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Biomedical subjects

K Holt

Publications and source records attributed to K Holt.

30 records · Page 2Linked to original sources
PubMed1980

Permanent retinal damage following massive dapsone overdose.

A massive dose of 7.5 g of 4,4'-diamino, diphenyl sulphone (dapsone) taken as a suicide attempt in a patient on long-term therapy for tuberculoid leprosy resulted in permanent bilateral retinal necrosis, previously unreported side effect of this drug. The patient developed a severe haemolytic anaemia, methaemoglobinaemia, and acute renal failure requiring peritoneal dialysis. It is proposed that the retinal damage was due to a combination of severe hypoxaemia and the physical effects of red cell fragmentation producing vascular occlusion in the macular and perimacular region, with consequent ischaemic necrosis.

Acute Kidney Injury↗
PubMed1980

Ion binding by small molecular weight substances (1,000-10,000 daltons) in urine.

The reliability of calculated activity products as an index of the urinary saturation of calcium oxalate was tested by comparing the solubility of calcium oxalate in various urine preparations. Urine samples were collected from six control subjects and nine patients with nephrolithiasis. From each sample four urine preparations were prepared: centrifugation at 1400 g. 0.22-mu filtration, ultrafiltration through a 10,000 daltons cutoff filter, and ultrafiltration through a 1000 daltons cutoff filter. Each preparation was incubated with an excess of calcium oxalate to steady-state, and the activity product of calcium oxalate was calculated for the ambient solution. Our findings suggest that most calcium and/or oxalate conplexes in urine that are not recognizable by available computational techniques for activity products probably reside in the fraction of 1000 to 10,000 daltons.

Adult↗
PubMed1979

Attenuation by monosodium urate of the inhibitory effect of glycosaminoglycans on calcium oxalate nucleation.

The interaction between mucopolysaccharide (glycosaminoglycans) and monosodium urate, with respect to their effects on spontaneous precipitation of calcium oxalate, was explored in vitro. Heparin and, to a lesser extent, chondroitin sulfate were found to inhibit calcium oxalate precipitation. The formation product ratio (FPR, limit of metastability or the minimum supersaturation required for spontaneous nucleation) of calcium oxalate was increased 29 per cent by 0.05 mg of heparin per liter, and by 70 per cent with 1 mg of heparin per liter. The increment produced by heparin was much less pronounced when the solution containing the mucopolysaccharide was preincubated with crystalline monosodium urate. Pretreatment of the solution containing heparin (0.05 mg per liter) by monosodium urate (0.5 mg per ml) virtually eliminated the inhibitory action of heparin. Studies with radioactive heparin indicated that monosodium urate binds heparin. In contrast, the inhibitory effect of chondroitin sulfate was unaltered by prior exposure to monosodium urate. The results indicated that monosodium urate may attenuate the inhibitor activity of certain mucopolysaccharides such as heparin and facilitate the calcium oxalate precipitation. The findings provide further support for the important etiologic role of hyperuricosuria in the formation of calcium oxalate stones.

Calcium Oxalate↗
PubMed1977

Mechanism for calcium urolithiasis among patients with hyperuricosuria: supersaturation of urine with respect to monosodium urate.

Since monosodium urate (NaU) may play an important etiologic role in the formation of renal stones containing Ca in patients with hyperuricosuria, the current studies were undertaken to define some of the physiocochemical factors which determine the formation of NaU. In solutions containing Na, uric acid was rapidly transformed to NaU at pH greater than 6. The results indicated that NaU, and not uric acid, was the stable phase above this pH. A reliable and simple method for the calculation of the state of saturation of urine with respect to NaU was developed from the ratio of concentration products of Na and total dissolved urate (Upi) in the ambient fluid before and after incubation of urine with synthetic NaU. The concentration product ratio closely approximated the ratio of activity products of Na+ and acid urate ion. In contrast, the relative saturation ratio, or the ratio of activity product of original sample and the thermodynamic solubility product of NaU, often differed from the activity product ratio in the individual urine samples. With the concentration product rate, it was found in 45 urine samples that a critical determinant for the supersaturated state with respect to NaU was the high concentration of UT. At UT greater than 300 mg/liter, urine samples were invariably supersaturated with respect to NaU. These results suggest that the nidus of NaU could potentially form in the urine of patients with hyperuricosuria and Ca stones.

Calcium↗
PubMed1976

Nucleation and growth of brushite and calcium oxalate in urine of stone-formers.

The physicochemical factors involved in the formation of calcium-containing renal stones have been elucidated previously and some of the techniques for their quantitation are currently available. Accordingly, urinary activity product ratio (state of saturation), formation product ratio (limit of metastability), and crystal growth of brushite and calcium oxalate in 24-hr urine samples were compared between a control group without stones and stone-forming groups composed of patients with absorptive hypercalciuria, normocalciuric nephrolithiasis, and primary hyperparathyroidism. The activity product ratios of brushite and calcium oxalate were significantly elevated in stone-forming groups, largely because of the high renal excretion of calcium. The formation product ratios were reduced in most stone-forming groups, and the crystal growth was increased in the group with primary hyperparathyroidism. Thus, the physicochemical environment of urine in stone-forming groups was favorable to the nucleation of the nidi of brushite and calcium oxalate; in primary hyperparathyroidism, it may be conducive to the subsequent growth of nidi as well.

Adult↗
PubMed1975

Effect of diphosphonate on crystallization of calcium oxalate in vitro.

Reliable techniques for the calculation of activity product (state of saturation), formation product (limit of metastability) and crystal growth of calcium oxalate were devised. The activity product at saturation was 2.53 times 10 minus 9 M2, and was independent of duration of incubation, solid-to-solution ratio, pH, calcium concentration or ionic strength. These tehcniques were utilized to assess the effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on crystallization of calcium oxalate in an aqueous salt solution in vitro. EHDP increased the formation product of calcium oxalate, indicating an inhibition of nucleation of calcium oxalate. Further, it inhibited the crystal growth of calcium oxalate.

Calcium↗
PubMedDate not supplied

Acetaldehyde stimulates collagen and noncollagen protein production by human fibroblasts.

The mechanisms responsible for the increased hepatic collagen deposition in alcoholic cirrhosis remain unknown. The question of whether ethanol or acetaldehyde has a direct effect on collagen and noncollagen protein production was investigated in human fibroblasts with no detectable activity of alcohol dehydrogenase to distinguish the effects of these metabolites. To eliminate environmental factors, protein production by confluent human skin, fetal and hepatic fibroblasts was studied after three passages. Cells were labeled with [5-3H]proline for 4 hr in the presence of 0.2 mM ascorbate alone or with addition of either ethanol (50 mM) or acetaldehyde (0 to 300 microM). Rates of protein production were calculated from the radioactivities of collagenase-sensitive and collagenase-resistant proteins. Skin fibroblasts from alcoholic individual either with cirrhosis or without liver disease have comparable rates of collagen and noncollagen protein production. Acetaldehyde, in a concentration found in the liver during ethanol abuse, significantly increased collagen production by human skin fibroblasts (up to 140%), fetal fibroblasts (up to 240%) and hepatic fibroblasts (up to 70%) but the addition of ethanol had no significant effect on basal collagen production. The effect of acetaldehyde was dose-related and affected noncollagen protein production in a similar manner. Acetaldehyde did not cause changes in either proline transport or the specific activity of the proline precursor pool. This newly recognized stimulation of collagen production by acetaldehyde may be a possible mechanism of fibrogenesis in alcoholic individuals.

Acetaldehyde↗
PubMedDate not supplied

An immunoepidemiological approach to asthma: identification of in-vitro T-cell response patterns associated with different wheezing phenotypes in children.

BACKGROUND: Increasing evidence suggests that patterns of T-cell immunity to inhalant allergens in genetically diverse human populations are more heterogeneous than previously assumed, and that covert differences in expression patterns might underlie variations in airway disease phenotypes. We tested this proposition in a community sample of children. METHODS: We analysed data from 172 individuals who had been recruited antenatally to a longitudinal birth cohort study. Of the 194 birth cohort participants, data from the 147 probands (age range 8.6-13.5 years) who consented to blood collection were included along with data from 25 consenting siblings (mean age 11 years [range 7.4-17.4]). We ascertained clinical phenotypes related to asthma and allergy. We measured T-cell responses to allergens and mitogens, together with blood eosinophils and IgE/IgG antibodies, and assessed associations between these indices and clinical phenotypes. FINDINGS: Atopy was associated with allergen-specific T-helper (Th)2 responses dominated by interleukin 4, interleukin 5, interleukin 9, interleukin 13, whereas interleukin 10, tumour necrosis factor alpha, and interferon gamma responses were common to both atopics and non-atopics. The wheal size from skin prick with allergen was positively associated with in-vitro interleukin 5 and interferon gamma responses, and negatively associated with interleukin 10. Asthma, especially in atopics, was strongly associated with eosinophilia/interleukin 5, and bronchial hyper-responsiveness (BHR) was associated with eosinophilia plus polyclonal interferon gamma production. BHR in non-atopics was associated with elevated allergen-specific and polyclonal interleukin 10 production. INTERPRETATION: Parallel immunological and clinical profiling of children identified distinctive immune response patterns related to asthma and wheeze compared with BHR, in atopics non-atopics. Immunological hyper-responsiveness, including within the Th1 cytokine compartment, is identified as a hallmark of BHR. RELEVANCE TO PRACTICE: These findings highlight the heterogeneity of immune response patterns in asthmatic children, including those with seemingly homogeneous Th2-driven atopic asthma. Further elucidation of the covert relationships between wheezing phenotypes and underlying immunophenotypes in this age group will potentially lead to more effective treatments for what is an unexpectedly heterogeneous collection of disease subtypes.

Adolescent↗