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Biomedical subjects

K C Loh

Publications and source records attributed to K C Loh.

At least 37 records · Page 2Linked to original sources
PubMed1999

Facilitation of cometabolic degradation of 4-chlorophenol using glucose as an added growth substrate.

This paper reports on the feasibility of using glucose as an added substrate for cometabolic transformation of 4-chlorophenol (4-cp). When glucose was fed as the added growth substrate, only 78% and 43% of the initial 4-cp concentrations of 100 and 200 mg l-1, respectively, were transformed before the pH dropped to below 4.5 and stopped all reactions. By maintaining the medium pH, complete removal of 4-cp was achieved even at the high initial concentration of 200 mg l-1. Phenol induction prior to inoculation was not a prerequisite to ensure transformation of 4-cp when glucose was the added growth substrate. Compared with phenol as the added growth substrate, cells grown on glucose displayed a longer acclimation phase and, in general, a lower specific transformation rate. The volumetric transformation rate of 4-cp, however, was greatly enhanced due to the increased cell density. The results of this work suggest that 4-cp itself induced the enzymes necessary for its cometabolism. With NADH regenerated effectively through metabolism of glucose, 4-cp was transformed in the absence of added phenol. Consequently, the competitive inhibition involved in cometabolism was avoided and the risks associated with addition of toxic growth substrates such as phenol were eliminated.

Biodegradation, Environmental↗
PubMed1999

Influence of lymphocytic thyroiditis on the prognostic outcome of patients with papillary thyroid carcinoma.

Both the association between lymphocytic thyroiditis (LT) and papillary thyroid carcinoma (PTC), and the prognostic significance of lymphocytic infiltrate in patients with thyroid malignancy, remain controversial. We examine the above relationships by retrospectively reviewing our series of patients treated for differentiated nonmedullary thyroid carcinoma at University of California-San Francisco over a 25-yr period (1970-1995). Of the 631 patients with complete data for analysis, 128 patients (20.3%) showed concomitant histologic evidence of LT and 503 patients (79.7%) had no evidence of LT. Prognostic outcome was assessed using Kaplan-Meier survival plots and analysis of risk factors by Cox's proportional-hazard modeling. The cohort with LT revealed a higher frequency of PTC (97.7% vs. 87.3%) and female patients (85.2% vs. 66.8%), a lower frequency of extrathyroidal invasion (7.8% vs. 23.3%) and nodal metastases (25.8% vs. 43.3%), and absence of distant metastases (0% vs. 4.8%), respectively, compared with those without LT. At initial surgery, a significantly greater proportion of patients with LT belonged to lower pathological tumor-node-metastasis stages, compared with those without LT (stage 1, 86.7% vs. 73%; stage 2, 4.7% vs. 8.3%; stage 3, 8.6% vs. 15.3%; and stage 4, 0% vs. 3.4%). Over a mean +/- SE follow-up period of 11.1 +/- 0.4 yr, patients with LT had significantly lower cancer recurrence rate (6.3% vs. 24.1%; P < 0.0001) and cancer mortality rate (0.8% vs. 8.0%; P = 0.001), respectively, compared with those without LT. In summary, our series showed a relatively common occurrence of LT in patients with PTC, and we believed that lymphocytic infiltration developed mainly in response to the tumor itself. We also found a more favorable course of PTC in the presence of LT; this supports the hypothesis that lymphocytic infiltration represents a form of immune reaction to control tumor growth and proliferation.

Adolescent↗
PubMed1999

Cyclical Cushing's syndrome--a trap for the unwary.

A woman with cyclical Cushing's syndrome due to periodic hormonogenesis from a corticotropin (ACTH) secreting pituitary adenoma is discussed. This patient presented with acute steroid-induced psychosis but she was found to have subtle cushingoid features that went undetected for two years. Laboratory evaluation for Cushing's syndrome showed incongruous results due to periodic ACTH production by the tumour. Cyclical Cushing's syndrome may be an under-recognised phenomenon and incorrect interpretation of investigative results may lead to wrong tumour localisation and inappropriate surgery. This case highlights the subtleties and complexities that one may encounter in the diagnostic evaluation of patients with Cushing's syndrome, and emphasises that the laboratory results must always be interpreted in the appropriate clinical context.

ACTH Syndrome, Ectopic↗
PubMed1999

Approach to a patient with suspected primary aldosteronism.

A typical case of a patient with suspected mineralocorticoid hypertension is discussed. The presentation follows sequential steps through the diagnostic evaluation and treatment of primary aldosteronism. The diagnostic approach can be classified into three phases: screening tests, confirmatory tests, and subtype differentiation studies. It is essential to follow the evaluation steps to elucidate the cause of primary aldosteronism, as this determines the appropriate treatment. Another lesson to learn is the need to critically appraise the value of any endocrine test, particularly if it is likely to influence the management strategy in an individual patient.

Aldosterone↗
PubMed1998

Clinical profile of primary hyperparathyroidism in adolescents and young adults.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is an uncommonly diagnosed condition among adolescents and young adults. We review the clinical characteristics of these patients based on our institutional experience. SUBJECTS: Patients aged 12-28 years treated for PHPT at our institution from 1990 to 1996 were evaluated by a review of medical records and current follow-up data. This consisted of 22 patients (8M:14F), constituting approximately 3% of all patients operated for PHPT during this period. MEASUREMENTS: Serum and urinary calcium concentrations, renal function, and serum intact parathyroid hormone (IPTH) levels were measured in all patients. After biochemical confirmation of diagnosis, the patients completed a questionnaire to evaluate the presence of symptoms and/or conditions associated with PHPT. All the patients underwent parathyroidectomy and their tumour characteristics were evaluated. Surgical outcome was determined by measurements of serum calcium and IPTH levels postoperatively and during long-term follow-up. RESULTS: A third of the patients were diagnosed by routine serum chemistry whereas two-thirds presented with symptoms or conditions associated with hypercalcaemia. Non-specific complaints such as fatigue or exhaustion, and weakness or lethargy constitute the most common findings on questionnaire review. A family history of PHPT was present in only 2 patients. The preoperative peak serum calcium levels ranged from 2.67 to 4.19 mmol/l (norm: 2.10-2.54 mmol/l), with a median of 3.07 mmol/l. Surgical pathologies revealed 59% solitary adenoma, 27% hyperplasia, 9% multiple adenomas and 5% carcinoma. Comparison between the adolescents (aged 12-18 years) and young adults (aged 19-28 years) revealed no differences in the clinical, pathological or laboratory profiles, except for a male predominance in adolescent patients. Fifteen patients had resection of one or more adenomas while 7 underwent subtotal parathyroidectomy. Six patients (27%) were reoperated cases, all received primary treatment elsewhere. All patients with benign PHPT were cured surgically, with a median follow-up of 47 months (range 3-77 months). One reoperated patient developed permanent hypocalcaemia. One patient with carcinoma underwent several operations for recurrence; he is now eucalcaemic despite persistent disease at 80 months from diagnosis. CONCLUSIONS: We found a high incidence of multiglandular disease and relatively non-specific symptomatology in our adolescent and young adult patients with primary hyperparathyroidism. In view of the heterogeneous clinical expression noted in young patients, one should consider primary hyperparathyroidism in the differential diagnosis of unexplained non-specific complaints, and perform serum calcium estimations more readily in these subjects. Our experience suggests that primary hyperparathyroidism can be a serious disease with significant morbidity if left untreated, whereas parathyroidectomy provides successful results.

Adolescent↗
PubMed1998

Riedel's thyroiditis presenting with hypothyroidism and hypoparathyroidism: dramatic response to glucocorticoid and thyroxine therapy.

Riedel's thyroiditis is a rare fibro-inflammatory process originating in the thyroid gland with progressive extension and invasion of surrounding tissues. Patients frequently present with a stony hard thyroid mass suggestive of anaplastic carcinoma. We report a striking case of Riedel's thyroiditis associated with hypothyroidism, hypoparathyroidism and bilateral vocal cord paralysis. A dramatic response to high dose prednisone and levothyroxine therapy was seen, with recovery of parathyroid and vocal cord function. Our case suggests that early initiation of combination therapy may be important, particularly in the presence of severe disease.

Drug Therapy, Combination↗
PubMed1998

Fractional esterification rate of HDL particles in patients with type 2 diabetes. Relation to coronary heart disease risk factors.

OBJECTIVE: To study the fractional esterification rate of cholesterol on HDL particles (FERHDL) in adults with type 2 diabetes and assess its correlation with serum lipids and other coronary heart disease (CHD) risk factors. RESEARCH DESIGN AND METHODS: FERHDL was measured in 90 adult (57 men, 33 women) patients by an isotopic assay method involving several steps, including preparation of VLDL- and LDL-depleted plasma, labeling of the sample with a trace amount of tritiated cholesterol, separation of free and esterified cholesterol fractions by chromatography post incubation, and subsequent counting of radioactivity in the individual fractions. RESULTS: Male patients have higher FERHDL values than their female counterparts. When HDL cholesterol was controlled for in a multivariate regression analysis, the sex factor was not significant. There was a significant positive correlation between FERHDL and plasma total cholesterol (r = 0.32), triglycerides (r = 0.82), apolipoprotein B (apo B; r = 0.48), insulin (r = 0.46), BMI (r = 0.31), and waist-to-hip ratio (WHR; r = 0.50). There was a negative correlation between FERHDL and HDL cholesterol (r = -0.76) and apolipoprotein AI (r = -0.60). When both HDL cholesterol and triglycerides were controlled for, the only significant correlation was between FERHDL and BMI. CONCLUSIONS: Non-insulin-requiring type 2 diabetic patients have FERHDL, which correlated positively with triglycerides and negatively with HDL cholesterol. The positive correlation of FERHDL with serum insulin, WHR, total cholesterol, and apo B, but not that with BMI, loses its significance when HDL cholesterol and triglycerides are controlled. The sex difference between men and women in FERHDL also loses its significance when HDL cholesterol is controlled.

Adult↗
PubMed1998

Hyperthyroidism with gynaecomastia as the initial complaint: a case report.

Although gynaecomastia is a well-documented manifestation among male patients with hyperthyroidism, it is extremely rare to present as the initial or chief complaint in a subject with undiagnosed hyperthyroidism. We report a case of a 38-year-old Chinese man presenting with painful enlargement of both breasts of one month's duration. Examination revealed bilateral tender gynaecomastia. In addition, he was noted to have warm and moist peripheries, resting tachycardia and an enlarged goitre. Hyperthyroidism was confirmed biochemically. Treatment of thyrotoxicosis resulted in resolution of the gynaecomastia. This case report demonstrates that gynaecomastia may predominate over the commonly recognised, more manifest and urgent symptoms of hyperthyroidism.

Adult↗
PubMed1998

Occult virilizing ovarian tumours in postmenopausal women: problems in evaluation with reference to a case.

A 53-year-old postmenopausal presented with hirsutism, acne, receding hairline, male-pattern baldness, and deepening of voice developing over the last five years. Her left ovary had been removed at the age of 38 years old for a benign cyst and vaginal hysterectomy was performed one year later for cervical carcinoma. She had taken premarin 0.625 mg daily since her surgeries. Initial hormonal studies revealed elevated serum concentrations of total testosterone 524 ng/dL (N: 6-86 ng/dL), free testosterone 20.9 pg/mL (N: 0.3-2.7 pg/mL), and 17-hydroxyprogesterone 270 ng/dL (N: < 70 ng/dL); but normal baseline concentrations of dehydroepiandrosterone-sulfate, androstenedione, and cortisol. Computed tomographic (CT) scans of the adrenals and ultrasonography of the pelvis were negative. Magnetic resonance imaging (MRI) of the abdomen and pelvis similarly were non-revealing. She was given glucocorticoids without effect. Subsequently, retrograde selective venous sampling showed a marked testosterone gradient in the right ovarian vein. A laparoscopic right oophorectomy was performed and a 11 mm Leydig cell tumour of hilus cell type was detected on histologic examination. Postoperative testosterone levels returned to normal and she had slow regression of hirsutism. Our case illustrates that a virilizing ovarian neoplasm can be small and elude imaging studies. We suggest bilateral oophorectomy for postmenopausal women with severe recent-onset virilization and without Cushing's syndrome and with normal adrenal imaging. This approach avoids unnecessary investigations and delays in definitive management.

Diagnostic Imaging↗
PubMed1997

Role of polyethyleneimine in the purification of recombinant human tumour necrosis factor beta.

The chromatographic behaviour of recombinant human tumour necrosis factor beta (rhTNF-beta) (pI approximately 9.0) during cation-exchange chromatography at pH 7.5 is investigated. Without prior treatment of the Escherichia coli cell extract with polyethyleneimine (PEI), very little rhTNF-beta was bound to the column. However, upon addition of 5% PEI (100 microliters ml-1) to the cell lysate, rhTNF-beta was shown to bind to cation-exchange columns normally. TNF-beta was readily precipitated from the clarified cell extract by 20% ammonium sulphate, but ony ca. 25% of this precipitate could be re-solubilized for further purification. However, when 5% PEI was included in the solubilization buffer, the balance of the rhTNF-beta could be recovered. It is proposed that charge interaction between rhTNF-beta and nucleic acids in the cell extract is responsible for both of these anomalous phenomena, and that PEI (a cationic polyelectrolyte) was able to disrupt this interaction by displacing rhTNF-beta from the charge complex.

Ammonium Sulfate↗
PubMed1997

The treatment of malignant pheochromocytoma with iodine-131 metaiodobenzylguanidine (131I-MIBG): a comprehensive review of 116 reported patients.

Iodine-131 metaiodobenzylguanidine (131I-MIBG), a radiopharmaceutical agent used for scintigraphic localization of pheochromocytomas, has been employed to treat malignant pheochromocytomas since 1983 in a few specialized centers around the world. We review our clinical experience together with the published experience of 23 other centers in 10 countries, regarding the use of 1311-MIBG for treating patients with malignant adrenal pheochromocytomas or extra-adrenal paragangliomas. There were a total of 116 evaluable patients: 3 were from our current report and another 113 were reported in the literature from 1983 to 1996. A majority of the patients were selected for treatment based upon positive tracer uptake studies. The cumulative dose of 131I-MIBG administered ranged from 96 to 2,322 mCi (3.6 to 85.9 GBq), with a mean (+/-SD) of 490+/-350 mCi (18.1+/-13.0 GBq). The subjects received a mean single therapy dose of 158 mCi (5.8 GBq) and the number of doses administered ranged from 1 to 11, with a mean of 3.3+/-2.2 doses. Initial symptomatic improvement was achieved in 76% of patients, tumor responses in 30%, and hormonal responses in 45%. Five patients had complete tumor and hormonal responses, ranging from 16 to 58 months, which were sustained at the time of reporting. Patients with metastases to soft tissue had more favorable responses to treatment than those with metastases to bone. No difference was noted in the age between the responders and non-responders. Adverse effects, recorded in 41% of the treated patients, were generally mild except for one fatality from bone marrow aplasia. Among 89 patients with follow-up data, 45% of the responders had relapsed with recurrent or progressive disease after a mean interval of 29.3+/-31.1 months (median 19 months). Of patients with an initial response to 1311-MIBG, death was reported in 33% after a mean of 23.2+/-8.1 months (median 22 months) following treatment. Of non-responders, death was reported in 45% after a mean of 14.3+/-8.3 months (median 13 months). In conclusion, this review suggests that 131I-MIBG therapy may be a useful palliative adjunct in selected patients with malignant pheochromocytoma or paraganglioma. Although controlled studies are lacking, our review raises the hope that this therapeutic modality may prolong survival with an occasional sustained complete remission or possible cure.

3-Iodobenzylguanidine↗
PubMed1997

Familial nonmedullary thyroid carcinoma: a meta-review of case series.

Familial occurrence of nonmedullary thyroid carcinoma is extremely rare but this has been increasingly recognized over the recent years. Earlier reports of such occurrence were primarily confined to individuals with previous radiation exposure, history of familial adenomatous polyposis (Gardner's syndrome) or multiple hamartomas (Cowden's syndrome), or monozygotic twins. The author reviews 15 case reports/series of familial nonmedullary thyroid carcinoma available in the literature involving kindreds with no obvious associated pathogenetic factors as mentioned above. There were a total of 87 kindreds with 178 affected individuals available for analysis, with a male to female ratio of 1:2.2. The modal age group at diagnosis was 30-39 years in both gender groups. Papillary thyroid carcinoma constituted 91% of the cases, followed by follicular (6%) and anaplastic (2%) varieties. There was one case (0.5%) each of combined papillary and medullary thyroid carcinoma and Hurthle cell carcinoma, respectively. Six of the 15 series observed that patients with familial history generally have more aggressive tumour characteristics compared to the sporadic counterparts. The incidences of multifocality, local invasion, and distant metastases at diagnosis were 49, 32, and 5%, respectively. The incidences of locoregional recurrence, distant metastases, and deaths were 29, 10, and 5.4%, respectively, at a mean follow-up period of 11 years. The actual prognostic outcome of familial nonmedullary thyroid carcinoma is still unclear in view of the limited clinical data. Although several authors have advocated an aggressive approach in managing these patients, no conclusion can be reached on the basis of this review to support this position. The author recommends that patients with familial disease should be treated according to the disease stage and other risk factors, similar to those with spontaneously occurring well-differentiated papillary or follicular thyroid carcinomas. In addition, one might consider and perform follow-up of first-degree relatives with similar degree of caution as patients who have undergone head and neck irradiation in childhood.

Adolescent↗
PubMed1997

Phaeochromocytoma: a ten-year survey.

We retrospectively evaluated our experience with phaeochromocytoma from January 1986 to December 1995. There were 18 patients with surgically-proven phaeochromocytoma: three males, 15 females, aged 12-81 years (mean 42 years) at diagnosis. Sixteen were hypertensive; only 6/18 presented with two or more of the classical triad of headaches, palpitations and diaphoresis. One patient presented with hypertensive crisis. Duration of symptoms prior to diagnosis was 2 weeks to 6 years, mean 16.4 months. Sixteen patients had adrenal tumours and two had extra-adrenal tumours or paragangliomas. One had bilateral adrenal tumours and two had a combination of both adrenal and extra-adrenal tumours. There were four familial cases: two had multiple endocrine neoplasia type IIA (MEN-IIA), one had neurofibromatosis type I (NF-I) and one von Hippel-Lindau (VHL) disease. One patient had Cushing's syndrome arising from ectopic production of adrenocorticotropic hormone (ACTH) by the phaeochromocytoma. Disease was recurrent in three patients. Pre-operative diagnosis was confirmed mainly by elevated urine vanillylmandelic acid (VMA) and/or catecholamine levels. Twelve patients had plasma catecholamine determinations: noradrenaline was elevated in all, adrenaline in six and dopamine in two. Pre-operative localization was by CT scan or MR imaging in all patients. At follow-up of 1-10 years (median 4.8 years), 15 patients were cured surgically while two were asymptomatic despite recurrence of disease. One patient with recurrent paragangliomas died post-operatively.

Adrenal Gland Neoplasms↗
PubMed1997

Pathological tumor-node-metastasis (pTNM) staging for papillary and follicular thyroid carcinomas: a retrospective analysis of 700 patients.

The TNM classification (tumor-node-metastasis) was adopted by the American Joint Committee on Cancer and the International Union against Cancer a decade ago to avoid heterogeneity of prognostic classification schemes used for differentiated thyroid cancers. To date, however, clinical data based on this classification are lacking. We retrospectively evaluate the prognosis of 700 patients (208 men and 492 women) with papillary (89%) and follicular (11%) thyroid cancers according to the pathological TNM (pTNM) staging system, treated over a 25-yr period (1970-1995). Patients who received primary treatment at our center constituted 87.4% of the cases; the majority underwent total thyroidectomy, followed by 131I ablative therapy in high risk groups, as standard treatment. Clinical and follow-up data were obtained from the medical records and our cancer registry. Disease-free and cancer-specific survival data were analyzed by Kaplan-Meier product limit estimates and Cox proportional hazard models. Patient distribution by the pTNM system were: stage I, 516 patients; stage II, 57 patients; stage III, 104 patients; and stage IV, 23 patients. Over a mean +/- SE follow-up of 11.3 +/- 0.3 yr, the overall cancer recurrence and mortality rates were 20.5% and 8.4%, respectively. However, the respective cancer recurrence and mortality rates were distinctly different in the various pTNM stages: 15.4% and 1.7% in stage I, 22% and 15.8% in stage II, 46.4% and 30% in stage III, and 66.7% and 60.9% in stage IV tumors. Using actuarial survival plots, a clear separation in both disease-free survival and cancer-specific survival was noted among all the stages (P < 0.0001). Risk factors analyses showed a significant association between all the prognostic variables used in TNM staging (age, tumor size, extent of primary tumor, and presence of nodal or distant metastases) and the observed end points of recurrence or death from thyroid cancer. After correcting for TNM stages, the risk of cancer recurrence was halved in female compared to male patients, whereas this was 1.7-fold higher in multifocal than unifocal tumors. Conversely, cancer mortality was 3.4-fold higher in follicular than papillary thyroid cancer. In the analysis of effect of primary treatment among 492 patients with tumor more advanced than the T1N0M0 category, patients who underwent less extensive surgery (lobectomy or subtotal thyroidectomy) had a 2.5-fold risk of cancer recurrence (P < 0.0001) and a 2.2-fold risk of death (P < 0.01) compared to those who underwent total or near-total thyroidectomy. Patients not treated with 131I ablation had a 2.1-fold greater risk of cancer recurrence (P < 0.0001) than those given 131I ablation, although no difference was noted in deaths from thyroid cancer. Based on our data, the pTNM classification is useful in distinguishing patients with different prognostic outcomes. However, the small patient numbers in pTNM stages other than stages I precludes us from evaluating its usefulness as a guide for therapy. Until prospective data could be accrued from controlled treatment trials, we support the standard practice of total thyroidectomy followed by 131I ablative therapy (if focal iodide uptake was noted) in patients with papillary thyroid cancer more advanced than the T1N0M0 category or of multicentric nature and in the majority of patients with follicular thyroid cancer.

Adenocarcinoma, Follicular↗
PubMed1997

Diabetes insipidus from sarcoidosis confined to the posterior pituitary.

A young white man with new-onset central diabetes insipidus was discovered to have a posterior pituitary mass on magnetic resonance imaging. No other radiological abnormalities were noted in the anterior pituitary, infundibulum or hypothalamus. No other endocrinopathies were present: laboratory investigations showed normal basal concentrations of anterior pituitary hormones, including prolactin. The patient was suspected to have sarcoidosis affecting the posterior pituitary, because of the discovery of pulmonary sarcoidosis during his diagnostic evaluation. His symptoms of polydipsia and polyuria responded promptly to intranasal administration of 1-desamino-8-D-arginine vasopressin (DDAVP). The patient demonstrated complete regression of the posterior pituitary mass after a course of corticosteroid therapy. However, his diabetes insipidus persisted and he continues to need DDAVP treatment, currently at 12 months of follow-up. The resolution of the neurohypophysial mass was compatible with the diagnosis of pituitary sarcoidosis and this precluded the need for a transsphenoidal biopsy or surgery.

Adrenal Cortex Hormones↗
PubMed1997

Ectopic Cushing's syndrome in a young female with atypical [corrected] bronchial carcinoid tumour.

A 17-year-old female with a large mass in the left thorax presenting with ectopic Cushing's syndrome is described. Biochemical evaluation revealed a corticotropin(ACTH)-dependent hypercortisol state. Surgical resection of the tumour resulted in clinical remission and correction of hypercortisolism and normal plasma ACTH levels. The histology was that of an atypical carcinoid. Bronchial carcinoid tumour is an extremely uncommon but well recognised cause of ectopic Cushing's syndrome. These patients may pose diagnostic dilemma in distinguishing form those with Cushing's disease because of the similarity in the clinical, biochemical and radiologic findings.

ACTH Syndrome, Ectopic↗