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Biomedical subjects

J W Keeling

Publications and source records attributed to J W Keeling.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prenatal malformed lumbar vertebral corpora in trisomies 21, 18, and 13, evaluated radiographically and histologically.

The aim of the present study was to compare, both radiographically and histologically, malformed vertebral lumbar corpora in trisomies 21, 18 and 13 with earlier reported normal corporal development in the axial lumbar region. Axial skeletons of human fetuses (GA 15-22 wk) derived from therapeutically induced abortion were investigated in connection with requested autopsy. The number of lumbar vertebral corpora examined for each genotype was as follows: 20 from trisomy 21, 10 from trisomy 18, and 10 from trisomy 13. After radiography in frontal, lateral and axial projections, the individual vertebral corpora were decalcified and horizontally embedded in paraffin. The blocks were serially sectioned and stained with toluidine blue and alcian blue/van Gieson. The radiographic characteristics of the vertebral corpora varied from an almost normal appearance of the corporal bone to complete clefting of the bony corpora. Histological examination showed accumulations of cartilage centrally, in some cases associated with amorphous material. Pronounced metachromatic differences were observed in the cartilaginous ground substance. The study showed identical phenotypic characteristics in the corpora from trisomy 21, trisomy 18, and trisomy 13. It is characteristic of all three genotypes that there are central anomalies, corresponding to the location of the notochord in normal corpora, and marked regional differences in metachromasia in the ground substance of the cartilage.

Abortion, Induced↗
PubMed1999

Detection of pyrogenic toxins of Staphylococcus aureus in sudden infant death syndrome.

It has been suggested that pyrogenic toxins of Staphylococcus aureus are involved in the series of events leading to some cases of sudden infant death syndrome (SIDS). The objectives of the study were to screen tissues from SIDS infants for pyrogenic toxins and to compare incidence of identification of these toxins among these infants from different countries. An enzyme-linked immunosorbent assay (ELISA) and a flow cytometry method were used to screen body fluids and frozen or formalin-fixed tissues for pyrogenic toxins of S. aureus, toxic shock syndrome toxin 1 (TSST), staphylococcal enterotoxins A (SEA), B (SEB), and C1 (SEC). Toxins were identified in tissues of 33/62 (53%) SIDS infants from three different countries: Scotland (10/ 19, 56%); France (7/13, 55%); Australia (16/30, 53%). In the Australian series, toxins were identified in only 3/19 (16%) non-SIDS deaths (chi2 = 5.42, P < 0.02). The flow cytometry method was useful for toxin detection in both frozen and fixed tissues, but ELISA was suitable only for frozen tissues or those fixed for less than 12 months. Identification of pyrogenic toxins in > 50% of SIDS infants from three different countries indicated further investigation into the role the toxins play in cot deaths might result in development of additional measures to reduce further the incidence of these infant deaths.

Bacterial Toxins↗
PubMed1999

Skeletal malformations in fetuses with Meckel syndrome.

In six fetuses with Meckel syndrome (gestational age 16-23 weeks, crown-rump length 130-170 mm) the skeleton was examined as part of the autopsy procedure using whole body radiography and special radiographic techniques. In the upper and lower limbs we found similar types of polydactyly. We noted four types, based on the number and morphology of metacarpals and metatarsals. In the individual fetus there was more often similarity in the pattern of malformation in the two hands or in the two feet than there was between the pattern of malformation seen in the hands and that seen in the feet. Only one foot was normal. Malformations of the cranial base (the basilar part of the occipital bone or the postsphenoid bone) occurred in five cases, and the vertebral bodies in the lumbar region of the spine were malformed (cleft) in three cases. It is proposed that a skeletal analysis be included in the future evaluation of phenotypes in Meckel syndrome.

Abnormalities, Multiple↗
PubMed1999

Pituitary gland and axial skeletal malformations in human fetuses with spina bifida.

The purpose of the present study was to describe the pituitary gland and axial skeleton, including the sella turcica, in human fetuses with spina bifida. Ten fetuses with gestational ages (GA) 15 1/2-28 weeks were investigated radiographically (Faxitron X-ray apparatus) and immunohistochemically. Four of the fetuses have been described previously. The study showed that nine fetuses had minor or no skeletal abnormalities in the vertebral bodies of the spine, and one fetus had severely malformed vertebral bodies. In all cases the sella turcica and the pituitary gland were malformed. Adenopituitary tissue was in all cases located in both the sella turcica and the pharyngeal submucosa. The most severe sella turcica/pituitary gland malformation was seen in the fetus with the malformed spine. The connection between the prenatally registered sella turcica/pituitary gland malformation and the endocrinological status of children with spina bifida should be emphasized in future studies.

Fetus↗
PubMed1999

Malformations of cranial base structures and pituitary gland in prenatal Meckel syndrome.

The sella turcica region, including the clivus and the pituitary gland, was studied histologically in five human fetuses with Meckel syndrome (MS). All cases had malformed sella turcica and malformed clivus with irregularly shaped notochordal remnants. We consider that these three characteristics are constant phenotypic traits in MS. The adenohypophysis was present in three cases. In one of these, ectopia of the gland occurred with adenopituitary tissue overlying the dorsum sella, and in another remnants were found in the pharyngeal submucosa. In two fetuses the neurohypophysis was not found. The findings in the region were compared to normal findings and to findings in trisomy 18, where cranial base structures radiographically appeared similar to those in MS. We conclude that in MS specific characteristics are found in the cranial base region and that radiographic analysis needs to be supplemented by histological analysis when studying this specific region.

Abnormalities, Multiple↗
PubMed1999

Histological changes in the hearts of non-survivors of the UK collaborative trial of neonatal ECMO (extra corporeal membrane oxygen).

AIMS: To study the cardiac pathology of infants enrolled in the UK collaborative trial of neonatal ECMO (extra corporeal membrane oxygen) who died following random allocation to a trial arm. METHODS: During the trial, 81 infants died. The hearts of 26 babies were received and examined without knowledge of treatment regimen. The control group consisted of 14 infants who received conventional treatment. Twelve were allocated to ECMO; seven received this treatment. RESULTS: In the control group, four showed minor histological changes. The other hearts were histologically normal. In the group treated with ECMO, four had multiple foci of micro-infarction throughout both ventricles and papillary muscles. There was variable thrombotic vascular occlusion. Three were normal. There was no correlation between cardiac pathology and clinical features. There was a significant difference in the length of survival between the two groups. CONCLUSIONS: ECMO treatment seems to be associated with clinically significant cardiac pathology. The changes observed may reflect the longevity of survival in the ECMO group rather than an association with the treatment itself. Nevertheless, the findings have significant implications for those monitoring the development of infants surviving ECMO treatment and suggest that the monitoring of myocardial function will be crucial.

Cadaver↗
PubMed1998

Pituitary gland and sella turcica in human trisomy 21 fetuses related to axial skeletal development.

The purpose of the present investigation was to study the sella turcica/pituitary gland region in trisomy 21 fetuses and to relate the findings in the region to the ossification pattern in the axial skeleton formed by the cranial base and spine. Material from 22 human fetuses with trisomy 21, CRL 80 mm to CRL 190 mm, corresponding to gestational ages from 14 to 21 weeks, was examined and compared with material from gestation-matched normal controls. After radiography, tissue blocks from the cranial base, including the pituitary gland, were examined and compared with those of normal fetuses. Four different types of sella turcica/ pituitary gland morphology were observed. Thirteen fetuses (Type I) were morphologically normal. Minor abnormalities occurred in the sella turcica and pituitary gland (adenopituitary gland tissue pharyngeally) in six fetuses (Types II and III). There was agreement between the histologically recorded deviations in the sella turcica and the radiographic observations of the basisphenoid bone. In three cases (Type IV) out of 22, more pronounced structural abnormalities occurred in the sella turcica, and radiographically the basisphenoid bone appeared cleft. All sella turcica changes observed in trisomy 21 were situated anteriorly in the base of the sella. In all cases the basilar part of the occipital bone was normal. Minor changes in the sella turcica region were mainly accompanied by cervical vertebral abnormalities, while the most severe abnormalities occurred in association with malformations in the lumbar vertebrae. There was no association between sella turcica malformations and the absence or presence of the nasal bone.

Bone and Bones↗
PubMed1998

Hand development in trisomy 21.

The purpose of the present study was to evaluate hand size and maturity in fetuses with trisomy 21 (Down syndrome). Twenty-five fetuses, crown-rump length (CRL) 55-222 mm, foot length (FL) 8-42 mm, were included in the study. After whole-body radiography (Hewlett Packard Faxitron), special radiographs of the hand and foot were taken. Hand length was measured as the length of the third finger from the distal tip of the distal phalanx to the proximal tip of the metacarpal bone, the digital-metacarpal length (DML). The lengths of the proximal phalangeal bone (PPL) and the metacarpal bone (MCL) of the third finger were also measured. The DML, PPL, and MCL values of each fetus were related to CRL and FL. The individual hand bones were evaluated with regard to time of appearance on radiographs, sequence in comparison with the normal sequence of appearance, and morphology. The hand length is normal during the first half of the fetal period, whereas the length of individual bones in the third finger is reduced. The normal sequence of ossification, with the middle phalanx of the fifth finger last to ossify, also occurred in Down syndrome; however, this bone appeared later in Down syndrome. In four of the fetuses it did not appear.

Bone Development↗
PubMed1998

Pituitary gland and sella turcica in human trisomy 18 fetuses.

The purpose of this study was to elucidate the phenotypic conditions in the sella turcica/pituitary gland complex in human trisomy 18 fetuses. Fourteen human fetuses with gestational ages from 12 to 39 weeks were included in the study. Normal fetuses at corresponding ages were used as controls. Whole body and special radiographic examination was undertaken before the midsagittal cranial base block, including the pituitary gland, was excised and analyzed histologically and immunohistochemically (keratin wide spectrum [KWS], thyroid-stimulating hormone [TSH], and neurophysin [Nph]). In all trisomy 18 fetuses, TSH-positive adenopituitary tissue was present in the sella and in greater or lesser amounts pharyngeally. The neurohypophysis was Nph-positive and located normally in the sella turcica. The adenohypophyseal tissue reacted either KWS-faint or KWS-negative, whereas KWS-positive reaction occurs in normal fetuses. This circumstance might suggest an altered cytoskeletal structure of the surface ectoderm in the pituitary placode in trisomy 18. The sella turcica was malformed in all the fetuses. Very broad craniopharyngeal canals were observed in some of the fetuses. Because endocrine disorders occur in many congenital malformations, it is essential in future studies to chart the sella turcica/pituitary gland region systematically in different genotypes.

Abnormalities, Multiple↗
PubMed1998

Clinical phenotype of desmosterolosis.

We describe a child with lethal multiple malformations and generalised accumulation of desmosterol. The infant had macrocephaly, a hypoplastic nasal bridge, thick alveolar ridges, gingival nodules, cleft palate, total anomalous pulmonary venous drainage, ambiguous genitalia, short limbs, and generalised osteosclerosis. Gas chromatography-mass spectrometry demonstrated an abnormal accumulation of desmosterol in kidney, liver. and brain. Higher than normal levels of the same sterol were detected in plasma samples obtained from both parents. The biochemical phenotype in this infant is highly suggestive of a novel inborn error of cholesterol biosynthesis caused by an autosomal recessive deficiency of 3betahydroxysterol-delta24-reductase. A phenotypic overlap of this case with Raine syndrome was noted; however, desmosterol accumulation was not found on postmortem tissue samples from a previously reported case of this disorder.

Abnormalities, Multiple↗
PubMed1998

Hepatoblastoma: DNA nuclear content, proliferative indices, and pathology.

Hepatoblastoma (HB) is the most frequent malignant liver tumor in infancy, and both its biological features and its prognostic behavior are still under investigation. DNA content and proliferative activity of the tumor have been considered as biological parameters related to the tumor's aggressiveness. The present study attempts to investigate the possible association between histologic subtype, DNA content, and proliferative indices in HB. DNA content and the proportion of cells in the S-phase were assessed by flow cytometry in 34 cases of HB (14 prior to chemotherapy, 20 after chemotherapy), using formalin-fixed, paraffin-embedded archival samples. The proliferative cell nuclear antigen (PCNA) labeling index was also evaluated by immunohistochemistry, and both the flow cytometry (FC) and the immunohistochemical data were correlated with tumor pathology. A significant association was found between histological type, DNA content and the percentage of cells in the S-phase, with aneuploidy and the highest proportions of S-phase cells significantly associated with embryonal tumors. The PCNA labeling index was found to be significantly higher in embryonal than in fetal phenotype. The biological heterogeneity of HB is Confirmed by the different nuclear content of the fetal (diploid) and embryonal (aneuploid) epithelial components of the tumor, also ruling out the likelihood of fetal (diploid) clones deriving from the embryonal (aneuploid) neoplastic cells. Since the highly proliferative neoplastic clones (i.e., embryonal) are thought to be more sensitive to antimitotic drugs, further studies are indicated to determine the relationship between ploidy, proliferative indices and chemoresponsiveness.

Child↗
PubMed1997

Pattern of malformations in the axial skeleton in human triploid fetuses.

We examined the axial skeleton in 15 human triploid fetuses (10 with XXX and 5 with XXY sex chromosomes). All fetuses 14-29 weeks of gestational age (GA), underwent whole-body radiography, permitting analysis of the nasal bone and the spine. From 9 of these, detailed radiographs were taken of midsagittal blocks of the cranial base and the spine, permitting detailed analysis of the cranial base. NASAL BONE: Of 14 fetuses, where the nasal bone was seen on lateral projection, it appeared short in 10 cases. SPINE: The spine was normal in 7 of 15 fetuses; malformations occurred in 8. These were osseous fusions between 2 or more vertebral bodies, most frequently in the cervical and thoracic regions, and disproportions in the sizes of the cervical bodies. Fusions occurred in 5 cases alone, and in one case in combination with disproportions of vertebral size. Disproportions alone occurred in 2 cases. CRANIAL BASE: Malformation of the basilar part of the occipital bone was found in 5 of the 9 fetuses investigated. Of 9 fetuses, bilateral ossification centers of the postsphenoid bone occurred in 7, and shell-like ossification centers in 2. There was no difference in the type of malformations in the different axial fields related to genotype (XXX and XXY). CONCLUSION: The most remarkable findings in the axial skeleton of triploid fetuses are vertebral fusions in 6 of 15 cases; clefts of vertebral bodies, previously reported as common findings in trisomy fetuses, are not demonstrated.

Abnormalities, Multiple↗
PubMed1997

Pattern of malformations in the axial skeleton in human trisomy 13 fetuses.

The purpose of this study was to analyse the development of the axial skeleton in human trisomy 13 fetuses and to define which fields in the axial skeleton are affected in this condition. We investigated nine human fetuses with trisomy 13 and gestational ages of 14-19 weeks. Whole body radiographs and radiographs of midsagittal tissue blocks of the cranial base and the spine were studied. In the youngest fetus, 14 w GA, no malformations were observed. In eight fetuses, 17-19 weeks GA, malformations occurred in the lumbosacral spine. In four fetuses additional malformations were observed in the thoracic spine. The study showed that there was a correspondence between the extent of malformation in the lumbosacral spine and the thoracic spine. When mild malformation occurred in the lumbosacral region, no malformation was observed in the thoracic region, whereas malformation was observed in the thoracic region when there was extensive malformation in the lumbosacral region. Malformations did not occur in the cervical spine or the basilar part of the occipital bone, but the postsphenoidal part of the sphenoid bone was small and irregular in the six cases where it could be examined. In seven fetuses there was malformation or agenesis of the nasal bone. This pattern of axial skeletal malformations in trisomy 13 fetuses was not described previously. Comparisons are made with previous studies of the fetal axial skeleton in trisomy 18 and trisomy 21, where the pattern of malformations was different. We reiterate our recommendation that axial skeletal radiography should be part of the postmortem examination of fetuses with suspected or verified chromosome abnormalities.

Abnormalities, Multiple↗
PubMed1997

Pattern of malformations in the axial skeleton in human trisomy 21 fetuses.

In the present study, we analyzed the development of the axial skeleton in human trisomy 21 fetuses and defined the fields in the axial skeleton affected in this form of aneuploidy. We investigated 31 human fetuses with trisomy 21, gestational ages 12-24 weeks, on the basis of radiographs of midsagittal tissue blocks of the axial skeleton, comprising the cranial base and the spine. Malformation or agenesis of the nasal bone was present in 19 of 31 fetuses. Nineteen cases had vertebral malformations. Fourteen fetuses had malformations in the cervical region, four in the thoracic and eight in the lumbosacral region. In 1 of 31 fetuses, malformation was seen in the basilar part of the occipital bone. The basisphenoid component appeared scallop-shaped in 30 cases. The pattern of axial skeletal malformations in trisomy 21 fetuses recorded here has not been described previously. Comparison is made with our recent study of trisomy 18, where the pattern of axial skeletal malformations was quite different. It is recommended that axial skeletal radiography should be part of the autopsy of fetuses where chromosome abnormalities are known or suspected.

Bone and Bones↗
PubMed1996

Pattern of malformations in the axial skeleton in human trisomy 18 fetuses.

We examined and described the development and abnormalities of the axial skeleton in 10 human trisomy 18 fetuses. Whole-body radiographs and radiographs of midsagittal tissue blocks of the cranial base and the spine were studied. In 3 fetuses no spinal radiographs were available. Seven osseous regions or fields along the body axis were analyzed, four in the spine, and three in the cranial base and nasal bones. Malformations occurred in the occipital field in all fetuses. This was a characteristic notching, either unilateral or bilateral, of the basilar part of the occipital bone. Nasal bones were abnormal in 8 cases, either absent or hypoplastic. Malformations were found in the thoracic and/or lumbosacral field in 7 fetuses. A single abnormality was found in the cervical spine in one fetus. The pattern of axial skeletal malformation in trisomy 18 fetuses recorded in the present study has not been described previously. Axial skeletal radiography should be included in autopsies of fetuses when chromosome disorders are present or suspected. The methods applied here are unaffected by autolysis.

Chromosomes, Human, Pair 18↗
PubMed1996

Developmental and environmental factors that enhance binding of Bordetella pertussis to human epithelial cells in relation to sudden infant death syndrome (SIDS).

Asymptomatic infection due to Bordetella pertussis has been suggested to be one cause of sudden infant death syndrome (SIDS). We examined developmental and environmental factors previously found to affect binding of another toxigenic species, Staphylococcus aureus, to human epithelial cells: expression of the Lewis(a) antigen; infection with respiratory syncytial virus (RSV); exposure to cigarette smoke; and the inhibitory effect of breast milk on bacterial binding. Binding of two strains of B. pertussis (8002 and 250825) to buccal epithelial cells was significantly reduced by treating the cells with monoclonal antibodies to Lewis(a) (P < 0.05) and Lewis(x) (P < 0.01) antigens. Both strains bound in significantly greater numbers to cells from smokers compared with cells from non-smokers (P < 0.05). HEp-2 cells infected with RSV subtypes A or B had higher binding indices for both 8002 (P < 0.001) and 250825 (P < 0.01). On RSV-infected cells, there was significantly enhanced binding of monoclonal antibodies to Lewis(x) (P < 0.05), CD14 (P < 0.001) and CD18 (P < 0.01); and pre-treatment of cells with anti-CD14 or CD18 also significantly reduced binding of both strains of B. pertussis. Pre-treatment of the bacteria with human milk significantly reduced their binding to epithelial cells. The results are discussed in relation to our three-year survey of bacterial carriage among 253 healthy infants, their mothers and local SIDS cases between 1993-1995 and in relation to the change to an earlier immunisation schedule for infants and the recent decline in SIDS in Britain.

Antibodies, Monoclonal↗