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Biomedical subjects

G P Sadler

Publications and source records attributed to G P Sadler.

11 recordsLinked to original sources
PubMed2007

Minimally invasive parathyroidectomy without intraoperative parathyroid hormone monitoring in patients with primary hyperparathyroidism.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) is the preferred operation for patients with primary hyperparathyroidism (HPT) and positive preoperative imaging. This non-randomized case series assessed the long-term results of MIP performed without the use of intraoperative parathyroid hormone (ioPTH) monitoring. METHODS: The study involved prospective collection of demographic, biochemical and operative details on a consecutive, unselected cohort of 298 patients who underwent surgery for non-familial primary HPT during a 5-year interval. The mean preoperative serum calcium level was 3.00 mmol/l with a mean parathyroid hormone concentration of 25.8 pmol/l. (99m)Tc-labelled sestamibi scanning and neck ultrasonography were performed in 262 patients. RESULTS: Sestamibi scan showed unilateral uptake in 182 patients and a single parathyroid adenoma was confirmed on ultrasonography in 161 patients. MIP was performed in 150 patients. The mean duration of operation was 25 (range 8-65) min. Four patients needed conversion to conventional neck exploration. There was one postoperative haematoma and three cases of temporary recurrent laryngeal nerve neuropraxia. All but four patients were normocalcaemic after MIP. All the parathyroid tumours removed were adenomas, with a mean weight of 1.3 (range 0.1-17.4) g. No patient developed recurrent HPT after a median follow-up of 16 (range 3-48) months. CONCLUSION: The outcome of MIP without ioPTH monitoring was comparable to that reported in series that used ioPTH monitoring.

Adolescent↗
PubMed2006

Parafibromin mutations in hereditary hyperparathyroidism syndromes and parathyroid tumours.

OBJECTIVE: To investigate two patients with the hyperparathyroidism-jaw tumour (HPT-JT) syndrome and three patients with familial isolated hyperparathyroidism (FIHP), together with 31 parathyroid tumours (2 HPT-JT, 2 FIHP and 27 sporadic) for HRPT2 mutations. The HPT-JT syndrome and FIHP are autosomal dominant disorders that may be caused by abnormalities of the HRPT2 gene, located on chromosome 1q31.2. HRPT2 encodes a 531 amino acid protein, parafibromin, which interacts with human homologues of the yeast Paf1 complex. DESIGN: Leukocyte and tumor DNA was used with HRPT2-specific primers for polymerase chain reaction amplification of the 17 exons and their splice junctions, and the DNA sequences of the polymerase chain reaction products determined. RESULTS: Three heterozygous germline HRPT2 mutations, two in HPT-JT and one in FIHP patients, were identified. These consisted of one 1-bp duplication (745dup1bp), 1 nonsense (Arg234Stop) and 1 missense (Asp379Asn) mutation. One parathyroid tumour from an FIHP patient was demonstrated to harbour a germline deletion of 1 bp together with a somatic missense (Leu95Pro) mutation, consistent with a 'two-hit' model for hereditary cancer. The 27 sporadic benign parathyroid tumours did not harbour any HRPT2 somatic mutations. Six HRPT2 polymorphisms with allele frequencies ranging from 2% to 15% were detected. CONCLUSIONS: Our results have identified three novel HRPT2 mutations (two germline and one somatic). The Asp379Asn mutation is likely to disrupt interaction with the human homologue of the yeast Paf1 complex, and the demonstration of combined germline and somatic HRPT2 mutations in a parathyroid tumour provide further evidence for the tumour suppressor role of the HRPT2 gene.

Adult↗
PubMed2003

Review of surgical management of aldosterone secreting tumours of the adrenal cortex.

AIMS: To evaluate the investigation and surgical management of primary hyperaldosteronism. Retrospective case note analysis of thirty-three patients who underwent adrenalectomy for primary hyperaldosteronism between 1982 and 2001 and a current relevant literature review. METHODS: The records of twelve male and twenty-one female patients, age range 18 to 81 (mean 48 years) were reviewed. Eleven operations were performed by an open approach and twenty-two laparoscopically. Preoperative investigations included computed tomography (CT), magnetic resonance imaging (MRI), selective venous sampling and seleno-cholesterol isotope scanning, along with biochemical and hormonal assays. Twenty-six benign adenomas, three nodular hyperplastic lesions, one primary adrenal hyperplasia and three functional carcinomas were excised. Mean follow up was 12 months. RESULTS: Patients had a mean blood pressure of 185/107 mmHg for 6.2 years mean duration. The mean severity of hypokalaemia was 2.7 mmol/l. Sensitivity of CT scanning was 85%, and of MRI 86%. Fifty percent of seleno-cholesterol scans were accurate. Mean operating time was 158 min for laparoscopic adrenalectomy whilst open surgery took 129 min (p=0.2, NS). Two cases commenced laparoscopically required open access for control of primary haemorrhage whilst one other bleed was managed via the operating ports. Mean postoperative stay was significantly shorter for the laparoscopic group (3 days compared with 7.9 days, p<0.0001). Thirty day mortality was zero. There were three infective complications in the open group (two chest, one wound) with no postoperative complications in the laparoscopic group. All patients were cured of hypokalaemia, whilst 62% cure of hypertension was achieved. Of those patients whose blood pressure was improved preoperatively by spironolactone 78% were cured by adrenalectomy. Adrenalectomy led to an overall reduction in the mean number of anti-hypertensive medications (2.3 drugs preoperative to 0.6 postoperative, p<0.0001). Of those not cured, 58% had improved blood pressure control requiring less medication on average (1.6 drugs compared with 2.6 drugs, p=0.08). Mean age of patients not cured by surgery was 55 years, whilst those cured was 44 years (p=0.03). CONCLUSIONS: Primary hyperaldosteronism is a rare but important cause of hypertension. Selective venous sampling is a useful tool where investigations are inconclusive and fail to lateralise secretion. Patients with primary hyperaldosteronism enjoy lower complication rates and earlier discharge with the advent of laparoscopic surgery. Most patients will be cured of their hypertension and all of hypokalaemia. Laparoscopic adrenalectomy is now the accepted method of surgery for benign hyperaldosteronism. Those with bilateral disease due to idiopathic hyperaldosteronism (IHA) are not candidates for surgery and should be treated medically.

Adenoma↗
PubMed1998

Role of octreotide on release of intact 1-84 parathyroid hormone from human parathyroid cells.

BACKGROUND: Octreotide has been shown to lower urinary calcium in primary hyperparathyroidism although the mechanism remains unclear. This study examined the effect of octreotide on parathyroid hormone (PTH) secretion from human parathyroid cells in culture and as isolated cells. Additionally in situ hybridization was performed for somatostatin receptor messenger RNA (mRNA) and immunocytochemistry for somatostatin in eight parathyroid adenomas. METHODS: Tissue from three hyperplastic glands and three adenomas was studied as dispersed cell suspensions. Incubation was in buffers containing high (2.0 mmol/l) and low (0.5 mmol/l) calcium concentrations, with or without octreotide 200 ng/ml. Cells were also seeded into tissue culture wells for 24 h to allow receptors to regenerate. Supernatant was removed at regular intervals and PTH levels were estimated using a two-site chemiluminescent assay. RESULTS: Mean(s.e.m.) PTH secretion at 90 min in hyperplastic cells was 445(75) pmol/l in low calcium and 160(42) pmol/l in high calcium (P< 0.02), and in adenoma cells was 170(21) pmol/l in low calcium and 137(27) pmol/l in high calcium (P=0.37). There was no significant difference in secretion of PTH from cells incubated with octreotide either in culture or as dispersed cells. In situ hybridization failed to demonstrate any mRNA for the somatostatin receptors and no somatostatin was detected in any cells with immunocytochemistry. CONCLUSION: Somatostatin has no direct action on PTH production and release from human parathyroid cells and is unlikely to be of any therapeutic value in the treatment of hyperparathyroidism.

Adenoma↗
PubMed1996

Epidermal growth factor receptor status in hyperparathyroidism: immunocytochemical and In situ hybridization study.

The epidermal growth factor receptor (EGFr) family has been increasingly recognized as an important component in the control of normal cell proliferation and the pathogenesis of cancer. We have studied EGFr expression in 104 cases of hyperparathyroidism by immunocytochemistry (ICC) and by in situ hybridization (ISH). Using two different monoclonal antibodies, ICC for EGFr was performed on 66 cryostat sections and 38 wax-embedded parathyroid glands. ISH was performed on 49 of these glands using a cocktail of three anti-sense probes to EGFr mRNA and a nonspecific control probe to human HPV-18 virus. Breast and prostate tumors were employed as positive controls for both ICC and ISH. Controls demonstrated positive EGFr staining. None of the 104 parathyroid glands showed any ICC positivity. ISH displayed positive staining for EGFr mRNA in five of six carcinomas and eight of nine nonrenal hyperplastic glands. Only 3 of 15 adenomas and 3 of 19 renal hyperplastic glands showed positive staining. This difference was statistically significant between adenoma and carcinoma (p < 0.05) and between adenoma and nonrenal hyperplasia (p < 0.01) (Tukey's multiple comparison test). This study demonstrates that EGFr mRNA is present in parathyroid tumors. Expression in carcinoma and nonrenal hyperplasia is significantly different from adenoma and renal hyperplastic glands. In contrast, ICC failed to demonstrate EGFr protein expression. These findings suggest that either receptor numbers are too low to detect by ICC or there is a failure of mRNA translation. More studies are needed to establish whether the EGFr plays a role in the development of parathyroid cancer or hyperplasia.

Adenoma↗
PubMed1996

Effect of growth factors on growth of bovine parathyroid cells in serum-free medium.

Published work has suggested a possible role of the epidermal growth factor receptor (EGFr) in parathyroid disease. Bovine parathyroid cells (BPCs) are frequently used as a tissue model for studying parathyroid disorders. We have studied the effect of the EGFr ligands EGF and transforming growth factor alpha (TGFalpha), alone and with insulin-like growth factors IGF-I and IGF-II on BPC growth. Experiments were run in triplicate and repeated three times. Cell numbers were assessed on day 5 by colorimetric MTT assay as well as by tritiated thymidine uptake. Results show that TGFalpha alone (p < 0.05) and IGF-I and IGF-II alone (p < 0.05) significantly stimulated growth over controls (t-test). Furthermore, the combination of TGFalpha with IGF-I and IGF-II exhibited significant enhancement above that seen with IGF-I and IGF-II alone (p < 0.01). EGF did not stimulate growth over controls. EGFr may be expressed in BPCs, but TGFalpha exhibits a more potent growth stimulus than EGF. Addition of IGF-I or IGF-II to the growth medium further enhances this effect.

Animals↗
PubMed1994

Role of fine-needle aspiration cytology and needle-core biopsy in the diagnosis of lobular carcinoma of the breast.

Fine-needle aspiration cytology (FNAC) plays a key role in the preoperative diagnosis of carcinoma of the breast but is less reliable in the diagnosis of infiltrating lobular carcinoma. The method of diagnosis was reviewed in 56 patients with lobular carcinoma who had attended screening and symptomatic clinics. In 29 patients FNAC results demonstrated malignant cells; 15 of these had palpable disease and the mean tumour size was 21 mm. In 27 patients FNAC failed to demonstrate malignant cells; 13 lesions were palpable and the mean tumour size was 23 mm. Ten patients were diagnosed by needle-core biopsy when FNAC was not diagnostic. FNAC may fail to diagnose even large lobular carcinoma and needle-core biopsy is strongly recommended in this situation.

Aged↗
PubMed1992

Day-case paediatric surgery: the only choice.

Since January 1989 a policy of day-case surgery has been adopted for suitable paediatric procedures by one firm (MEF) at East Glamorgan Hospital. There have been 184 children treated to date, with an age range of 4 weeks to 13 years. There were 58 circumcisions, 48 hernias, 35 orchidopexies, 18 hydrocoeles and 25 miscellaneous procedures performed with no significant complications. All children were given a general anaesthetic, 42 procedures (22%) were performed using endotracheal intubation, the remainder with a facemask. Postoperative analgesia was provided in most cases by local wound infiltration with bupivacaine 0.25%. The average length of stay before January 1989 was 3 days and 2 nights for similar cases. Cost analysis shows significant potential financial savings of 105 pounds per patient treated. The implications for future planning are discussed.

Adolescent↗
PubMedDate not supplied

Laparoscopic cholecystectomy.

The technique of laparoscopic cholecystectomy is probably the most significant major surgical advance of the last decade. It allows shorter hospitalization, rapid recovery and early return to work. Significant financial savings may be achieved over current conventional treatment. In this article the procedure is reviewed and its advantages and drawbacks are discussed.

Cholangiography↗