risk of small for gestational age (SGA) birth were calculated for individual SNPs and inferred haplotypes in the newborns and in the mothers using logistic regression. For 162 mother--newborn pairs the parental transmission of the haplotypes could be inferred, and the risks for SGA birth were calculated for the three common haplotypes in this sample. RESULTS: Three INS SNPs exhibited significant association with risk for SGA birth. The SNP alleles associated with increased risk for SGA were opposite in the maternal and newborn genomes, implying opposing influences on the rate of fetal growth. Consistent with these results, haplotypes composed of complementary nucleotide sequences (CAC at rs3842738, rs689 and rs3842748, respectively, in the newborn versus GTG in the mother) were significantly associated with risk for SGA birth. In analyses of haplotypes according to parental transmission, the same trend in risk for SGA was observed for both maternally and paternally transmitted haplotypes, although a significant difference in risk was observed only for paternally transmitted haplotypes. CONCLUSION: Polymorphisms near the 5' end of the INS-IGF2 locus are significantly associated with risk for SGA birth with a major effect due to the paternally transmitted haplotype, which is preferentially expressed due to imprinting.

Measurement of coronary artery calcification by electron beam computerized tomography in persons with chronic spinal cord injury: evidence for increased atherosclerotic burden.

BACKGROUND/OBJECTIVE: Individuals with spinal cord injury (SCI) have been reported to have an increased prevalence of premature cardiovascular disease. Whether the increased risk of disease is owing to clustering of traditional cardiac risk factor or is over and above that predicted by risk factors was addressed. METHODS: Ninety-one persons with chronic SCI were studied for subclinical atherosclerosis. Cardiac risk factors and coronary artery calcium (CAC) was compared to matched non-SCI controls. The 273 controls were 3:1 matched for age, gender, ethnicity and risk factors and were drawn from a national database of over 30,000 asymptomatic persons undergoing coronary scanning. RESULTS: Seventy-six men and 15 women were studied. Average age was 49.7+/-12 years. Duration of injury was 19.7+/-10 years. The ethnicity of the study cohort included 36% Caucasian, 49% Latino, 10% African American, and 5% other. The mean calcium score of the SCI group was significantly greater than the control group (75+/-218 versus 28+/-104, P<0.001). The prevalence of any CAC score was greater in the SCI population than the control population (51 versus 39%, P<0.05), as was CAC score >100 (16 versus 7%, P<0.01). Women with SCI had a significantly lower CAC score than men (mean score: 12 versus 86, P<0.01). CONCLUSION: Patients with SCI were shown to have greater atherosclerotic burden than able-bodied controls. Of note, and unexplained, this finding is beyond that explained by the clustering of traditional risk factors. On the basis of these findings, increased attention should be directed toward the prevention of coronary heart disease in those with SCI.

Multigene phylogeny of the Old World mice, Murinae, reveals distinct geographic lineages and the declining utility of mitochondrial genes compared to nuclear genes.

Despite its great diversity and biomedical importance, the rodent subfamily Murinae is poorly resolved phylogenetically. We present the first cladistic analysis sampling multiple representatives of most major groups based on DNA sequence for three nuclear (GHR, RAG1, and AP5) and one mitochondrial (COII and parts of COI and ATPase 8) fragments. Analyzed separately, the four partitions agree broadly with each other and the combined analysis. The basal split is between a clade of Philippine Old Endemics and all remaining murines. Within the latter, rapid radiation led to at least seven geographically distinct lineages, including a Southeast Asian Rattus clade; a diverse Australo-Papuan and Philippine clade; an African arvicanthine group including the otomyines; an African Praomys group; and three independent genera from Africa and Asia, Mus, Apodemus, and Malacomys. The murines appear to have originated in Southeast Asia and then rapidly expanded across all of the Old World. Both nuclear exons provide robust support at all levels. In contrast, the bootstrap proportions from mitochondrial data decline rapidly with increasing depth in the tree, together suggesting that nuclear genes may be more useful even for relatively recent divergences (< 10MYA).

Long-term survival after resection for primary hepatic carcinoid tumor.

BACKGROUND: Primary hepatic carcinoid tumors (PHCTs) are extremely rare, and fewer than 50 cases have been reported in the English-language literature. We report a patient with a PHCT and review the cases in the literature. METHODS: Our patient presented with symptoms and underwent liver resection for PHCT and regional lymph node metastasis. He underwent two more liver resections over the following 7 years for recurrent PHCT. Cases reported in the English-language literature were reviewed and survival analysis was performed with the Kaplan-Meier method. The survival impacts of age, gender, tumor foci, extrahepatic metastasis, unilobar versus bilobar disease, and type of preoperative treatment were determined by means of log-rank test. RESULTS: Our patient has been free of symptoms for 14 years of follow-up and free of disease for 8 years of follow-up. Forty-eight cases of PHCT were found in the literature, and 92% of these patients underwent resection. Actuarial 5- and 10-year survival for all patients was 78% and 59%, respectively, whereas for resected patients, 10-year survival was 68%. The administration of preoperative chemotherapy, radiation therapy, or chemoembolization did not impact survival, nor did age, gender, presence of extrahepatic metastasis, number of tumors, or distribution of the tumor within the liver. CONCLUSIONS: Resection is the treatment of choice for PHCT and has provided favorable outcomes. Resection for PHCT can be performed in most patients and offers long-term survival.

How well are we doing? Families of adolescents or young adults with cerebral palsy share their perceptions of service delivery.

PURPOSE: The satisfaction of families of adolescents and young adults with a diagnosis of cerebral palsy with the service delivery they had experienced in the areas of health, education, recreation, employment, housing and transportation was examined. Common themes across the six service areas were identified. METHOD: Forty-nine adolescents (13-15 years) and 39 young adults (19-23 years) and their families rated their satisfaction with services and then participated in semi-structured interviews to discuss their experiences. RESULTS: Using a constant comparative method of analysis, common themes were identified from the transcribed interviews. Four themes were identified and named: caring and supportive people; fighting and fatigue; communication/information; and disability awareness. CONCLUSIONS: Families continue to experience dissatisfaction and frustration with service delivery in the six areas examined. Both bureaucratic structure and attitudes of service providers contribute to their dissatisfaction.

Levels of plasma homocysteine in persons with spinal cord injury.

BACKGROUND: Premature coronary vascular disease is a leading cause of morbidity and mortality in persons with chronic spinal cord injury (SCI). Evidence indicates that an elevated plasma homocysteine level is an independent risk factor for vascular disease. METHODS: Plasma homocysteine levels were collected in 845 subjects with SCI and compared to those in a reference population. Differences in plasma homocysteine were determined for sex, race/ethnicity, neurological deficit, and age, as well as for serum creatinine concentration. RESULTS: Plasma homocysteine was significantly higher in men than in women. Men were more likely to have moderately or severely elevated plasma homocysteine levels. Stratifying by male sex, greater percentages of whites and African Americans had severely elevated plasma homocysteine levels (>20 micromol/L) compared with Latinos (12% and 14% versus 8%; P > .01). For the total group with SCI, plasma homocysteine levels were not significantly different by race/ethnicity or neurological deficit subgroup. For the total group (P < .05) and within each sex (men, P < .05; women, P < .01), the older age group with SCI (>50 years) had significantly higher mean plasma homocysteine levels than the younger age group. Age was positively related to plasma homocysteine levels in men (P < .05) and women (P < .01). Plasma homocysteine levels were higher among men for any given age than among women (P < .0001) by an average of 3.19 +/- 0.51 micromol/L. Regardless of age or sex, persons with SCI tended to have higher levels of plasma homocysteine than able-bodied persons matched for age and sex. CONCLUSION: Because the risk of a vascular event increases with age, elevated levels of plasma homocysteine place older persons with SCI at further increased risk for a vaso-occlusive event. Of note, there was a stepwise increase in plasma homocysteine concentration for each quartile of higher serum creatinine concentration. Patients who have elevated levels of plasma homocysteine should receive a trial course of daily supplementation with oral folic acid and vitamin B12. If that is ineffective, they should receive vitamin B6 supplementation to lower their plasma homocysteine levels.

The effect of dietary intervention on lipid profiles in individuals with spinal cord injury.

OBJECTIVE: The purpose of this study was to evaluate the effects of a simple dietary intervention for individuals with chronic spinal cord injury (SCI) and moderately elevated total cholesterol. METHODS: Baseline and follow-up serum lipid values were obtained on 222 persons with SCI. Eighty-six individuals with total cholesterol >200 mg/dL were referred for dietary consultation (group 1). The remainder with values <200 mg/dL and no consultation served as controls (group 2). RESULTS: At average follow-up of 16 months, group 1 demonstrated significant declines in total cholesterol and low-density lipoprotein cholesterol (LDL-C), whereas group 2 demonstrated significant increases in total cholesterol. Triglyceride levels followed similar but nonsignificant patterns. There were no significant changes in high-density lipoprotein cholesterol for either group. In group 1, 17% had clinically significant reductions in total cholesterol to <200 mg/dL and 21% had reductions of LDL-C from >135 mg/dL to <135 mg/dL. CONCLUSIONS: Dietary intervention should be an initial treatment for those with SCI and moderately elevated total cholesterol, with the expectation that approximately 20% will respond favorably.

Coordinating the segregation of sister chromatids during the first meiotic division: evidence for sexual dimorphism.

Errors during the first meiotic division are common in our species, but virtually all occur during female meiosis. The reason why oogenesis is more error prone than spermatogenesis remains unknown. Normal segregation of homologous chromosomes at the first meiotic division (MI) requires coordinated behavior of the sister chromatids of each homolog. Failure of sister kinetochores to act cooperatively at MI, or precocious sister chromatid segregation (PSCS), has been postulated to be a major contributor to human nondisjunction. To investigate the factors that influence PSCS we utilized the XO mouse, since the chromatids of the single X chromosome frequently segregate at MI, and the propensity for PSCS is influenced by genetic background. Our studies demonstrate that the strain-specific differences in PSCS are due to the actions of an autosomal trans-acting factor or factors. Since components of the synaptonemal complex are thought to play a role in centromere cohesion and kinetochore orientation, we evaluated the behavior of the X chromosome at prophase to determine if this factor influenced the propensity of the chromosome for self-synapsis. We were unable to directly correlate synaptic differences with subsequent segregation behavior. However, unexpectedly, we uncovered a sexual dimorphism that may partially explain sex-specific differences in the fidelity of meiotic chromosome segregation. Specifically, in the male remnants of the synaptonemal complex remain associated with the centromeres until anaphase of the second meiotic division (MII), whereas in the female, all traces of synaptonemal complex (SC) protein components are lost from the chromosomes before the onset of the first meiotic division. This finding suggests a sex-specific difference in the components used to correctly segregate chromosomes during meiosis, and may provide a reason for the high error frequency during female meiosis.

Regional osteoporosis in women who have a complete spinal cord injury.

BACKGROUND: Regional bone loss in patients who have a spinal cord injury has been evaluated in males. In addition, there have been reports on groups of patients of both genders who had an acute or chronic complete or incomplete spinal cord injury. Regional bone loss in females who have a complete spinal cord injury has not been reported, to our knowledge. METHODS: In a study of thirty-one women who had a chronic, complete spinal cord injury, we assessed bone mineral density in relation to age, weight, and time since the injury. The results were compared with the bone mineral density in seventeen healthy, able-bodied women who had been age-matched by group (thirty years old and less, thirty-one to fifty years old, and more than fifty years old). Dual-energy x-ray absorptiometry was used to measure the bone mineral density of the lumbar spine, hip, and knee; Z-scores for the hip and spine were calculated. RESULTS: The mean bone mineral density in the spine in the youngest, middle, and oldest spinal-cord-injury groups was 98%, 108%, and 115% of the densities in the respective age-matched control groups (p < 0.0001), and the mean bone mineral density in the oldest spinal-cord-injury group was equal to that in the youngest control group. This gain in bone mineral density in the spine was reflected by the spine Z-scores, as the mean score in the oldest injured group averaged more than one standard deviation above both the norm and the mean score in the control group. The mean loss of bone mineral density in the knee in the youngest, middle, and oldest spinal-cord-injury groups was 38%, 41%, and 47% compared with the densities in the corresponding control age-groups (p < 0.0001). Furthermore, the oldest injured group had a mean reduction of knee bone mineral density of 54% compared with the youngest control group. The mean loss of bone mineral density in the hips of the injured patients was 18%, 25%, and 25% compared with the densities in the control subjects in the respective age-groups (p < 0.0001). CONCLUSIONS: The bone mineral density in the spine either was maintained or was increased in relation to the time since the injury. This finding is unlike that seen in healthy women, in whom bone mineral density decreases with age. The bone mineral density in the hips of the injured patients initially decreased approximately 25%; thereafter, the rate of loss was similar to that in the control group. The bone mineral density in the knees of the injured patients rapidly decreased 40% to 45% and then further decreased only minimally.

Are families with adolescents and young adults with cerebral palsy the same as other families?

This study compared adolescents with cerebral palsy (CP) and their families to adolescents without physical disabilities and their families as the child enters and leaves adolescence (age ranges 13 to 15 years and 19 to 23 years). Families of 90 individuals with CP (42 females, 48 males) and 75 individuals without physical disabilities (34 females, 41 males) participated. They completed the Family Assessment Device, Life Situation Survey, Multidimensional Scale of Perceived Social Support, and Future Questionnaire. There were few differences in family functioning, life satisfaction, or perceived social support between the groups. Expectations of young adults with CP and parents of both adolescents and young adults regarding future independence and success were lower than the expectations of the control group. While the group results emphasize similarities between families during the two stages of adolescence, individual families and individual family members report specific challenges.

Forced vital capacity in two large outpatient populations with chronic spinal cord injury.

OBJECTIVE: To determine the expected vital capacity in persons with chronic spinal cord injury (SCI) in relation to injury level, completeness of injury, smoking and duration of injury, as an aid to diagnosis and management of respiratory complications. SETTING: A New York City veterans' hospital and a Los Angeles public rehabilitation hospital. METHODS: Case series from the two hospitals were pooled. Participants (adult outpatients with SCI of duration >1 year, not ventilator-dependent) were evaluated by conventional forced expiratory spirometry. Cross-sectional analysis was performed, using multiple regression, on the entire population and defined subgroups. The principal outcome measure was forced vital capacity (FVC). RESULTS: In the subjects with complete-motor lesions, FVC ranged from near 100% of normal predicted values in the group with low paraplegia, to less than 50% in those with high tetraplegia. Incomplete lesions mitigated FVC loss in tetraplegia. In subjects with paraplegia, longer duration of injury was associated with greater loss, and smoking-related loss was evident at older but not at younger ages, presumably due to greater pack years in older subjects. CONCLUSIONS: Vital capacity/SCI level relationships determined here may have diagnostic and prognostic value. Smoking-related FVC loss is important in persons with SCI as in others, although at higher levels it may be obscured by SCI-related loss.

Episodic evolution of growth hormone in primates and emergence of the species specificity of human growth hormone receptor.

Growth hormone (GH) evolution is very conservative among mammals, except for primates and ruminant artiodactyls. In fact, most known mammalian GH sequences differ from the inferred ancestral mammalian sequence by only a few amino acids. In contrast, the human GH sequence differs from the inferred ancestral sequence by 59 amino acids. However, it is not known when this rapid evolution of GH occurred during primate evolution or whether it was due to positive selection. Also, human growth hormone receptor (GHR) displays species specificity; i.e., it can interact only with human (or rhesus monkey) GH, not with nonprimate GHS: The species specificity of human GHR is largely due to the Leu-->Arg change at position 43, and it has been hypothesized that this change must have been preceded by the His-->Asp change at position 171 of GH. Is this hypothesis true? And when did these changes occur? To address the above issues, we sequenced GH and GHR genes in prosimians and simians. Our data supported the above hypothesis and revealed that the species specificity of human GHR actually emerged in the common ancestor of Old World primates, but the transitional phase still persists in New World monkeys. Our data showed that the rapid evolution of primate GH occurred during a relatively short period (in the common ancestor of higher primates) and that the rate of change was especially high at functionally important sites, suggesting positive selection. However, the nonsynonymous rate/synonymous rate ratio at these sites was <1, so relaxation of purifying selection might have played a role in the rapid evolution of the GH gene in simians, possibly as a result of multiple gene duplications. Similar to GH, GHR displayed an accelerated rate of evolution in primates. Our data revealed proportionally more amino acid replacements at the functionally important sites in both GH and GHR in simians but, surprisingly, showed few coincidental replacements of amino acids forming the same intermolecular contacts between the two proteins.

Molecular phylogeny and divergence time estimates for major rodent groups: evidence from multiple genes.

The order Rodentia contains half of all extant mammal species, and from an evolutionary standpoint, there are persistent controversies surrounding the monophyly of the order, divergence dates for major lineages, and relationships among families. Exons of growth hormone receptor (GHR) and breast cancer susceptibility (BRCA1) genes were sequenced for a wide diversity of rodents and other mammals and combined with sequences of the mitochondrial 12S rRNA gene and previously published sequences of von Willebrand factor (vWF). Rodents exhibit rates of amino acid replacement twice those observed for nonrodents, and this rapid rate of evolution influences estimates of divergence dates. Based on GHR sequences, monophyly is supported, with the estimated divergence between hystricognaths and most sciurognaths dating to about 75 MYA. Most estimated dates of divergence are consistent with the fossil record, including a date of 23 MYA for Mus-Rattus divergence. These dates are considerably later than those derived from some other molecular studies. Among combined and separate analyses of the various gene sequences, moderate to strong support was found for several clades. GHR appears to have greater resolving power than do 12S or vWF. Despite its complete unresponsiveness to growth hormone, Cavia (and other hystricognaths) exhibits a conservative rate of change in the intracellular domain of GHR.

Lung mechanics in individuals with spinal cord injury: effects of injury level and posture.

Individuals with spinal cord injury (SCI) exhibit reduced lung volumes and flow rates as a result of respiratory muscle weakness. These features have not, however, been investigated in relation to the combined effects of injury level and posture. Changes in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), FEV(1)/FVC, forced expiratory flow at 50% vital capacity (FEF(50)), inspiratory capacity (IC), and expiratory reserve volume (ERV) were assessed by injury level in the seated and supine positions in 74 individuals with SCI. The main findings were 1) FVC, FEV(1), and IC increased with descending SCI level down to T(10), below which they tended to level off; 2) supine values of FVC and FEV(1) tended to be larger in the supine compared with the seated posture down to injury level T(1), caudad to which they were less than when seated; 3) IC increased proportionately more down to injury level L(1), below which it declined slightly and plateaued; 4) ERV was measurable even at high cervical injuries, was generally smaller in the supine position, reached peak values in both positions at T(10) injury level, and then rapidly declined at lower levels; 5) when subjects were separated according to current, former, and never smokers, only formerly smoking paraplegic individuals demonstrated spirometric values significantly less than paraplegic individuals who never smoked. Changes in spirometric measurements in SCI are dependent on injury level and posture. These findings support the concept that the increase in vital capacity in supine position is related to the effect of gravity on abdominal contents and increase in IC.

Parallel adaptive radiations in two major clades of placental mammals.

Higher level relationships among placental mammals, as well as the historical biogeography and morphological diversification of this group, remain unclear. Here we analyse independent molecular data sets, having aligned lengths of DNA of 5,708 and 2,947 base pairs, respectively, for all orders of placental mammals. Phylogenetic analyses resolve placental orders into four groups: Xenarthra, Afrotheria, Laurasiatheria, and Euarchonta plus Glires. The first three groups are consistently monophyletic with different methods of analysis. Euarchonta plus Glires is monophyletic or paraphyletic depending on the phylogenetic method. A unique nine-base-pair deletion in exon 11 of the BRCA1 gene provides additional support for the monophyly of Afrotheria, which includes proboscideans, sirenians, hyracoids, tubulidentates, macroscelideans, chrysochlorids and tenrecids. Laurasiatheria contains cetartiodactyls, perissodactyls, carnivores, pangolins, bats and eulipotyphlan insectivores. Parallel adaptive radiations have occurred within Laurasiatheria and Afrotheria. In each group, there are aquatic, ungulate and insectivore-like forms.

Bushbaby growth hormone is much more similar to nonprimate growth hormones than to rhesus monkey and human growth hormones.

Unlike other mammals, Old World primates have five growth hormone-like genes that are highly divergent at the amino acid level from the single growth hormone genes found in nonprimates. Additionally, there is a change in the interaction of growth hormone with its receptor in humans such that human growth hormone functions in nonprimates, whereas nonprimate growth hormone is ineffective in humans. A Southern blotting analysis of the genome of a prosimian, Galago senegalensis, revealed a single growth hormone locus. This single gene was PCR-amplified from genomic DNA and sequenced. It has a rate of nonsynonymous nucleotide substitution less than one fourth that of the human growth hormone gene, while the rates of synonymous substitution in the two species are less different. Human and rhesus monkey growth hormones exhibit variation at a number of amino acid residues that can affect receptor binding. The galago growth hormone is conservative at each of these sites, indicating that this growth hormone is functionally like nonprimate growth hormones. These observations indicate that the amplification and rapid divergence of primate growth hormones occurred after the separation of the higher primate lineage from the galago lineage.

Nonrandom segregation of the mouse univalent X chromosome: evidence of spindle-mediated meiotic drive.

A fundamental principle of Mendelian inheritance is random segregation of alleles to progeny; however, examples of distorted transmission either of specific alleles or of whole chromosomes have been described in a variety of species. In humans and mice, a distortion in chromosome transmission is often associated with a chromosome abnormality. One such example is the fertile XO female mouse. A transmission distortion effect that results in an excess of XX over XO daughters among the progeny of XO females has been recognized for nearly four decades. Utilizing contemporary methodology that combines immunofluorescence, FISH, and three-dimensional confocal microscopy, we have readdressed the meiotic segregation behavior of the single X chromosome in oocytes from XO females produced on two different inbred backgrounds. Our studies demonstrate that segregation of the univalent X chromosome at the first meiotic division is nonrandom, with preferential retention of the X chromosome in the oocyte in approximately 60% of cells. We propose that this deviation from Mendelian expectations is facilitated by a spindle-mediated mechanism. This mechanism, which appears to be a general feature of the female meiotic process, has implications for the frequency of nondisjunction in our species.

Pulmonary function in chronic spinal cord injury: a cross-sectional survey of 222 southern California adult outpatients.

OBJECTIVES: To evaluate risk factors for respiratory morbidity in chronic spinal cord injury (SCI). SETTING: Model SCI care system based at an urban public rehabilitation medical center. DESIGN: Case series with evaluation of pulmonary function by conventional spirometric testing. PARTICIPANTS: Two hundred twenty-two adults with SCI of more than 1-year duration who were not chronically dependent on mechanical ventilation, including 98 with tetraplegia (62 with complete and 26 with incomplete motor lesions) and 124 with paraplegia (87 with complete and 37 with incomplete motor lesions). MAIN OUTCOME MEASURES: Forced vital capacity (FVC), forced expired volume in 1 second (FEV1), and peak expiratory flow rate (PEFR), all measured in the supine and erect seated positions and compared with predicted normal values for industrial workers. RESULTS: FVC and FEV1 were normal in persons with low-level paraplegia who had never smoked, but both decreased similarly with rising SCI level, more markedly in those with tetraplegia. PEFR decreased with rising SCI level. Incomplete lesions mitigated function loss in those with tetraplegia. In middle-aged individuals with tetraplegia, longer duration of injury was associated with greater function loss, independent of age. Current smokers showed excess function loss, except for those with high tetraplegia. Most people with complete tetraplegia showed FVC and FEV1 increases in the supine position relative to the erect position. CONCLUSIONS: Pulmonary function is compromised by most lesions of the spinal cord, even in those with paraplegia, and is affected relative to the level of lesion. Efforts to help SCI patients minimize respiratory complications-in particular, assistance in smoking cessation-should be given high priority.

Molecular evolution of growth hormone and receptor in the guinea-pig, a mammal unresponsive to growth hormone.

Growth in the guinea-pig is completely unresponsive to endogenous or exogenous growth hormone, despite the fact that the guinea-pig produces normal to high levels of growth hormone and receptor. In primates and artiodactyls, growth hormone exhibits accelerated rates of evolution that appear to be correlated with changes in function. Surprisingly, both guinea-pig growth hormone and receptor exhibit slow rates of evolution similar to those seen in other mammals, implying that both proteins are as functionally conserved in the guinea-pig as in other mammals or that any loss or relaxation of functional constraint was very recent. However, the guinea-pig growth hormone and receptor both exhibit a single amino acid replacement at a site known to have functional significance. Nevertheless, it is unclear whether the aberrant nature of the guinea-pig growth hormone-growth hormone receptor axis is due to these replacements or whether it is due to a defect in post-receptor signalling.