Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 21
Filter
1.
Med J Malaysia ; 78(5): 583-588, 2023 09.
Article in English | MEDLINE | ID: mdl-37775483

ABSTRACT

INTRODUCTION: Fragrance allergy remains an important cause of contact dermatitis. We aim to describe the characteristics of patients with contact sensitisation to fragrances who underwent patch testing in the Department of Dermatology Hospital Kuala Lumpur. MATERIALS AND METHODS: This is a 5-year retrospective study of patients who developed positive reactions to fragrance allergens at the Department of Dermatology, Hospital Kuala Lumpur, Malaysia between January 2017 and December 2021. Patch tests were performed with European Baseline Series and relevant extended series. Patch test readings were recorded according to the International Contact Dermatitis Research Group recommendation. RESULTS: A total of 854 patients underwent patch test during the study period with 133 (15.6%) patients developing at least one positive reaction to fragrance allergens. The median age of patients at presentation was 40 years (range 16-79) old with 78.2% females. The most common initial presentation was hand eczema (55.6%). Other commonly involved sites include face (38.3%), leg (35.3%) and trunk (22.6%). The most frequent sensitising fragrance allergens were Fragrance Mix I (10.5%), Balsam of Peru (7.1%) and Fragrance Mix II (4.9%). Sixty patients (45%) developed positive reaction to more than one fragrance allergens. Twelve patients (9%) developed positive patch test reactions to their own products such as skincare, hair dye and hand wash. Current relevance was recorded in 96 patients (72.2 %). CONCLUSION: Contact sensitisation to fragrance allergens was detected in about 15% of our patients who underwent patch test. The most common sensitising allergens were Fragrance Mix I and II and Balsam of Peru.


Subject(s)
Dermatitis, Allergic Contact , Dermatology , Perfume , Female , Humans , Adolescent , Young Adult , Adult , Middle Aged , Aged , Male , Allergens/adverse effects , Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/epidemiology , Dermatitis, Allergic Contact/etiology , Odorants , Retrospective Studies , Perfume/adverse effects , Hospitals
2.
Phytochem Anal ; 26(6): 395-403, 2015.
Article in English | MEDLINE | ID: mdl-26095961

ABSTRACT

INTRODUCTION: Understanding the complex chemical signalling of plants and insects is an important component of chemical ecology. Accordingly, the collection and analysis of chemical cues from plants in their natural environment is integral to elucidation of plant-insect communications. Remote plant locations and the need for a large number of replicates make in situ headspace analyses a daunting logistical challenge. A hand-held, portable GC-MS system was used to discriminate between damaged and undamaged Centaurea solstitialis (yellow starthistle) flower heads in both a potted-plant and natural setting. OBJECTIVE: To determine if a portable GC-MS system was capable of distinguishing between undamaged and mechanically damaged plant treatments, and plant environments. METHODOLOGY: A portable GC-MS utilising needle trap adsorbent technology was used to collect and analyse in situ headspace volatiles of varying yellow starthistle treatments. Principal component analysis (PCA) was used to distinguish treatments and identify biomarker volatiles. Analysis of variance (ANOVA) was used to determine differences between treatment volatile amounts. RESULTS: The portable GC-MS system detected 31 volatiles from the four treatments. Each GC-MS run was completed in less than 3 min. PCA showed four distinct clusters representing the four treatments - damaged and undamaged potted plant, and damaged and undamaged natural plant. Damage-specific volatiles were identified. CONCLUSION: The portable GC-MS system distinguished the treatments based on their detected volatile profiles. Additional statistical analysis identified five possible biomarker volatiles for the treatments, among them cyclosativene and copaene, which indicated damaged flower heads.


Subject(s)
Centaurea/chemistry , Gas Chromatography-Mass Spectrometry/instrumentation , Gas Chromatography-Mass Spectrometry/methods , Inflorescence/chemistry , Volatile Organic Compounds/analysis , Environment , Inflorescence/growth & development , Passive Cutaneous Anaphylaxis
3.
Anal Chem ; 84(3): 1637-44, 2012 Feb 07.
Article in English | MEDLINE | ID: mdl-22243393

ABSTRACT

A simple method was developed for detection of Bacillus anthracis (BA) endospores and for differentiation of them from other species in the Bacillus cereus group. Chemical profiles that include lipids (i.e., fatty acids), carbohydrates (i.e., sugars), and the spore-specific biomarker, dipicolinic acid, were generated by one-step thermochemolysis (TCM) at 140 °C in 5 min to provide specific biomarker signatures. Anthrose, which is a biomarker characteristic of the B. cereus group of bacteria, was determined from a fragment produced by TCM. Surprisingly, several virulent BA strains contained very low levels of anthrose, which confounded their detection. A statistical discrimination algorithm was constructed using a combination of biomarkers, which was robust against different growth conditions (medium and temperature). Fifteen endospore-forming Bacillus species were confirmed in a statistically designed test (~90%) using the algorithm, including six BA strains (four virulent isolates), five B. thuringiensis (BT) isolates, and one isolate each for B. cereus (BC), B. mycoides (BM), B. atrophaeus (BG), and B. subtilis (BS). The detection limit for B. anthracis was found to be 50,000 endospores, on the basis of the GC/MS detection limits for 3-methyl-2-butenoic acid methyl ester, which is the biomarker derived from TCM of anthrose.


Subject(s)
Bacillus anthracis/metabolism , Gas Chromatography-Mass Spectrometry , Algorithms , Bacillus/metabolism , Biomarkers/analysis , Carbohydrates/analysis , Fatty Acids/analysis , Picolinic Acids/analysis , Spores, Bacterial/metabolism
4.
Anal Methods ; 3(2): 245-258, 2011 Feb 01.
Article in English | MEDLINE | ID: mdl-32938021

ABSTRACT

Methyl sulfate (MeSO4-) salts were explored as thermochemolysis-methylation (TCM) reagents for gas chromatographic (GC) analysis of dipicolinic acid (DPA) as its dimethyl ester (Me2DPA) from bacterial endospores. The reaction was carried out under non-pyrolytic conditions by inserting a small coiled wire filament coated with the sample and reagents directly inside a GC injection port at 290 °C. Above 10 : 1 methyl donor/DPA ratios, alkali metal salts of MeSO4- effected 80-90% conversion of DPA to Me2DPA, which was 10-20 times more active than the same amount of tetramethylammonium hydroxide (TMA-OH) at this temperature. A quaternary salt mixture consisting of 1 : 3 : 1 : 3 TMA+/Na+/OH-/MeSO4- methylated spore DPA with an average conversion of 86% (mean conversion by TMA-OH under the same conditions was 4%). Therefore, the sensitivity for detection of bacterial endospores was increased over 20-fold compared to that observed with the more commonly employed TMA-OH methylating reagent. The limit of detection by this method was 9 × 104 total spores. Mechanisms describing the observed behavior are proposed and discussed. This is the first use of MeSO4- as a TCM reagent for GC.

5.
J Chromatogr A ; 1216(40): 6852-7, 2009 Oct 02.
Article in English | MEDLINE | ID: mdl-19717158

ABSTRACT

A simple device for field sampling and concentration of analytes for subsequent introduction into an injection port for gas chromatographic (GC) analysis has been developed. It consists of a tiny, coiled platinum wire filament (CWF) that is attached to a retractable plunger wire, which fits inside a syringe needle housing. Sampling is accomplished by dipping the end of the CWF in a liquid sample, which is drawn into the wire coil by capillary action, and introducing it into the injection port either before or after allowing the solvent to evaporate. The CWF can be used with or without a nonvolatile chemical coating. A major advantage of this sampling device is that nonvolatile sample matrix components remain on the wire coil, reducing the required injection port and liner cleaning frequency and contamination of the head of the chromatographic column. The coil itself can be easily cleaned between analyses by rinsing and/or burning off residual material in a small flame. The sampling coil facilitates specifically designed chemical reactions in the injection port, such as thermochemolysis and methylation. Applications demonstrated in this work include: (1) direct introduction of samples with little or no pre-treatment, (2) simultaneous thermochemolysis and methylation of lipid-containing samples such as bacteria and bacterial endospores for analysis of biomarkers, and (3) solid phase micro-extraction (SPME) using temporary wire coatings. The CWF allowed for significant reduction in sample preparation time, in most cases to less than a few minutes. The peak shapes examined for polycyclic aromatic hydrocarbon analytes (PAHs) were significantly better (asymmetry factors <1.3) when using the CWF sampling technique compared to splitless and on-column injection techniques (asymmetry factors >1.3). Extraction efficiencies for SPME (especially for high boiling point components such as PAHs) improved by an average of 2.5 times when using the CWF compared to the performance of commercially available SPME fibers. Coiled wire filaments and GC injection port liners were used for more than 100 Bacillus endospore thermochemolysis methylation analyses without the need for cleaning or replacement.


Subject(s)
Bacteria/chemistry , Chromatography, Gas/instrumentation , Lipids/analysis , Spores, Bacterial/chemistry , Chromatography, Gas/methods
6.
Environ Microbiol ; 11(2): 349-59, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19196269

ABSTRACT

The extent to which cultured strains represent the genetic diversity of a population of microorganisms is poorly understood. Because they do not require culturing, metagenomic approaches have the potential to reveal the genetic diversity of the microbes actually present in an environment. From coastal California seawater, a complex and diverse environment, the marine cyanobacteria of the genus Synechococcus were enriched by flow cytometry-based sorting and the population metagenome was analysed with 454 sequencing technology. The sequence data were compared with model Synechococcus genomes, including those of two coastal strains, one isolated from the same and one from a very similar environment. The natural population metagenome had high sequence identity to most genes from the coastal model strains but diverged greatly from these genomes in multiple regions of atypical trinucleotide content that encoded diverse functions. These results can be explained by extensive horizontal gene transfer presumably with large differences in horizontally transferred genetic material between different strains. Some assembled contigs showed the presence of novel open reading frames not found in the model genomes, but these could not yet be unambiguously assigned to a Synechococcus clade. At least three distinct mobile DNA elements (plasmids) not found in model strain genomes were detected in the assembled contigs, suggesting for the first time their likely importance in marine cyanobacterial populations and possible role in horizontal gene transfer.


Subject(s)
Gene Transfer, Horizontal , Genetic Variation , Geologic Sediments/microbiology , Plasmids , Synechococcus/classification , Synechococcus/genetics , Amino Acid Sequence , California , Codon/genetics , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Interspersed Repetitive Sequences , Molecular Sequence Data , Sequence Alignment , Sequence Analysis, DNA , Synechococcus/isolation & purification
7.
J Org Chem ; 66(19): 6217-28, 2001 Sep 21.
Article in English | MEDLINE | ID: mdl-11559166

ABSTRACT

Oligosaccharyl transferase (OT) catalyzes the co-translational transfer of a dolichol-linked tetradecasaccharide (Dol-PP-GlcNAc(2)Man(9)Glc(3), 1a) to an asparagine side chain of a nascent polypeptide inside the lumen of the endoplasmic reticulum (ER). The glycosyl acceptor requires an Asn-Xaa-Thr/Ser sequon, where Xaa can be any natural amino acid except proline, for N-linked glycosylation to occur. To address the substrate specificity of the glycosyl donor, three unnatural dolichol-linked disaccharide analogues (Dol-PP-GlcNTFA-GlcNAc 1c, Dol-PP-2DFGlc-GlcNAc 1d, and Dol-PP-GlcNAc-Glc 1e) were synthesized and evaluated as substrates or inhibitors for OT from yeast. The synthetic analogue Dol-PP-GlcNAc-Glc 1e, with substitution in the distal sugar, was found to be a substrate (K(m)(app)() = 26 microM) for OT. On the other hand, the analogues Dol-PP-GlcNTFA-GlcNAc 1c (K(i) = 154 microM) and Dol-PP-2DFGlc-GlcNAc 1d (K(i) = 252 microM), with variations in the proximal sugar, were inhibitors for OT. The dolichol-linked monosaccharide Dol-PP-GlcNAc 3 was found to be the minimum unit for glycosylation to occur.


Subject(s)
Disaccharidases/metabolism , Disaccharidases/pharmacology , Dolichols/metabolism , Hexosyltransferases , Membrane Proteins , Transferases/antagonists & inhibitors , Transferases/metabolism , Disaccharidases/chemical synthesis , Glycopeptides/metabolism , Glycosylation , Kinetics , Oligopeptides/metabolism , Polyisoprenyl Phosphate Monosaccharides/metabolism , Substrate Specificity , Yeasts/metabolism
8.
J Acquir Immune Defic Syndr ; 26(5): 443-8, 2001 Apr 15.
Article in English | MEDLINE | ID: mdl-11391163

ABSTRACT

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.


Subject(s)
Adipose Tissue/metabolism , Anti-HIV Agents/adverse effects , Body Composition , HIV Infections/drug therapy , HIV-1 , Reverse Transcriptase Inhibitors/adverse effects , Adult , Cross-Sectional Studies , HIV Protease Inhibitors/adverse effects , HIV Wasting Syndrome , Humans , Male , Retrospective Studies
9.
Bioorg Med Chem ; 9(5): 1133-40, 2001 May.
Article in English | MEDLINE | ID: mdl-11377171

ABSTRACT

N-Acetylglucosaminyl(diphosphodolichol) N-acetylglucosaminyl transferase, also known as Enzyme II, is the second enzyme in the dolichol pathway. This pathway is responsible for the assembly of the tetradecasaccharide pyrophosphate dolichol, which is the substrate for oligosaccharyl transferase. In order to study the specificity of Enzyme II, four unnatural dolichol diphosphate monosaccharides were synthesized, with the C-2 acetamido group in the natural substrate Dol-PP-GlcNAc 1a replaced by fluoro, ethoxy, trifluoroacetamido, and amino functionalities. These analogues 1b-e were evaluated as glycosyl acceptors for Enzyme II, which catalyzes the formation of dolichol diphosphate chitobiose (Dol-PP-GlcNAc(2)) from UDP-GlcNAc and Dol-PP-GlcNAc. Enzyme II from pig liver was found to be highly specific for its glycosyl acceptor and the acetamido group shown to be a key functional determinant for this glycosylation reaction.


Subject(s)
Dolichols/metabolism , N-Acetylglucosaminyltransferases/chemistry , N-Acetylglucosaminyltransferases/metabolism , Polyisoprenyl Phosphate Monosaccharides/chemical synthesis , Polyisoprenyl Phosphate Monosaccharides/metabolism , Animals , Enzyme Activation/physiology , Microsomes, Liver/metabolism , Substrate Specificity/physiology , Swine
10.
J Am Geriatr Soc ; 48(12): 1690-6, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11129763

ABSTRACT

In recent years, there has been increasing recognition that the classical textbook presentation of celiac disease with a malabsorption syndrome and a flat jejunal mucosa is only part of a broad spectrum of clinical and histological features associated with gluten sensitivity. Diagnosis of this treatable condition is often delayed or missed because of a failure to appreciate that celiac disease can present at any age and that symptoms are often subtle and not clearly related to gastrointestinal disease. Nonspecific symptoms and nutritional deficiencies are especially common in older patients and may not always be investigated thoroughly. Use of serological screening tests has improved ease of detection of celiac disease in patients without classical symptoms.


Subject(s)
Celiac Disease/diagnosis , Geriatric Assessment , Nutrition Assessment , Age Distribution , Age Factors , Aged , Biopsy , Celiac Disease/blood , Celiac Disease/diet therapy , Celiac Disease/epidemiology , Celiac Disease/etiology , Diagnosis, Differential , Female , Glutens , Humans , Male , Mass Screening/methods , Nutrition Disorders/diagnosis , Nutrition Disorders/etiology , Risk Factors , Sex Distribution
11.
J Acquir Immune Defic Syndr ; 23(1): 35-43, 2000 Jan 01.
Article in English | MEDLINE | ID: mdl-10708054

ABSTRACT

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.


Subject(s)
Body Composition/drug effects , HIV Infections/metabolism , HIV Protease Inhibitors/pharmacology , Hyperlipidemias , Insulin Resistance , Adult , Fasting , Female , HIV Infections/drug therapy , Humans , Hydrocortisone/blood , Longitudinal Studies , Male , Middle Aged , Testosterone/blood
12.
Scand J Infect Dis ; 31(5): 485-7, 1999.
Article in English | MEDLINE | ID: mdl-10576128

ABSTRACT

The effects of bedside inoculation, heparinized containers and liquid culture media on the recovery of Mycobacterium tuberculosis from pleural aspirates were evaluated in this study. Of 155 patients, 63 were diagnosed to have pleural effusion tuberculous in origin. The overall recovery of M. tuberculosis was 57.1%. Bedside inoculation of the specimens produced a significantly higher yield than laboratory inoculation using non-heparinized specimens. When the pleural aspirates were transported in heparinized containers, the recovery rate was comparable to that from bedside inoculation, but lower when non-heparinized containers were used. No significant difference was found in recovery rate between the two liquid media, but the rate was significantly higher with the use of liquid media than conventional solid media. Thus, bedside inoculation of pleural aspirates, use of heparinized containers for transport for delayed inoculation in the laboratory and use of liquid culture media are recommended.


Subject(s)
Bacteriological Techniques , Mycobacterium tuberculosis/isolation & purification , Specimen Handling/methods , Tuberculosis, Pleural/microbiology , Anticoagulants , Culture Media , Heparin , Humans
13.
JPEN J Parenter Enteral Nutr ; 23(6 Suppl): S202-9, 1999.
Article in English | MEDLINE | ID: mdl-10571456

ABSTRACT

Body wasting and loss of lean body mass (LBM) have been associated with increased mortality and disease progression, and reduced quality of life, in patients with human immunodeficiency virus (HIV) infection. The failure of nutritional therapies and, more recently, of effective viral suppression, to consistently restore LBM has prompted investigation of the pharmacologic use of a number of specific protein anabolic agents, including recombinant human growth hormone (rhGH), insulin-like growth factor I (rhIGF-I), and synthetic testosterone derivatives, such as nandrolone decanoate, oxandrolone, and oxymetholone. In a placebo-controlled trial, treatment with rhGH resulted in a significant and sustained increase in weight that was accompanied by an even greater increase in LBM and a decrease in fat, and improvement in treadmill work output. Preliminary data suggest that short-term rhGH treatment may be effective in mitigating weight loss in patients with secondary infections. Open-label studies of nandrolone decanoate suggest that this injectable agent also can increase weight and LBM. Two oral agents, oxandrolone and oxymetholone, can increase weight, but their effects on LBM in placebo-controlled trials have not been reported. Taken together, these studies demonstrate that HIV-infected individuals can regain weight and LBM under the proper therapeutic circumstances. The effects of reversal of wasting on survival and disease progression, long-term safety, and the potential value of these therapies in the treatment of fat redistribution remain to be determined.


Subject(s)
HIV Wasting Syndrome/drug therapy , Human Growth Hormone/therapeutic use , Hormones/therapeutic use , Humans , Insulin-Like Growth Factor I/therapeutic use , Testosterone/therapeutic use
15.
J Am Soc Nephrol ; 9(6): 1080-4, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9621292

ABSTRACT

A cross-sectional study was performed in a group of dialysis patients and control subjects to identify the determinants of serum levels of leptin, the protein product of the obese (ob) gene. Twenty-eight patients on dialysis (19 patients on hemodialysis [HD] and nine patients on peritoneal dialysis [PD]) and 41 healthy control subjects were studied. For each subject, blood was drawn for measurement of serum leptin levels and body composition was analyzed by dual-energy x-ray absorptiometry. Regression analyses were performed to determine the predictors of leptin levels, the independent contribution of HD and PD, and the relationship between leptin levels and markers of malnutrition and protein intake in the patients on dialysis. As expected, percentage of body fat was strongly correlated with leptin levels in the group as a whole and in each subgroup when analyzed separately. However, the slope of the relationship was significantly greater for dialysis patients than for control subjects (P < 0.05). Multivariate regression analysis showed that patients on HD and PD had higher leptin levels than control subjects even after adjustment for age, gender, and percentage of body fat. Univariate analyses were performed to assess the relationship between leptin levels and markers of nutritional status such as albumin, blood urea nitrogen, protein catabolic rate (PCR), transferrin, cholesterol, and lean body mass per height. There was a significant negative correlation between leptin levels and serum albumin (r = -0.598, P < 0.001) and between leptin and PCR (r = -0.433, P < 0.05) in the patients on dialysis. It is concluded that leptin levels adjusted for percentage of body fat are increased in dialysis patients compared with control subjects, particularly in those on PD. In addition, increased leptin levels are associated with low serum albumin levels and PCR in dialysis patients.


Subject(s)
Body Composition , Nutrition Disorders/blood , Nutrition Disorders/metabolism , Peritoneal Dialysis , Proteins/analysis , Renal Dialysis , Adult , Biomarkers , Body Composition/physiology , Female , Humans , Leptin , Male , Middle Aged , Multivariate Analysis , Nutritional Status , Reference Values , Regression Analysis
16.
J Clin Endocrinol Metab ; 83(5): 1542-7, 1998 May.
Article in English | MEDLINE | ID: mdl-9589652

ABSTRACT

In previous studies, treatment with recombinant human GH (rhGH) produced sustained increases in weight and lean body mass (LBM) and decreases in fat mass in patients with human immunodeficiency virus (HIV)-associated wasting. To evaluate the effects of chronic rhGH treatment on components of energy balance, we recruited separate subgroups of HIV-positive patients with an involuntary weight loss of 10% or more to undergo paired measurements of resting energy metabolism (n = 6) or food intake (n = 11) before and during the final week of a 3-month rhGH (0.1 mg/kg.day) treatment period. In the energy metabolism subset, resting energy expenditure (REE) and substrate oxidation rates were measured by indirect calorimetry during brief admissions to a metabolic ward. Patients in the energy intake subset prepared written 4-day food intake diaries. Body composition was measured in both groups by bioelectrical impedance analysis. Changes in weight (+2.2 +/- 0.9 and +2.2 +/- 0.6 kg), LBM (+3.2 +/- 0.6 and +3.8 +/- 0.5 kg), and fat (-1.0 +/- 0.5 and -1.6 +/- 0.5 kg) in the energy metabolism and energy intake subsets, respectively, did not differ between groups and were comparable to changes seen in a larger group of patients who received rhGH in a randomized, double blind, placebo-controlled multicenter study. In the energy metabolism subset, REE (+232 +/- 69 Cal/day; P = 0.020) and lipid oxidation (+3.1 +/- 1.0 Cal/kg LBM.day; P = 0.016) increased, whereas protein oxidation decreased (-1.3 +/- 1.0 Cal/kg LBM.day; P = 0.027) during rhGH therapy. These changes in REE and substrate oxidation are comparable to changes we noted previously in a study of the effects of short term rhGH treatment in patients with HIV-associated wasting. Moreover, the sustained increases in lipid oxidation are consistent with the decreases in body fat content that occur with rhGH treatment. In the energy intake subset, a trend for increased daily energy intake (+203 +/- 262 Cal; P = 0.456) is obviated when adjustments for changes in weight or LBM are made (+1.3 +/- 4.0 and -0.5 +/- 5.0 Cal/kg BW and LBM, respectively). Taken together, these results demonstrate that increases in weight and LBM that occur with chronic rhGH therapy are accompanied by sustained increases in REE and lipid oxidation and decreases in protein oxidation. These changes in body composition occur without a significant increase in energy intake and may, instead, represent a redistribution of body energy stores.


Subject(s)
Energy Intake , Energy Metabolism , HIV Wasting Syndrome/drug therapy , Human Growth Hormone/therapeutic use , Adult , Body Composition , Calorimetry, Indirect , Double-Blind Method , Electric Impedance , Female , HIV Wasting Syndrome/metabolism , Human Growth Hormone/administration & dosage , Humans , Lipid Metabolism , Male , Oxidation-Reduction , Proteins/metabolism , Weight Gain
17.
Lancet ; 351(9106): 867-70, 1998 Mar 21.
Article in English | MEDLINE | ID: mdl-9525364

ABSTRACT

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.


Subject(s)
Adipose Tissue/pathology , Body Composition , HIV Infections/pathology , HIV-1 , Adult , Anti-HIV Agents/therapeutic use , Back , HIV Infections/blood , HIV Infections/drug therapy , Humans , Hydrocortisone/blood , Male , Middle Aged , Protease Inhibitors/therapeutic use
18.
Brain Res ; 772(1-2): 87-94, 1997 Oct 24.
Article in English | MEDLINE | ID: mdl-9406959

ABSTRACT

The nervous system responds to both internal and external cues, integrating these signals to coordinate behavior and physiology. Mating interactions can promote dramatic changes in neuroendocrine cells which trigger successful copulation, ovulation, fertilization, and pregnancy. The neurons that transduce behavioral cues into neuroendocrine signals are distributed in a loose continuum along the medial ventral forebrain where they produce and secrete gonadotropin-releasing hormone (GnRH). In the past we have reported changes in GnRH-immunoreactive (GnRH-ir) cell numbers in brains of female musk shrews sacrificed during, and after, brief mating interactions. The purpose of the current study was twofold: first to determine which aspect of intracellular GnRH production is stimulated by behavioral interactions; second, to characterize the specific aspects of the social exchange that trigger GnRH production. We report that 1 h after copulation the production of proGnRH protein is stimulated. Non-copulatory behavioral interactions resulted in a rapid decrease in the numbers of neurons containing GnRH-ir peptide. This change was accompanied by an increase in the GnRH-ir fibers in the median eminence, but no surge in luteinizing hormone. These data suggest that behavioral interactions stimulate release of mature GnRH peptide from cell bodies followed by accumulation of available GnRH in cell terminals. Copulation triggers increased production of proGnRH in cell bodies. The data highlight the usefulness of behavioral paradigms for the examination of the dynamics of neuropeptide production.


Subject(s)
Gonadotropin-Releasing Hormone/analysis , Neurons/chemistry , Protein Precursors/analysis , Sexual Behavior, Animal/physiology , Shrews/metabolism , Animals , Cell Count , Female , Humans , Immunohistochemistry , Male , Shrews/psychology , Time Factors
19.
Article in English | MEDLINE | ID: mdl-9215653

ABSTRACT

Body wasting is an increasingly prevalent AIDS-defining condition and an independent risk factor for mortality in patients infected with HIV. Largely on the basis of studies conducted early in the epidemic, HIV-associated wasting has been assumed to feature a disproportionate loss of lean tissue. We report the results obtained from cross-sectional and longitudinal studies that differ from these earlier observations. In a cross-sectional analysis, weight and body composition determined by dual-energy x-ray absorptiometry and bioelectrical impedance analysis in 32 HIV-infected men with documented weight loss of > or = 10% were compared to those in 46 HIV-positive men without significant weight loss and 32 HIV-negative controls. Fat, lean body mass (LBM), and body cell mass (BCM) were significantly lower in men with weight loss relative to controls (p < 0.001 for fat and BCM; p = 0.01 for LBM). Two thirds of the difference in weight was fat. For the longitudinal analysis, the composition of weight lost over time was evaluated in paired measurements in men grouped by body fat content (<15% or >15%, n = 10 per group). Weight loss in patients with baseline fat of more than 15% was only 16% LBM, but the composition of weight lost in men with baseline fat of less than 15% was 70% LBM. We conclude that progressive decreases in fat and lean tissue occur in men with HIV infection, with the composition of weight lost depending on baseline fat content. These results argue against the widely held notion that HIV-associated wasting is characterized by preservation of fat at the expense of lean tissue.


Subject(s)
Body Composition , HIV Infections/metabolism , Adipose Tissue/metabolism , Adult , Cross-Sectional Studies , Humans , Longitudinal Studies , Male , Weight Loss
SELECTION OF CITATIONS
SEARCH DETAIL
...