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Biomedical subjects

M Ho

Publications and source records attributed to M Ho.

At least 127 records · Page 7Linked to original sources

Factors affecting the pharmacokinetics of parenteral chloramphenicol in enteric fever.

Chloramphenicol pharmacokinetics were studied in 29 Nepalese adults diagnosed with uncomplicated enteric fever and randomized to receive succinate ester 30 mg/kg i.v. or i.m. Serial plasma concentrations of chloramphenicol, and iothalamate (to estimate glomerular filtration rate), antipyrine (hepatocellular function) and Indocyanine Green (liver blood flow) were measured by HPLC and kinetic parameters estimated by non-compartmental analysis. In culture-positive patients (n = 16), mean residence times (MRTs) and steady-state volumes of distribution (V(d)ss) for i.v. chloramphenicol (mean +/- S.D.; 4.9 +/- 0.9 h and 1.9 +/- 0.8 L/kg; n = 7) were less than after i.m. chloramphenicol (12.3 +/- 7.3 h and 3.7 +/- 2.5 L/kg; n = 9; P < 0.05), with a higher peak plasma concentration after i.v. (16.2 +/- 9.1 versus 7.8 +/- 3.6 mg/L; P < 0.05); plasma clearance (Cl(p)) was similar in the two groups (368 +/- 172 and 310 +/- 224 mL/kg/min after i.v. and i.m. respectively). In 17 patients examined during convalescence, MRT and Vdss were less than in acute illness regardless of route chloramphenicol administration. There were similar changes in chloramphenicol kinetic parameters in culture-negative patients. Antipyrine Cl(p) and liver blood flow correlated weakly with chloramphenicol Cl(p) in culture-positive patients (P < 0.1) and were higher in convalescence; no such associations were seen for iothalamate Cl(p). These data indicate that i.v. chloramphenicol produces peak plasma concentrations which are on average twice those after i.m. injection of the same dose, due principally to a smaller V(d)ss. Cl(p) is uninfluenced by route of administration and is determined more by hepatic metabolism than renal excretion. Intramuscular treatment may result in sub-therapeutic chloramphenicol concentrations initially, but continued regular i.v. dosing is more likely to produce levels at which bone marrow toxicity occurs.

Adolescent↗

Microvascular abnormalities in patients with vibration white finger.

In vivo nailfold capillary microscopy was performed on 10 men with vibration white finger (VWF) and 10 age-matched male controls. The observed nailfold capillaries required adaptation of Maricq's classifications and addition of new morphological scoring systems. These new classifications produced numerical scores for assessing capillary: dropout, tortuosity, elongation, visualization of subpapillary venular plexus, and the degree of disarrangement of nailfold capillary polarity. Application of these new scores showed, for the first time, a complex pattern of abnormal-nailfold capillaries in patients with VWF. Capillary dropout was evident in 7/10 patients, with an associated disarrangement in nailfold capillary polarity in five. All 10 controls had normal capillary morphology. Tortuosity of the capillary loops and elongation of their length was observed in 30% of patients. These significant morphological alterations seen in VWF suggest a local small-vessel vasculitis.

Adult↗

Specificity and functional activity of anti-Burkholderia pseudomallei polysaccharide antibodies.

The lipopolysaccharide (LPS) of Burkholderia pseudomallei, the causative agent of melioidosis, consists of two O-antigenic polysaccharides designated O-PS I and O-PS II. In this study, the O-PS specificity and functional activity of a protective polyclonal antiserum and an immunoglobulin M (IgM) monoclonal antibody were determined. The polyclonal antiserum recognized both O-PS I and O-PS II, while the monoclonal antibody was O-PS II specific. Both mediated phagocytic killing of B. pseudomallei by polymorphonuclear leukocytes. Patients acutely infected with B. pseudomallei also produced antibodies to the two O-PSs, but these antibodies were not produced by asymptomatic individuals from an area of endemicity who were seropositive by an indirect hemagglutination test using sonicated heat-killed whole organisms as antigen. IgM antibodies were detected only in patients with localized infection. IgG antibodies were detected in all acutely infected patients, but there was no significant difference in antibody levels among patients with localized infection, patients who survived septicemic illness, and patients who died from septicemic illness. Further analysis of the IgG response revealed production of IgG1 and IgG2 antibodies by all patient groups, while an IgG3 response was seen only in survivors of septicemic infection. IgG4 was not detectable even when a fivefold-lower serum dilution was used. Patient sera also mediated phagocytic killing by polymorphonuclear leukocytes, and the killing effect was enhanced by complement. These results suggest that antibodies to the LPS O-polysaccharides of B. pseudomallei are protective by promoting phagocytic killing. The antibodies develop during human infection and may facilitate clearance of the organisms, as seen in a diabetic rat model of B. pseudomallei infection.

Antibodies, Bacterial↗

Characterization of the capsular polysaccharide of Burkholderia (Pseudomonas) pseudomallei 304b.

Burkholderia (Pseudomonas) pseudomallei is the causative agent of melioidosis, a bacterial infection of considerable morbidity in areas of endemicity of Southeast Asia and northern Australia. Clinical isolates of B. pseudomallei have been demonstrated to produce a lipopolysaccharide (LPS) containing two separate and chemically distinct antigenic O polysaccharides against which infected patients produced antibodies. A putative capsular polysaccharide (CPS) has also been reported and is thought to be antigenically conserved based on results of serological studies with clinical B. pseudomallei isolates. In the present study, the CPS isolated from B. pseudomallei 304b from northeastern Thailand was found to have an [alpha]D of +99 degrees (water), was composed of D-galactose (D-Gal), 3-deoxy-D-manno-2-octulosonic acid (KDO), and O-acetyl 3:1:1), and was a linear unbranched polymer of repeating tetrasaccharide units having the following structure: -3)-2-O-Ac-beta-D-Galp-(1-4)-alpha-D-Galp-(1-3)-beta-D -Galp-(1-5)-beta-D-KDOp-(2-. Sera from 13 of 15 patients with different clinical manifestations of melioidosis but not normal controls recognize the CPS, which suggests that it is immunogenic and raises the possibility that it may have a role as a vaccine candidate and/or diagnostic agent.

Antibodies, Bacterial↗

New, ultrasensitive enzyme immunoassay for detecting vaccine- and disease-induced hepatitis A virus-specific immunoglobulin G in saliva.

Although detection of disease-induced hepatitis A virus (HAV)-specific antibodies in saliva has been successfully utilized in a few epidemiological studies, available assays fail to detect lower salivary anti-HAV levels associated with vaccine-induced immunity. We present a new capture enzyme immunoassay which employs a three-layer antibody recognition system. Evaluation of paired saliva-serum specimens from 1,025 international travellers, 134 other volunteers, and 91 hepatitis A vaccine recipients demonstrated 99.6% (95% confidence interval, 98.4 to 99.9) specificity and 98.7% (95% confidence interval, 97.7 to 99.4) sensitivity of this salivary assay in differentiating between immune and susceptible individuals, compared with serum-based methods. We conclude that this assay is sufficiently sensitive for reliable detection of both vaccine- and infection-induced HAV-specific immunoglobulin G in saliva, even when corresponding anti-HAV levels in serum are very low (< 1 IU/ml).

Antibodies, Viral↗

Fatty acid composition of adipose tissue, an indication of dietary fatty acids, and breast cancer prognosis.

PURPOSE: Fatty acid composition of adipose tissue is an indicator of the long-term ingestion pattern of several specific fatty acids. There is good correlation of antecedent diet with the essential fatty acids, and there is reflection of the diet with the fatty acids that can be synthesized. The relationship between the fatty acid levels and lymph node status and clinical outcome was examined. METHODS: At the time of diagnostic surgery, 161 women with clinical stage T1NO breast cancer had subcutaneous adipose tissue (breast and abdominal) aspirated. The concentrations of 35 fatty acids, seven summed classes, and six fatty acid groups were measured by capillary gas chromatography. Lymph node status was determined with axillary dissection, and patients were followed-up (mean, 7.3 years) for clinical outcome. RESULTS: There was no significant association of any adipose tissue fatty acids with overall survival, although few (16 of 161 women) died of breast cancer. However, the odds of having positive lymph nodes (57 of 161 women) were significantly higher for women with a greater adipose tissue proportion of oleic acid (odds ratio [OR], 7.56; 95% confidence interval [CI], 1.78 to 32.1) or total saturated acids (OR, 8.43; 95% CI, 1.48 to 40.0) and significantly lower with a higher proportion of trans fatty acids (OR, 0.24; 95% CI, 0.07 to 0.77), as assessed by multivariate logistic regression. CONCLUSION: These data support previous research with dietary questionnaire methodology, suggesting that specific dietary fatty acids may be associated with breast cancer promotion. Further research with long-term clinical follow-up is necessary to investigate these observations in large, diverse populations before dietary recommendations can be envisioned.

Abdomen↗

Randomized trial of varying mineral intake on total body bone mineral accretion during the first year of life.

OBJECTIVE: The effect of varying mineral intakes on total body bone mass accretion during the first year of life in healthy full-term infants is unknown. The purpose of this study was to determine whether total body bone mass accretion during the first year of life was influenced by the calcium and phosphorus intake of an infant and whether early differences in bone accretion persist through 1 year of age. DESIGN: This prospective, randomized trial was conducted in two phases. In phase I, 67 infants were randomized within the first 2 weeks of life into either a low (439 mg of calcium per liter and 240 mg of phosphorus per liter) or moderate (510 mg of calcium per liter and 390 mg of phosphorus per liter) mineral-containing formula feeding group. An additional group of 34 human milk-fed (low mineral) infants also was enrolled. Phase II involved an additional randomization of all infants at 6 months of age into moderate-mineral formula (see above), high-mineral formula (1350 mg of calcium per liter and 900 mg of phosphorus per liter), or cow milk (1230 mg of calcium per liter and 960 mg of phosphorus per liter) feeding group. Anthropometric measurements, nutrient intake, and total body bone mineral content (BMC) by dual-energy x-ray absorptiometry were measured at 1, 3, 6, 9, and 12 months. RESULTS: During the first 6 months, the moderate-mineral group had a greater increase in weight (3.42 +/- 0.62 kg) compared with the human milk group (2.93 +/- 0.56 kg); the low-mineral group (3.19 +/- 0.62 kg) was intermediate. Bone mass accretion differed in a similar direction, with the moderate-mineral feeding group having a greater increase than the human milk group and the low-mineral group being intermediate of the two. Including weight, length, and bone area as covariates, both the low-mineral formula- and human milk-fed groups had similar BMC, which was lower than that of the moderate-mineral group at 3 and 6 months of age. Adjusted mean BMC values for the moderate-mineral formula-fed group compared with the low-mineral formula- and human milk-fed groups were 127.8 +/- 1.5 (SEM) g vs 119. 2 +/- 1.5 and 122.1 +/- 1.4 g, respectively, at 3 months of age and 168.7 +/- 2.5 g vs 157.6 +/- 2.5 and 158.7 +/- 2.4 g, respectively, at 6 months of age. The BMC at 6 months of age among the formula-fed infants was correlated with both average dietary phosphorus intake (r = .592) and average daily calcium intake (r = .620) during the first 6 months. The relationships between BMC and these minerals remained significant even after controlling for caloric intake. It was not possible to determine the independent effects of dietary calcium and phosphorus on BMC because of the strong correlation of these minerals with each other. Despite significant differences in both calcium and phosphorus intakes during the second 6 months of life, there were no differences in growth parameters or bone mass accretion. Means for BMC, adjusted for body weight, length, and bone area, were not significantly different among feeding groups at either 9 or 12 months of age. Adjusted means were 199 +/- 2 (SEM) and 237 +/- 3 g at 9 and 12 months of age for infants receiving moderate-mineral formula; 198 +/- 2 and 236 +/- 3 g at 9 and 12 months of age for infants receiving the high-mineral formulas and 202 +/- 5 and 233 +/- 5 g at 9 and 12 months of age for infants receiving cow milk. The gain in bone mass during the second 6 months differed by the first 6-month feeding group; mean changes in BMC between 6 and 12 months, adjusted for changes in weight, length, and bone area, were greater in human milk-fed infants than in either the low- or moderate-mineral-containing formula groups: 81 +/- 16 g in human milk-fed infants and 73 +/- 15 and 71 +/- 15 g in the low- and moderate-mineral formula groups, respectively. Infants fed whole cow milk during the second 6 months were excluded from this analysis because of the small number of infants completing the study. By 12 months of age t

Absorptiometry, Photon↗

Is the quality of diabetes care better in a diabetes clinic or in a general medicine clinic?

OBJECTIVE: To compare the quality of ambulatory diabetes care delivered by physicians in the diabetes clinic versus the general medicine clinic of a university-affiliated Veterans Administration medical center. RESEARCH DESIGN AND METHODS: This is a retrospective study that involved the review of medical records against predetermined process-of-care criteria. A total of 112 patients with diabetes were randomly selected, of whom 56 were cared for in the general medicine clinic and 56 in the diabetes clinic. The following main outcome measures were examined: 1) the compliance with individual criteria; and 2) the proportion of patient visits in each clinic receiving minimally acceptable quality, defined as a blood pressure measurement, a record of type of hypoglycemic medication, a glycated hemoglobin measurement within the past year, a urinalysis within the past year, an ophthalmologist or optometrist eye examination within the past year or scheduled in the next six months, a record of change in therapeutic management, and a scheduled return visit. RESULTS: The diabetes clinic performed significantly better than the general medicine clinic on the following criteria: a record of a patient's self-monitoring of blood glucose levels; a foot examination; a comprehensive eye examination; a glycated hemoglobin measurement; and a referral for diabetic education. The proportion of patient visits meeting the minimally acceptable levels of quality was better in the diabetes clinic than the general medicine clinic (73 vs. 52%, P = 0.02). CONCLUSIONS: Patients cared for by physicians in the diabetes clinic receive better quality of diabetes care than do patients cared for by physicians in the general medical clinic. If patient care is to be shifted from specialists to generalists, additional attention needs to be paid to ensure that generalists have the knowledge and system resources necessary to deliver an acceptable quality of diabetes care.

Blood Glucose Self-Monitoring↗

Opisthorchis viverrini infection in Thailand: studies on the morbidity of the infection and resolution following praziquantel treatment.

A community study on opisthorchiasis was conducted in Prachinburi Province in eastern Thailand during 1990-1992. The morbidity from opisthorchiasis in the community and reversibility of biliary pathology following treatment with praziquantel at a single dose of 40 mg/kg were assessed by longitudinal investigations of clinical, laboratory, and ultrasonographic changes. A total of 913 voluntary subjects infected with Opisthorchis viverrini were randomly selected for longitudinal study, and 579 subjects without liver fluke infection were recruited as controls. The majority of the study group suffered from mild and moderate infections that were associated with nonspecific gastrointestinal symptoms. Grade I and II ultrasonographic changes, which indicated chronic inflammation of the biliary tract and gallbladder, were detected in 32% of the infected individuals. Clinical symptoms and ultrasonographic changes were common in subjects 21-40 years of age and older. Satisfactory resolution of morbidity was observed during two years follow-up on days 0, 60, 180, 360, and 720, as shown by significant clinical improvement, normalization of laboratory parameters, and downgrading of ultrasonographic abnormalities. Portable ultrasonography has proved to be a reliable noninvasive technique in the evaluation of the morbidity due to opisthorchiasis in rural areas.

Adolescent↗

A combination of the effects of rare genotypes at the XK and KEL blood group loci results in absence of Kell system antigens from the red blood cells.

The 22 antigens of the Kell blood group system are located on a red blood cell (RBC) membrane glycoprotein that shows sequence homology with a family of metalloendopeptidases. Expression of the Kell system antigens is partially governed by XK, an X-linked gene that encodes the Kx protein; absence of Kx results in reduced Kell antigen expression. Almost total absence of Kell antigens from the RBCs of a German man with no symptoms of neuroacanthocytosis could not be due to the Kell-null phenotype, Ko, because his RBCs had very weak expression of Kx antigen and his three children were Kp(a + b+). Kell antigens were normal on the RBCs of his son but weak on those of his two daughters. An Nla III restriction fragment-length polymorphism within the KEL gene showed the Kpa/Kpa genotype in the propositus. Sequencing of his XK gene showed a single base change within the donor splice consensus sequence of intron 2. A BsaAl restriction fragment-length polymorphism showed the mutation in both of his daughters but not in his son. The extreme depression of the Kell antigens of the propositus must be due to a combination of effects, ie, homozygosity for Kpa and deficiency of Kx protein, each of which is capable of causing some degree of weakening of Kell antigens.

Erythrocyte Membrane↗

Receptor specificity of clinical Plasmodium falciparum isolates: nonadherence to cell-bound E-selectin and vascular cell adhesion molecule-1.

The pathogenicity of Plasmodium falciparum is due largely to the parasite's unique ability to adhere to capillary and postcapillary venular endothelium during the second-half of the 48-hour life cycle. The resulting sequestration of infected erythrocytes (IRBC) in deep vascular beds leads to tissue hypoxia, metabolic disturbances, and organ dysfunction which characterize severe falciparum malaria. Several endothelial receptors of cytoadherence have been identified, but their clinical relevance remains controversial. In the present report, the receptor specificity of 60 clinical P falciparum isolates was determined using transfectants each expressing one of CD36, intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1). All isolates tested adhered to CD36 and ICAM-1, but the adherence to CD36 was at least 10-fold higher. Seven isolates adhered to E-selectin whereas none of 19 isolates adhered to VCAM-1. From a population standpoint, about 30% of IRBC in each isolate adhered to CD36, and 2% to 3% adhered to ICAM-1. The percentage adherent to E-selectin and VCAM-1 was negligible. IRBC selected on CD36 adhered almost exclusively to CD36 whereas 80% to 90% of IRBC selected on ICAM-1 could also adhere to CD36. Selected IRBC did not adhere to E-selectin or VCAM-1. These findings indicate that cytoadherence to multiple endothelial receptors is a rare occurrence with natural P falciparum isolates, but do not exclude a role for the adhesion molecules in promoting other IRBC-endothelial interactions such as rolling under flow conditions. Receptor specificity in vivo may be dictated by the ligand-receptor combination which provides the best survival potential for the parasite.

Animals↗

The effect of blood transfusion on tumor growth in sarcoma-bearing rats.

BACKGROUND: The effect of blood transfusion on tumor growth is controversial. Under experimental conditions, even similar animal models can give varied results. This study was undertaken to characterize the nature of the effect of blood transfusion on tumor growth. METHODS: Sixty-five Fischer 344 rats subcutaneously implanted with a methylcholanthrene-induced sarcoma were studied with additive blood transfusion at 1% tumor burden in two separate experiments. In experiment 1, the effects of syngeneic fresh whole blood transfusion (5, 10, and 15 ml/kg) and allogeneic (5 ml/kg) were tested. To determine if stored blood influenced the results, experiment 2 was performed with syngeneic blood transfusion (15 ml/kg) and allogeneic blood transfusion at 5 ml/kg. Tumor dimensions were determined daily by external measurement, and tumor weight and growth rate were calculated. RESULTS: No significant differences in final tumor weights or tumor growth rates were found in transfused rats compared with controls. This held true for syngeneic blood transfusion regardless of dose, allogeneic blood transfusion, and regardless of whether the blood was fresh or stored. CONCLUSIONS: Additive blood transfusion does not affect tumor growth in this animal model. This finding, together with the general inconclusiveness in the reported literature on this topic, speaks against a dominant role for the effect of blood transfusion on tumor behavior.

Animals↗

Gender and race differences in bone mass during infancy.

The purpose of this study was to determine whether race or gender differences in total body bone mineral content (BMC) are evident within the first 18 months of age. Total body bone mineral measurements were obtained on 64 healthy infants 1-18 months of age. There were no significant differences in age, weight, or height between race and gender groups. Taking into account weight and age, both bone mineral density (BMD) and BMC were greater in male infants compared with female infants (both, P = 0.02) and BMD was slightly higher in black infants compared with white infants (P = 0.07).

Age Factors↗

Increased incidence of Clostridium difficile-associated diarrhea following decreased restriction of antibiotic use.

Removal of antimicrobial agents from formulary restriction status at our center was followed by an increase in the incidence of Clostridium difficile-associated diarrhea. The mean monthly incidence of C. difficile diarrhea for the 12-month period before institution of decreased restriction of antibiotic use was 3.4 infections per 1,000 admissions and rose to 6.2 infections per 1,000 admissions during the following 4-month period (P < .05). Patients who developed disease before and after decreased restriction of antibiotics were similar in terms of the mean number of antimicrobial agents administered and mean duration of therapy. The most commonly administered agents whose use preceded the onset of disease were cefazolin, trimethoprim-sulfamethoxazole, ampicillin, ticarcillin/clavulanate, and gentamicin (the latter drug was always used in combination with other agents). Immunoblot typing indicated that there was no association between C. difficile strains and administration of specific agents. There was no coincidental epidemic to account for the increased incidence of infection. The increased incidence of C. difficile disease is a potential problem that may occur following removal of extended-spectrum antimicrobial agents from formulary restriction status.

Adult↗

Use of antiherpes drugs and the risk of Kaposi's sarcoma: data from the Multicenter AIDS Cohort Study.

To determine if use of antiherpes drugs protects against the development of AIDS-associated Kaposi's sarcoma (KS), data from 935 homosexual men with AIDS from the Multicenter AIDS Cohort Study were analyzed. In nested case-control analysis, neither acyclovir use for human immunodeficiency virus infection (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.56-1.26; P = .39) nor acyclovir use for any indication (OR, 1.02; 95% CI, 0.76-1.38; P = .89) was associated with a reduced risk of KS as initial AIDS diagnosis. In longitudinal analysis, acyclovir was also not protective against developing KS as a late manifestation of AIDS (after initial non-KS AIDS diagnosis). Among men with cytomegalovirus disease, ganciclovir use (relative risk [RR], 0.56; 95% CI, 0.22-1.44; P = .23) and foscarnet use (RR, 0.40; 95% CI, 0.051-3.10; P = .38) were associated (although not significantly) with a reduced risk of KS. Thus, acyclovir use does not appear to reduce the risk of KS, but further study of other antiherpes drugs such as ganciclovir and foscarnet is warranted.

AIDS-Related Opportunistic Infections↗

Neurodevelopmental outcome of infants with viral meningitis in the first three months of life.

We prospectively evaluated the neurodevelopmental outcome of infants with documented viral meningitis to determine (1) whether deficits in physical growth, development, speech and language, hearing, or intelligence occur; and (2) if so, at what age these deficits can be detected. Sixteen infants with documented enteroviral meningitis under the age of 90 days and a control group of 13 patients matched for age, race, sex, and socioeconomic status were followed up prospectively for 3 years with annual evaluations, which included a developmental evaluation by a pediatric developmentalist, articulation and language tests by a speech-language pathologist (Sequenced Inventory of Communication Development, Receptive-Expressive Emergent Language Scale (REEL), Preschool Language Scale (PLS), Revised Peabody Picture Vocabulary Test (PPVT-R), Photo Articulation Test, audiometric screening), and intelligence tests by a psychometrist (Bayley Scales of Infant Development [BSID] and Stanford-Binet). No deficits were demonstrated in growth, development, hearing, BSID, articulation, and expressive language. Subtle but significant (P < 0.05) deficits were documented in the study group compared with the control group in the receptive component of the REEL, all subsections of the PLS, the PPVT-R, and the verbal comprehension/language-processing section (Factor II) of the Stanford-Binet. These differences could be reliably detected by 3 years of age. We conclude that viral meningitis in young infants may cause subtle deficits in language skills, particularly receptive language. We recommend that children who have had enteroviral meningitis during early infancy be monitored carefully for language development and, perhaps, receive increased language stimulation in the home prior to school entry in order to optimize their learning potential.

Analysis of Variance↗