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Biomedical subjects

J C Lo

Publications and source records attributed to J C Lo.

17 recordsLinked to original sources
PubMed2001

Metabolic effects of indinavir in healthy HIV-seronegative men.

BACKGROUND: Therapy with HIV protease inhibitors (PI) has been associated with hyperglycemia, hyperlipidemia and changes in body composition. It is unclear whether these adverse effects are drug related, involve an interaction with the host response to HIV or reflect changes in body composition. METHODS: Indinavir 800 mg twice daily was given to 10 HIV-seronegative healthy men to distinguish direct metabolic effects of a PI from those related to HIV infection. Fasting glucose and insulin, lipid and lipoprotein profiles, oral glucose tolerance (OGTT), insulin sensitivity by hyperinsulinemic euglycemic clamp, and body composition were measured prior to and after 4 weeks of indinavir therapy. RESULTS: Fasting glucose (4.9 +/- 0.1 versus 5.2 +/- 0.2 mmol/l; P = 0.05) insulin concentrations (61.7 +/- 12.2 versus 83.9 +/- 12.2 pmol/l; P < 0.05), insulin : glucose ratio (12.6 +/- 1.7 versus 15.9 +/- 1.9 pmol/mmol; P < 0.05) and insulin resistance index by homeostasis model assessment (1.9 +/- 0.3 versus 2.8 +/- 0.5;P < 0.05) all increased significantly. During OGTT, 2 h glucose (5.1 +/- 0.4 versus 6.5 +/- 0.6 mmol/l; P < 0.05) and insulin levels (223.1 +/- 48.8 versus 390.3 +/- 108.8 pmol/l;P =0.05) also increased significantly. Insulin-mediated glucose disposal decreased significantly (10.4 +/- 1.4 versus 8.6 +/- 1.2 mg/kg x min per microU/ml insulin; 95% confidence interval 0.6--.0;P < 0.01). There was no significant change in lipoprotein, triglycerides or free fatty acid levels. There was a small loss of total body fat (15.8 +/- 1.4 versus 15.2 +/- 1.4 kg;P = 0.01) by X-ray absorptiometry without significant changes in weight, waist : hip ratio, and visceral or subcutaneous adipose tissue by computed tomography. CONCLUSIONS: In the absence of HIV infection, treatment with indinavir for 4 weeks causes insulin resistance independent of increases in visceral adipose tissue or lipid and lipoprotein levels.

Adult↗
PubMed2001

Altered fat distribution in HIV-positive men on nucleoside analog reverse transcriptase inhibitor therapy.

To determine whether HIV infection, the wasting syndrome, or nucleoside analog reverse transcriptase inhibitor (NRTI) or protease inhibitor (PI) therapy uniquely affect fat distribution in men, we performed manual regional analysis of total, appendicular, trunk, and central abdominal fat measured by dual-energy X-ray absorptiometry (DEXA). Five groups of study subjects were identified for this cross-sectional analysis: HIV-negative controls (HIV-; N = 44) and four groups of HIV-positive subjects: antiretroviral (ARV)-naive or with limited prior use of NRTIs (ARV-; N = 23); on NRTIs for > or =6 months but PI-naive (NRTI; N = 30); on an NRTI/PI regimen for > or =6 months but with no complaints of abnormal fat distribution (NRTI/PI; N = 26); and those on NRTIs but PI-naive with the wasting syndrome (NRTI/WS; N = 40). Total, appendicular, trunk, and central abdominal fat was significantly lower in NRTI/WS. The ratio of trunk fat to appendicular fat was virtually identical in HIV- and ARV-. This ratio was significantly higher in the NRTI, NRTI/PI, and NRTI/WS groups, and values in these three groups were similar. These cross-sectional data suggest that HIV-infected men receiving NRTIs have an altered pattern of fat distribution, compared with HIV-negative men and HIV-positive men who are not receiving antiretroviral therapy. This effect was independent of the concomitant use of a PI or a diagnosis of the wasting syndrome. We saw no evidence of a unique effect of HIV infection per se on regional fat distribution. Although the fat ratio is increasingly employed, its physiologic significance is unclear. Our results, which have been obtained retrospectively, are intended to provide the impetus for prospective, controlled studies of the interactions among drug and host factors in the development of fat distribution abnormalities.

Adipose Tissue↗
PubMed2001

Pregnancy outcomes in women with congenital virilizing adrenal hyperplasia.

Although low fertility rates have traditionally been reported among women with classic CAH and especially among women with the salt-wasting variant, more recent data suggest that fertility rates are significantly improved, largely owing to earlier treatment of CAH, improved compliance with therapy, and surgical advances in genital reconstruction. Furthermore, ovulation induction and assisted reproductive techniques are now available to women who remain infertile despite effective adrenal androgen suppression. Although the pregnancy experience in women with classic CAH remains limited, it is apparent that, once pregnant, these women have a high probability of successful outcome. Key issues should be emphasized in the management of CAH during gestation, including the need for assessing adrenal steroid replacement and adrenal androgen suppression, particularly in light of the interplay between maternal hyperandrogenism and the protective effect of placental aromatase activity, which provides a relatively large margin of safety for the female fetus. Maternal hormone levels should be evaluated in the context of laboratory-specific reference ranges for pregnancy. The infant should be examined for ambiguous genitalia and monitored for evidence of adrenal insufficiency. Although an affected female infant with classic CAH has not been reported as a pregnancy outcome of a mother with classic virilizing CAH, these concerns should be discussed during preconception counseling. Patients should also be aware of the importance of medication compliance and careful hormonal monitoring during the entire pregnancy. In most cases, successful gestational management requires the close coordination of care between the obstetrician and endocrinologist.

Adrenal Hyperplasia, Congenital↗
PubMed2000

Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection.

Although protease inhibitor (PI) therapy has improved the clinical status of patients with HIV infection, concerns have arisen that such treatment may have deleterious effects on glucose control, lipid metabolism, and body fat distribution. To determine whether initiation of PI therapy uniquely affects glucose and lipid metabolism, we analyzed paired data in HIV-infected patients before and after beginning antiretroviral therapy that included a PI (PI; N = 20) or lamivudine (3TC) but no PI (3TC; N = 9); and a control group on stable regimens that included neither of these agents (CONT: N = 12). Measurements included fasting glucose; insulin; triglycerides; total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol; HIV RNA; CD4+ lymphocytes; weight; and total and regional body composition. Neither weight nor total or regional fat content changed significantly in any group during the period of observation. Nonetheless, in patients beginning PI therapy, there were significant increases in glucose (+9+/-3 mg/dl; p = .0136), insulin (+12.2+/-4.9 U/ml; p = .023), triglycerides (+53+/-17 mg/dl; p = .0069), and total and LDL cholesterol (+32+/-11 and +18+/-5 mg/dl; p = .0082 and .0026, respectively). None of these parameters changed significantly in the 3TC or CONT groups. The PI and 3TC groups experienced comparable increases in CD4+ lymphocytes, suggesting that the observed metabolic effects may be associated with PIs uniquely, rather than improvement in clinical status. However, it is also possible that the metabolic effects of PIs are associated with more effective viral suppression, because a greater proportion of patients in the PI group achieved undetectable levels of virus. We conclude that changes in glucose and lipid metabolism are induced by PI therapy in the absence of significant changes in weight or fat distribution. Longer periods of follow-up will be required to determine the clinical significance of these changes. However, at the moment, the risks associated with these metabolic effects do not appear to outweigh improvements in survival seen with PI therapy.

Adult↗
PubMed2000

Exposure to solvents in a synthetic leather manufacturing plant.

The objective of this study was to evaluate the exposure of synthetic leather workers to dimethylformamide (DMF), epichlorohydrin (ECH) and toluene, in a manufacturing plant. The correlation between biological and environmental monitoring for DMF was also investigated. Environmental monitoring of the three solvents included personal and area sampling based on time of day (morning and afternoon). Urine samples were taken at the end of the shift and urinary N-methylformamide (NMF) was then used to biologically monitor DMF levels. Results for solvent concentrations based on air sampling were considerably higher in area than in personal sampling. Of 41 area samples, 15 (36.6%) and five (12.2%) exceeded permissible exposure levels for DMF and ECH, respectively, compared with 22 (28.6%) and three (3.9%) based on 77 personal samples. Overall, urinary NMF concentrations were lower than the Biological Exposure Index (BEI) suggested by the American Conference of Governmental Industrial Hygienists (ACGIH). A significant correlation (r = 0.32; P < 0.05) was found between environmental and biological monitoring. Even though urinary NMF concentration was within permissible levels for Taiwan, the authors recommend that immediate measures be taken to decrease DMF and ECH concentrations in synthetic leather manufacturing plants.

Adult↗
PubMed2000

Pyrolysis kinetics and residue characteristics of petrochemical industrial sludge.

This study investigated the pyrolysis characteristics of sludge from wastewater treatment plants in the petrochemical industry and focused on the pyrolysis kinetics, elemental composition of residue, and volatile organic compounds (VOCs) of exhaust gas. As pyrolysis temperature increased to 773 K, the increasing rate of crude oil production tended to a stable condition. The result indicated that the optimal temperature of crude oil and water mixed production was 773 K. When pyrolysis temperature increased from 673 to 973 K, carbon, oxygen, nitrogen, and hydrogen concentrations of residue decreased and the sulfur concentration of residue increased. The concentrations of benzene, toluene,ethylbenzene, and styrene increased by the increasing pyrolysis temperature. We found that the reaction order of sludge pyrolysis was 2.5 and the activation energy of the reaction was 11.06 kJ/mol. We believe that our pyrolysis system is transitional between devolatilization and combustion.

Gases↗
PubMed1999

Differential mobility of skeletal and cardiac tropomyosin on the surface of F-actin.

Polarized phosphorescence from the triplet probe erythrosin-5-iodoacetamide attached to sulfhydryls in rabbit skeletal and cardiac muscle tropomyosin (Tm) was used to measure the microsecond rotational dynamics of these tropomyosins in a complex with F-actin. The steady-state phosphorescence anisotropy of skeletal tropomyosin on F-actin was 0.025 +/- 0.005 at 20 degrees C; the comparable anisotropy for cardiac tropomyosin was 0.010 +/- 0. 003. Measurements of the anisotropy as a function of temperature and solution viscosity (modulated by addition of glycerol) indicated that both skeletal and cardiac tropomyosin undergo complex rotational motions on the surface of F-actin. Models assuming either long axis rotation of a rigid rod or torsional twisting of a flexible rod adequately fit these data; both analyses indicated that cardiac Tm is more mobile than skeletal Tm and that the increased mobility on the surface of F-actin reflected either the rotational motion of a smaller physical unit or the torsional twisting of a less rigid molecule. The binding of myosin heads (S1) to the Tm-F-actin complexes increased the anisotropy to 0.049 +/- 0.004 for skeletal and 0.054 +/- 0.007 for cardiac tropomyosin. The titration of the skeletal tropomyosin-F-actin complex by S1 showed a break at an S1/actin ratio of 0.14; this complex had an anisotropy of 0.040 +/- 0.007, suggesting that one bound head effectively restricted the motion of each skeletal tropomyosin. A similar titration with cardiac tropomyosin reached a plateau at an S1/actin ratio of 0.4, suggesting that 2-3 myosin heads are required to immobilize cardiac Tm. Surface mobility is predicted by structural models of the interaction of tropomyosin with the actin filament while the decrease in tropomyosin mobility upon S1 binding is consistent with current theories for the proposed role of myosin binding in the mechanism of tropomyosin-based regulation of muscle contraction.

Actins↗
PubMed1999

Different mismatch repair deficiencies all have the same effects on somatic hypermutation: intact primary mechanism accompanied by secondary modifications.

Somatic hypermutation of Ig genes is probably dependent on transcription of the target gene via a mutator factor associated with the RNA polymerase (Storb, U., E.L. Klotz, J. Hackett, Jr., K. Kage, G. Bozek, and T.E. Martin. 1998. J. Exp. Med. 188:689-698). It is also probable that some form of DNA repair is involved in the mutation process. It was shown that the nucleotide excision repair proteins were not required, nor were mismatch repair (MMR) proteins. However, certain changes in mutation patterns and frequency of point mutations were observed in Msh2 (MutS homologue) and Pms2 (MutL homologue) MMR-deficient mice (for review see Kim, N., and U. Storb. 1998. J. Exp. Med. 187:1729-1733). These data were obtained from endogenous immunoglobulin (Ig) genes and were presumably influenced by selection of B cells whose Ig genes had undergone certain mutations. In this study, we have analyzed somatic hypermutation in two MutL types of MMR deficiencies, Pms2 and Mlh1. The mutation target was a nonselectable Ig-kappa gene with an artificial insert in the V region. We found that both Pms2- and Mlh1-deficient mice can somatically hypermutate the Ig test gene at approximately twofold reduced frequencies. Furthermore, highly mutated sequences are almost absent. Together with the finding of genome instability in the germinal center B cells, these observations support the conclusion, previously reached for Msh2 mice, that MMR-deficient B cells undergoing somatic hypermutation have a short life span. Pms2- and Mlh-1-deficient mice also resemble Msh2-deficient mice with respect to preferential targeting of G and C nucleotides. Thus, it appears that the different MMR proteins do not have unique functions with respect to somatic hypermutation. Several intrinsic characteristics of somatic hypermutation remain unaltered in the MMR-deficient mice: a preference for targeting A over T, a strand bias, mutational hot spots, and hypermutability of the artificial insert are all seen in the unselectable Ig gene. This implies that the MMR proteins are not required for and most likely are not involved in the primary step of introducing the mutations. Instead, they are recruited to repair certain somatic point mutations, presumably soon after these are created.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Normal female infants born of mothers with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, especially those patients with the salt-losing form, have decreased fertility rates. Pregnancy experience in this population is limited. We report the pregnancy outcomes and serial measurements of maternal serum steroid levels in four women with classic 21-hydroxylase deficiency, three of whom were female pseudohermaphrodites with the salt-losing form. These glucocorticoid-treated women gave birth to four healthy female newborns with normal female external genitalia, none of whom were affected with 21-hydroxylase deficiency. In three women, circulating androgen levels increased during gestation, but remained within the normal range for pregnancy during glucocorticoid therapy. In the fourth patient, androgen levels were strikingly elevated during gestation despite increasing the dose of oral prednisone from 5 to 15 mg/day (two divided doses). Notwithstanding the high maternal serum concentration of androgens, however, placental aromatase activity was sufficient to prevent masculinization of the external genitalia of the female fetus and quite likely the fetal brain, consistent with the idea that placental aromatization of androgens to estrogens is the principal mechanism that protects the female fetus from the masculinizing effects of maternal hyperandrogenism. These four patients highlight key issues in the management of pregnancy in women with 21-hydroxylase deficiency, particularly the use of endocrine monitoring to assess adrenal androgen suppression in the mother, especially when the fetus is female. Recommendations for the management of pregnancy and delivery in these patients are discussed.

Adrenal Hyperplasia, Congenital↗
PubMed1998

"Buffalo hump" in men with HIV-1 infection.

BACKGROUND: Enlargement of the dorsocervical fat pad ("buffalo hump") has been reported in numerous HIV-1-infected patients. Some investigators have speculated that this finding is associated with protease-inhibitor treatment. METHODS: Between June, 1995, and October, 1997, we studied eight HIV-1-infected men who had developed a buffalo hump while otherwise stable on antiretroviral therapy. Measurement of 24 h urinary free cortisol excretion and an overnight low-dose dexamethasone suppression test were done to screen for Cushing's syndrome. In one patient, plasma cortisol concentrations were measured every 4 h for 24 h to assess the circadian rhythm of cortisol. Results of total and regional body-composition analysis by dual-energy X-ray absorptiometry, and glucose, cholesterol, triglyceride, and cortisol concentrations were compared with those obtained in a control population of 15 HIV-1-positive men whose age, body-mass index (BMI), and CD4-lymphocyte count were within the range of values in the eight study patients. FINDINGS: The eight patients with a buffalo hump were clinically stable on various antiretroviral regimens, four of which included a protease inhibitor. No other signs of Cushing's syndrome were observed, and plasma cortisol values did not differ significantly from those of controls. 24 h urinary free cortisol excretion was normal in seven patients and slightly raised in one (248 nmoles). In this patient, a repeat 24 h urinary free cortisol was 175 nmoles and plasma cortisol concentrations over 24 h showed a normal circadian pattern (nadir 83 nmol/L at 2400 h). All eight patients had normal suppression of cortisol values after dexamethasone 1 mg (plasma cortisol less than 83 nmol/L). When compared with HIV-1-positive controls, men with a buffalo hump had a significantly greater proportion of fat in the trunk region, suggesting central fat accumulation. Triglyceride but not cholesterol values were higher in the patients than in controls but this difference was not significant. Fasting glucose values did not differ significantly. INTERPRETATION: The development of a buffalo hump cannot be attributed to hypercortisolism in these eight men. Furthermore, its occurrence is not unique to patients on protease inhibitors. Although the mechanism for dorsocervical fat accumulation is unclear, we speculate that regional abnormalities in lipogenesis and lipolysis occur, possibly influenced by the hormonal and metabolic changes seen with HIV-1 infection and its treatment.

Adipose Tissue↗
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

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

Familial papillary thyroid cancer: a case report.

Familial occurrence of medullary thyroid cancer is well known in families as an isolated malignancy or in association with multiple endocrine neoplasia syndrome type II. Conversely, papillary thyroid cancer almost always presents sporadically except for reports of familial clustering in individuals with radiation exposure, inherited syndromes of colonic polyposis or multiple harmatomas, and rarely in monozygotic twins. We report a case of papillary thyroid cancer diagnosed incidentally in a 53-year-old woman who underwent surgery for excision of an adenomatous nodule. It was noted that her mother suffered from a similar thyroid malignancy some 33 years ago, and several of her maternal relatives had either Graves' disease or hypothyroidism. The possible existence of this familial entity and its likely genetic basis is discussed.

Biopsy, Needle↗
PubMed1997

Modified reverse sural artery flap.

BACKGROUND: Reverse sural artery flap is a useful flap for defect reconstruction in the distal leg, ankle and heel. The major problem encountered with the reverse sural artery flap is its unreliability. It may be compromised by venous congestion and peripheral arterial insufficiency when the flap is transferred with its pedicle tunneled subcutaneously. METHODS: In this study we describe modifications of this procedure consisting of a wider pedicle during flap design and transferring it without passing the pedicle through a subcutaneous tunnel. The pedicle is then divided in a second-stage operation. Four patients with defects at various locations over the distal leg and heel had reconstruction with reverse sural artery flap in this fashion. RESULTS: No failure developed among these cases and the wounds healed without complication. These patients were satisfied with this procedure. CONCLUSION: Reverse flow flap vascularity is maintained and its viability is ensured with this technical modification.

Aged↗
PubMed1996

Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion.

We report a case of a 44-year-old woman who developed Fanconi's syndrome in association with the oral ingestion of L-lysine. L-lysine is widely available in health food stores and has been recommended in the lay press for the treatment and prevention of recurrent herpes simplex. The development of a severe tubulointerstitial nephritis, and eventual progression to chronic renal failure, underscores the importance of this entity, heretofore unrecognized in humans.

Adult↗