Circuit obstruction.
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Airway Obstruction↗
Biomedical subjects
G M Cooper
Publications and source records attributed to G M Cooper.
Cranial base changes following coronal suturectomy in craniosynostotic rabbits.
It has been suggested that surgical release of synostosed sutures may ameliorate various cranial base abnormalities in craniosynostotic patients. The present study was designed to test this hypothesis in a rabbit model with familial coronal suture synostosis (CSS). Data were collected from 56 New Zealand White rabbits: 32 unaffected controls, 11 with unoperated CSS, and 13 with CSS released by suturectomy performed at 25 days of age. Serial radiographs were taken at 25, 42 and 84 days. Linear, angular and triangular shape cranial base measurements were compared using ANOVA and tensor biometric analysis. Results revealed that at 84 days, both groups of CSS rabbits had significantly (p < 0.05) different anterior and total cranial base lengths, flatter cranial base angles, and dysmorphic anterior cranial base shapes when compared with normals. Significant (p < 0.05) differences were noted only for palatal and cranial base angles and posterior cranial base shape between CSS rabbits with and without suturectomy. However, significant (p < 0.05) changes were noted between pre- and postoperative measurements in posterior and total cranial base lengths and anterior and posterior cranial base shapes in CSS rabbits with suturectomy. Results revealed that surgical release of synostosed coronal sutures through suturectomy did not normalize cranial base growth patterns in CSS rabbits. These findings may be explained by the relatively late age of surgical release or suturectomy site resynostosis with continued dysmorphic cranial base growth. Alternatively, cranial base abnormalities seen in CSS rabbits may be early primary malformations, not secondary deformations amenable to surgical modification.
Analysis of Variance↗
Confidential enquiries into maternal deaths, 1997-1999.
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Anesthesia, Obstetrical↗
Maternal deaths from anaesthesia. An extract from Why mothers die 1997-1999, the Confidential Enquiries into Maternal Deaths in the United Kingdom.
This article is reprinted from Why Mothers Die 1997-1999, the fifth report of the Confidential Enquiries into Maternal Deaths in the United Kingdom.
Anesthesia, Obstetrical↗
Correction of coronal suture synostosis using suture and dura mater allografts in rabbits with familial craniosynostosis.
OBJECTIVE: Resynostosis following surgical correction of craniosynostosis is a common clinical correlate. Recent studies suggest that the dura mater is necessary to maintain suture patency. It has also been hypothesized that dura mater from synostotic individuals may provide aberrant biochemical signals to the osteogenic fronts of the calvaria, which result in premature suture fusion and subsequent resynostosis following surgery. This study was designed to test this hypothesis by surgically manipulating the coronal suture and dura mater in rabbits with familial craniosynostosis to prevent postsurgical resynostosis. DESIGN: Craniofacial growth and histomorphometric data were collected from 129 rabbits: 72 normal controls and 57 rabbits with bilateral coronal suture synostosis (15 unoperated on controls; 13 surgical controls; 9 dura mater transplant only; 10 suture transplant only; and 10 suture and dura mater transplant). At 10 days of age, all rabbits had radiopaque amalgam markers placed on either side of the coronal, frontonasal, and anterior lambdoidal sutures. At 25 days of age, 42 synostosed rabbits had a 3 to 5-mm wide coronal suturectomy. Coronal sutures and/or underlying dura mater allografts were harvested from same-aged, wild-type, isohistogenic control rabbits and transplanted onto the dura mater of synostosed host rabbits. Serial radiographs were taken at 10, 25, 42, and 84 days of age, and the suturectomy sites were harvested at 84 days of age in 44 rabbits and serially sectioned for histomorphometric examination. RESULTS: Results revealed that cranial vault growth was significantly (p < .05) improved following surgical release of the fused coronal suture compared with synostosed rabbits who were not operated on but was still significantly different (p < .05) from that of normal control rabbits. By 84 days of age, significant (p < .05) differences were noted in calvarial suture marker separation, cranial vault shape indices, and cranial base angles between rabbits with and without dura mater allografts, probably as a result of resynostosis of the suturectomy site or suture-only allografts. Qualitative histological examination revealed that at 84 days of age rabbits with suture and dura allografts had patent coronal sutures, suture-only allografts had fused coronal sutures with extensive endosteal hyperostosis, dura mater-only allografts had some new bone in the suturectomy site that resembled rudimentary osteogenic fronts, and suturectomy controls had extensive endosteal bone formation and resynostosis of the suturectomy site. Significantly (p < .05) more bone was found in the suturectomy sites of rabbits without dura mater allografts compared with rabbits with dura mater allografts. CONCLUSIONS: Results support the initial hypothesis that normal dura mater allografts will maintain suture or suturectomy site patency and allow unrestricted craniofacial growth. However, it is still unclear whether the dura mater from normal rabbits was providing biochemical signals to the transplanted sutures or suturectomy sites or simply acting as a barrier to prevent abnormal biochemical signals from the dura mater of synostosed rabbits from reaching the calvaria. The clinical and therapeutic implications of these procedures are discussed.
Analysis of Variance↗
Cranial base growth and morphology in second-trimester normal human fetuses and fetuses with cleft lip.
OBJECTIVE: The present radiographic study describes the size and shape of the cranial base from the sagittal aspect for a sample of 77 second-trimester "normal" control fetuses (n = 61) and fetuses (n = 16) exhibiting isolated, unilateral clefts of the lip (CL), ranging in fertilization age from 10 to 22 weeks. METHODS: Fetuses were placed in a cephalostat, and standardized, lateral head radiographs were taken. The radiographs were traced, and 15 cephalometric landmarks were identified and digitized for analysis. Growth curves for cranial base lengths, angles, and areas were compared between control and CL groups. Also, cranial base triangles were constructed and shape comparisons were made using tensor biometric analysis. RESULTS: No significant differences (p >.05) in regression line slopes were noted for any comparisons between the control and CL samples. Tensor biometric analysis also revealed no significant differences in the shapes of various cranial base triangles between the control and CL samples. CONCLUSION: This report presents second-trimester baseline growth curves for various cranial base components in CL human fetal specimens, and these data suggest that CL fetuses may also be used as an appropriate control sample for prenatal growth comparison studies of cleft lip and palate and cleft palate.
Biometry↗
Trigonocephaly in rabbits with familial interfrontal suture synostosis: the multiple effects of premature single-suture fusion.
Previous studies from our laboratory have characterized the craniofacial morphology and growth patterns of an inbred strain of rabbits with autosomal dominant coronal suture synostosis. A number of rabbit perinates from this colony have been collected sporadically over a 5-year period with premature interfrontal suture synostosis. The present study describes the very early onset of craniofacial dysmorphology of these rabbits and compares them to similar-aged normal control rabbits. A total of 40 perinatal New Zealand White rabbits were used in the present study. Twenty-one comprised the sample with interfrontal suture synostosis and ranged in age from 27 to 38 days postconception (term = 31 days) with a mean age of 33.53 days (+/-2.84 days). Nineteen rabbits served as age-matched, normal controls (mean age = 33.05 days +/-2.79 days). Lateral and dorsoventral radiographs were collected from each rabbit. The radiographs were traced, computer digitized, and 12 craniofacial measurements, angles, and indices were obtained. Mean measures were compared using an unpaired Student's t-test. All synostosed rabbits were stillborn or died shortly after birth. Grossly, these rabbits exhibited extreme frontal bossing, trigonocephaly with sagittal keeling, and midfacial shortening. No somatic anomalies were noted. Radiographically, rabbits with interfrontal suture synostosis had significantly (P < 0.05) narrower bifrontal widths, shorter cranial vault lengths, kyphotic cranial base angles, and different cranial vault indices (shapes) compared to controls. Results reveal severe and early pathological and compensatory cranial vault changes associated with premature interfrontal suture synostosis in this rabbit model. The 100% mortality rate noted in this condition may be related to the inheritance of a lethal genetic mutation or to neural compression from reduced intracranial volume. Results are discussed in light of current pathogenic hypotheses for human infants with premature metopic suture synostosis.
Animals↗
Direct binding and activation of STAT transcription factors by the herpesvirus saimiri protein tip.
The Tip protein from Herpesvirus saimiri specifically binds to and activates the protein tyrosine kinase, p56(lck). It has been demonstrated that the expression of Tip in T cells is capable of inducing the DNA binding of members of the signal transducers and activators of transcription (STAT) family of transcription factors. We have examined the mechanism behind which STATs 1 and 3 are activated by Tip expression. Tip becomes tyrosine phosphorylated by p56(lck) at two sites in the amino-terminal tail region. One site of phosphorylation lies within a consensus YXPQ binding motif for the SH2 domains of STATs 1 and 3. We demonstrate that tyrosine phosphorylation of Tip at this site is required for the binding of STATs, and the induction of STAT dependent transcription. Furthermore, we demonstrate that, similar to STAT activation by v-Src, the optimum induction of STAT-dependent transcription by Tip requires Ras/Rac mediated signaling events.
Binding Sites↗
Intra and inter technologist variability in the quality assessment of respiratory tract specimens.
The majority of microbiology laboratories have implemented quality improvement procedures such as a Q scoring system to assess the nature of clinical specimens. Our study reviewed the sources and the amount of variation when Q scoring of lower respiratory secretions was performed. In total, 450 slides representing lower respiratory tract secretions were Q scored by three experienced technologists. Total agreement regarding the number of neutrophils, squamous epithelial cells and Q scores was 76%, 57% and 57% respectively. The major factor influencing Q score values was the enumeration of epithelial cells. From our findings, we expect that there is greater variability in Q scoring then is generally acknowledged and there is a substantial degree of subjectivity on part of individual technologists reading gram stains.
Diagnostic Techniques, Respiratory System↗
National obstetric anaesthetic practice in the UK 1997/1998.
In the United Kingdom, the Royal College of Obstetricians and Gynaecologists requires maternity units recognised for training to complete annual statistical returns. Analysis of these data revealed that anaesthetists were directly involved in more than 251 000 procedures in the peripartum period in 1997/1998. There had been an increase in the number of women delivered by Caesarean section (18. 5% of all deliveries) compared with previous reports. The proportion of Caesarean sections performed under regional anaesthesia had increased for both elective and emergency Caesarean section deliveries (85.5% and 70.2%, respectively). For pain relief in labour, there had been neither an increase nor a decrease in the uptake of regional analgesia (23.6%). There were limited training opportunities for anaesthetists in general anaesthesia for Caesarean section and for obstetricians in vaginal breech delivery. The known admissions to intensive care units equated to over 100 women per month in the United Kingdom requiring intensive care as a result of childbirth.
Analgesia, Obstetrical↗
Age-related changes in intracranial pressure in rabbits with uncorrected familial coronal suture synostosis.
OBJECTIVE: Chronic, elevated intracranial pressure (ICP) in craniosynostotic infants may result in ocular and neurocapsular problems; however, not all infants exhibit elevated ICP. Clinical ICP studies are further confounded by small and heterogeneic samples, multiple-suture involvement, and varying surgical management protocols. The present study was designed to describe longitudinal changes in ICP in a large, homogenous sample of rabbits with uncorrected familial, nonsyndromic coronal suture synostosis. METHODS: Ninety-one rabbits were divided into four groups: (1) normal rabbits (n = 28), (2) rabbits with delayed-onset coronal suture synostosis (DOCS; n = 25), (3) rabbits with unilateral coronal suture synostosis (UCS; n = 12), and (4) rabbits with bilateral coronal suture synostosis (BCS; n = 26). ICP was measured at 24 and 42 days of age using a Codman epidural microtransducer. RESULTS: Rabbits with BCS had a significantly (p < .05) higher mean ICP at 25 days of age than rabbits in the other three groups by approximately 146%. However, by 42 days of age, mean ICP in normal control rabbits and rabbits with DOCS was significantly (p < .01) increased compared with their mean ICP values seen at 25 days of age, while mean ICP in BCS rabbits significantly (p < .01) decreased (by 32%) over the same time period. ICP in rabbits with UCS was between that seen in normal control rabbits and rabbits with BCS and did not significantly (p > .05) change over time. CONCLUSIONS: These findings suggest that the degree of suture involvement may be related to early increases in ICP. Possible multifactorial explanations for intracranial decompression and compensation in the craniosynostotic rabbit model are discussed.
Aging↗
Identification of COUP-TF as a transcriptional repressor of the c-mos proto-oncogene.
The c-mos proto-oncogene is specifically expressed in the male and female germ cells of the mouse and other vertebrates. We previously identified a 15-base pair sequence element (B2) as the binding site of a candidate repressor of c-mos transcription in somatic cells. In the present study, we used the yeast one-hybrid system to isolate HeLa cell cDNAs encoding proteins that specifically bound to the c-mos B2 element. Nucleotide sequencing identified several of the clones isolated in this screen as the orphan nuclear receptors COUP-TFI and COUP-TFII. A COUP-TF-binding site was then identified within the B2 sequence. Complexes formed between purified COUP-TFs and the c-mos B2 probe comigrated in electrophoretic mobility shift assays with those formed using whole nuclear extracts of NIH 3T3 or HeLa cells. Moreover, the complexes formed with NIH 3T3 nuclear extracts and B2 probe were supershifted with antibody against COUP-TF, identifying COUP-TF as the candidate repressor previously detected in these somatic cell extracts. Substitution of a consensus COUP-TF-binding site for the c-mos negative regulatory element suppressed expression from the c-mos promoter in transfected somatic cells, demonstrating the functional activity of COUP-TF as a repressor of c-mos transcription.
3T3 Cells↗
Cardiac arrhythmias in children during outpatient general anaesthesia for dentistry: a prospective randomised trial.
BACKGROUND: Deaths in children associated with outpatient general dental anaesthesia may be attributable to sudden cardiovascular collapse precipitated by ventricular arrhythmias. A causal link between halothane anaesthesia, ventricular arrhythmias, and deaths has been suggested. We did a prospective, randomised trial to investigate the frequency and character of arrhythmias during anaesthesia with halothane and the alternative anaesthetic agent, sevoflurane. METHODS: 150 children, aged 3-15 years, who needed dental extraction under general anaesthesia were randomly assigned sevoflurane or halothane supplementation of 66% nitrous oxide in oxygen with spontaneous ventilation. The halothane group (n=50) received halothane introduced in 0.75% increments, every two to three breaths, to a maximum of 3.0%, with maintenance at 1.5%. The incremental sevoflurane group (n=50) received sevoflurane introduced in 2% increments increased to a maximum of 8%, with maintenance at 4%. The 8% sevoflurane group (n=50) received sevoflurane introduced at 8%, with maintenance at 4%. FINDINGS: 24 (48%) children receiving halothane had arrhythmias compared with four (8%) receiving incremental sevoflurane (difference 40% [95% Ci for differences 24-56] p<0.0001), and eight (16%) receiving 8% sevoflurane (difference 32% [15-50] p=0.0013). Halothane-associated arrhythmias occurred during dental extraction or emergence and were mainly ventricular. Six (12%) children in the halothane group had ventricular tachycardia. The methods of sevoflurane administration did not differ significantly for the frequency of arrhythmias (p=0.357). Sevoflurane-associated arrhythmias were mainly single supraventricular ectopic beats. INTERPRETATION: There was a strong association between halothane and ventricular arrhythmias, especially ventricular tachycardia. The use of sevoflurane in preference to halothane could contribute to a decline in morbidity and mortality associated with dental anaesthesia.
Adolescent↗
Editorial: epidural blood patch. Eur J Anaesthesiol 1999; 16: 211-213.
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Fibrin Tissue Adhesive↗
Coronal suture response to distraction osteogenesis in rabbits with delayed-onset craniosynostosis.
Recent studies have identified a subpopulation of persons with craniosynostosis who exhibit progressive or delayed-onset synostosis and mild cranial vault deformities. These persons may be good candidates for nonextirpation distraction osteogenesis. The present studies were designed to determine force-displacement parameters and assess the effects of distraction osteogenesis on coronal suture growth and morphologic characteristics in a rabbit model with congenital, delayed-onset craniosynostosis. Data were collected from a total of 178 rabbits: 71 normal controls; 16 normal controls with distraction; 72 with delayed-onset coronal suture synostosis; and 19 with delayed-onset coronal suture synostosis and distraction. At 10 days of age, all rabbits had amalgam markers placed on both sides of the coronal suture. In the force-displacement study, force-displacement distractors were placed across the coronal suture and distracted acutely for 1.0 mm at 42 days of age. Force-displacement curves for the coronal suture were best described by a third-order polynomial regression equation for both normal and synostosed groups. Significant differences (P < 0.05) were found in the mean force necessary to distract a normal suture 1 mm in distance (13.72 kg) compared with a suture with delayed-onset synostosis (48.39 kg). A significant (P < 0.05) relationship was also found between the extent of synostosis and the distractive force in rabbits with delayed-onset synostosis. In the distraction study, internal distractors were fixed across the coronal suture at 25 days of age and percutaneously and intermittently activated at an average of 0.11 mm/day for 42 days (4.54 mm total). Serial radiographs were taken at 10, 25, 42, and 84 days of age. Results revealed that rabbits with delayed-onset synostosis and distraction had significantly (P < 0.01) more coronal suture growth rates compared with rabbits with delayed-onset synostosis and no distraction. Coronal sutures were harvested at 84 days of age for qualitative histologic examination. Normal, distracted coronal sutures showed widened sutural ligaments and thin, active osteogenic fronts. In contrast, distracted coronal sutures from rabbits with delayed-onset synostosis showed narrowed sutural ligaments, thickened and blunt osteogenic fronts, and increased collagen and bony matrix deposition compared with controls. Results suggest that distraction osteogenesis without corticotomy may be a treatment alternative in persons with progressive, delayed-onset synostosis. However, these preliminary data also suggest that distractive forces may accelerate or stimulate osteogenesis differentially in persons with craniosynostosis, possibly through an underlying genetic disorder of bone and cytokine regulation. These differential osteogenic responses to distraction, if validated clinically, will need to be taken into account when planning distraction rate and rhythm protocols for patients with craniosynostosis.
Age of Onset↗
Increased intracranial pressure after coronal suturectomy in craniosynostotic rabbits.
It has been suggested that the complications associated with intracranial hypertension in craniosynostotic infants may be managed with surgical release of the synostosed sutures. However, both postoperative increases and decreases in intracranial pressure (ICP) have been reported in heterogeneous samples of infants with syndromic and nonsyndromic craniosynostoses. The present study was designed to describe longitudinal changes in ICP in a homogeneous sample of rabbits with uncorrected and corrected familial coronal suture synostosis and compare them with age-matched normal control rabbits. Fifty-three rabbits were divided into three groups: normal rabbits (n = 28), rabbits with uncorrected bilateral coronal suture synostosis (n = 9), and rabbits with bilateral coronal suture synostosis with coronal suturectomy at 25 days of age (n = 16). ICP was measured at 25 and 42 days of age using a Codman epidural microtransducer. Results revealed that rabbits with uncorrected craniosynostosis had significantly (P < 0.05) higher ICP at 25 days of age than normal control rabbits by approximately 86%. However, by 42 days of age, ICP in normal rabbits increased by 75%, whereas ICP in rabbits with uncorrected craniosynostosis decreased by 69% over the same time. Synostotic rabbits with coronal suturectomy showed a 50% decrease in ICP immediately after surgical release and then followed the normal, age-related ICP pattern, which significantly increased by 75% at 42 days of age. Results suggest that, in the rabbit model, the postsuturectomy rise in ICP may simply be normal, age-related changes, although a longer follow-up will be needed to determine the recurrence of pathological ICP. Possible multifactorial explanations for intracranial decompression and compensation in the craniosynostotic rabbit model are also discussed.
Analysis of Variance↗
B-Raf inhibits programmed cell death downstream of cytochrome c release from mitochondria by activating the MEK/Erk pathway.
Growth factor-dependent kinases, such as phosphatidylinositol 3-kinase (PI 3-kinase) and Raf kinases, have been implicated in the suppression of apoptosis. We have recently established Rat-1 fibroblast cell lines overexpressing B-Raf, leading to activation of the MEK/Erk mitogen-activated protein kinase pathway. Overexpression of B-Raf confers resistance to apoptosis induced by growth factor withdrawal or PI 3-kinase inhibition. This is accompanied by constitutive activation of Erk without effects on the PI 3-kinase/Akt pathway. The activity of MEK is essential for cell survival mediated by B-Raf overexpression, since either treatment with the specific MEK inhibitor PD98059 or expression of a dominant inhibitory MEK mutant blocks the antiapoptotic activity of B-Raf. Activation of MEK is not only necessary but also sufficient for cell survival because overexpression of constitutively activated MEK, Ras, or Raf-1, like B-Raf, prevents apoptosis after growth factor deprivation. Overexpression of B-Raf did not interfere with the release of cytochrome c from mitochondria after growth factor deprivation. However, the addition of cytochrome c to cytosols of cells overexpressing B-Raf failed to induce caspase activation. It thus appears that the B-Raf/MEK/Erk pathway confers protection against apoptosis at the level of cytosolic caspase activation, downstream of the release of cytochrome c from mitochondria.
Animals↗
Brain growth rates in craniosynostotic rabbits.
OBJECTIVE: It has been suggested that abnormal brain morphology or growth rates may be a primary causal factor of craniosynostosis due, in part, to a lack of normal growth stretch and tension at the sutural margins. The purpose of the present study was to quantify cerebral hemisphere morphology and growth in a rabbit model of nonsyndromic coronal suture synostosis to determine whether cerebral dysmorphology is primary or secondary to synostosis in this model. DESIGN: Fifty-seven brains (114 hemispheres) were examined from 40 normal control rabbits and 17 rabbits with bilateral coronal suture synostosis ranging in age from 25 to 450 days postconception (synostosis occurs at approximately 23 days postconception in this model). The calvariae were removed, the brains were fixed in 10% paraformaldehyde, and in situ bilateral measurements of cerebral hemisphere length and cerebral hemisphere width were obtained using a Wild microscope with a camera lucida attachment and digital caliper. Regression analysis was used to compare cerebral cortex growth rates by age between the two groups. RESULTS: Cerebral hemisphere width and cerebral index regression line slopes had similar y intercepts (23 day postconception) with significantly (p < .05) diverging slopes over time. Normal rabbits increased more rapidly than synostosed rabbits. No significant (p > .05) differences were noted in regression line slopes between groups for cerebral hemisphere length by age or length by width. CONCLUSIONS: Cerebral dysmorphologies are probably a compensatory, secondary (postsynostotic) event and not a primary causal factor of craniosynostosis in this rabbit model of human familial, nonsyndromic coronal suture synostosis.
Aging↗