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Biomedical subjects

M D Davis

Publications and source records attributed to M D Davis.

At least 127 records · Page 7Linked to original sources

The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema.

The prevalence of macular edema and its relationship to a number of risk factors were examined in a population-based study in southern Wisconsin. Macular edema was determined from its presence on stereoscopic fundus photographs or from past history as recorded and documented in clinic records and photographs. For participants whose age at diagnosis of diabetes was less than 30 years and who were taking insulin (n = 919), prevalence rates of macular edema varied from 0% in those who had diabetes less than 5 years to 29% in those whose duration of diabetes was 20 or more years. In these persons, macular edema was associated with longer duration of diabetes, presence of proteinuria, diuretic use, male gender and higher glycosylated hemoglobin. For those whose age at diagnosis was 30 years or older (n = 1121), prevalence rates of macular edema varied from 3% in those who had diabetes less than 5 years to 28% in those whose duration of diabetes was 20 or more years. In these persons, presence of macular edema was associated with longer duration of diabetes, higher systolic blood pressure, insulin use, higher glycosylated hemoglobin, and presence of proteinuria.

Adolescent↗

Diabetic retinopathy. Assessment of severity and progression.

This study describes a classification of overall retinopathy severity based on the presence and severity of lesions graded in the Airlie House classification of diabetic retinopathy, and demonstrates its use in assessing progression of retinopathy over a 6-year period in a group of insulin-taking patients. One hundred and ninety-one insulin-taking patients with diabetes of at least 5 years' duration were identified from their doctors' records in 1970-1971. Patients were seen again in 1972-1973 and 1976-1977. Stereoscopic color fundus photographs of 7 fields in each eye were taken at each visit. All photos were graded using a modification of the Airlie House classification, which specified 6 levels of retinopathy for a given eye; when both eyes are considered an 11-step grading scheme results. Of all patients seen at the 2-year visit whose retinopathy was at risk of progressing, 41.2% showed progression of one level or more on the scale, 19.2% progression of two or more levels. At the 6-year examination comparable rates were 75.0% and 58.4%. Of patients whose retinopathy was level 4 in each eye (nonproliferative retinopathy of "moderate" severity) at the baseline visit, 13/21 (72%) had progressed to proliferative retinopathy in at least one eye at the 6-year examination. The classification scheme proposed appears useful for characterizing overall retinopathy severity of patients on the basis of gradings of fundus photographs. The data presented may be of help in planning trials of treatment aimed at slowing the development or progression of retinopathy.

Adolescent↗

Early postnatal development of pituitary intermediate lobe control in the rat by dopamine neurons.

In fetal and postnatal rats, serum melanophore-stimulating hormone (MSH) levels, pituitary 3H-spiperone binding, pituitary catecholamine content, and other parameters were measured to characterize the development of pars intermedia pituitary control by the tubero-hypophyseal dopamine system. Bioassay of serum for MSH revealed low but significant levels 6 days before birth (gestational day 17), rising to a peak 4 days after birth (postnatal day 5). Levels declined after PN 6, reached a low 2 weeks after birth, and then rose gradually throughout the next several weeks until adult values were attained. From excised pituitaries, significant catecholamine fluorescence in the neurointermediate lobe was first demonstrated on the 2nd postnatal day, with the highest density of fibers being attained at 2 weeks after birth. Thereafter, the density of terminals decreased in the pars intermedia until the adult pattern of innervation was observed at day 60. Total dopamine content of the neurointermediate lobe roughly paralleled the morphological observations through the first 2 weeks after birth. Later, content was seen to stabilize, while concentration decreased in line with the reduction in terminal density. Dopamine levels exceeded norepinephrine concentration by a factor of 10. 3H-spiperone binding sites were present in the pituitary before birth. Their density increased rapidly in the neurointermediate lobe during the 2 postnatal weeks, then diminished until adult densities were reached at day 30. Binding in the anterior pituitary slowly rose throughout the first 30 days after birth, although values were only about one-quarter of that found in the neurointermediate lobe. In vitro incubation of neurointermediate lobes with dopamine showed a dose-dependent inhibition of spontaneous MSH secretion as early as 2 days after birth. Blockade of dopaminergic binding sites by i.p. administration of cis-flupenthixol (1 mg/kg) to rat pups had no effect until days 8, 15, and 22 where there was a significant rise in serum MSH levels as compared with controls. These data indicate that the intermediate lobe is responsive to dopamine at around birth, while the inhibitory dopaminergic control develops only during the 1st postnatal week, in conjunction with marked changes in circulating MSH levels.

Animals↗

Kinetic properties of pyridoxamine (pyridoxine)-5'-phosphate oxidase from rabbit liver.

The kinetic properties of pyridoxamine (pyridoxine)-5'-phosphate oxidase have been studied using the physiological substrates pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP) at 25 degrees C and pH 8.0. Under steady-state conditions with different concentrations of PNP and O2, a series of parallel lines and competitive substrate inhibition with a KI of 50 microM are seen in double reciprocal plots. This is suggestive of a binary complex mechanism. Secondary plots yield a turnover number of 42 min-1 and Km values for both PNP (8.2 microM) and O2 (182 microM). A large deuterium isotope effect, VH/VD of 6.5, was observed with [4',4'-2H]PNP. In analogous studies using PMP, a turnover number of 6.2 min-1 and respective Km values for PMP and O2 of 3.6 and 85 microM were calculated. No significant substrate inhibition and a small deuterium isotope effect (VH/VD = 1.1) were observed with PMP. Anaerobic stopped flow data showed that the enzyme-bound flavin was reduced at a rate similar to catalytic turnover with PNP as a substrate, whereas with PMP, the rate of enzyme reduction is 500-fold faster than turnover. Stopped flow kinetic data also showed the reduced enzyme to react with O2 at rates at least 10(2)-10(3) faster than turnover. These results indicate that enzyme reduction is rate-limiting when the alcohol form (PNP) is the substrate, but in the case of the amine (PMP), the rate-limiting step in catalysis occurs subsequent to reduction. With PMP as substrate, release of product from the complex with reduced enzyme is 15-fold slower than turnover, and thus, it is suggested that oxygen reacts with the complex. The pH dependence of the deuterium isotope effect and the Km for PMP showed substantial change in the pH range between 6.0 and 7.5, whereas little or no pH dependence was observed for PNP. These data show that the kinetic mechanism of pyridoxamine (pyridoxine)-5'-phosphate oxidase can function via either a binary or ternary complex mechanism, depending upon the nature of the substrate.

Animals↗

Is cigarette smoking associated with diabetic retinopathy?

The relationship between cigarette smoking and diabetic retinopathy is examined in this report. All participants were examined between September 1980 and July 1981 as part of a population-based study in southwestern Wisconsin. Exposure data on cigarette smoking at the time of examination were derived from a set of questions about present or past smoking history, duration of smoking, and number of cigarettes smoked per day. Retinopathy status was determined according to the modified Airlie House classification. The rate of diabetic retinopathy varied from 21% in those who had diabetes for 0-4.9 years to 97% in those who had diabetes for 15 or more years, for persons diagnosed before 30 years of age, and from 28% to 78% for comparable durations in those diagnosed at 30 years or older. There was no association between smoking history and duration of diabetes. In participants diagnosed before age 30, the relative risk for the presence of retinopathy in smokers compared with those who had never smoked was 1.06 (95% confidence limits (CL) 0.97-1.18); in participants diagnosed at 30 years or older it was 0.89 (95% CL 0.75-1.06). There was no relationship between the risk or severity of retinopathy and number of cigarettes smoked daily, or the number of pack-years smoked while diabetic. These data suggest that there is no excess risk of retinopathy in smokers or ex-smokers when contrasted with those who never smoked.

Adolescent↗

Charge transfer complexes between pteridine substrates and the active center molybdenum of xanthine oxidase.

Anaerobic addition of lumazine (2,4-dihydroxypteridine) to xanthine oxidase leads to a rapid bleaching of the enzyme with concomitant formation of a long wave-length species with maximum absorbance at 650 nm. At the conclusion of the reaction there is a net increase in absorbance at wavelengths greater than 550 nm. A spectrally similar species is obtained when violapterin is added to dithionite-reduced enzyme. This long wavelength absorbance is not accompanied by an EPR signal characteristic of flavin neutral radical and it is produced equally well in flavin-free xanthine oxidase. Its production is eliminated by the inhibitors, cyanide and allopurinol, which react at the molybdenum center. We conclude that this new species is a charge transfer complex between Mo(IV) and the product of the reaction, violapterin (2,4,7-trihydroxypteridine). A similar, though less intense, absorbance at 650 nm is also obtained when lumazine is bound to the reduced enzyme. These Mo(IV)-pteridine charge transfer compounds are optically active and exhibit intense circular dichroism centered at 630 nm.

Anaerobiosis↗

Nutritional status of children with bacterial meningitis.

A study undertaken to determine whether there is any association between nutritional status and bacterial meningitis showed that of 304 children with bacterial meningitis seen in a 2-year period at Baragwanath Hospital, only 20,4% had protein energy malnutrition (PEM), whereas 34% of all children admitted had avert malnutrition. Relating these figures to the nutritional status of the population served by this hospital showed that the prevalence of PEM in children with meningitis did not differ from that in the community in which they lived. Possible reasons for the absence of an association between PEM and malnutrition are discussed.

Age Factors↗

Scleral buckling procedure for retinal detachments secondary to proliferative diabetic retinopathy.

Ninety-two patients (99 eyes) underwent scleral buckling procedures for retinal detachment associated with proliferative diabetic retinopathy. Fifty-three procedures were for rhegmatogenous retinal detachment and 46 for tractional retinal detachment. The average follow-up period was 38 months. Anatomic success was assessed in terms of closure of retinal breaks (59/69, 86%), macular reattachment (42/90, 46%), and reduction in extent of retinal detachment postoperatively as compared to preoperatively (62/99, 63%). The visual acuity was better postoperatively in 33/99 (34%) of the eyes; 58/99 (58%) of the eyes maintained finger counting visual acuity. Improvement in visual acuity was more frequent in eyes with rhegmatogenous detachment (23/53, 43%) than in those with traction detachment (10/46, 22%). Although improvement is generally limited, some patients are markedly benefitted by scleral buckling procedures.

Adolescent↗

Isoniazid pharmacokinetics in kwashiorkor.

Isoniazid plasma half-life and clearance rates were studied in children with kwashiorkor before and after nutritional rehabilitation. Isoniazid half-life rates fell and clearance increased with nutritional rehabilitation. The changes documented in this report are not an indication that isoniazid therapy should be altered in malnourished children, but may indicate that this should be done in malnourished adults.

Half-Life↗

Clinicopathologic correlation of xenon arc and argon laser photocoagulation. Procedure in human diabetic eyes.

Xenon arc and argon laser lesions applied as scatter treatment to two diabetic patients were studied clinically and histopathologically. Seventy-one burns were grouped as very severe, severe, and moderately severe, according to pigmentation and diameter of the retinal scar. All lesions except half of the moderately severe ones showed full-thickness retinal involvement. In very severe xenon burns, whether xenon or argon, only proliferated retinal pigment epithelium provided a thin retinal scar, corresponding to an ophthalmoscopic appearance of "bare sclera". In the center of severe and moderately severe lesions, both glial cells and pigment epithelium bridged the retinal defect, forming a thick pigmented scar that contained pigment-laden macrophages. Rephotocoagulation over such thick scars may be less hazardous than is generally assumed. Nonvascular preretinal membranes were frequently present over very severe xenon lesions but rarely over very severe argon burns.

Adult↗