Cord blood thyroxine and thyroid stimulating hormone screening for congenital hypothyroidism: how useful are they?

AIM: To determine and compare the usefulness of cord blood screening for free thyroxine (FT4) and thyroid stimulating hormone (TSH). BACKGROUND: There is a vast amount of literature on capillary heel prick screening tests, but relatively little on cord blood testing particularly FT4. For a decade all infants born at Tawam Hospital had cord blood FT4 and at Oasis Hospital cord TSH measured through the hospital-based screening programme. On January 1st 1998, the national screening programme (NSP) for congenital hypothyroidism (CH) in the United Arab Emirates (UAE) started using capillary TSH measurement (Delfia method). Since then newborns in both hospitals have been screened both ways, i.e. cord blood and capillary blood screening. METHODS: We reviewed retrospectively all infants born from January 1998 until the end of June 2004 with CH who had double screening: cord FT4 or TSH and 4th-5th day TSH screening. RESULTS: Thirteen infants (one in 1,778) had CH in Tawam Hospital. In six of these the cord blood FT4 was low (<9.1 pm/l) (0.73 ng/dl) and in seven the cord blood FT4 was normal, i.e., over half were missed. Eight infants (one in 1,198) had CH in the Oasis Hospital. Cord blood TSH was high in six of them (>13 IU/l) and two were normal. Cord FT4 detected the most severe cases, but missed most others. Cord TSH detected six out of eight cases, but there was a recall rate of one in 23. CONCLUSIONS AND RECOMMENDATIONS: Cord FT4 identifies only infants with severe CH. Cord TSH is more sensitive than cord FT4 screening. Capillary TSH dried blood spot testing on the 3rd-5th day is the most sensitive method.

Essential role of biliary glycoprotein (CD66a) in morphogenesis of the human mammary epithelial cell line MCF10F.

Normal mammary epithelial cells express the cell surface protein biliary glycoprotein (BGP or CD66a) in a polarized manner, suggesting that this protein may play a role in the formation of mammary acini. In order to test this hypothesis, we interrupted the expression of BGP in the mammary epithelial line MCF10F when cultured in or on Matrigel, a source of extracellular matrix (ECM). When analyzed by immunofluorescence confocal microscopy, the BGP staining is confined to the lumenal surface and colocalizes with actin. Sequential scanning electron microscopy demonstrates that the MCF10F cells migrate to form clusters, followed by apoptotic cell death within the center, resulting in lumen formation. Transmission electron micrographs reveal the presence of tight junctions and desmosomes between the cells, microvilli along the lumenal surface, and typical apoptotic bodies within the lumen. When the MCF10F cells are transfected with the BGP antisense gene and grown in Matrigel, they exhibit reduced acini formation (12% and 20%) compared to untransfected cells (52%) or to cells transfected with vector only (62%). Acini formation is also significantly reduced when MCF10F cells grown in Matrigel are treated with anti-BGP antibody (18% at 100 microgram/ml), or recombinant soluble BGP (18% at 0.4 microM). In contrast, the BGP-negative MCF7 breast tumor cell line, which does not form acini when grown in matrigel, exhibits >60% cell death with the occasional formation of acini, when transfected with the BGP sense gene and grown in Matrigel. These results support the hypothesis that BGP plays a role in the normal differentiation program of mammary epithelial cells, indicating that its expression is essential to the formation of the lumen. Furthermore, and as shown by others, the differentiation program depends on the presence of ECM. The lack of expression of BGP in the MCF7 breast cancer cell line suggests that the downregulation of BGP expression confers a growth advantage to these cells in ECM. In addition, we found that the MCF10F cells could be separated into a BGP-positive epithelial fraction (MCF10F-e), and a BGP-negative myoepithelial fraction (MCF10F-m). When the myoepithelial cell-enriched fraction is grown on Matrigel, web-like structures are formed. These cells have a typical spindle shape cell morphology and express keratin, alpha-smooth muscle actin and vimentin, markers of the myoepithelial cell phenotype. When MCF10F-m cells are treated with IFNgamma, they express CEA (carcinoembryonic antigen) but not BGP. Since breast carcinomas, especially in situ carcinomas, express CEA, this finding may suggest a heretofore unappreciated relationship between myoepithelial cells and breast cancer.

Technical options in venous valve reconstruction.

PURPOSE: Several modifications and details of techniques that were found useful in venous valve reconstruction are described. Related technical outcome data are also presented. METHODS: Five hundred eighty-two valve segments were reconstructed in 347 limbs using a variety of different techniques. RESULTS: Intraoperative valve competence was achieved in 86% of 347 limbs. The incidence of technical stenosis was 4%, thrombosis of repair <1%, loss due to hematoma/infection <1%, and operative mortality 0%. Postoperative duplex competence was achieved fully in 78% and partially in 16%; 6% remained refluxive. Rapid postoperative healing of stasis ulcer occurred in 93%. CONCLUSIONS: The expanded variety of technical options in valve reconstruction allows optimization for the individual patient. Regardless of pathology, a functional venous valve can be reconstructed in most patients utilizing one of the described techniques.

Single- and double-lung transplantation. Problems and possible solutions.

There is a resurgence of interest in single- and double-lung transplantation for end-stage disease. An experience with six double-lung and three single-lung transplants is reported. The lungs were procured from a distance of up to 600 miles and the heart was shared with another team for transplantation in seven of nine instances. The operative mortality rate was 33%. Early transplant infections of donor origin were lethal. Late transplant pneumonitis was well tolerated and recovery was the rule. Three of nine cases had significant tracheal suture line stenosis and were managed conservatively. A technique of bronchial artery implantation using a conduit tailored from donor aorta is described. Transplant rejection was easily diagnosed and treated. Other notable complications included occasional massive pleural fluid loss, temporary space problem, and a delay in the 'resetting' of chemoreceptors resulting in moderate post-transplant hypercarbia accompanied by episodes in which the patient felt hypoxemic despite the maintenance of excellent levels of blood gases. A comprehensive rehabilitation program begun before operation is essential for success.

Atrial natriuretic factor (ANF): a preliminary report of cervical heart transplant model for study.

The allograft canine heart transplanted to the neck of a recipient provides a useful model for direct measurement of atrionatriuretic factor (ANF) in the single inflow artery and the single outflow vein (pulmonary artery). The normal peripheral blood levels of ANF in the dog ranged from 25-77 pg/ml, whereas the post-transplant level in transplant outflow blood was 2262 pg/ml 30 minutes after transplant resuscitation. The cervical heart transplant model is applicable to a variety of ANF investigations.

Successful single lung transplantation.

We have presented a successful case of lung transplantation in a man with pulmonary fibrosis. We believe it is the first successful attempt in the United States, following demonstration of its feasibility in Toronto, Canada. Twenty years after the first lung transplantation, several factors have evolved that help to secure a successful outcome, including a strong, dynamic organ procurement system; static, hypothermic lung preservation; omental wrapping of the bronchial anastomosis; improved immunosuppressive agents; and improved postoperative care.

Cynical hostility and vulnerability to disease: social support, life stress, and physiological response to conflict.

Previous research has indicated that high scores on the Cook and Medley Hostility (Ho) scale are associated with increased risk of coronary heart disease and other illness. Our study attempts to clarify this relationship by providing additional evidence concerning the construct assessed by the Ho scale, examining the level of physiological reactivity during interpersonal conflict in high- and low-Ho groups, and assessing the psychosocial profile associated with this characteristic. Extremely high and low Ho groups were selected from a pool of male undergraduates. Consistent with previous findings, high-Ho participants reported greater anger proneness and a more cynical, disparaging view of others than did low-Ho participants. The high-Ho group also tended to be more hostile and less friendly during role-played interactions involving high and low levels of interpersonal conflict, respectively. High-Ho persons also displayed greater diastolic blood pressure reactivity during interpersonal conflict. Finally, the high-Ho group reported less social support and more negative life events and daily irritants then did the low-Ho group. These results support the interpretation of the Ho scale as a measure of cynical hostility and are consistent with the hypothesis that it is related to disease by way of excessive physiological reactivity and a generally stressful, unsupportive social network.

The ubiquitous fibroblast. Multiple oncogenic potentials with illustrative cases.

The wide range of oncogenic proliferative potentials of the fibroblast is demonstrated with a series of eight patients. Diagnoses included infantile digital fibromatosis, "aggressive fibromatosis," aggressive fibromatosis progressing to poorly differentiated sarcoma, infantile myofibromatosis, recurrent desmoid tumor, fibrosarcoma arising in a keloid, dermatofibrosarcoma protuberans, and malignant fibrous histiocytoma of left atrium. Still other types of fibroblastic tumefactions might have been included. Oncogenic factors that may have been operative in the causation of the lesions presented include: genetic factors, sex-linked factors, hormonal factors, numerous growth factors, and certain viruses, especially retroviruses. Certain fibromatoses in children are commonly self-limited and need only be monitored carefully as the process regresses. Aggressive fibromatosis, on the other hand, can prove fatal if the lesion is not completely resected with a wide margin and, occasionally, the process may become frankly malignant, with metastases. The standard triad of excisional surgery, radiotherapy, and chemotherapy has been used to treat frankly malignant fibrous tumors with variable results.

What of the next 25 years?

The early history of the Society for Surgery of the Alimentary Tract has been reviewed, and the remarkable progress in gastrointestinal surgery over the first 25 years of its existence has been acknowledged. The challenging dimensions of the problems that remain unsolved have been emphasized, and the directions that fruitful research may take in the next quarter century have been suggested. The alimentary tract surgeon will be called upon to adapt to change, and to move into new fields of clinical physiology and surgery. The discoveries and progress to be anticipated in the years to come are vast.

Cushing's disease today. Late follow-up of 17 adrenalectomy patients with emphasis on eight with adrenal autotransplants.

Cushing's disease has come full cycle. As originally asserted more than 50 years ago, modern diagnostic techniques now demonstrate an adrenocorticotropic hormone (ACTH) secreting pituitary adenoma in approximately 80% of such patients. At this historical juncture, we report a long-term follow-up of our 17 patients who underwent adrenalectomy (8) or later adrenalectomy plus adrenal autotransplantation (9) between 1955 and 1976. Two patients died soon after surgery and five others died later of "natural" causes. Four others moved away but were stable when last contacted. Of the six patients who remain available for current follow-up, three have undergone hypophyseal surgery. Another patient has evidence of pituitary enlargement, and the remaining two are yet to undergo computerized tomography (CT) scan. Four illustrative cases are reviewed in some detail. One case presented with Nelson's syndrome and acute onset blindness. The second represented multiple endocrine adenomatosis with hyperparathyroidism in addition to Cushing's disease. The third exhibited Cushing's syndrome from the autotransplants, finally cured by hypophysectomy. The fourth exhibited huge ACTH levels from a large pituitary adenoma that could not be totally resected and recurrent Cushing's syndrome associated with large autotransplant "adenomas." The initial surgical treatment of choice is pituitary adenectomy. Bilateral adrenalectomy will remain useful where curative pituitary surgery is not feasible. Neither pituitary irradiation nor medical therapy has been truly effective in our patients. Adrenal autotransplants survive, to some extent, in virtually all patients. However, the degree of function is variable, and the full function may not be achieved for many months or even years. Functioning autotransplants have not prevented Nelson's syndrome, and they would appear to offer little practical benefit at this time.