bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized trial of parathyroidectomy in mild, asymptomatic primary hyperparathyroidism as measured by the SF-36 health survey
Authors: Talpos G B , Rao D S , Bone H G , Parfitt A M , Kleerekoper M , Alam M , Honasoge D , Divine G 
Published: March 2003

Abstract

Background
Management of patients with asymptomatic primary hyperparathyroidism (HPT) remains controversial despite a National Institutes of Health consensus statement on this issue. As part of the above statement, a randomized clinical trial was recommended since none exist to address this issue.

Methods
Informed consent was obtained from 53 asymptomatic patients with confirmed primary HPT who agreed to participate in this randomized clinical trial of parathyroidectomy versus observation. Upon entry to the study and 24 months later the patients completed the SF-36 health survey which is an instrument that measures nine different levels of function. Scores were tabulated and the difference over 24 months between operated and non-operated patients was compared with Student's t test.

Results
Fifty-three patients (42 women and 11 men) with asymptomatic, mild primary HPT (serum calcium 10·1–11·5 mg dl−1) who agreed to participate were randomized into either a surgical group or an observation group. Mean serum calcium for these patients was 10·3 mg dl−1. The only demographic difference between the groups was age; the operated group was older (66·7 versus 62·6 years; P &lt; 0·03). Scores on three of the nine domains (health perception, emotional problems and social functioning) on the SF-36 were significantly different (P &lt; 0·05), all favouring the operated group.

Conclusion
Improved function, as measured by the SF-36 health assessment tool, is seen after parathyroidectomy compared with non-operated patients. This work supports surgical management of mild primary HPT at the time of diagnosis since many patients have reversible non-classical symptoms of the disease.
Hypothyroidism following hemithyroidectomy: incidence, risk factors and management
Authors: McHenry C R , Slusarczyk S J 
Published: March 2003

Abstract

Background
Hypothyroidism is often an unrecognized sequela of hemithyroidectomy. The purpose of this study was to determine the incidence, risk factors and management of hypothyroidism occurring after hemithyroidectomy for nodular thyroid disease.

Methods
All euthyroid patients who underwent hemithyroidectomy from 1992 to 1999 were evaluated for age, sex, preoperative and postoperative serum thyroid-stimulating hormone (TSH) levels, pathology and follow-up. Time of diagnosis and therapeutic doses of thyroid hormone were determined for patients with hypothyroidism. Patients who underwent completion thyroidectomy and those who were on thyroid hormone before operation for TSH suppression or after operation for prevention of recurrent disease were excluded.

Results
During the study period, 70 euthyroid patients underwent hemithyroidectomy. Postoperative hypothyroidism was diagnosed in 25 (36 per cent) with a mean(s.d.) TSH level of 8·51(6·53) (units l−1). Hypothyroidism was subclinical in 16 and overt in nine patients. There were no significant sex or age differences between hypothyroid and euthyroid patients. The mean(s.d.) preoperative serum TSH level was 1·94(1·00) (units l−1) in patients diagnosed with postoperative hypothyroidism compared with 1·08(0·75) (units l−1) in euthy-roid patients (P &lt; 0·05). Associated lymphocytic thyroiditis was present in ten of 25 hypothyroid patients compared with ten of 45 euthyroid patients (P &gt; 0·05). Nineteen patients received thyroid hormone treatment in doses varying from 0·5 to 1·9 (mean 1·3) g kg−1. Follow-up varied from 1 month to 7 years (mean 1 year). All but one hypothyroid patient was diagnosed within 2 months of surgery.

Conclusion
Postoperative hypothyroidism occurs in 36 per cent of patients following hemithyroidectomy. It is usually asymptomatic, and can be diagnosed early after surgery. Hypothyroid patients have higher preoperative TSH levels than euthyroid patients and treatment is accomplished with lower than normal replacement doses of thyroid hormone.
Value of intra-arterial calcium-stimulated venous sampling for regionalization of pancreatic insulinomas
Authors: Lo C-Y , Chan F-I , Tam S C F , Fan S-T , Lam K S L 
Published: March 2003

Abstract

Background
Although the need for routine preoperative localization of insulinoma is challenged, accurate preoperative localization is regarded as the prerequisite for successful laparoscopic resection of insulinoma. Intra-arterial calcium stimulation with hepatic venous sampling for insulin gradients (ASVS) has been reported to be the most sensitive preoperative localization technique. The authors' experience with ASVS to localize and guide management of insulinomas is reviewed.

Methods
Between 1991 and 1999, 20 patients underwent surgical resection for insulinomas. Sixteen patients (11 men, five women; median age 43 years) underwent ASVS for preoperative localization of insulinoma based on equivocal standard imaging studies. Intraoperative ultrasonography was performed routinely. The accuracy of ASVS was compared with that of intraoperative findings and other methods of localization.

Results
There was no complication arising from the procedure. A median step-up of tenfold (right 3–37-fold; left 3–72-fold) in insulin level 30–60 s after injection to at least one feeding artery was observed in 14 patients. Enucleation and distal resection were performed in six and ten patients respectively. In the era of laparoscopy, open enucleation and laparoscopic resection were adopted for two tumours each located at the pancreatic head and tail respectively. Twelve of the 14 solitary tumours were located correctly; all four at the head, one of three in the body and all seven at the tail. Two patients with multiple endocrine neoplasia type 1 and multiple tumours had the dominant tumours located at the tail. The overall accuracy of this test was 88 per cent compared with 11, 31, 43 and 67 per cent for ultrasonography, computed tomography, magnetic resonance imaging and endoscopic ultrasonography respectively. Intraoperative ultrasonography readily located two tumours missed by ASVS which, in turn, guided the removal of a tumour located at the splenic hilum that eluded detection by intraoperative ultrasonography.

Conclusion
ASVS is the most accurate preoperative localization tool for localizing insulinomas. It guides the adoption of the minimally invasive approach and, in combination with intraoperative ultrasonography, enhances surgical success in the management of insulinoma.
Neutralizing vascular endothelial growth factor activity inhibits thyroid cancer growth in vivo
Authors: Soh E Y , Kim K J , Eigelberger M S , Wong M G , Duh Q-Y , Clark O H 
Published: March 2003

Abstract

Background
Without angiogenesis, tumours cannot grow larger than a few millimetres in size, the limit of diffusion. Vascular endothelial growth factor (VEGF) is an endothelial-specific mitogen and is a major regulator of physiological and pathological angiogenesis. Higher levels of VEGF messenger RNA expression and VEGF production and secretion have been found in FTC-133 cells than normal thyroid cells.

Methods
To investigate the relationship between VEGF and thyroid tumour angiogenesis and growth, human dermal matrix inoculated with FTC-133 cells was xenografted into nude mice or directly injected subcutaneously. To block the function of VEGF, the neutralizing anti-VEGF monoclonal antibody A.4.6.1 (mAb A.4.6.1) was injected intraperitoneally 100 μg per 0·2 ml twice weekly. As control, an antibody of the same isotype (immunoglobulin G1), directed against the gP120 protein (Ab 5B6), or phosphate-buffered saline (PBS) was used. To evaluate the dermal matrix as a model for angiogenesis studies, rhVEGF was inoculated into the dermal matrix pocket and xenografted into mice.

Results
In vivo study using the dermal matrix showed that the number of blood vessel ingrowths paralleled the concentration of rhVEGF and was highest at the concentration of 100 ng ml−1. Mice treated with the mAb A.4.6.1 developed fewer blood vessels (mean 7 per high-power field (HPF)) than control mice (18 per HPF in Ab 5B6 and 22 per HPF in PBS) (P &lt; 0·01). The size of tumours between mAb A.4.6.1- and Ab 5B6- or PBS-treated groups showed a significant difference from the second week after the inoculation of FTC-133 cells. The tumours from mice treated with mAb A.4.6.1 were smaller (mean(s.d.) 0·09(0·02) g at 5 weeks) than tumours from mice treated with Ab 5B6 (5·38(1·15) g) or PBS (4·00(0·72) g) (P &lt; 0·001, two-tailed unpaired t test).

Conclusion
VEGF is produced by thyroid cancer cell line FTC-133 and stimulates angiogenesis and growth of thyroid cancer. More importantly, this stimulation can be blocked by mAb A.4.6.1.
Role of antiapoptotic genes in genetic control of programmed cell death in Hashimoto's thyroiditis
Authors: Hammond L J , Palazzo F F , Murphy B J , Goode A W , Mirakian R 
Published: March 2003

Abstract

Background
In Hashimoto's thyroiditis (HT) thyroid cells die by apoptosis, programmed cell death. In addition to the reported abnormal Fas expression on thyrocytes, a decreased expression of the Bcl-2 antiapoptotic genes has also been demonstrated in thyrocytes. The ratio of the expression of death antagonists (e.g. Bcl-2 and Bcl-Xl) to death agonists (Bax, Bak, Bcl-Xs and Bad) appears to determine the survival or death of thyrocytes under both physiological and pathological conditions.

Methods
The constitutive expression of Bcl-X was investigated in thyroid cells from ten multinodular goitre (MNG), ten Graves disease and four HT samples by immunofluorescence, confocal microscopy and Western blotting. The effect of proinflammatory cytokines (interferon (IFN) γ, tumour necrosis factor (TNF) α and interleukin (IL) 1 on Bcl-X expression on cultured thyrocytes was also studied.

Results
By in situ staining, an overall decreased Bcl-X expression was observed within the thyrocyte compartment in HT samples in comparison to that seen on thyrocytes from ten samples of MNG thyroid. Intrathyroidal lymphocytes were positive for Bcl-X. These findings were quantified using confocal microscopy which demonstrated an intensity of Bcl-X staining in MNG twice that of HT specimens. The ten specimens of Graves disease showed an intermediate and patchy staining on thyrocytes. In vitro studies have confirmed constitutive Bcl-X expression both by flow cytometry and Western blotting analysis with the latter showing a 27-kDa signal in all samples that corresponds to Bcl-Xl. IFN-γ, alone and in combination with TNF-α and IL-I, decreased Bcl-X expression on thyrocytes.

Conclusion
HT thyrocytes underexpress Bcl-X whereas intrathyroidal lymphocytes have been found to be positive. It is proposed that the decreased Bcl-X expression on thyrocytes of HT glands occurs as a result of proinflammatory cytokine release by infiltrating activated lymphocytes. The overall impairment of antiapoptotic gene protection may contribute to the susceptibility of HT thyrocytes to apoptosis.
Heat-stable plasma constituent responsible for caspase activation in Hashimoto's thyroiditis
Authors: Palazzo F F , Hammond L J , Murphy B J , Goode A W , Mirakian R 
Published: March 2003

Abstract

Background
Autoimmune thyroid disease is characterized by a spectrum of thyroid activity, with Graves disease (GD) and Hashimoto's thyroiditis (HT) at the extremes of over and under activity respectively. Hypothyroidism in HT is caused by apoptotic thyrocyte death, which is achieved via a cascade of cysteine protease (caspase) activity. It is still unclear whether thyrocyte death is the result of caspase activation secondary to extrinsic Fas/FasL interaction with the activation of procaspase 8 and/or of cytochrome C release from thyrocyte mitochondria consequent to impaired expression of the Bcl2/Bcl-X thyrocyte survival genes. This study was designed to clarify whether plasma constituents have a role in thyrocyte apoptosis and whether differential apoptotic kinetics can be observed in thyroid diseases.

Methods
Cultured thyrocytes from fresh surgical specimens were incubated with 5 and 20 per cent plasma from patients with multinodular goitre (MNG), GD and HT for between 5 and 180 min. Procaspase 8, caspase 3 and cytochrome C activities were monitored using Western blotting on thyroid lysates. Procaspase 8 was also studied microscopically using light microscopy and immunofluoroscopy. To ascertain the role of complement activity in the induction of apoptosis, thyrocytes from MNG, GD and HT thyroids were also exposed to heat-treated plasma (56°C for 45 min) for varying time intervals before caspase 8 estimation.

Results
Western blot and immunofluoroscopy confirmed that human plasma induces procaspase 8 in thyrocytes; Western blots also showed activation of cytochrome C and caspase 3 in these cells. At 30 min and up to 90 min thyrocyte procaspase 8 expression and the expression of breakdown products of this protein appeared to be more marked in the thyrocytes treated with HT plasma than MNG and GD plasma. Procaspase 8 expression was not altered by the heat of plasma. Thyrocytes exposed to plasma of patients with autoimmune and non-autoimmune conditions showed similar bands for caspase 3 and cytochrome C. The cytochrome C signal was stronger in the cells exposed to HT plasma at 30 min.

Conclusion
A heat-stable constituent of human plasma induces programmed cell death in thyrocytes. Plasma from patients with HT appears to induce a greater death stimulus than that from patients with other thyroid conditions. Fas/FasL interaction appears to be involved in apoptotic thyrocyte death. The role of mitochondrial cytochrome C in the induction of cell death is unclear.
Thyroid transcription factor 2 gene expression in thyroid malignancy
Authors: Sequeira M J , Fuehrer D , Ludgate M , Wheeler M H 
Published: March 2003

Abstract

Background
Expression of thyroid-specific proteins such as thyroglobulin is controlled by several transcription factors. Thyroid transcription factor (TTF) 2 is the most recently characterized and has a temporal expression during thyroid embryogenesis suggesting a role in initiating differentiation. Studies on other thyroid-specific genes have shown a gradual loss in differentiation as a tumour progresses, although a good marker to distinguish follicular adenoma from follicular carcinoma is still needed. There is no information on TTF-2 expression in varying thyroid pathologies. Given its central role in thyroid differentiation, reverse transcriptase–polymerase chain reaction (PCR) was used to investigate this in both archival and fresh thyroid tissues and fine-needle aspirates.

Methods
Thyroid tissue was obtained with informed consent, snap frozen, and total RNA and messenger RNA (mRNA) was extracted. Since TTF-2 has no introns in the coding region, it was necessary to use mRNA. The RNA was reverse transcribed using oligo(dT) and MMV reverse transcriptase. The quality of the complementary DNA (cDNA) was verified by PCR using intron–exon boundary spanning primers for the phosphoglucokinase (PGK) housekeeping gene; a 250-base pair (bp) product is derived from cDNA but a 650-bp product from amplification of contaminant genomic DNA. PCR amplification of TTF-2 used two sets of primers; A + D spans the DNA-binding region and gives a product of 460 bp while primers P + E generate a product of 370 bp in the carboxyl end of the coding region. Products were analysed by agarose gel electrophoresis and compared with a 100-bp ladder.

Results
A single band of 250 bp was obtained in all 33 thyroid tissue samples but in only three of eight fine-needle aspirates, after 40 cycles, using the PGK primers. Appropriate size products were obtained, after 30 cycles, invariably with both sets of TTF-2 primers, in all 18 benign thyroid nodules of varying pathology, including all five follicular adenomas, and in five of 15 malignant thyroid nodules. Four of five papillary carcinomas and one of seven follicular carcinomas expressed TTF-2; neither of two anaplastic carcinomas and one other carcinoma did not. One of six benign and one of two malignant thyroid nodules expressed TTF-2 on fine-needle aspiration cytology.

Conclusion
The results suggest loss of TTF-2 expression in poorly differentiated thyroid tumours and that TTF-2 may be helpful in distinguishing follicular adenoma from follicular carcinoma.
Neosphincters in the management of faecal incontinence
Authors: Niriella D A , Deen K I 
Published: March 2003

Abstract

Background
Surgical treatment of end-stage faecal incontinence has its origin in the early 1950s. Interest has been revived as a result of technical advances achieved in the recent past. The purpose of this article is to review the principles that underlie the use of skeletal muscle transposition around the anal canal and of electrical stimulation in the treatment of incontinence, and to explore new methods of treatment of this condition.

Methods
A literature search was performed using Pubmed and Medline, employing keywords related to treatment of faecal incontinence by neosphincter reconstruction. Basic science and clinical aspects of neosphincter reconstruction were gathered from relevant texts, original articles and recently published abstracts.

Results
The electrically stimulated gracilis neoanal sphincter seems to be the popular choice of biological neosphincter. It is more likely to produce higher resting anal canal pressures than the unstimulated neosphincter, and hence improved continence. However, electrostimulator failure may result in explantation in a proportion of patients. Impairment of evacuation is a functional setback in approximately one-third of patients with the gracilis neosphincter. Overall, improvement of continence may be expected in up to 90 per cent of patients according to some reports. By contrast, experience with the artificial neosphincter, which is less expensive, has been limited to a few tertiary centres across the world. Reported continence of stool is 100 per cent, and that of gas and stool 50 per cent, following implantation of the artificial sphincter. Both of the above operations have been associated with implant-related infection and impaired evacuation.

Conclusion
Neoanal sphincter operations are technically demanding, require a considerable learning experience and should be confined to specialist colorectal centres. Patients are likely to benefit from a plan that incorporates preoperative counselling and a selective approach.
Biological behaviour and clinical implications of micrometastases
Authors: Kell M R , Winter D C , O'Sullivan G C , Shanahan F , Redmond H P 
Published: March 2003

Abstract

Background
The most important prognostic determinant in cancer is the identification of disseminated tumour burden (metastases). Micrometastases are microscopic (smaller than 2 mm) deposits of malignant cells that are segregated spatially from the primary tumour and depend on neovascular formation (angiogenesis) to propagate.

Methods
The electronic literature (1966 to present) on micrometastases and their implications in malignant melanoma and epithelial cancers was reviewed.

Results
Immunohistochemical techniques combined with serial sectioning offer the best accuracy for detection of nodal micrometastases. Molecular techniques should be reserved for blood samples or bone marrow aspirates. Detection of micrometastases in regional lymph nodes and/or bone marrow confers a poor prognosis in epithelial cancers. The concept of sentinel node biopsy combined with serial sectioning and dedicated screening for micrometastases may improve staging procedures. Strategies against angiogenesis may provide novel therapies to induce and maintain micrometastatic dormancy.

Conclusion
The concept of micrometastases has resulted in a paradigm shift in the staging of epithelial tumours and our overall understanding of malignant processes.
Need for secondary interventions after endovascular repair of abdominal aortic aneurysms. Intermediate-term follow-up results of a European collaborative registry (EUROSTAR)
Authors: Laheij R J F , Buth J , Harris P L , Moll F L , Stelter W J , Verhoeven E L G 
Published: March 2003

Abstract

Background
The frequency of secondary interventions after endovascular repair of abdominal aortic aneurysms (AAAs) was assessed and correlated with findings at clinical and imaging examination during follow-up.

Methods
Data were studied from 1023 patients with a follow-up of 12 months or longer, collected by 56 institutions in a multicentre data registry (EUROSTAR). Surveillance data were provided by the centres between September 1996 and November 1999.

Results
Overall, 186 patients (18 per cent) had a secondary intervention occurring a mean of 14 months after the initial endograft procedure. Twelve per cent of the interventions were transabdominal, 11 per cent consisted of an extra-anatomic bypass and 76 per cent involved a transfemoral procedure. The rates of freedom from intervention at 1, 3 and 4 years were 89, 67 and 62 per cent respectively. Migration (relative risk (RR) 8·9) and rupture (RR 22·6) were the most frequent causes of secondary transabdominal interventions. Graft limb thrombosis was the principal indication for extra-anatomic bypass (RR 37·5 for clinical evidence of graft limb thrombosis). Endoleak, graft kinking, stenosis or thrombosis and device migration were significant causes for secondary transfemoral interventions (RR 2·5–6·9).

Conclusion
The high incidence of late secondary interventions is a cause for concern with regard to broad application of endovascular AAA repair, and emphasizes the need for lifelong surveillance.
Experimental sodium phosphate and polyethylene glycol induce colonic tissue damage and oxidative stress
Authors: Coskun A , Uzunkoy A , Duzgun S A , Bozer M , Ozardali I , Vural H 
Published: March 2003

Abstract

Background
Bowel washout solutions may damage colonic mucosa and cause shallow ulceration, which may result in diagnostic errors and complications. The effects of polyethylene glycol (PEG) and sodium phosphate on rat colon were investigated histologically and by measurement of indicators of oxidative stress.

Methods
Thirty Wistar albino rats were divided into three groups and received PEG, sodium phosphate or tap water alone (control). After 8 h, histological changes in colonic mucosa were evaluated. The tissue concentration of malonyldialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in colon homogenates was also measured.

Results
Animals in the sodium phosphate and PEG groups had significantly more colonic mucosal damage than controls, the damage induced by sodium phosphate being worse than that caused by PEG. MDA levels were significantly higher in the sodium phosphate and PEG groups than in controls and were higher in the sodium phosphate group than in the PEG group, whereas differences in SOD and GSH-Px activities were significant only between control and both sodium phosphate and PEG groups.

Conclusion
Sodium phosphate and PEG cause histological damage and trigger oxidative stress on colonic mucosa. The tissue damage and oxidative stress induced by sodium phosphate is more profound than that produced by PEG.