Predicting relapse in Crohn's disease: a biopsychosocial model.

BACKGROUND: Crohn's disease (CD) is a chronic relapsing inflammatory bowel disorder. Both biological and psychosocial factors may modulate the illness experience. AIM: The aim of this study was to identify clinical, biological and psychosocial parameters as predictors of clinical relapse in quiescent CD. METHODS: Patients in medically induced remission were followed prospectively for 1 year, or less if they relapsed. Disease characteristics were determined at baseline. Serum cytokines, anti-Saccharomyces cerevisiae antibodies, C-reactive protein (CRP), erythrocyte sedimentation rate and intestinal permeability were measured every 3 months. Psychological distress, perceived stress, minor life stressors and coping strategies were measured monthly. A time-dependent multivariate Cox regression model determined predictors of time to relapse. RESULTS: 101 patients (60 females, 41 males) were recruited. Fourteen withdrew and 37 relapsed. CRP (HR = 1.5 per 10 mg/l, 95% CI 1.1 to 1.9, p = 0.007), fistulising disease (HR = 3.2, 95% CI, 1.1 to 9.4, p = 0.04), colitis (HR = 3.5 95% CI 1.2 to 9.9, p = 0.02) and the interaction between perceived stress and avoidance coping (HR = 7.0 per 5 unit increase for both scales, 95% CI 2.3 to 21.8, p = 0.003) were predictors of earlier relapse. CONCLUSIONS: In quiescent CD, a higher CRP, fistulising disease behaviour and disease confined to the colon were independent predictors of relapse. Moreover, patients under conditions of low stress and who scored low on avoidance coping (ie, did not engage in social diversion or distraction) were least likely to relapse. This study supports a biopsychosocial model of CD exacerbation.

Imaging of tophaceous gout: computed tomography provides specific images compared with magnetic resonance imaging and ultrasonography.

OBJECTIVE: To determine the usefulness of computed tomography (CT), magnetic resonance imaging (MRI), and Doppler ultrasonography (US) in providing specific images of gouty tophi. METHODS: Four male patients with chronic gout with tophi affecting the knee joints (three cases) or the olecranon processes of the elbows (one case) were assessed. Crystallographic analyses of the synovial fluid or tissue aspirates of the areas of interest were made with polarising light microscopy, alizarin red staining, and x ray diffraction. CT was performed with a GE scanner, MR imaging was obtained with a 1.5 T Magneton (Siemens), and ultrasonography with colour Doppler was carried out by standard technique. RESULTS: Crystallographic analyses showed monosodium urate (MSU) crystals in the specimens of the four patients; hydroxyapatite and calcium pyrophosphate dihydrate (CPPD) crystals were not found. A diffuse soft tissue thickening was seen on plain radiographs but no calcifications or ossifications of the tophi. CT disclosed lesions containing round and oval opacities, with a mean density of about 160 Hounsfield units (HU). With MRI, lesions were of low to intermediate signal intensity on T(1) and T(2) weighting. After contrast injection in two cases, enhancement of the tophus was seen in one. Colour Doppler US showed the tophi to be hypoechogenic with peripheral increase of the blood flow in three cases. CONCLUSION: The MR and colour Doppler US images showed the tophi as masses surrounded by a hypervascular area, which cannot be considered as specific for gout. But on CT images, masses of about 160 HU density were clearly seen, which correspond to MSU crystal deposits.

Efficacy of an insulin-like growth factor-interleukin-3 fusion protein in reversing the hematopoietic toxicity associated with azidothymidine in mice.

The effect of 406, a novel fusion protein between the N-terminal sequence of the insect insulin-like peptide, bombyxin, human insulin-like growth factor II and mouse interleukin 3 was investigated in its capacity to abrogate the toxic effects of azidothymidine (AZT) in C57BL/6 mice. Mice receiving 2.5 mg/ml AZT in their drinking water were concurrently treated with daily s.c. injections of 14, 140 or 1400 ng 406 for 4 wk. AZT-treated mice had a lower total weight, hemoglobin content and white blood cells than non treated controls. 406 significantly increased the number of circulating white blood cells at all doses, and the optimal effects were observed at a dose of 140 ng/mouse. Using this optimal dose, 406 completely abrogated the AZT-mediated weight loss. The effects on erythroid cells depended on the severity of the AZT-induced anemia. The amounts of hemoglobin were equal or slightly lower than those of controls under conditions of mild anemia, but were significantly higher than controls under conditions of severe anemia. 406 significantly increased the number of all hematopoietic colony-forming cells in bone marrow and spleen, but the effects were particularly striking in granulocyte-macrophage precursors. Blood glucose levels did not change at optimal or suboptimal 406 doses but increased at a dose of 1.4 microg/mouse. These experiments demonstrate the usefulness of these IGF-cytokine fusion proteins, whose low cost production represents a significant advantage for future in vivo studies.

Treating hypertension. Are the right drugs given to the right patients?

OBJECTIVE: To evaluate whether physicians are prescribing antihypertensive drugs appropriately and according to the recommendations of the Canadian Hypertension Society. DESIGN: Retrospective cohort study. SETTING: Family medicine teaching clinic in Montreal. PARTICIPANTS: A cohort of 183 patients followed between 1993 and 1995. Of 350 patients registered at the clinic, 167 were excluded because diagnosis of hypertension was not supported by chart review, their charts contained insufficient information, they were pregnant or younger than 18 years, or they had secondary hypertension and complex medical conditions. MAIN OUTCOME MEASURES: The dependent variable was the antihypertensive medication. Independent variables were age and sex of patients, duration of hypertension, total number of visits and number of visits for hypertension, number of physicians consulted at the clinic, associated medical conditions, diagnosis of target organ damage, blood pressure readings, and associated medications. RESULTS: Diuretics were prescribed most frequently (45.9%). Angiotensin-converting enzyme (ACE) inhibitors ranked second (28.4%), followed by calcium channel blockers (26.2%) and beta-blockers (18.0%). Age, sex, duration of hypertension, and blood pressure readings were not associated with medications. Prescription of beta-blockers was strongly associated with previous myocardial infarction, but not with diagnosis of angina pectoris. Patients with contraindications to beta-blockers were less likely to receive them and more likely to receive calcium channel blockers. Only 32% of diabetic patients received ACE inhibitors. CONCLUSION: Results suggest that some prescriptions for antihypertensive medications are inappropriate, but that physicians are following some of the Canadian Hypertension Society's recommendations. A better understanding of physicians' prescribing behaviours could help target continuing education interventions to improve prescribing for hypertension.

Evaluation of consultative skills in respiratory medicine using a structured medical consultation.

An essential component of competency in respiratory medicine is the acquisition of consultative skills. The American Board of Internal Medicine (ABIM) and other certification bodies have recommended a greater emphasis on the evaluation of clinical skills by direct observation. In this study, consultative abilities are assessed using the format of an objective structured clinical examination (OSCE). A six-case, 160-min-long, examination was administered to three groups of physicians: faculty members, respiratory residents, and junior residents in internal medicine. The overall quality of the consultations was significantly better for the attending physicians when compared with the junior residents, and there was a systematic trend for the quality to improve with increased training. The educational value of the consultation improved significantly with the level of training. There was a tendency for physicians with greater experience to report less of the findings from the history and physical on their consultations. Patient satisfaction, as measured by the standardized patients using an ABIM patient satisfaction questionnaire, did not differ between groups of examinees. The test reliability for the overall quality of consultation score was 0.65. The reliability of a 14-station exam was estimated to be 0.81. This exam proved to be a useful, valid, and moderately reliable tool for assessing the consultative skills of physicians and could prove to be of benefit to clinical training programs.

The release from metaphase arrest in blue mussel oocytes.

In Mytilus edulis, shed oocytes are arrested at metaphase I of meiosis until fertilization. We previously suggested (Dubé and Dufresne, J. Exp. Zool. 256:323-332, 1990) that such a metaphase arrest depends upon a continuous synthesis of short-lived proteins, the destruction of which is sufficient to induce meiosis resumption. We further investigated the mechanism of metaphase release in blue mussel oocytes as triggered either by fertilization or by inhibition of protein synthesis (emetine) or phosphorylation (6-dimethylaminopurine, 6-DMAP). Treatment of unfertilized oocytes (UF) with emetine induces completion of the first meiotic cycle including extrusion of the polar body, followed by chromosome decondensation and by the formation of large membrane-bound nuclei, as visualized by Hoechst staining and transmission electron microscopy (TEM). Inhibition of protein phosphorylation with 6-DMAP induces directly chromosome decondensation and the formation of multiple nuclei surrounded by nuclear membrane. These interphasic nuclei exhibit continuous 3H-thymidine incorporation. p13 precipitation of p34 and associated proteins reveals "putative" cyclins in UF, no longer detected after metaphase/anaphase transition due to fertilization or emetine treatment. In the presence of 6-DMAP, new migrating forms are observed. The phosphorylated p34cdc2 homolog becomes dephosphorylated after fertilization or emetine treatment, whereas 6-DMAP induces its phosphorylation on tyrosine. Histone H1 kinase activity is reduced after these treatments, compared to the UF sample. Our results suggest that the metaphase/anaphase transition triggered by fertilization in blue mussel oocytes is induced by the rapid destruction of a set of continuously synthesized proteins accompanied by decreased histone H1 kinase activity. These events can be mimicked by inhibiting protein synthesis. Inhibition of protein phosphorylation would drive the cell to interphase without commitment to meiosis I.

Effects of 6-dimethylaminopurine on the length of the cell cycle and on the state of phosphorylation of putative intermediate filament proteins in sea urchin embryos.

The effects of 6-dimethylaminopurine (6-DMAP) on the length of the cell cycle and on the state of phosphorylation of a putative intermediate filament protein, p117, have been studied in sea urchin embryos. Embryos were transferred into sea water containing 600 microM 6-DMAP at 0.5, 2 or 5 min after insemination, and incubated for 30 or 90 min. The effects of 6-DMAP on cell cycle length were studied by determining the time required for completion of mitosis upon return of the embryos in normal sea water. In all instances, except for the embryos transferred 0.5 min after insemination (AI) and incubated for 30 min, the duration of the M phase was shortened compared to controls, being faster in the embryos incubated for 90 minutes compared to the 30 min incubation period. However, embryos transferred 0.5 min AI have a longer M-phase than those transferred 2 minutes or later after fertilization, suggesting that between 0.5 and 2 min after fertilization, critical phosphorylating events occur which affect the commitment of the cells to enter M-phase. To study the pattern of p117 phosphorylation during the cell cycle, the eggs were transferred 2 minutes after fertilization in presence of 600 microM 6-DMAP and with 200 microCi/ml of 32P-orthophosphate. Analyses of 32P-labelled proteins after exposure of SDS-PAGE gels and their corresponding blots suggested that phosphorylation of p117 greatly increases at the time of pronuclear fusion, and then declines slightly at prophase-metaphase. This decrease is markedly enhanced when the cells are treated with 6-DMAP during metaphase in order to induce a premature breakdown of the mitotic apparatus. A causal link is suggested between the level of phosphorylation of p117 and its state of assembly.

Severe skin necrosis associated with heparin in hemodialysis.

Skin necrosis is a well-recognized although rare complication of continuous heparin therapy. We report the case of a 66-year-old diabetic woman with end-stage renal failure who received intermittent intravenous heparin during hemodialysis. She developed severe necrotic cutaneous ulcers over both legs, with typical histological findings. Thrombocytopenia never occurred but platelet studies demonstrated enhanced aggregation when heparin was added in vitro. Platelet-aggregating immunoglobulins produced in response to heparin can lead to thrombotic events. Thrombocytopenia usually develops prior to the onset of cutaneous lesions, but as in this case, may be absent. Heparin should be discontinued when the condition is recognized. Unfortunately, a poor outcome is frequently observed.

Gametogenesis and Spawning of the Sea Cucumber Psolus fabricii (Duben and Koren).

The reproductive cycle of the sea cucumber Psolus fabricii was studied in a population from the St. Lawrence Estuary in eastern Canada from May 1988 through August 1989. The gonad consists of numerous germinal tubules which vary greatly in size. The mean diameter of the tubules and gonadal mass follow annual cycles, increasing from early winter through spring, and dropping abruptly during spawning in the summer. Gametogenesis is generally a prolonged process and begins in small tubules in January. By summer the ovarian tubules contain oocytes with a modal diameter of 400-600 {mu}m, and the testicular tubules contain an abundance of early spermatogenic stages, but rarely spermatozoa. These small tubules of the gonad do not spawn until the following year, and there is little gametogenic activity within them until January, when oocyte growth and the production of later spermatogenic stages resumes. The latter production continues until summer and results in a marked increase in the diameter of the tubules. Then, during spawning, these now large fecund tubules are transformed into small tubules. Following spawning, the predominant activity within the spent tubules is phagocytosis of the residual gametes. The active phase of gametogenesis (January to summer) coincides with an increasing photoperiod regime, and an accelerated gametogenesis occurs in March when temperature and food availability begin to increase. Spawning was one month later in 1989 than in 1988 and did not show a consistent relationship with either temperature or light conditions. However, in both years, spawning coincided with a decrease in the freshwater run-off into the Estuary and with the predicted annual increase in phytoplankton.

Acetazolamide in hemodialysis patients: a rational use after ocular surgery.

Acetazolamide is a weak diuretic used to decrease production of aqueous humor in the eye. Hemodialysis patients undergoing ocular surgery may benefit from acetazolamide; however, no pharmacokinetic data are available for this group of patients. We report a patient who received acetazolamide 250 mg every 6 hours after ophthalmic surgery and developed reversible neurological side effects associated with very high plasma concentrations. Using pharmacokinetic analysis, we suggest an alternate administration of acetazolamide for end-stage renal patients.

An objective structured clinical examination for the licentiate: report of the pilot project of the Medical Council of Canada.

The Medical Council of Canada (MCC) administers a qualifying examination for the issuance of a license to practice medicine. To date, this examination does not test the clinical skills of history taking, physical examination, and communication. The MCC is implementing an objective structured clinical examination (OSCE) to test these skills in October 1992. A pilot examination was developed to test the feasibility, reliability, and validity of running a multisite, two-form, four-hour, 20-station OSCE for national licensure. In February 1991, 240 volunteer first- and second-year residents were tested at four sites. The candidates were randomly assigned to one of two forms of the test and one of two sites for two of the four sites. Generalizability analysis revealed that the variance due to form was 0.0 and that due to site was .16 compared with a total variance of 280.86. The reliabilities (inter-station) were .56 and .60 for the two forms. Station total-test score correlations, used to measure station validity, were significant for 38 of the 40 stations used (range .14-.60). The results of the OSCE correlated moderately with the MCC qualifying examination; these correlations were .32 and .35 for the two test forms. Content validity was assessed by postexamination questionnaires given to the physician examiners using a scale of 0 (low) to 10 (high). The physicians' mean ratings were: importance of the stations, 8.1 (SD, 1.8); success of the examination in testing core skills, 8.1 (SD, 1.6); and degree of challenge, 7.8 (SD, 2.1). The results indicate that a full-scale national administration of an OSCE for licensure is feasible using the model developed. Aspects of validity have been established and strategies to augment reliability have been developed.

How to clean and maintain urinary leg bags: 'easy on the nose'.

People with a dysfunctional bladder may have to wear a urinary collection bag. The authors found that the current practice of rinsing leg bags with water and cleaning them in the Cidamatic washer did not fully clean the bags. A trial of cleaning with Urolux showed that the bags were cleaner, smelled better and lasted longer, as well as that the procedure was easy and cost effective.

Effects of 6-dimethylaminopurine on microtubules and putative intermediate filaments in sea urchin embryos.

The effects of 6-dimethylaminopurine (6-DMAP) (a putative phosphorylation inhibitor) on the state of assembly of microtubules and intermediate filaments have been studied during the first cell cycle of the sea urchin Strongylocentrotus droebachiensis. Changes in the spatial organization of cytoskeletal structures were studied by indirect immunofluorescence with anti-tubulin and anti-IFa antibodies. The rates and patterns of protein phosphorylation in control and treated eggs were also investigated. The transfer of fertilized eggs to 600 microM 6-DMAP within 4 min following insemination inhibits pronuclear migration and syngamy. This also prevents male pronuclear decondensation, while chromatin condensation and nuclear envelope breakdown do not occur in the female pronucleus. Immunolabeling with anti-tubulin antibodies reveals the presence of cortical microtubules as early as 15 min after fertilization in both control and treated eggs. However, no sperm astral microtubules could be detected in the treated eggs. At later stages, from syngamy (40 min) up to nuclear envelope breakdown (90 min), 6-DMAP affects neither cortical microtubule organization nor the state of chromatin condensation but it precludes nuclear envelope breakdown and entry into mitosis. Treatment of the fertilized eggs after nuclear envelope breakdown induces permanent chromosome decondensation and premature disappearance of the mitotic apparatus. This last event involves disruption of the spatial organization of both microtubules and putative intermediate filaments. Quantitative measurements of protein phosphorylation show that 6-DMAP efficiently and reversibly inhibits 32P incorporation into proteins. Qualitative analysis of the autoradiograms of 32P-labeled proteins separated by SDS-PAGE reveals that a major protein band, migrating with an apparent molecular weight of 31 x 10(3)Mr, is specifically dephosphorylated in eggs treated with 6-DMAP. This study suggests that protein phosphorylation is required for sperm aster microtubule growth and migration, but not for cortical microtubule polymerization. It also strengthens the hypothesis that, in sea urchin eggs, putative intermediate filaments are tightly associated with spindle microtubules. Finally, it confirms that inhibiting protein phosphorylation before nuclear envelope breakdown reversibly prevents the entry into mitosis.

Protein phosphorylation during activation of surf clam oocytes.

We have investigated the increase of phosphorylated proteins upon activation of surf clam (Spisula solidissima) oocytes, by measuring the cumulative incorporation of 32P in proteins and by performing an SDS-PAGE and autoradiographic analysis of 32P-labeled proteins, from oocytes initially radiolabeled with 32P-orthophosphate. The phosphorylation inhibitor 6-dimethylaminopurine (6-DMAP) inhibits both germinal vesicle breakdown (GVBD) and the normal increase in phosphorylated proteins observed upon activation by KCl, in a reversible and dose-dependent manner. Using different artificial seawaters (normal, Ca(2+)-free, Na(+)-free), we observed that the increase of phosphorylated proteins, upon K+ stimulation, occurs only when GVBD is allowed to proceed along with an increased Ca2+ influx, in normal or Na(+)-free seawater. Stimulation of oocytes by ammonia, which directly raises intracellular pH (pHi) but does not trigger GVBD, is without effect on the level or pattern of phosphorylated proteins. The link between the Ca2+ influx and the level of phosphorylated proteins was further investigated using conditions altering the duration or the level of Ca2+ influx upon K+ stimulation. In all conditions tested, both GVBD and the level of phosphorylated proteins were similarly affected by alterations of the Ca2+ influx, indicating that these processes are tightly coupled one with another. Upon activation of oocytes, six major proteins of estimated molecular weights of 31, 41, 48, 56, 80 and 86 kDa undergo an increased phosphorylation that is reversibly sensitive to 6-DMAP. Our results suggest that increased protein phosphorylation, sensitive to 6-DMAP, is necessary for GVBD and that it is indirectly linked to the increased Ca2+ influx that stands as an upstream trigger for activation, while an elevated pHi alone has no effect on these processes.

Irreversible renal failure associated with triamterene.

A 66-year-old man was admitted with acute oliguric renal failure. The patient was known to have chronic heart failure (ejection fraction 13%) and his medication included furosemide, digoxin and triamterene. Physical examination was unremarkable, and blood pressure was 170/80 mm Hg. Serum creatinine was 1,173 mumol/l. Renal ultrasound, CT scan and angiogram were normal. Despite correction of potential reversible factors and discontinuation of triamterene, renal function did not improve. Renal biopsy showed tubular obstruction with deposition of birefringent crystals and interstitial lymphocytic infiltration; the crystals emitted a blue autofluorescence at 425 nm, typical of triamterene. Renal tissue contained large amounts of triamterene (6.44 mg/g kidney at the initial biopsy and 400 micrograms/g kidney 5 months later). Triamterene has been previously reported to cause acute reversible renal failure, but to our knowledge, this is the first case of irreversible renal failure due to intratubular obstruction by triamterene crystal deposition.

Kinetics of actin assembly attending fertilization or artificial activation of sea urchin eggs.

Changes in the state of actin assembly triggered by fertilization or by artificial activation of sea urchin eggs were quantified using the DNase I inhibition assay. Insemination of Lytechinus pictus or Strongylocentrotus purpuratus eggs induces a cyclic variation in the level of G-actin as follows: between 0 and 30 s after insemination, the G-actin content decreases. This is followed by an increase in the amount of monomeric actin between 30 and 60 s, and then from 60 s to 5 min postinsemination there is a progressive decrease in the egg's level of G-actin. This latter decrease is more pronounced in S. purpuratus eggs than in L. pictus eggs. Using sperm mimetics that trigger an increase in intracellular calcium concentration (A23187 in sodium-free seawater), a cytoplasmic alkalinization (NH4Cl), a plasma membrane depolarization (seawater enriched with potassium ions), or all three of these phenomena (A23187 in normal seawater), each phase depicted at fertilization correlates with the following metabolic events accompanying egg awakening: phase 1, of uncertain origin (possibly related to plasma membrane depolarization); phase 2, elevation of intracellular calcium concentration; phase 3, alkalinization of the intracellular milieu but only if the transient intracellular calcium rise has taken place.

Protein kinase C and meiotic maturation of surf clam oocytes.

We report here that phorbol ester, a potent activator of protein kinase C, induces germinal vesicle breakdown in surf clam oocytes. However, phorbol ester-induced activation is slow and is not accompanied by an increased Ca2+ influx. Simultaneous additions of phorbol ester and various amounts of K+ ions, which induce Ca2+ influx of different amplitudes, result in successful activation within the normal time schedule at K+ concentrations inefficient alone in activating the oocytes. In vivo, increased protein phosphorylation triggered by phorbol ester amounts to about one third that seen after fertilization. These results suggest that increased Ca2+ influx and protein kinase C activation act in synergy to cause resumption of meiotic maturation in these oocytes.

Interrelationships between circulating vitamin D metabolites in normocalciuric and hypercalciuric renal stone formers.

Serum 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D [24,25(OH)2D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] were studied in renal stone formers while on a diet containing 1,000 or 300 mg calcium per day. The patients were divided into four groups and identified as (a) normocalciuric (NSF), (b) absorptive hypercalciuric (AH), (c) renal hypercalciuric (RH) and (d) as having primary hyperparathyroidism (PHP). The results indicate that, on the 1,000-mg Ca diet, the mean 25(OH)D, 24,25(OH)2D and 1,25(OH)2D concentrations were within the normal range in all groups of patients. On the low-calcium diet, 25(OH)D concentrations decreased significantly in patients with AH and RH while 24,25(OH)2D concentrations were not affected by the low-calcium diet. 1,25(OH)2D concentrations increased significantly during dietary calcium restriction in all groups of patients. When the relationship obtained on each diet between the circulating 25(OH)D concentrations and the 25(OH)D/1,25(OH)2D concentration ratio was compared, it suggested that the increase in the 1,25(OH)2D concentrations during dietary calcium restriction may have been due to an increase in the capacity of the 25(OH)D-1 alpha-hydroxylase, or to an increase in the circulating half-life of the hormone. These results indicate that renal stone formers are able to adapt themselves to dietary calcium restriction as shown by highly significant increases in the circulating 1,25(OH)2D concentrations while on a low-calcium diet. Moreover, the increase in the circulating 1,25(OH)2D concentrations did not happen at the expense of the 24,25(OH)2D production in any of the groups of patients studied.

Influence of dietary calcium on serum 1,25-dihydroxyvitamin D concentrations in renal stone formers.

The role of 1,25-dihydroxyvitamin D (1,25(OH)2D) in the pathogenesis of idiopathic hypercalciuria was studied in 37 renal stone formers who, during two 10-day periods, followed first a normal and then a low calcium diet. The following samples were taken during each diet; 24 h urine; fasting blood and urine; blood and urine following a 1 g oral calcium load. Patients were divided according to serum calcium level, 24 h urinary calcium excretion on the first diet and fasting calcium excretion on the second diet. Eight patients were found to be normocalciuric (NSF), 16 had absorptive hypercalciuria (AH), five renal hypercalciuria (RH) and eight primary hyperparathyroidism. In NSF and AH, a positive correlation was found between the fasting and the 24 hour urinary calcium (r = 0.787, P less than 0.001), while negative correlations were found between the fasting urinary calcium and the serum parathyroid hormone (r = -0.703, P less than 0.001) or the fasting urinary cyclic AMP (r = -0.434, P less than 0.01). Patients with RH had higher serum PTH and urinary cAMP levels for a given degree of fasting calciuria mainly on the low calcium diet. Mean serum 1,25(OH)2D was similar in NSF (43.6 +/- 4.5 pg/ml), AH (43.6 +/- 2.3 pg/ml) and RH (40.4 +/- 4.8 pg/ml) on the first diet; increases were similar in all groups after 10 d of calcium restriction. A positive correlation was found between the serum 1,25(OH)2D concentrations and the 24 h urinary calcium excretion on the first diet in NSF (r = 0.889, P less than 0.001) but not in AH or RH. There was no evidence of such correlation with the low calcium diet. No correlation between the calciuric response to calcium loading and the serum concentrations of 1,25(OH)2D was found. The results suggest that serum concentrations of 1,25(OH)2D may be related to urinary calcium excretion in NSF more than in AH or RH. The factors responsible for the hyperabsorption of calcium in the latter patients remain to be elucidated.