PubMed Health⌕ Search

Biomedical subjects

L M Hart

Publications and source records attributed to L M Hart.

11 recordsLinked to original sources
PubMed1998

[A new subtype of diabetes mellitus: maternally inherited diabetes and deafness (MIDD)].

Diabetes mellitus comprises many subtypes, the pathogenesis of each of which involves a combination of inherited and environmental factors. Recently a new subtype of diabetes mellitus was recognized in a Dutch pedigree, designated as 'maternally inherited diabetes and deafness' (MIDD). Impaired hearing is an associated phenomenon of the disease. Approximately 1.3% of all diabetic cases in the Netherlands exhibit the MIDD subtype. MIDD shows a strictly maternal heredity. In MIDD there is a guanine-for-adenine substitution at position 3243 in mitochondrial DNA. Mitochondria carrying this mutation exhibit a decreased functionality. In carriers of the MIDD mutation the insulin secretion by the pancreas in response to stimulation by glucose is impaired.

Adult↗
PubMed1997

Detection of mitochondrial DNA deletions in human skin fibroblasts of patients with Pearson's syndrome by two-color fluorescence in situ hybridization.

Pearson's marrow/pancreas syndrome is a disease associated with a large mitochondrial DNA (mtDNA) deletion. The various tissues of a patient contain heteroplasmic populations of wild-type (WT) and deleted mtDNA molecules. The clinical phenotype of Pearson's syndrome is variable and is not correlated with the size and position of the deletion. The histo- and cytological distribution of WT and deleted mtDNA molecules may be factors that correlate with the phenotypical expression of the disease. Here we introduce a new application of two-color FISH to visualize WT and deleted mtDNA simultaneously in a cell population of in vitro cultured skin fibroblasts of two patients with Pearson's syndrome. At the third passage of culturing, fibroblasts showed a remarkable heterogeneity of WT and deleted mtDNA: about 90% of the cells contained almost 100% WT mtDNA, and 10% of the cells contained predominantly deleted mtDNA. At the tenth passage of culturing, fibroblasts showed a reduction of intercellular heteroplasmy from 10% to 1%, while intracellular heteroplasmy was maintained. This new approach enables detailed analysis of distribution patterns of WT and deleted mtDNA molecules at the inter- and intracellular levels in clinical samples, and may contribute to a better understanding of genotype-phenotype relationships in patients with mitochondrial diseases.

Bone Marrow Diseases↗
PubMed1996

An insulin receptor mutant (Asp707 --> Ala), involved in leprechaunism, is processed and transported to the cell surface but unable to bind insulin.

We have identified a homozygous mutation near the carboxyl terminus of the insulin receptor (IR) alpha subunit from a leprechaun patient, changing Asp707 into Ala. Fibroblasts from this patient had no high affinity insulin binding sites. To examine the effect of the mutation on IR properties, the mutant IR was stably expressed in Chinese hamster ovary cells. Western blot analysis and metabolic labeling showed a normal processing of the mutant receptor to alpha and beta subunits. No increase in high affinity insulin binding sites was observed on Chinese hamster ovary cells expressing the mutant receptor, and also, affinity cross-linking of 125I-labeled insulin by disuccinimidyl suberate to these cells failed to label the mutant alpha subunit. Biotinylation of cell surface proteins by biotin succinimidyl ester resulted in efficient biotinylation of the mutant IR alpha and beta subunits, showing its presence on the cell surface. On solubilization of the mutant insulin receptor in Triton X-100-containing buffers, 125I-insulin was efficiently cross-linked to the receptor alpha subunit by disuccinimidyl suberate. These studies demonstrate that Ala707 IR is normally processed and transported to the cell surface and that the mutation distorts the insulin binding site. Detergent restores this site. This is an example of a naturally occurring mutation in the insulin receptor that affects insulin binding without affecting receptor transport and processing. This mutation points to a major contribution of the alpha subunit carboxyl terminus to insulin binding.

Abnormalities, Multiple↗
PubMed1996

Association of the insulin-receptor variant Met-985 with hyperglycemia and non-insulin-dependent diabetes mellitus in the Netherlands: a population-based study.

One of the characteristics of non-insulin-dependent diabetes mellitus (NIDDM) is the presence of insulin resistance. Most NIDDM patients have a normal sequence of the insulin receptor, indicating that, if insulin-receptor mutations contribute to the development of NIDDM, they will be present only in a minor fraction of the NIDDM population. The goal of the present study was to examine whether insulin-receptor mutations contribute to the development of NIDDM. We examined 161 individuals with NIDDM and 538 healthy controls from the population-based Rotterdam study for the presence of mutations in the insulin-receptor gene by SSCP. A heterozygous mutation changing valine-985 into methionine was detected in 5.6% of diabetic subjects and in 1.3% of individuals with normal oral glucose tolerance test. Adjusted for age, gender, and body-mass index, this revealed a relative risk for diabetes of 4.49 (95% confidence interval 1.59-12.25) for Met-985 carriers. When the total study group was analyzed, the prevalence of the mutation increased with increasing serum glucose levels (test for trend P < .005). We conclude that the Met-985 insulin-receptor variant associates with hyperglycemia and represents a risk factor for NIDDM.

Blood Glucose↗
PubMed1990

Postoperative pain experiences: relevant patient and staff attitudes.

Postoperative pain continues to occur, despite both advances in analgesic techniques and recognition of the damaging effect of pain upon recovery. This study set out to describe the pain experiences of successive cholecystectomy patients in a large teaching hospital, using three different pain measures and self-reports of anxiety and pain-related attitudes and experiences. Nurses and doctors in surgical wards provided parallel information about their pain-related attitudes and practices. A substantial proportion of patients suffered significant postoperative pain, apparently related to their fear of addiction and reluctance to ask for extra analgesic help. Nurses were more convinced than patients that patients should have more control of their own pain relief. Barriers to effective pain relief are seen to include cognitive, attitudinal and systemic factors; some suggestions are offered for reform of relevant hospital practices.

Analgesics, Opioid↗
PubMed1981

One-minute electrochemical enzymic assay for cholesterol in biological materials.

In this rapid and specific micro-scale electrochemical enzymic assay for cholesterol and cholesterol esters, 10 microL of standard or sample is injected directly into a heated (50 degrees C) thermostated, oxystated cuvet containing pH 7.25 buffer, cholesterol oxidase (EC 1.1.3.6), and cholesterol esterase (EC 3.1.1.13). The cholesterol esters are hydrolyzed by the esterase, and the cholesterol is simultaneously oxidized by the oxidase. The hydrogen peroxide produced from oxidation of the unesterified cholesterol is measured by a polarographic anode covered with an acetate/polycarbonate membrane. The membrane allows hydrogen peroxide to diffuse to the platinum anode, where it is oxidized, but prevents the diffusion of ascorbic acid, uric acid, and bilirubin to the electroactive surface. Turbidity does not interfere. The correlation (r) between results by our method and the Abell-Kendall method for 105 samples of serum was 0.9994 and for 105 samples of plasma was 0.9997. Our method is convenient for the analysis of high-density lipoprotein cholesterol in plasma and serum supernates and in many kinds of tissue homogenates. Its limitations are also described.

Cholesterol↗
PubMedDate not supplied

Phenytoin in wound healing.

OBJECTIVE: To describe a patient with a massive Grade IV pressure ulcer that responded rapidly to treatment with topical phenytoin and to review the literature supporting the use of this therapy. CASE SUMMARY: A 55-year-old morbidly obese white man (266 kg), with respiratory failure secondary to obesity-hypoventilation syndrome and heart failure, developed pressure ulcers on his lower back and sacrum with the first 2 weeks of hospitalization. Traditional methods of treatment were unsuccessful, and by day 79, the wound involved the entire lumbosacral area and buttocks, and had extensive undermining and sinus tract formation. Within 2 days of applying topical phenytoin, fresh granulation was apparent. After 54 days of treatment, nearly all the sinus tracts were healed. Four months after treatment with topical phenytoin had facilitated the healing of the wounds, even though the patient's multiple underlying medical problems had not resolved. DISCUSSION: Phenytoin has been used in the healing of pressure sores, venous stasis and diabetic ulcers, traumatic wounds, and burns. Many of the existing clinical studies have methodologic flaws, such as inappropriate statistical analysis, inadequate control groups, and the absence of randomization and double-blinding. Nevertheless, all the studies have reported enhancement of wound healing, with insignificant adverse effects. Phenytoin may promote wound healing by a number of mechanisms, including stimulation of fibroblast proliferation, facilitation of collagen deposition, glucocorticoid antagonism, and antibacterial activity. CONCLUSIONS: Phenytoin promoted the healing of a massive necrotizing soft tissue wound that was unresponsive to conventional treatment. Clinical success in this difficult case and the other reports in the literature suggest that phenytoin is effective in would healing and deserves further investigation.

Administration, Cutaneous↗