Application and feasibility of systemic lupus erythematosus reproductive health care quality indicators at a public urban rheumatology clinic.

OBJECTIVES: Quality indicators (QIs) are evidence-based processes of care designed to represent the current standard of care. Reproductive health QIs for the care of patients with systemic lupus erythematosus (SLE) have recently been developed, and examine areas such as pregnancy screening for autoantibodies, treatment of pregnancy-associated antiphospholipid syndrome, and contraceptive counseling. This study was designed to investigate our performance on these QIs and to explore potential gaps in care and demographic predictors of adherence to the QIs in a safety-net hospital. METHODS: We performed a record review of patients with a diagnosis of SLE at Denver Health Medical Center (DH) through an electronic query of existing medical records and via chart review. Data were limited to female patients between the ages of 18 and 50 who were seen between July 2006 and August 2011. RESULTS: A total of 137 female patients between the ages of 18 and 50 were identified by ICD-9 code and confirmed by chart review to have SLE. Of these, 122 patients met the updated 1997 American College of Rheumatology SLE criteria and had intact reproductive systems. Only 15 pregnancies were documented during this five-year period, and adherence to autoantibody screening was 100 percent. We did not have any patients who were pregnant and met criteria for pregnancy-associated antiphospholipid syndrome. Sixty-five patients (53%) received potentially teratogenic medications, and 30 (46%) had documented discussions about these medications' potential risk upon their initiation. Predictors of whether patients received appropriate counseling included younger age (OR 0.92, CI 0.87-0.98) and those who did not describe English as their primary language (OR 0.24, CI 0.07-0.87) in the multivariate analysis. CONCLUSIONS: We were able to detect an important gap in care regarding teratogenic medication education to SLE patients of childbearing potential in our public health academic clinic, as only one in two eligible patients had documented appropriate counseling at the initiation of a teratogenic medication.

Effects of reduced renal perfusion pressure and acute volume expansion on proximal tubule and whole kidney angiotensin II content in the rat.

In previous studies high luminal concentrations of angiotensin II (Ang II) were found in rat proximal tubules. The physiological role of intraluminal Ang II remains to be established. In the present study, we investigated whether the luminal angiotensin II concentration in the proximal tubules ([Ang II]prox) can be modulated. Micropuncture studies were performed in control rats (C, N = 8) and rats subjected to acute volume expansion (VE, N = 8) or reduced renal perfusion pressure (RRP, N = 7). Changes in [Ang II]prox were compared to changes in whole kidney Ang II content ([ANG II]kidney) and the plasma concentration ([Ang II] plasma). In C rats, [Ang II]prox was 460 +/- 48 pmol/liter (10 to 20 times lower than hitherto reported), while [Ang II]kidney and [Ang II]plasma were 369 +/- 81 pmol/kg and 90 +/- 29 pmol/liter, respectively. In agreement with previous data, VE failed to suppress [Ang II]prox (674 +/- 132 pmol/liter), while at the same time [Ang II]kidney (42 +/- 10 pmol/kg) and [Ang II]plasma (12 +/- 3 pmol/liter) were markedly suppressed. This points to dissociated regulation of [Ang II] in the renal luminal compartment on the one hand and the extraluminal renal and systemic plasma compartments on the other hand. During RRP, [Ang II]prox increased significantly to 1675 +/- 465 pmol/liter. No dissociation between the three compartments was observed in this situation, as [Ang II]kidney (969 +/- 85 pmol/kg) and [Ang II]plasma (245 +/- 72 pmol/liter) increased in parallel. In summary, we confirm that Ang II is present in proximal tubules of rat kidneys at concentrations which exceed those in plasma. Its concentration could be modulated (approximately 3.5 increase) by reduction of renal perfusion pressure but not by acute volume expansion. In the latter condition, we observed a clear dissociation from Ang II generation in the extraluminal renal compartment, as whole kidney Ang II content was markedly suppressed.

Contrast-enhanced dynamic magnetic resonance imaging of the rat kidney.

This study was designed to assess whether contrast-enhanced dynamic 1H magnetic resonance imaging (DMRI) can be used to detect the effects of the loop diuretic furosemide and the vasoactive peptide angiotensin II on tubular water reabsorption in the rat kidney. A bolus of gadolinium-DTPA-dimeglumine (Gd-DTPA) (0.025 or 0.1 mmol/kg) was used as a contrast agent. The signal intensity in the magnetic resonance images relative to the precontrast signal intensity (RSI) was assessed as a function of time in the cortex and medulla. In the cortex, no differences were observed between high and low bolus injection, and between different treatment groups and controls. In the medulla, RSI patterns were different between high and low bolus, with the high bolus showing lower RSI values, because of T2 shortening at high Gd-DTPA concentrations. No difference was observed between controls and angiotensin II-infused animals. This is in line with the finding that angiotensin II did not alter medullary water reabsorption, as evidenced by unchanged urine flow and osmolality compared with controls. Medullary RSI patterns during furosemide infusion differed markedly from controls, in a manner suggesting that a lower concentration of Gd-DTPA was present compared with controls. This agrees with the well-known inhibiting effect of furosemide on medullary water reabsorption. It was concluded that, with the method used, small concentration differences of Gd-DTPA in the cortex resulting from small changes of plus or minus 20% in tubular water reabsorption, previously found to be present by direct micropuncture measurements, cannot be detected in rats. However, large changes in renal concentrating ability do result in different RSI patterns in the medulla.

Adenosine and renal sodium handling: direct natriuresis and renal nerve-mediated antinatriuresis.

Adenosine infusion is associated with natriuresis as well as antinatriuresis. The physiologic significance of these opposite effects is unknown but may have to do with different conditions of ischemia, in which adenosine accumulates. These effects were characterized in the rat. First, intrarenal and systemic infusions within one animal were performed. Infusing 10 micrograms/min into the left renal artery increased sodium by approximately 50%; however, the subsequent infusion of 50 micrograms/min into the thoracic aorta decreased sodium excretion by approximately 60%, in association with a small reduction of blood pressure. Second, to explore the effect of intrarenal adenosine in tubular sodium handling, free-flow micropuncture experiments were performed. The intrarenal infusion of 10 micrograms/min again caused sodium excretion, but no change in GFR, volume, and sodium deliveries up to the early distal tubule was found. Apparently, the direct effect of adenosine in the kidney is sodium excretion, by a tubular action beyond the early distal tubule. Third, to further characterize the indirect effect, which apparently is sodium retention, adenosine was infused systemically at low rates, in order to avoid a decrease in blood pressure. A 25 micrograms/min infusion again caused sodium retention, in the absence of a fall in blood pressure. After acute left renal denervation, the antinatriuretic effect disappeared in the denervated kidney but remained in the right kidney. These data suggest that increased intrarenal adenosine suppresses sodium reabsorption at some distal nephron site, appropriately decreasing the workload of the kidney. On the other hand, systemic adenosine stimulates sodium reabsorption, an effect that is appropriate to improve systemic circulation and depends on the renal nerves.

Effects of low-dose angiotensin II infusion on loop segment reabsorption: a free-flow micropuncture study in rats.

1. Little direct information is available on the actions of angiotensin II beyond the proximal tubule. We therefore studied the effect of a mildly vasoconstrictive dose of angiotensin II on tubular handling of water, sodium (Na+) and lithium (Li+) in rats by means of free-flow micropuncture at the late proximal tubule and the early distal tubule. 2. Endogenous angiotensin II was suppressed by pretreatment with enalapril. Compared with a control group, angiotensin II increased mean arterial pressure by 15 mmHg. Glomerular filtration rate decreased from 1.32 +/- 0.05 to 1.10 +/- 0.05 ml/min, Na+ excretion from 0.43 +/- 0.09 to 0.13 +/- 0.03 mumol/min, fractional delivery of water at the late proximal tubule from 50.1 +/- 1.7 to 42.9 +/- 3.2%, fractional delivery of Na+ at the late proximal tubule from 46.5 +/- 1.3 to 39.1 +/- 3.5% and fractional delivery of water at the early distal tubule from 26.4 +/- 1.4 to 21.9 +/- 1.0% (P < 0.05 for each variable). Fractional delivery of Na+ at the early distal tubule did not change significantly. 3. Similar experiments were performed during partial aortic constriction to exclude the effects of increased perfusion pressure. The data obtained were similar, except that in this group the fractional delivery of Na+ at the early distal tubule decreased from 8.6 +/- 0.7 to 6.8 +/- 0.9% (P < 0.05). 4. The relation between late proximal tubule Na+ delivery and Na+ reabsorption between late proximal and early distal tubule was not disturbed by angiotensin II. For water, however, this relation tended to shift to a higher reabsorption rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostaglandin synthesis inhibition stimulates lithium reabsorption in Henle's loop in rats.

The effect of prostaglandin (PG) synthesis inhibition on tubular lithium (Li) handling in the rat was studied by micropuncture at the late proximal (LPT) and early distal (EDT) tubules. Animals received no treatment (N = 7), meclofenamate (MECLO; 5 mg/kg i.p. and 5 mg/kg i.v.; N = 7) or indomethacin (INDO, 1 mg/kg i.v.; N = 6). Whole kidney fractional Li excretion fell from 26.2 +/- 1.5% in control rats to 12.8 +/- 1.3% and 14.6 +/- 1.3% in MECLO and INDO treated rats. Fractional delivery of Li to the LPT was not affected by PG synthesis inhibition. All of the rise in tubular Li reabsorption took place between the LPT and EDT; at the EDT fractional Li delivery fell from 32.3 +/- 2.0% in the control group to 19.1 +/- 1.6% and 20.0 +/- 1.4% in the rats given MECLO or INDO. Water reabsorption between the LPT and EDT also increased. The tubular fluid/plasma Li concentration ratio ([T/P]Li) at the LPT was approximately 1.15 in all groups of rats. At the EDT, this ratio was approximately 1.06 in control rats, but only approximately 0.82 (P < 0.01) in rats subjected to PG synthesis inhibition. The finding that the [T/P]Li fell from values exceeding unity at the LPT to values below unity at the EDT during PG synthesis inhibition indicates that reabsorption of Li between these sites was stimulated to a greater extent than that of water. This dissociation strongly suggests that at least part of the increased Li reabsorption between the LPT and EDT took place in the water-impermeable thick ascending limb.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of furosemide or acetazolamide infusion on renal handling of lithium: a micropuncture study in rats.

Renal lithium (Li) handling was studied by micropuncture at the late proximal (LPT) and early distal (EDT) tubules in control rats and rats infused with furosemide (FUR) or acetazolamide (ACTZ). In control rats, the tubular fluid-to-plasma Li concentration ratio [(T/P)Li] at the LPT exceeded unity (1.05 +/- 0.02, P < 0.05). Some 25% of the filtered load (FL) of Li and water was reabsorbed in proportion between the LPT and the EDT, and consequently the (T/P)Li at the EDT (1.03 +/- 0.03) did not change. FUR inhibited Li reabsorption in the proximal convoluted tubules (PCT), by approximately 7% of the FL. Reabsorption of Li and water in the loop segment was also inhibited, virtually in proportion, by approximately 10% of the FL. These data suggest that FUR-sensitive Li reabsorption in the loop mainly takes place in the pars recta. However, a small increase in the (T/P)Li at the EDT (to 1.10 +/- 0.01) suggested inhibition of some Li transport (approximately 2% of the filtered load of Li) without water, most likely in the thick ascending limb (TAL). In the PCT, ACTZ reduced Li reabsorption by approximately 16% of its FL. Although it is likely that ACTZ also inhibited the pars recta, net Li reabsorption in the loop was not reduced. This suggests that TAL Li reabsorption can compensate for increased delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride-sensitive lithium reabsorption in rats: a micropuncture study.

It has been suggested that in sodium-restricted rats lithium is being reabsorbed in the collecting tubule, and that such reabsorption can be prevented by amiloride. We studied these options in rats by means of cortical micropuncture. Indeed, an important fraction of the filtered lithium (10.5%) was reabsorbed beyond the early distal tubule in sodium-restricted rats. Amiloride infusion abolished this reabsorption. The dosage used did not affect the reabsorption of water, sodium and lithium in the proximal tubule, and also did not change the reabsorption of water and sodium in the loop segment. However, the reabsorption of lithium in this segment tended to be higher during amiloride (P = .06), and the delivery of lithium to the early distal puncture site was significantly less (26.1 +/- 1.2%) than in the control rats (31.4 +/- 1.8%, P < .05). The reason for this apparent increase in lithium reabsorption in the loop segment is not clear. Interestingly, amiloride increased urine flow and decreased urine osmolality. The mechanism underlying this effect needs further exploration. We conclude that in sodium-restricted rats lithium reabsorption beyond the early distal tubule level occurs. Lithium clearance data therefore underestimate end-proximal delivery under these conditions. Lithium reabsorption beyond the early distal tubule can be prevented by amiloride treatment. However, because amiloride may stimulate lithium reabsorption further upstream, lithium clearance data obtained during amiloride infusion may still underestimate end-proximal delivery of water and sodium.

Efficient induction of Semliki Forest virus and mumps virus neutralizing anti-anti-idiotypic antibodies using Quil A as adjuvant.

Rabbit anti-idiotypic sera were prepared against Semliki Forest virus (SFV) neutralizing monoclonal antibody (MAb) UM 1.13 and mumps virus neutralizing MAb UM 10B. From these sera anti-idiotypic antibodies were purified by ammonium sulphate precipitation and subsequent affinity column chromatography. Anti-iso- and anti-allotypic antibodies were removed by binding to normal mouse serum immunoglobulins coupled to CNBr activated Sepharose. Peak protein fractions eluted from columns loaded with homologous MAb were used for anti-anti-idiotypic immunization of BALB/c mice to raise virus neutralizing anti-anti-idiotypic antibodies. Two intracutaneous immunizations, five weeks apart, with affinity purified rabbit polyclonal anti-idiotypic antibody (40 micrograms protein per animal) coupled to keyhole limpet hemocyanin and mixed with the adjuvant Quil A (50 microliters per animal) were sufficient to evoke neutralizing antibodies against either virus. Moreover the mice who developed SFV neutralizing serum antibodies upon anti-idiotypic immunization all survived an otherwise lethal challenge with virulent SFV.

Competition binding assay in cell culture for identification of epitopes on enveloped and naked viruses.

Virus infected monolayers, in wells of 96-well plates, could be used as antigen in competition binding assays to identify epitopes on respectively Semliki Forest virus, encephalomyocarditis virus and mumps virus.

Interpretation of the resonance Raman spectrum of bathorhodopsin based on visual pigment analogues.

Resonance Raman spectra of visual pigment analogues have been used to evaluate various models for the structure of the retinal chromophore in bathorhodopsin. Deuteration or removal of the 18-methyl on the beta-ionyl ring or of the 19-methyl on the polyene chain demonstrates that the three intense low wavenumber bands of bathorhodopsin at 853, 875, and 920 cm-1 are not due to exomethylene or ring modes. Rather, assignment of these lines to out-of-plane vinyl hydrogen motions on the chain best accounts for the experimental data. Our calculations show that the intensity of these vibrations can be explained by twists of 10-30 degrees about chain single bonds. The 1100-1400-cm-1 Raman fingerprint indicates that the configuration of the double bonds is trans. This suggests that the structure of the bathorhodopsin chromophore is twisted all-trans.