Peter Koch Jensen

Renal function in streptozotocin-diabetic rats

SummaryRenal function was examined with micropuncture methods in the insulin-treated streptozotocin-diabetic rat. Kidney glomerular filtration rate was significantly higher in the diabetic rats (1.21 ml/min) than in the control group (0.84 ml/min) Nephron glomerular filtration rate increased in proportion to the rise in kidney glomerular filtration rate (diabetic rats: 37.0 nl/min; control rats: 27.9 nl/min). Likewise renal plasma flow was significantly higher in the diabetic rats (4.1 ml/min) than in the control group (3.0 ml/min). Glomerular capillary pressure was identical in both groups (56.0 and 56.0 mmHg, respectively). The proximal intratubular pressure was significantly reduced in the diabetic rats (10.4 mmHg; control value: 12.5 mmHg). The effective glomerular ultrafiltration coefficient was slightly but not significantly higher in the diabetic rats (0.027 nl s-1mmHg-1) than in the control group (0.023 nl s-1mmHg-1). Kidney weight was significantly higher in the diabetic rats (1.15 g; control rats: 0.96 g) while body weight was similar in both groups (diabetic rats: 232 g; control rats: 238 g). Calculations indicate that the increases in transglomerular hydraulic pressure, renal plasma flow and ultrafiltration co-efficient of the glomerular membrane contribute about equally to the rise in glomerular filtration rate. The increases in the values of the determinants of glomerular filtration rate may be the result of renal hypertrophy. These studies suggest that this model provides a useful method for investigating kidney function in diabetes, which may have relevance for our understanding of the kidney abnormalities in human diabetes.

Optic nerve oxygenation.

The oxygen tension of the optic nerve is regulated by the intraocular pressure and systemic blood pressure, the resistance in the blood vessels and oxygen consumption of the tissue. The oxygen tension is autoregulated and moderate changes in intraocular pressure or blood pressure do not affect the optic nerve oxygen tension. If the intraocular pressure is increased above 40 mmHg or the ocular perfusion pressure decreased below 50 mmHg the autoregulation is overwhelmed and the optic nerve becomes hypoxic. A disturbance in oxidative metabolism in the cytochromes of the optic nerve can be seen at similar levels of perfusion pressure. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. The risk for progressive optic nerve atrophy in human glaucoma patients is six times higher at a perfusion pressure of 30 mmHg, which corresponds to a level where the optic nerve is hypoxic in experimental animals, as compared to perfusion pressure levels above 50 mmHg where the optic nerve is normoxic. Medical intervention can affect optic nerve oxygen tension. Lowering the intraocular pressure tends to increase the optic nerve oxygen tension, even though this effect may be masked by the autoregulation when the optic nerve oxygen tension and perfusion pressure is in the normal range. Carbonic anhydrase inhibitors increase the optic nerve oxygen tension through a mechanism of vasodilatation and lowering of the intraocular pressure. Carbonic anhydrase inhibition reduces the removal of CO2 from the tissue and the CO2 accumulation induces vasodilatation resulting in increased blood flow and improved oxygen supply. This effect is inhibited by the cyclo-oxygenase inhibitor, indomethacin, which indicates that prostaglandin metabolism plays a role. Laboratory studies suggest that carbonic anhydrase inhibitors might be useful for medical treatment of optic nerve and retinal ischemia, potentially in diseases such as glaucoma and diabetic retinopathy. However, clinical trials and needed to test this hypotheses.

Treatment for Retinopathy of Prematurity in Denmark in a Ten-Year Period (1996–2005): Is the Incidence Increasing?

OBJECTIVE. The objective of this study was to analyze the population incidence of retinopathy of prematurity treatment in Denmark in the 10-year period from 1996 to 2005. METHODS. Patient charts of infants treated for retinopathy of prematurity and the national birth registry provide information about neonatal parameters. These parameters, along with birth in the latter half of the period (2001–2005), were analyzed as risk factors for retinopathy of prematurity. The national registry for blind and visually impaired children was accessed to obtain information about visual impairment attributable to retinopathy of prematurity in both treated and untreated infants. RESULTS. The study population consisted of 5467 Danish preterm infants born in 1996 to 2005, with a gestational age of <32 weeks, who survived for ≥5 postnatal weeks; 2616 were born in 1996 to 2000, and 2851 were born in 2001 to 2005. The incidence of treated retinopathy of prematurity cases increased significantly from 1.3% in 1996 to 2000 to 3.5% in 2001 to 2005. Significant risk factors for retinopathy of prematurity treatment were low gestational age, small for gestational age, male gender, and multiple birth. Other, yet unknown factors contributed to the increased incidence in the latter half of the period. Of the study population, 0.6% were registered as visually impaired because of retinopathy of prematurity within 2 years after birth (early-detected visual impairment). The incidences were not significantly different between 1996 to 2000 and 2001 to 2005. Of all of the early-detected, visually impaired children, 16% had not been treated for retinopathy of prematurity and were considered screening failures. CONCLUSIONS. The incidence of retinopathy of prematurity treatment in Denmark has more than doubled during the past half-decade. This increase could not be fully explained by increased survival rates for the infants or by changes in the investigated neonatal risk factors.

Optic nerve oxygen tension: effects of intraocular pressure and dorzolamide

AIM To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide. METHODS Domestic pigs were used as experimental animals. Oxygen tension was measured by means of a polarographic electrode in the vitreous 0.5 mm anterior to the optic disc. This entity is called the optic nerve oxygen tension. Intraocular pressure was controlled by a hypodermic needle inserted into the anterior chamber and connected to a saline reservoir. RESULTS When the intraocular pressure was clamped at 20 cm H2O optic nerve oxygen tension was 20 (5) mm Hg (n=8). Intravenous administration of dorzolamide caused an increase in optic nerve oxygen tension of 43 (8)% (n=6). Both before and after administration of dorzolamide optic nerve oxygen tension was unaffected by changes in intraocular pressure, as long as this pressure remained below 60 cm H2O. At intraocular pressures of 60 cm H2O and below, dorzolamide significantly increased optic nerve oxygen tension. CONCLUSION Intravenous administration of 500 mg dorzolamide increases the oxygen tension at the optic nerve head during acute increases in intraocular pressure.

FLUORESCEIN IN HUMAN PLASMA IN VITRO

A method to determine fluorescein in human plasma is described. By aid of ultrafiltration a separation between fluorescein bound to plasma proteins and fluorescein free in the water is obtained. Both fractions are quantitated. Fluorescein is bound to plasma proteins. The protein binding is reversible, not sensitive to practically appearing changes in pH, temperature and gas tensions. For a normal person it appeared that at a total plasma concentration between (10‐6–10‐4) g·ml‐1 approximately 15% was free while at a total concentration of 10‐3 g·ml‐1 45% was free, pointing towards a limited amount of protein binding sites.

Three‐dimensional structure of human retinal vessels studied by vascular casting

Abstract. A new casting technique for studying the three‐dimensional structure of the human retinal vascular system on post mortem tissue was developed. The technique was designed to provide an overview presentation of the retinal vasculature such that localized areas with vascular pathology could be identified for further analysis of three‐dimensional structure. The paper presents qualitative characteristics of three‐dimensional structure in the normal human retinal vascular bed, to provide a basis for future studies on vascular impairment in retinal disease.

Dorzolamide Increases Retinal Oxygen Tension after Branch Retinal Vein Occlusion

PURPOSE To study the effect of dorzolamide on the preretinal oxygen tension (RPO(2)) in retinal areas affected by experimental branch retinal vein occlusion (BRVO) in pigs. METHODS Experimental BRVO was induced by diathermy close to the optic disc. RPO(2) was measured with an oxygen-sensitive electrode 0.5 mm above the BRVO-affected area, which was compared to the retinal areas not affected by BRVO. In one group of five pigs, RPO(2) was measured at baseline, 1 and 3 hours after BRVO, and after intravenous injection of 500 mg dorzolamide. In a second group of five pigs, RPO(2) was measured 1 week after the BRVO, both before and after intravenous injection of 500 mg dorzolamide. RESULTS The average baseline RPO(2) was 2.64 +/- 0.09 kPa (mean +/- SD). In the BRVO-affected areas, RPO(2) decreased significantly (by 0.67 +/- 0.29 and 0.94 +/- 0.13 kPa) at 1 hour and 3 hours after BRVO induction. In the non-BRVO areas RPO(2) increased significantly (by 0.51 +/- 0.14 kPa) 1 hour after BRVO induction, but subsequently decreased and reached baseline 3 hours after BRVO induction. One week after BRVO induction, RPO(2) was 0.67 +/- 0.29 kPa lower in affected areas when compared with the non-BRVO areas. In the BRVO-affected areas, dorzolamide increased RPO(2) significantly (by 0.36 +/- 0.21 kPa at 3 to 4 hours and by 0.67 +/- 0.40 kPa) 1 week after BRVO induction. CONCLUSIONS Retinal hypoxia induced by experimental BRVO remained significant 1 week after BRVO. Dorzolamide increased retinal oxygen tension in the BRVO-affected areas both at 4 hours and 1 week after experimental BRVO in pigs.

Optic nerve oxygen tension: the effects of timolol and dorzolamide

Background/aims: The authors have previously reported that carbonic anhydrase inhibitors such as acetazolamide and dorzolamide raise optic nerve oxygen tension (ONPO2) in pigs. The purpose of the present study was to investigate whether timolol, which belongs to another group of glaucoma drugs called β blockers, has a similar effect. In addition, the effect of dorzolamide and timolol in combination was studied. Methods: Polarographic oxygen electrodes were placed transvitreally over the optic disc in anaesthetised pigs and ONPO2 was recorded continually. Drugs were administered intravenously either as 100 mg timolol followed by 500 mg dorzolamide (n = 5), 500 mg dorzolamide followed by 100 mg timolol (n = 5), or 100 mg timolol and 500 mg dorzolamide given simultaneously (n = 5). Arterial blood pressure, blood gasses, and heart rate were recorded. Results: ONPO2 was unaffected by administration of 100 mg timolol as an intravenous injection (n = 5). Administration of 500 mg dorzolamide by itself significantly increased ONPO2 from 2.96 (SD 0.62) kPa to 3.69 (SD 0.88) kPa (n = 4, p = 0.035). The dorzolamide induced ONPO2 increase was not significantly different from the ONPO2 increases were seen when dorzolamide was administered simultaneous with (n = 5) or 35 minutes (n = 5) after 100 mg timolol. Conclusion: Systemic administration of timolol does not affect the optic nerve oxygen tension despite its lowering effect on the intraocular pressure. Additionally, timolol does not affect the ONPO2 increasing effect of dorzolamide.

A New Risk-Based Screening Criterion for Treatment-Demanding Retinopathy of Prematurity in Denmark

OBJECTIVE: The aim of this study was to uncover the most effective and safe criterion to implement for retinopathy of prematurity screening in Denmark. METHODS: This retrospective national cohort study is based on data from 3 national registers. These registers provided on infants treated for retinopathy of prematurity, infants in need of treatment but missed by the present screening program, and the candidate neonates for advanced retinopathy of prematurity development A nonlinear logistic regression model was fitted to the data, and various screening criteria were evaluated. RESULTS: During the study period (2002–2006), 116 infants were treated for retinopathy of prematurity, no treatment-demanding retinopathy of prematurity infants were missed by the screening program, and 182 premature infants were candidates for developing treatment-demanding retinopathy of prematurity. Screening criteria combining gestational age at delivery and birth weight limits and new risk-based criteria were compared with regards to their effectiveness. The risk-based criteria were the most effective. Use of the 0.13% risk-based criterion to define the population to be screened resulted in the detection of all treated infants in the study period and 17.4% fewer infants to screen. The model predicted this criterion to result in 1 missed case of treatment-demanding retinopathy of prematurity every 11 years and 1 case of blindness every 18 years in Denmark. CONCLUSIONS: Screening criteria based on risk estimates of developing treatment-demanding retinopathy of prematurity are the most effective for retinopathy-of-prematurity screening. The risk-based criterion of 0.13% can safely be implemented for future retinopathy-of-prematurity screening in Denmark.

Angiotensin II induced reduction of peritubular capillary diameter in the rat kidney.

SummaryLarge peritubular capillaries were infused consecutively (20 nl · min−1) in random sequence with isotonic saline and angiotensin II (20–80 ng · ml−1). The diameters of the infused capillaries were measured, without knowledge of the infusate used, from colour photographs of the infused area.Angiotensin II induced a significant (p<0.001) decrease in capillary diameter (Δ=−1.2±0.2 (SE) μm and Δ=−2.1±0.2 (SE) μm with 20 ng · ml−1 and 80 ng · ml−1 angiotensin II infusates, respectively). This decrease was shown to be independent of external tubular compression: separate experiments in which the surrounding tubules were collapsed by injection of oil blocks yielded similar results. The possibility that the observed reduction in diameter was caused by an angiotensin II induced change in capillary permeability to the staining solution was excluded, since the angiotensin II effect was unchanged when fluorescent dextran (mol. wt. 150000) was substituted for lissamin green.These experiments indicate that peritubular capillaries contract actively when infused with angiotensin II.