Biomedical subjects

S Christensen

Publications and source records attributed to S Christensen.

At least 109 records · Page 6Linked to original sources

PubMed1993

Effect of chronic lithium treatment upon the Na(+)-coupled cotransporters in renal brush border membranes.

While the most frequent and prominent side effect of the chronic lithium (Li) administration is dysfunction of collecting ducts and polyuric syndrome, some reports also suggest defects in functions of proximal tubules. We determined the transport properties of brush border membranes (BBM) from kidneys of rats chronically fed for four weeks a chow containing Li (60 mmol/kg; Li-rats) and compared them with BBM from placebo-treated controls. BBM from Li-rats did not differ from controls in Na(+)-gradient-dependent transport of 32Pi, D-[3H]-glucose or L-[3H]-proline, but showed a considerable increase in the transport rates of [14C]-citrate (delta + 53%; P < 0.001) and [14C]-succinate (delta + 48%, P < 0.005), and also enhanced the rate of Na(+)-H+ antiport across BBM (delta + 30%, P < 0.05). In contrast, direct addition of 1 mM Li to BBMV in vitro inhibited Na(+)-dependent transports of both citrate and succinate. The Li-rats had higher plasma level of citrate and decreased (delta - 50%) renal clearance of citrate. Our results show that chronic exposure to oral Li in vivo results in increased Na(+)-gradient-dependent transport of polycarboxylic acids and increased Na(+)-H+ antiport in BBM of proximal tubules; these changes are contrary to effects of Li added to isolated BBM in vitro.

Animals↗

PubMed1993

N-acetylcysteine inhibits angiotensin converting enzyme in vivo.

Nitrate tolerance has been explained by 1) a direct loss of pharmacological effect due to reduced bioconversion and 2) an indirect effect due to activation of the renin/angiotensin system and counter-regulatory vasoconstriction. The sulfhydryl compound N-acetylcysteine (NAC) has been shown to attenuate and partly counteract tolerance to nitrates, and this effect has been attributed to a nitrate/sulfhydryl interaction and increased production of vasoactive intermediates. The effect of NAC on counter-regulatory mechanisms is, however, unknown. This study examined whether NAC modulates the function of the renin/angiotensin system in normal rats and in nitrate-tolerant healthy volunteers. Animal study: Conscious rats received NAC (5 mmol/kg/hr i.v., n = 8) or placebo (N-acetylserine, n = 8). Two hours of NAC infusion significantly reduced the pressor effect of angiotensin I (ANG I) by 39 +/- 14% (mean +/- SEM) and reduced angiotensin converting enzyme activity by 31% in plasma (N-acetylserine: 74 +/- 9 nmol/min/mg, NAC: 51 +/- 7) and 43% in kidney (N-acetylserine: 0.9 +/- 0.3, NAC: 0.5 +/- 0.1 nmol/min/mg protein) (P < .05). Clinical study: Isosorbide dinitrate (5 mg/hr) was infused into six male volunteers for 48 hr. NAC (2 g i.v. followed by 5 mg/kg/hr) was co-infused from 24 to 48 hr. Plasma angiotensin II (ANG II) increased during the first 24 hr of isosorbide dinitrate infusion and decreased from 28 +/- 4 to 14 +/- 2 ng/l after 2 hr of NAC infusion (P < .05). The results suggest that sulfhydryl supplementation modifies the function of the renin/angiotensin system in vivo, an effect probably mediated by inhibition of angiotensin converting enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗

PubMed1993

Effects of angiotensin-converting enzyme inhibition on renal adaptations to acute furosemide administration in conscious rats.

During administration of loop diuretics the initial volume depletion activates Na-conserving mechanisms, which reduces glomerular filtration rate (GFR) and stimulates renal tubular reabsorption of Na and water. By i.v. infusion of the angiotensin-converting enzyme inhibitor enalaprilat (100 micrograms bolus; 100 micrograms/h) we examined the role of angiotensin II for the compensatory renal responses occurring during furosemide administration in conscious rats. To evaluate the significance of hydration for the compensatory renal effects of angiotensin II, experiments were performed in groups of rats with or without i.v. replacement of urinary volume losses. Furosemide was administered i.v. (6 mg/kg/h) for 3 1/2 hr. Furosemide infusion produced a short-lasting increase in urine flow rate, Na, Li and K excretion after which the renal excretion rates returned toward pretreatment levels, along with significant reductions in effective renal plasma flow and GFR and increases in effective filtration fraction and effective renal vascular resistance. Sustained increases in urine flow and urinary excretion rates of Na, Li and K were observed in absence of changes in GFR in rats given furosemide with volume replacement. Enalaprilat did not alter the tubular response to furosemide during either euvolemia or volume depletion. However, enalaprilat attenuated the furosemide-induced increases in effective filtration fraction and effective renal vascular resistance. It is concluded that angiotensin II is not essential for the compensatory response of decreased GFR and increased tubular Na reabsorption. However, angiotensin II is an important mediator of renal vasoconstriction during furosemide infusion.

Absorption↗

PubMed1992

Bovine alpha 2-antiplasmin. N-terminal and reactive site sequence.

Bovine alpha 2-antiplasmin (alpha 2AP) has been purified and partially characterized. The amino acid composition is very similar to that of human alpha 2AP, and the N-terminal (23 residues determined) and reactive site loop sequences (42 residues determined) are highly homologous to those of the human protein. Compared with human alpha 2AP, bovine alpha 2AP has an 18-residue N-terminal extension, homologous with part of the pre-sequence of human alpha 2AP. A re-investigation of the N-terminal sequence of freshly prepared human alpha 2AP reveals a new form extended by 12 residues.

Amino Acid Sequence↗

PubMed1992

Lithium clearance in dogs: effects of water loading, amiloride and lithium dosage.

1. The influences of lithium dosage, urine flow rate and acute administration of amiloride on the renal handling of lithium in normal conscious dogs were investigated. 2. Lithium was administered in the diet at daily doses of 100 mg or 2 mg of lithium carbonate for the 2 days preceding the investigation. Urine flow rate was altered by water loading with and without arginine vasopressin infusion (5 pg min-1 kg-1). Amiloride was administered as an intravenous bolus (130 micrograms/kg) followed by a continuous infusion (1.22 micrograms h-1 kg-1). 3. Glomerular filtration rate (exogenous creatinine clearance) did not change within series and was not different between series; it averaged 3.27 ml min-1 kg-1. Control levels of fractional lithium excretion (12.4 +/- 1.2%, mean +/- SEM) were not influenced by hydration, hydration plus arginine vasopressin administration or the lithium dosage. However, in hydrated dogs having a plasma lithium concentration of 130-140 mumol/l, amiloride administration was associated with a 5% increase in fractional lithium excretion (P less than or equal to 0.01). 4. It is concluded that distal tubular lithium reabsorption may take place in sodium-replete conscious dogs undergoing water diuresis. The low fractional lithium excretion even during amiloride infusion (14.1-16.8%) may well be due to a high fractional reabsorption of lithium in the proximal tubules; however, a significant reabsorption of lithium distal to the proximal straight tubules by amiloride-insensitive pathways cannot be excluded.

Amiloride↗

PubMed1992

Regional and subcellular localization of Li+ and other cations in the rat brain following long-term lithium administration.

Rats were given LiCl in their diet (40 mmol/kg dry weight) for at least 3 months to elucidate the regional and subcellular localization of Li+ in the brain as well as the effect of chronic lithium administration on the distribution of other cations. At steady-state the mean concentrations of Li+ were 0.66 mmol/kg wet weight in the whole brain and 0.52 mM in plasma. The tissue/plasma concentration ratio exceeded unity in all anatomical regions. No region showed excessive accumulation of Li+. Whole brain or regional contents of Na+ or K+ were unaffected by lithium treatment. Subcellular Li+ localization was demonstrated in nuclear, crude mitochondrial, and microsomal fractions of whole brain homogenate. Subfractionation of the crude mitochondrial fraction revealed energy-independent intrasynaptosomal and intramitochondrial Li+ and K+ localization at 0-4 degrees C. Li+ administered in vivo disappeared within 10 min from synaptosomes incubated at 37 degrees C. Li+ added in vitro at 1 mM attained a synaptosomal steady-state concentration within 30 min at 37 degrees C. In control rats, synaptosomal concentrations and synaptosomal/medium concentration gradients of cations paralleled their respective in vivo concentrations and gradients. Lithium treatment caused synaptosomal depletion of K+ and Mg2+ and hence probably partial membrane depolarization. Addition of 1 mM Li+ in vitro also caused synaptosomal Mg2+ depletion. The results indicate that Li+ is "accumulated" in brain sediments and synaptosomes following its long-term treatment. The estimated intracellular and intrasynaptosomal Li+ concentrations are lower than predicted by passive distribution according to the Nernst equation, evidencing active extrusion of Li+.

Animals↗

PubMed1992

Renal effects of alpha-adrenoceptor blockade during furosemide diuresis in conscious rats.

Clearance experiments were performed in conscious rats in order to investigate whether intravenous infusion of the non-selective alpha-adrenoceptor antagonist phentolamine could block compensatory sodium reabsorption during furosemide-induced volume contraction. By measuring inulin clearance, urinary excretion rates of sodium and water, and lithium clearance, the effects on proximal and distal nephron segments were dissociated. The renal effect of intravenous infusion of 0.3 mg/kg/hr phentolamine (n = 6) was compared with time control animals (n = 9). Furosemide was administered as constant intravenous infusion (7.5 mg/kg/hr) with simultaneous phentolamine infusion at four dose levels: 0 (n = 9), 0.3 (n = 6), 1.0 (n = 7) and 3.0 mg/kg/hr (n = 6). Phentolamine infusion reduced norepinephrine-induced increase in blood pressure at all three dose levels (n = 5). Phentolamine infusion induced transient antidiuresis and a prolonged antinatriuretic response. Compared with rats given furosemide only, phentolamine attenuated dose-dependently the diuretic and natriuretic peak response to furosemide. This effect was associated with dose-dependent reductions in mean arterial pressure. The reduced natriuretic response was due to a reduced fractional sodium excretion in the distal nephron segment (at all doses of phentolamine) and a reduction of the glomerular filtration rate (1.0 and 3.0 mg/kg/hr phentolamine). The fractional lithium excretion (FELi) increased to 65 +/- 3% at 0.3 mg/kg/hr phentolamine during the natriuretic peak response of furosemide, while it only increased to 52 +/- 3% during furosemide alone. At steady-state conditions (120-180 min. after start of furosemide infusion) after infusion with furosemide plus 0.3 mg/kg/hr phentolamine the animals were still volume-depleted, but the compensatory tubular Na reabsorption in the proximal tubules was inhibited (FELi = 48 +/- 2% versus 39 +/- 1% in rats given furosemide alone). During furosemide infusion plasma epinephrine increased 700% and plasma norepinephrine increased 50%. These results are compatible with increased systemic sympathetic nervous activity and a contributory role of proximal tubular alpha-adrenoceptors in mediating compensatory sodium reabsorption during acute furosemide-induced volume contraction.

Adrenergic alpha-Antagonists↗

PubMed1992

The subsidy provided under Medicare to current enrollees.

Contributions made by or for current enrollees to Medicare will cover less than a third of the costs of their expected lifetime benefits, on average. This subsidy is of concern for two reasons. First, because the subsidy is provided regardless of income, some transfers are effectively made to Medicare enrollees from needier groups in the non-Medicare population. Second, as the ratio of Medicare beneficiaries to the working-age population increases in future years, the current generosity of the program may be difficult to maintain.

Actuarial Analysis↗

PubMed1992

Treatment of Bartholin's abscess. Marsupialization versus incision, curettage and suture under antibiotic cover. A randomized study with 6 months' follow-up.

Conventional marsupialization was compared with incision plus curettage and primary suture of the abscess cavity under antibiotic (Clindamycin) cover in a prospective, randomized study of 32 patients with Bartholin's abscess. The median time to healing was 5 days less after suture than after marsupialization alone. The difference was statistically significant. 29 patients were followed up for 6 months. Recurrence of abscesses tended not to be more frequent after suture, making suture an attractive, safe and convenient alternative treatment for Bartholin's abscess.

Abscess↗

PubMed1992

Medicare: looking for pareto optimal changes.

Medicare enrollees are at risk for potentially unlimited out-of-pocket costs for acute care, defined here as prescription drug costs and copayments on covered services. As a result, many enrollees supplement Medicare with Medigap insurance, which increases their premium costs and their use of Medicare-covered services. The objective of this study was to limit enrollees' risk for acute care costs without increasing federal spending. The study found that savings from prohibiting Medigap would be sufficient to provide a copayment cap under Medicare. If Medicare's copayment requirements were also restructured, the savings would finance a prescription drug benefit as well. Most enrollees could expect lower expenses for premiums and out-of-pocket costs combined, but expenses would be significantly higher for 5% of enrollees, all current Medigap policyholders.

Acute Disease↗

PubMed1992

Volume responses to exogenous changes in Medicare's payment policies.

The purpose of this study is to obtain estimates of the "volume offset," which is the slippage in the costs or the savings that would, in the absence of behavioral responses, result from exogenous changes in Medicare's payment policies. An estimate of this offset is essential to accurate cost estimation for fee proposals under Medicare. Estimates are obtained using Medicare claims data from Colorado for 1976 and 1978, before and after implementation of an abrupt and substantial change in the way Medicare's fees were determined. Reliable estimates could be obtained only for two specialty groups-general practitioners and internists. For these physicians, the results indicate that about half of an initial drop in their Medicare receipts caused by a change in payment policy would be offset by an increase in their volume of services. For physicians whose receipts would increase because of the policy change, the best estimates indicate that about a third of their initial gain would be offset by a fall in the volume of services they provide. The difference in response between gaining and losing practices is not a statistically significant one, however. One could conclude from this study that--for both gaining and losing practices--changes in volume would offset about half of any initial change in receipts caused by a payment change.

Colorado↗

PubMed1991

Alpha-1 blockade inhibits compensatory sodium reabsorption in the proximal tubules during furosemide-induced volume contraction.

The renal effects of alpha-1 adrenoceptor blockade (i.v. infusion of doxazosin, 50 micrograms/kg prime; 30 micrograms/kg/h) on tubular sodium reabsorption during acute furosemide-induced volume contraction (i.v. infusion of furosemide, 7.5 mg/kg/h for 3 h) was investigated by clearance technique in conscious rats. By measuring inulin clearance, lithium clearance and urinary excretion rates of sodium and water, the changes in proximal and distal tubular sodium handling were dissociated. In furosemide-infused rats given doxazosin (n = 11) or volume replacement (n = 9), the fractional lithium excretion increased from 30% (control) to a steady-state value of 51% (last hour of furosemide infusion), whereas in rats infused with furosemide only (n = 9), the fractional lithium excretion increased transiently to a peak value of 52% and then declined to a steady-state value of 39%. Doxazosin attenuated the acute natriuretic response to furosemide by 54%, mainly due to increased sodium reabsorption in the distal nephron segment. This effect was associated with a significant lower mean arterial pressure compared with rats given furosemide only. The results are compatible with a contributory role of proximal tubular alpha-1 adrenoceptors in mediating compensatory Na reabsorption during furosemide-induced volume contraction.

Adrenergic alpha-Antagonists↗

PubMed1991

[Arthroscopic synovial resection of the talocrural joint].

Arthroscopic resection of the synovial membrane was employed in the treatment of chronic pain antero-laterally in the talo-crural joint in eight patients. The ages of the patients varied from 12 to 45 years (median age 24 years). Ten patients had previously sustained traumatic sprains. The duration of the symptoms was, on an average, two years (1-15 years). Radiographic examination of the talo-crural joint revealed normal findings in all of the patients. Arthroscopically, in all of the patients, impingement of hypertrophic synovial tissue at the upper lateral corner of the talus was found. Trans-arthroscopic resection was performed with a shaver. A total of six patients became symptom-free and two experienced considerable relief of symptoms. The present authors have found the method to be suitable in selected cases of chronic pain in the talo-crural joint.

Adolescent↗

PubMed1991

Renal response to furosemide in conscious rats: effects of acute instrumentation and peripheral sympathectomy.

In order to investigate whether the renal sympathetic nerves contribute to the compensatory Na reabsorption observed during furosemide-induced volume contraction, furosemide was administered as constant i.v. infusion (7.5 mg/kg/h) in trained, chronically instrumented rats with or without guanethidine-induced peripheral sympathectomy. In addition, the effect of acute instrumentation was evaluated by measuring renal function before and after furosemide infusion in control rats recovering from surgery and halothane anesthesia. Lithium clearance was used as a marker for proximal tubular Na reabsorption, and [3H]inulin and [14C]tetraethylammonium were used as markers for the glomerular filtration rate and the effective renal plasma flow, respectively. Control values in chronically instrumented sympathectomized rats did not differ from values obtained in chronically instrumented control rats. In acutely instrumented control rats the control value for effective renal plasma flow was 20% lower than in both chronically instrumented groups; this was associated with increased arterial blood pressure and increased renal vascular resistance. There were no differences in the diuretic or the natriuretic furosemide response between chronically instrumented control and chronically instrumented sympathectomized rats, whereas the diuretic and natriuretic responses were reduced in acutely instrumented control rats. This was due to an accentuation of the initial fall in glomerular filtration rate during furosemide infusion. In control animals, either acutely or chronically instrumented, fractional Li excretion increased from 30% to 50% during furosemide peak response, after which it returned toward control values. In sympathectomized rats, the fractional Li excretion increased from 36% to 70% during furosemide peak response, after which it decreased to a steady-state value of 56%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Atubular glomeruli, renal function and hypertrophic response in rats with chronic lithium nephropathy.

Experimental lithium nephropathy was induced by administering lithium orally to newborn rats for 8 weeks; thereafter the rats were randomized into four groups which were studied after 8 weeks of further treatment. One group was left untreated, one group was given a high (40%) protein diet, one group was unilaterally nephrectomized and one group was unilaterally nephrectomized and received high protein diet after nephrectomy. Comparable control groups (not lithium-treated) were also studied. Stereological methods were used to estimate the total volume of different parts of the nephron, interstitial fibrosis, and the distribution of the volume of individual glomeruli. The structural integrity between the glomerulus and the proximal tubule was investigated on serial sections. No sclerotic glomeruli were present. The most extensive degree of hypertrophy with almost a doubling of the total volume of proximal and distal tubule cells was seen in the groups that were both nephrectomized and fed a high protein diet. In both controls and lithium-treated animals, high protein and nephrectomy induced enlargement of the glomerular tufts to volumes from 4 to 5 times the normal size. A pronounced heterogeneity of the glomerular population was found in the lithium-treated groups with 36-54% atubular glomeruli with small volumes, and 34-48% enlarged glomeruli connected to qualitatively normal proximal tubules. Only glomeruli connected to proximal tubules had a potential for hypertrophy. In multiple regression analysis the percentage of glomeruli connected to normal proximal tubules was correlated with the reciprocal of plasma creatinine, but the volume of fibrosis also contributed to the decreased renal function.

Animals↗

PubMed1991

Comparative study of clarithromycin and penicillin V in the treatment of streptococcal pharyngitis.

This study evaluated the safety and efficacy of clarithromycin in the treatment of patients with Group A beta-hemolytic streptococcal pharyngitis. Subjects were treated with either 250 mg clarithromycin twice daily or 250 mg penicillin V four times a day for 10 days and followed for approximately three weeks post-treatment. At the completion of therapy, 96% (45/47) of patients treated with clarithromycin and 89% (43/48) of patients treated with penicillin V were clinically cured or improved. Recurrence of symptoms occurred in 7 and 5 patients who were treated with clarithromycin and penicillin V respectively. Initial bacteriologic eradication was observed in all but one patient. Recurrence of Streptococcus pyogenes occurred in 5 (11%) patients who received clarithromycin and 7 (15%) patients who received penicillin V. The majority of adverse events reported during this study were mild and involved the gastrointestinal tract. Diarrhea was more frequent in patients who received clarithromycin. In this multicenter, randomized, double-blind trial, clarithromycin was as safe and effective as penicillin V in the treatment of Streptococcus pyogenes throat infections.

Adolescent↗

PubMed1991

Furosemide kinetics and dynamics in rats and humans.

1. Increasing doses of furosemide (F) were given intravenously to rats and humans and initial pharmacokinetics and pharmacodynamics were compared. 2. Weight-related initial renal excretion rate of F was twice as high in rats and serum concentration at 30 min was twice as high in humans (P less than 0.01). 3. Volume of distribution for F was 44% larger in rats (P less than 0.01). 4. Maximal weight-related diuretic and natriuretic responses were, like the theoretical maximal efficiency, 5-6 times higher in the rat. The potency was 230 times lower in the rats. 5. On a molecular basis species differences in kinetics disappeared when standardization was based on ERPF and species differences in dynamics disappeared when standardization was based on GFR.

Animals↗

PubMed1991

Amiloride-sensitive lithium reabsorption during doxazosin-induced blood pressure reduction in rats.

1. The effects of acute systemic alpha 1-adrenoceptor blockade by doxazosin on glomerular filtration rate, urine flow, sodium clearance and lithium clearance were investigated in acutely prepared conscious rats. 2. Clearance experiments were performed during water diuresis (20 mmol/l NaCl and 110 mmol/l glucose, 3 ml/h). After a control period, animals were randomized to one of the following treatments: time-control (n = 9), doxazosin (50 micrograms primer, 30 micrograms h-1 kg-1) (n = 10), amiloride (1 mg primer; 2.4 mg h-1 kg-1) (n = 10) and doxazosin plus amiloride (n = 9). 3. Doxazosin reduced the mean arterial blood pressure from 125 to 108 mmHg; this was associated with transient reductions in glomerular filtration rate, urine flow and lithium clearance. After the transient antidiuresis, the sodium excretion rate remained reduced in doxazosin-infused animals. Amiloride increased the sodium excretion rate without having effects on other variables. When doxazosin was given together with amiloride, the reduction in lithium clearance observed during the transient reduction in glomerular filtration rate and urine flow, was partly abolished. Thus the fractional lithium excretion was transiently increased in rats given doxazosin plus amiloride (from 29 to 40%), whereas in rats given doxazosin alone a non-significant reduction was observed (from 28 to 25%). The dissociation between lithium clearance and fractional lithium excretion in the two doxazosin-infused groups was only significant during the transient reduction in glomerular filtration rate and urine flow. 4. The results provide evidence for an amiloride-sensitive lithium reabsorption during acute systemic alpha 1-adrenoceptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗