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Biomedical subjects

R John

Publications and source records attributed to R John.

At least 73 records · Page 4Linked to original sources
PubMed1998

Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia.

Congenital hypothyroidism occurs in one of every three to four thousand newborns, owing to complete or partial failure of thyroid gland development. Although thyroid hypoplasia has recently been associated with mutations in the thyrotropin (TSH) receptor, the cause of thyroid agenesis is unknown. Proteins including thyroid transcription factors 1 (TTF-1; refs 4,5) and 2 (TTF-2; refs 6,7) and Pax8 (refs 8,9) are abundant in the developing mouse thyroid and are known to regulate genes expressed during its differentiation (for example, thyroid peroxidase and thyroglobulin genes). TTF-2 is a member of the forkhead/winged-helix domain transcription factor family, many of which are key regulators of embryogenesis. Here we report that the transcription factor FKHL15 (ref. 11) is the human homologue of mouse TTF-2 (encoded by the Titf2 gene) and that two siblings with thyroid agenesis, cleft palate and choanal atresia are homozygous for a missense mutation (Ala65Val) within its forkhead domain. The mutant protein exhibits impaired DNA binding and loss of transcriptional function. Our observations represent the first description of a genetic cause for thyroid agenesis.

Abnormalities, Multiple↗
PubMed1998

Congenital hypothyroidism in Wales (1982-1993): demographic features, clinical presentation and effects on early neurodevelopment.

OBJECTIVE: Neonatal screening for congenital hypothyroidism (CH) was introduced in Wales in 1982. The aim of the study was to evaluate the demographic features and characteristics of infants identified during the first 12 years of screening and their neurodevelopmental progress in the first 2 years of life. DESIGN: Prospective collection of biochemical and clinical data (including results of Griffiths Mental Development Scales) obtained from questionnaires sent to paediatricians responsible for the ongoing clinical care of children with CH. PATIENTS: In Wales, between 1982 and 1993, 136 infants with primary congenital hypothyroidism (CH) were identified by the neonatal screening programme. RESULTS: Of all new-borns, 99.8% were screened and the prevalence of CH was 1 in 3279 (1 in 2473 girls and 1 in 4770 boys). The prevalence of CH was increased in North Wales. CH was associated with increased birth weight (48.5% of infants weighed greater than 3.5 kg) and an increased prevalence of non-thyroidal congenital abnormalities (8%) and congenital heart disease (3%). Isotope scanning demonstrated an increased prevalence of normal or enlarged thyroid glands and fewer ectopic glands compared to those reported in other studies. The mean developmental quotients (DQs) for individual subsets of intellectual and behavioural functioning in children with CH aged 1 and 2 years were all above 100 (range: 103.5-111.9). In subjects with absent thyroids, these DQs were correlated with the serum concentrations of free thyroxine before treatment. CONCLUSIONS: The demographic features of infants with congenital hypothyroidism born in Wales are similar to those reported from other European studies although there are marked regional variations in prevalence within Wales for which there is no apparent explanation. The median age of starting therapy was 17 days and compares favourably with other screening programmes. The overall mental development of Welsh children aged 1 and 2 years with congenital hypothyroidism identified by neonatal screening is satisfactory.

Congenital Abnormalities↗
PubMed1998

Intra-abdominal hypertension after life-threatening penetrating abdominal trauma: prophylaxis, incidence, and clinical relevance to gastric mucosal pH and abdominal compartment syndrome.

OBJECTIVE: To define the incidence, prophylaxis, and treatment of intra-abdominal hypertension (IAH) and its relevance to gut mucosal pH (pHi), multiorgan dysfunction syndrome, and the abdominal compartment syndrome (ACS). METHODS: Seventy patients in the SICU at a Level I trauma center (1992-1996) with life threatening penetrating abdominal trauma had intra-abdominal pressure estimated by bladder pressure. pHi was measured by gastric tonometry every 4 to 6 hours. IAH (intra-abdominal pressure> 25 cm of H2O) was treated by bedside or operating room laparotomy. RESULTS: Injury severity was comparable between patients who had mesh closure as prophylaxis for IAH (n = 45) and those who had fascial suture (n = 25). IAH was seen in 10 (22.2%) in the mesh group versus 13 (52%) in the fascial suture group (p = 0.012) for an overall incidence of 32.9%. Forty-two patients had pHi monitoring, and 11 of them had IAH. Of the 11 patients, eight patients (72.7%) had acidotic pHi (7.10 +/- 0.2) with IAH without exhibiting the classic signs of ACS. The pHi improved after abdominal decompression in six and none developed ACS. Only two patients with IAH and low pHi went on to develop ACS, despite abdominal decompression. Multiorgan dysfunction syndrome points and death were less in patients without IAH than those with IAH and in patients who had mesh closure. CONCLUSIONS: IAH is frequent after major abdominal trauma. It may cause gut mucosal acidosis at lower bladder pressures, long before the onset of clinical ACS. Uncorrected, it may lead to splanchnic hypoperfusion, ACS, distant organ failure, and death. Prophylactic mesh closure of the abdomen may facilitate the prevention and bedside treatment of IAH and reduce these complications.

Abdomen↗
PubMed1998

Importance of CD49d-VCAM interactions in human monocyte adhesion to porcine endothelium.

By using a primate model of natural antibody depletion, we have previously shown that delayed rejection of porcine cardiac xenografts in unmodified primate recipients resulted from xenograft infiltration with monocyte/macrophage lineage cells. In the present study, we initially showed that human monocytes/macrophages demonstrated significantly greater adherence to unstimulated pig aortic endothelial cells (PAEC) than to human umbilical vein endothelial cells (HUVEC). Human TNF-alpha augmented monocyte adhesion to HUVEC by 5-fold higher levels than to PAEC. This effect could not be explained on the basis of incompatibility between human TNF-alpha and its receptor on PAEC since porcine VCAM expression increased by 75-85% after stimulation with TNF-alpha. TNF-augmented monocyte adherence was abrogated by either treatment of PAEC with an anti-VCAM Mab or monocytes with an anti-CD49d Mab. These results suggest that VCAM-CD49d interactions are important in adhesion of human monocytes to PAEC but may not be as effective as those between human monocytes and allogeneic endothelium, perhaps because of structural differences across species. Other interactions, as yet undefined, must explain the relative increase in adhesiveness of human monocytes for unstimulated PAEC versus HUVEC. In experiments investigating the functional consequences of this enhanced monocyte adherence, PAEC stimulation induced 10-fold higher levels of macrophage-derived IL-1 beta and 3-fold higher levels of T cell proliferation compared with HUVEC. Using an anti-DR Mab to interrupt antigen presentation by autologous macrophages markedly reduced the T cell proliferative response to PAEC. Together, these results indicate that the enhanced adherence of human monocytes to PAEC contributes to xenograft rejection beyond the hyperacute period by leading to tissue infiltration, elaboration of cytokines, and an augmented indirect pathway of T cell xenoantigen recognition.

Animals↗
PubMed1998

Exploring intra-ethnic diversity among four groups of Hispanic elderly: patterns and levels of service utilization.

This study investigates service use by a sample of 2,135 Hispanic elderly in order to address the issue of the homogeneity or heterogeneity within the older Hispanic population as revealed by the use of formal services. Factor analysis revealed a high degree of homogeneity in the patterns of formal service use among the four Hispanic groups in this study that follows three latent, but distinct, patterns of behavior: the use of federal entitlement programs, in-home services, and senior center services. Although the patterns of service use reflect substantial homogeneity among the Hispanics in this sample, there is a high degree of heterogeneity in the level of service use. Overall, service use was systematically lower among "Other" Hispanic elders and systematically higher among Puerto Rican elders, with somewhat more erratic use among Cuban American and Mexican American elders. Controlling for between-group differences in socio-demographic characteristics did little to reduce relatively systematic between-group differences in levels of service use.

Aged↗
PubMed1998

Role of cardiopulmonary bypass in single vessel coronary revascularization: implications for MID-CABG.

BACKGROUND: Minimally invasive direct coronary artery bypass grafting (MID-CABG) is being utilized for the treatment of coronary artery disease in selected patients. This innovative procedure has generated numerous technical issues relating to coronary revascularization, including whether to perform the revascularization with or without cardiopulmonary bypass (CPB). METHODS: We addressed this issue indirectly by analyzing the 1995 New York State CABG registry, comparing patients who had single vessel bypass without CPB (Non-CPB Group) to a similar cohort of patients who had CABG performed on CPB (CPB Group). The database showed stratification of patients selected for bypass grafting without CPB to a significantly higher risk group, as shown by increased age, higher incidence of reoperation, transmural MI, congestive heart failure, carotid/cerebrovascular disease, and peripheral vascular disease. RESULTS: Patients in the Non-CPB Group had a higher incidence of postoperative malignant ventricular arrhythmias and heart block requiring pacemaker insertion. Otherwise, the incidence of postoperative complications was similar between the two groups. CONCLUSIONS: There were no statistical differences in the hospital mortality or the length of hospitalization between the two groups. In conclusion, the data showed a definite trend toward doing higher risk cases off CPB. These cases had an acceptable early morbidity and mortality outcome. The results were comparable to a group of lower risk patients with single vessel CABG done on cardiopulmonary bypass. However, further follow-up are required to evaluate long-term outcomes and confirm the utility of this surgical option.

Aged↗
PubMed1998

Reattachment of a fractured maxillary incisor crown--case report.

Management of traumatic injuries to the teeth is a challenge to the practising dentist. It has no prescriptive method for occurring, possesses no significant predictable pattern of intensity or extensiveness and occurring at times when dentists are least prepared for it. It may not only leave physical scars but also a psychological impact on its victim. Yet, more than half of all children traumatize either their primary or permanent teeth before leaving the school, coupled with the dynamic panorama of sporting activity worldwide and the significant increase in violence among the populations. Tooth trauma and its management loom as a major challenge to the dental practitioner. A case of a 11 year old boy with Ellis Class 3 traumatic injury to the maxillary left central incisor is reported. A pulpectomy was performed followed by reinforcement and reattachment of the crown fragment and restoration with composite resin.

Accidental Falls↗
PubMed1997

Isolated myocyte contractile function is normal in postinfarct remodeled rat heart with systolic dysfunction.

BACKGROUND: Postinfarction ventricular remodeling is associated with lengthening and contractile dysfunction of the remote noninfarcted myocardium. Mechanisms underlying this phenomenon remain unclear. METHODS AND RESULTS: We studied serial changes in global left ventricular (LV) structure and function in infarcted (1, 2, 4, and 6 weeks after myocardial infarction) and sham-operated rat hearts and correlated them with structural and functional changes in myocytes isolated from the remote LV myocardium in the same hearts. Rats with myocardial infarction developed significant remodeling. The heart weight-to-body weight ratios were increased. LV volumes at filling pressure of 10 mm Hg were higher (305+/-28 versus 215+/-12 microL, P<.01). This was accompanied by global LV dysfunction (in vivo LV end-diastolic pressure, 4+/-1 versus 23+/-1.6 mm Hg; Langendorff LV developed pressure, 105+/-4 versus 62+/-9 mm Hg, P<.001 for both). Myocytes isolated from these hearts showed significant structural remodeling (LV myocytes, 24% longer and 15% wider; right ventricular myocytes, 38% longer and 31% wider, all P<.05). LV myocyte length correlated with changes in LV volume (r=.79) and function (LV developed pressure, r=-.81). However, LV myocytes from the same hearts showed normal contractile function and intracellular Ca2+ transients at baseline and during inotropic stimulation with increasing extracellular Ca2+ (1 to 6 mmol/L). The shortening-frequency relationship was also similar in myocytes from sham and myocardial infarction rats. CONCLUSIONS: Postinfarct LV remodeling occurs predominantly by myocyte lengthening rather than by myocyte slippage. However, contractile function of the unloaded myocytes from the remote noninfarcted LV myocardium of the remodeled heart is normal. Therefore, myocyte contractile abnormalities may not contribute to global dysfunction of the remodeled heart. Reduced myocyte mass and nonmyocyte factors like increased wall stress, altered LV geometry, and changes in the myocardial interstitium may be more important in the genesis of postinfarct LV dysfunction in this model.

Animals↗
PubMed1997

Risk factors for the development of bronchiolitis obliterans syndrome after lung transplantation.

OBJECTIVE: This study identifies specific clinical and immunologic factors in lung transplant recipients that influence the subsequent development of chronic allograft dysfunction. METHODS: The study group consisted of 132 consecutive patients who received lung allografts (76 single, 25 bilateral single, and 31 heart-lung) and survived at least 90 days. One hundred twenty-one patients were used in the analysis that modeled time to development of histologic obliterative bronchiolitis or bronchiolitis obliterans syndrome. RESULTS: Variables noted to have an effect on the time to development of bronchiolitis obliterans syndrome included cytomegalovirus pneumonitis (RR = 3.2, p = 0.001), late acute rejection (RR = 1.3, p = 0.02), human leukocyte antigen mismatches at the A loci (RR = 1.8, p = 0.02), total human leukocyte antigen mismatches (RR = 1.4, p = 0.04), and absence of donor antigen-specific hyporeactivity (52% vs 100% survival free from bronchiolitis obliterans syndrome at 2 years; p = 0.005). Cytomegalovirus pneumonitis had a significant effect on time to obliterative bronchiolitis (RR = 3.6, p = 0.0005), as did donor antigen-specific hyporeactivity (52% vs 100% survival free from obliterative bronchiolitis at 2 years; p = 0.01). In multivariate analysis, cytomegalovirus pneumonitis (RR = 3.2, p = 0.02), human leukocyte antigen mismatches at the A loci (RR = 2.4, p = 0.006), and late acute rejection (RR = 1.3, p = 0.02) were identified as predictors of bronchiolitis obliterans syndrome. Cytomegalovirus pneumonitis was associated with time to development of histologic obliterative bronchiolitis (RR = 2.3, p = 0.02). CONCLUSIONS: Several risk factors were associated with the development of chronic allograft dysfunction, which, in turn, had a significant impact on long-term survival. Early identification of lung allograft recipients with risk factors for the development of bronchiolitis obliterans syndrome may allow modification in immunosuppression and antiviral therapy to potentially decrease the prevalence of this disorder.

Adult↗
PubMed1997

Application of the fuzzy ART/MAP and MINMAX/MAP neural network models to radiographic image classification.

This paper concerns the classification analysis of exercise-induced lower leg pain by applying competitive neural network clustering and mapping techniques to type 1 and type 2 fuzzy descriptions of bone scan images of the tibia. The clusters are described and compared with each other and with the experts known classes that would be expected from medical findings. The discovered clusters provide training sets for supervised learning by an ARTMAP and similar neural network. These were used to classify the previously unclassified images and hence improve the classification process. The overall conclusion is that the use of the neural clustering methods has improved the classification process of the shin images despite the paucity of data and its inherent uncertainty.

Athletic Injuries↗
PubMed1997

Beyond familism?: Familism as explicit motive for eldercare among Mexican American caregivers.

This research explored eldercare among Mexican American primary family caregivers from Dallas and Fort Worth, Texas. Although these caregivers expressed feelings of burden, their ethnocultural values of familism placed burden in a broader cultural context in which caregiving was also viewed as an affirmation and fulfillment of core Mexican American cultural values. Mexican American familism includes expressions of family solidarity, ethnocultural determinants of informal caregiving, distrust of culturally alien institutions (particularly nursing homes), and a desire to care for the elderly within the family context regardless of the personal cost or consequences. In contrast to recent research, these findings suggest that it is premature to dismiss familism as a continuing and central influence in the lives of Mexican American family caregivers.

Journal Article↗
PubMed1997

Two years' experience with an enhanced chemiluminescent assay for neonatal blood spot TSH.

We have developed a blood spot assay for thyroid stimulating hormone (TSH) based on the Amerlite TSH-30 serum assay for use in the Welsh neonatal hypothyroid screening programme. A total of 67,656 infants were screened in 1994 and 1995, and 28 cases of primary hypothyroidism were detected, giving a prevalence of one in 2416. The method is sensitive and rapid, results being available within 3 h of receipt of samples. The assay enables much faster detection of primary hypothyroidism than was previously possible, and therefore contributes to earlier treatment of affected infants.

Congenital Hypothyroidism↗
PubMed1997

Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH.

The TSH receptor is a G protein-coupled receptor that mediates the effects of TSH in thyroid development, growth, and synthetic function. We report here that a child with features of TSH resistance, including markedly increased serum TSH concentrations and low normal thyroid hormone levels, is a compound heterozygote for two novel mutations in the TSH receptor gene. One allele has a G to A transition corresponding to an arginine to glutamine change at codon 109 (R109Q) in the extracellular domain of the receptor. The other allele has a G to A transition corresponding to a premature termination codon at tryptophan 546 (W546X) in the fourth transmembrane segment. Each parent is heterozygous for one mutation, and both parents have normal thyroid function. Cells transiently transfected with the R109Q mutant exhibited reduced membrane binding of [125I]TSH and impaired signal transduction in response to TSH. In contrast, the W546X mutant was nonfunctional, with negligible membrane radioligand binding. Our findings indicate that a single normal TSH receptor allele is sufficient for normal thyroid function, but that the compound abnormality in the proband leads to TSH resistance.

Amino Acid Sequence↗
PubMed1997

Setting priorities in aging populations: formal service use among Mexican American female elders.

This study establishes empirical patterns of formal service use by a sample of 483 elderly Mexican American women, and identifies the predictors of formal service utilization. Results indicated two patterns of service use-in the home and at senior centers. Regression analysis demonstrated that the best predictors of who used formal in-home services were those with functional impairment in Instrumental Activities of Daily Living (IADLs) and those with the least amount of assistance with IADLs provided by family members. Living alone and attending group social events were the best predictors of the use of senior center services. Anticipated changes in the Mexican American population portend a growing need for both in-home and senior center services. These findings can be used to establish policy and programming priorities for this neglected population. If resources are to be effectively targeted to frail elders, in-home services should receive priority, and the provision of in-home services should be modified to include additional programs that facilitate care of the elderly by the family.

Aged↗
PubMed1997

Rieger's syndrome: a case report.

Rieger's syndrome is a rare autosomal-dominant disorder characterized by dental, ocular, and periumbilical abnormalities. Essential ocular features include goniodysgenesis, which leads to increased intraocular pressure and subsequent glaucoma and visual loss. Dental findings include midfacial hypoplasia and the absence of primary and permanent incisors and second premolars. Comprehensive preventive dental care in the form of fluorides and sealants is required, especially in patients with severe hypodontia, to increase the resistance of the remaining teeth to dental caries. This article describes a case of Rieger's syndrome in a 9-year-old child and emphasizes the need for comprehensive oral rehabilitation.

Abnormalities, Multiple↗
PubMed1996

Age-independent indices in second-trimester serum screening for Down's syndrome are useless.

Serum screening for fetal Down's syndrome in the second trimester is far more efficient in older mothers than in younger ones because the risk calculation is based on maternal age. In recent publications, several authors have tried to better the 'classical' test for Down's syndrome screening by creating an age-independent index. This procedure, however, requires the assumption that at least for one parameter the mean MOM or the variance is not constant in relation to maternal age, leading to a smaller overlap in younger women. This study, based on almost 3000 normal cases and 161 cases with Down's syndrome, could not demonstrate any relationship between maternal age and MOM distribution for alpha-fetoprotein, unconjugated oestriol, total human chorionic gonadotropin (hCG), and free beta hCG. We conclude that for a constant false-positive rate, the detection rate of the 'classical' test for Down's syndrome screening in younger women cannot be bettered by creating an age-independent index.

Adult↗