| 1. |
- Breimer, Michael, 1951, et al.
(författare)
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Extracorporeal ("ex vivo") connection of pig kidneys to humans. I. Clinical data and studies of platelet destruction.
- 1996
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Ingår i: Xenotransplantation. - : Wiley. - 0908-665X .- 1399-3089. ; 3:4, s. 328-39
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Tidskriftsartikel (refereegranskat)abstract
- The pioneering experiment by Welsh et al. (Immunological Lett 1991:29:167-170) connecting a pig kidney to the human circulation has been repeated in a modified manner. Two volunteer dialysis patients were pretreated by daily plasmapheresis on days -2,-1, and 0 to remove the naturally occurring anti-pig xenoantibodies. The anti-pig lymphocytotoxic liters were reduced from 1:8 to 1:2 in patient 1 and from 1:8 to 1:1 in patient 2. No steroids or immunosuppressive drugs were administrated before or during the experiments. A sterile pig kidney was extracorporeally ("ex vivo") connected to the patients a/v fistula using an arterial and a venous pump similar to a dialysis. The two experiments gave different results. In the first experiment the perfusion pressure was kept at 100 mmHg for the initial 25 min by reducing the pump speed until the minimum blood flow of 30 ml/min was reached. Thereafter, the pressure rose continuously and the experiment was terminated at 65 min at a perfusion pressure of 200 mmHg. The patient did not feel any discomfort during the perfusion. In the second experiment, a stable blood flow of 200 ml/min was reached at a pressure of 100 mmHg after a few minutes. The perfusion was terminated at 15 min when the patient developed chest and abdominal pain, hypotension, and electrocardiographic signs of myocardial ischemia. The patient recovered quickly. In the first experiment, small volumes of clear urine was produced until the pressure rose above 100 mmHg, which resulted in hematuria. In the second experiment clear urine (4 ml/min) was produced. (51)Chromium clearance values were after 15 min <1 ml/min for kidney 1 and 12 ml/min (8 ml/min/100 g) for kidney 2. A drastic reduction in platelet count (128 to 48 and 64 to 8 × 10(9)/1, respectively) during the passage through the kidney was found in blood samples collected simultaneously before and after the organ. No change in hemoglobin values and leucocyte counts were found. Light- and electron-microscopical analysis of the kidney tissues revealed for kidney 1 focal areas with obliteration of the glomerular and peritubular capillaries by platelets and PMN cells and severe damage of the endothelial cells comparable to a picture of a hyperacute rejection. In kidney 2, all vessels were patent but in the capillaries large amount of membrane fragments were detected by electron microscopy and a discrete damage of the endothelial cells were seen in some segments. No intact platelets were present in the vascular tree. These human experiments support the hypothesis that hyperacute rejection of pig to human xenografts is delayed in time by removal of the preformed anti-pig xenoantibodies. A new finding was a very rapid destruction of platelets occurring in the kidney of patient 2 who had very low liters of xenoantibodies. The humoral immune response is described in detail in an accompanying paper (Rydberg et al., this issue).
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| 2. |
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| 3. |
- Hulthén, Lena, 1947, et al.
(författare)
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Salt intake in young Swedish men.
- 2010
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Ingår i: Public health nutrition. - 1475-2727. ; 13:5, s. 601-5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To measure dietary salt intake in a Swedish population. DESIGN: A cross-sectional study with measured 24 h urinary excretion of Na and K. Completeness of urine collection was assessed using p-aminobenzoic acid. The subjects were interviewed on their habitual food intake. SETTING: Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: Eighty-six young men (age 18-20 years), randomly selected from the population of Gothenburg. Seven men were excluded due to incomplete urine collection. RESULTS: The mean excretion of Na and K over 24 h was 198 and 84 mmol, respectively (corresponding to 11.5 g NaCl and 3.3 g K). The mean 24 h excretion in the highest quartile of Na excretion was 297 mmol Na and 105 mmol K, and in the lowest quartile, 100 mmol Na and 68 mmol K. The mean Na:K ratio was 2.3, and respectively 3.2 and 1.8 in the highest and lowest Na excretion quartiles. Calculated energy intake did not differ between the highest and lowest quartiles of Na excretion, but body weight, BMI and the intake of certain foods known to be Na-rich did. CONCLUSIONS: Salt intake in young men was alarming high and even subjects in the lowest quartile of Na excretion did not meet present recommendations to limit salt intake to 5-6 g/d. At this point we can only speculate what the consequences of the high salt intake may be for CVD and stroke later in life. Regulation of the salt content in processed and fast food and in snacks is advocated, to curtail the salt burden on society imposed by the food industry.
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| 4. |
- Aiff, Harald, et al.
(författare)
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Effects of 10 to 30 years of lithium treatment on kidney function
- 2015
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285. ; 29:5, s. 608-614
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Tidskriftsartikel (refereegranskat)abstract
- Long-term lithium treatment is associated with end-stage renal disease, but there is little evidence of a clinically significant reduction in renal function in most patients. We previously found that 1.5% of people who took lithium from the 1960s and 1970s developed end-stage renal disease; however, none of the patients who started after 1980 had end-stage renal disease. Here we aimed to study the prevalence and extent of kidney damage during the course of long-term lithium treatment since 1980. We retrieved serum lithium and creatinine levels from 4879 patients examined between 1 January 1981 and 31 December 2010. Only patients who started their lithium treatment during the study period and had at least 10 years of cumulative treatment were included. The study group comprised 630 adult patients (402 women and 228 men) with normal creatinine levels at the start of lithium treatment. There was a yearly increase in median serum creatinine levels already from the first year of treatment. About one-third of the patients who had taken lithium for 10-29 years had evidence of chronic renal failure but only 5% were in the severe or very severe category. The results indicate that a substantial proportion of adult patients who are treated with lithium for more than a decade develop signs of renal functional impairment, also when treated according to modern therapeutic principles. Our results emphasise that lithium treatment requires continuous monitoring of kidney function.
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| 5. |
- Aiff, Harald, et al.
(författare)
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End-stage renal disease associated with prophylactic lithium treatment
- 2014
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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 24:4, s. 540-544
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Tidskriftsartikel (refereegranskat)abstract
- The primary aim of this study was to estimate the prevalence of lithium associated end-stage renal disease (ESRD) and to compare the relative risk of ESRD in lithium users versus non-lithium users. Second, the role of lithium in the pathogenesis of ESRD was evaluated. We used the Swedish Renal Registry to search for lithium-treated patients with ESRD among 2644 patients with chronic renal replacement therapy (RRT)-either dialysis or transplantation, within two defined geographical areas in Sweden with 2.8 million inhabitants. The prevalence date was December 31, 2010. We found 30 ESRD patients with a history of lithium treatment. ESRD with RRT was significantly more prevalent among lithium users than among non-lithium users (p<0.001). The prevalence of ESRD with RRT in the lithium user population was 15.0‰ (95% CI 9.7-20.3), and close to two percent of the RRT population were lithium users. The relative risk of ESRD with RRT in the lithium user population compared with the general population was 7.8 (95% CI 5.4-11.1). Out of those 30 patients, lithium use was classified, based on chart reviews, as being the sole (n=14) or main (n=10) cause of ESRD in 24 cases. Their mean age at the start of RRT was 66 years (46-82), their mean time on lithium 27 years (12-39), and 22 of them had been on lithium for 15 years or more. We conclude that lithium-associated ESRD is an uncommon but not rare complication of lithium treatment. © 2014.
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| 6. |
- Aiff, Harald, et al.
(författare)
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The impact of modern treatment principles may have eliminated lithium-induced renal failure
- 2014
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285. ; 28:2, s. 151-154
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that lithium can cause end-stage renal disease (ESRD): however, this serious side-effect of lithium in prophylactic treatment of mood disorders may reflect the treatment regime of the 1960s and 1970s. Today's modern treatment routines, intended to reduce or eliminate lithium-induced ESRD (Li-ESRD), were introduced in Sweden in the early 1980s. The aim of the present study was to test the hypothesis that these routines have eliminated the risk of Li-ESRD. We used the Swedish Renal Registry to identify patients on renal replacement therapy (RRT), treated with dialysis or renal transplantation, with suspected Li-ESRD in two regions of Sweden with altogether about three million inhabitants. We reviewed their medical records to verify the exposure to lithium treatment, the diagnosis of Li-ESRD and the date of starting the lithium treatment. We found 32 RRT patients in whom lithium treatment was the sole or main contributing cause of ESRD. The starting year of their lithium treatment was between 1965-1980 in all patients. No patient started lithium treatment later than 1980. Modern lithium treatment may have eliminated the risk of Li-ESRD. Our findings support the continued use of lithium as a safe drug for the long-term treatment of mood disorders.
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| 7. |
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| 8. |
- Dahlöf, Björn, 1953, et al.
(författare)
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Addition of the calcium antagonist PN 200-110 to pindolol markedly augments the antihypertensive effect in essential hypertension.
- 1987
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 10 Suppl 10
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Tidskriftsartikel (refereegranskat)abstract
- Several large-scale studies have recently drawn attention to the fact that arterial hypertension frequently is inadequately controlled and that therapeutic alternatives other than the commonly employed stepped-care treatment may be needed in order to obtain normotension. For this reason PN 200-110, a new dihydropyridine calcium antagonist--at two different dose levels (average 3.8 mg b.i.d. or 5.7 mg b.i.d.)--or placebo was added in a double-blind cross-over trial to pindolol, 10 mg per day, in 20 patients with essential hypertension, after an initial 3-week placebo period. Ionized calcium in serum was determined repeatedly during the study. From an initial level of 157/100 mm Hg, PN 200-110 at the first dose level reduced blood pressure by 14/11 mm Hg (p less than 0.01/0.001) and at the second dose level reduced blood pressure by 22/18 mm Hg (p less than 0.001/0.001). The reduction in mean arterial pressure was significantly correlated to age (=0.050, p less than 0.05). There was no significant increase in heart rate, nor were there any significant correlations between ionized calcium and the effect of PN 200-110 nor between the changes in ionized calcium and the changes in blood pressure. Adverse effects were few and mild. One patient had to be withdrawn because of side effects, probably not related to the investigated drugs. Thus, addition of PN 200-110 to hypertensive patients treated with pindolol caused highly significant and clinically relevant further reductions in arterial pressure. The results show that a combination of this kind offers the possibility of good blood pressure control.
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| 9. |
- Herlitz, Hans, 1946, et al.
(författare)
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Failure of angiotensin II to suppress plasma renin activity in normotensive subjects with a positive family history of hypertension.
- 2005
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Ingår i: Clinical science (London, England : 1979). - 0143-5221. ; 109:3, s. 311-7
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Tidskriftsartikel (refereegranskat)abstract
- The renin-angiotensin system is implicated in the pathophysiology of hypertension. Renin release is regulated by a number of factors, including circulating Ang II (angiotensin II), the so-called short feedback loop. The aim of the present study was to investigate the responsiveness of circulating Ang II on PRA (plasma renin activity) in normotensive subjects with a PFH or NFH (positive or negative family history of hypertension respectively). PRA, renal haemodynamics and urinary sodium excretion were measured during infusion of Ang II without and with pretreatment with the AT1 (Ang II type 1) receptor blocker irbesartan. Normotensive men with a PFH (n=13) and NFH (n=10), with a mean age of 38 years, were given on different occasions intravenous Ang II infusions of 0.1, 0.5 and 1.0 ng.kg-1 of body weight.min-1 before and after pretreatment with 150 mg of irbesartan once a day for 5 consecutive days. RPF (renal plasma flow) and GFR (glomerular filtration rate) were also measured. Before Ang II infusion, the PFH and NFH groups did not differ with respect to BP (blood pressure), body mass index, PRA, RBF (renal blood flow) or urinary sodium. There was no difference in BP or renal haemodynamic response to the highest Ang II dose between the groups. PRA declined with the highest Ang II dose (P<0.01) in subjects with a NFH, but not in subjects with a PFH. After treatment with irbesartan when Ang II had no effect on BP in either group, Ang II also suppressed PRA in subjects with a PFH (P<0.01), and the difference between the groups at baseline was thus eliminated. In conclusion, these findings indicate that subjects with a PFH have a defective Ang II suppression of PRA, which is corrected by AT1 receptor blockade.
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| 10. |
- Jensen, Gert, 1950, et al.
(författare)
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Survival and quality of life after renal angioplasty: a five-year follow-up study.
- 2009
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 43:3, s. 236-41
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Renal percutaneous transluminal angioplasty (PTA) treatment of renal artery stenosis has been performed worldwide since 1978, but it is still a matter of debate as to what extent the patients benefit from the procedure in terms of quality of life and long-term survival. MATERIAL AND METHODS: Of 139 patients referred for renal angioplasty owing to hypertension or pending uraemia, 105 were subsequently treated with PTA. Eighty-eight patients survived for 5 years. Fifty-nine patients were re-examined according to a protocol including physical examination, blood pressure, drug therapy, glomerular filtration rate and quality of life assessment, and an additional 29 patients were interviewed by telephone regarding quality of life. PTA was not conducted in 34 patients owing to high risks as decided at joint radiology-nephrology conferences. RESULTS: The 5-year survival was 83% for PTA-treated patients with arteriosclerotic renovascular disease, 100% for patients with fibromuscular vascular disease and 47% for the non-PTA-treated patients. The main causes of death were cardiovascular and cerebrovascular events in both groups. Reduced blood pressure and reduced need for antihypertensive drug treatment were observed in the PTA-treated patients. The renal function was stable. A majority of the PTA-treated patients stated that they had "unrestricted" physical activity, and the physical, mental and social well-being was self-rated as level 4-5 (mostly good and very good) on a five-grade scale by 53%, 67% and 75% of the patients, respectively, at the follow-up investigation. The untreated patients were not interviewed. CONCLUSION: The study showed a high survival rate, improved blood pressure control and stable renal function 5 years after renal PTA, and a vast majority of the patients rated their physical, mental and social well-being favourably.
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