The long-term association of OCD and depression and its moderators: A four-year follow up study in a large clinical sample.

BACKGROUND: Depression is the most common comorbidity in obsessive-compulsive disorder (OCD). However, the mechanisms of depressive comorbidity in OCD are poorly understood. We assessed the directionality and moderators of the OCD-depression association over time in a large, prospective clinical sample of OCD patients. METHODS: Data were drawn from 382 OCD patients participating at the Netherlands Obsessive-Compulsive Disorder Association (NOCDA) study. Cross-lagged, structural equation modeling analyses were used to assess the temporal association between OCD and depressive symptoms. Assessments were conducted at baseline, two-year and four-year follow up. Cognitive and interpersonal moderators of the prospective association between OCD and depressive symptoms were tested. RESULTS: Cross-lagged analyses demonstrated that OCD predicts depressive symptoms at two-year follow up and not vice a versa. This relationship disappeared at four-year follow up. Secure attachment style moderated the prospective association between OCD and depression. CONCLUSIONS: Depressive comorbidity in OCD might constitute a functional consequence of the incapacitating OCD symptoms. Both OCD and depression symptoms demonstrated strong stability effects between two-year and four-year follow up, which may explain the lack of association between them in that period. Among OCD patients, secure attachment represents a buffer against future depressive symptoms.

Fetal osteocalcin levels are related to placental 11 beta-hydroxysteroid dehydrogenase activity in humans.

OBJECTIVE: Overexposure to glucocorticoids in utero reduces birth weight and, in animals, leads to persistent hypertension in the offspring. The fetus is normally protected from maternal glucocorticoids by placental 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) which catalyses the conversion of cortisol to inert cortisone. In adult humans, osteocalcin is a sensitive marker of glucocorticoid exposure. The aim of this study was to determine whether cord blood osteocalcin levels were related to the ability of placental 11 beta-HSD to inactivate maternal cortisol. DESIGN: Cross-sectional study examining the relation between cord blood levels of osteocalcin and placental glucocorticoid metabolism at term. PATIENTS: Twenty-one women attending for delivery at the Simpson Memorial Maternity Pavilion in Edinburgh had cord venous and arterial blood samples collected at delivery. MEASUREMENTS: Cord plasma levels of osteocalcin, cortisol and cortisone were measured by radioimmunoassay and indices of placental 11 beta-HSD activity were calculated. RESULTS: All indices of placental 11 beta-hydroxysteroid dehydrogenase activity correlated directly and significantly with cord blood osteocalcin levels. For cord blood osteocalcin and the placental 11 beta-HSD Activity Index, Pearson's r was +0.58, r2 = 0.33 and P < 0.02. CONCLUSION: We conclude that term cord blood osteocalcin level reflects the effectiveness of placental glucocorticoid inactivation, and may be a marker for the development of adult hypertension.

Systemic effects of high dose inhaled steroids: comparison of beclomethasone dipropionate and budesonide in healthy subjects.

BACKGROUND: Systemic absorption of inhaled corticosteroids may adversely influence the function of the hypothalamo-pituitary-adrenal axis, bone metabolism, and circulating leucocytes. These changes can be used to assess the safety of different types and modes of administration of these drugs. METHODS: The study was a randomised, double dummy, crossover design with nine healthy adults. It compared the effects of beclomethasone dipropionate and budesonide (given by metered dose aerosols with and without their respective large volume spacers (Volumatic and Nebuhaler) attached) on serum cortisol, 24 hour urinary free cortisol, and plasma osteocalcin concentrations, and circulating neutrophils and lymphocytes. Subjects inhaled the drug (1 mg) and matching placebo at 0900 and 2200 hours on each of six study days. Blood samples were taken hourly for six hours after the morning dose and at the end of the study period. RESULTS: All results were within the reference ranges. Both drugs caused similar reductions in serum cortisol four to six hours after inhalation. These changes were not affected by the use of a large spacer and did not persist at 24 hours. Use of spacers tended to increase the haematological effects of the steroids. Beclomethasone dipropionate inhaled through a Volumatic provoked a rise in circulating neutrophils compared with placebo although lymphocyte numbers were unaffected. Budesonide did not influence neutrophil numbers but did reduce circulating lymphocytes, numbers of which were further reduced when the Nebuhaler was used. There were no significant changes in plasma osteocalcin concentration or 24 hour urinary free cortisol excretion with budesonide, with or without a spacer. Beclomethasone dipropionate inhaled without a spacer reduced urinary cortisol and plasma osteocalcin at 24 hours; however, use of the Volumatic protected against these effects. CONCLUSIONS: Attaching a Volumatic reduces the systemic effects of 2 mg aerosol beclomethasone dipropionate on the hypothalamo-pituitary-adrenal axis and circulating osteocalcin concentrations. This study did not establish whether the Nebuhaler reduces the systemic effects of budesonide. When large spacers are used, 2 mg per day of beclomethasone dipropionate and budesonide seem to be equivalent in terms of unwanted effects.

Inhaled steroids for asthma: topical but not free of systemic effects - abstract

Although inhaled corticosteroids are now established in the treatment of bronchial asthma, there remains controversy regarding their potential for inducing systemic effects. We evaluated the systemic glucocorticoid effects of beclomethasone dipropionate (BDP), currently the most widely prescribed agent, across a therapeutically relevant dose range (400 - 2,000 æg/day). Sixteen (16) healthy adult subjects were studied using a double blind placebo-controlled crossover design. The impact of inhaling 100, 200, 350 and 500 æg BDP q6h was measured. Treatments were assigned in random order and of 10 days' duration separated by wash-out intervals of 18 days. End points of glucocorticiod exposure were the effects upon (1) the hypothalamic-pituitary-adrenal axis (HPA) and (2) bone-formation. Short metyrapone testing revealed significant impairment of HPA responsiveness at doses 800 æg/day and above (p < 0.001). There was evidence of impaired blood biochemistry at doses 400 æg/day and greater (p < 0.05). These data suggest that inhaled steroids are associated with systemic effects even in paediatric dosages. Though not widely available in the Caribbean, this form of therapy is popular and efficacious and is likely to be increasingly used in the foreseeable future. The prescription of inhaled steroids requires as much care and attention as obtains for systemic glycocorticoid therapy (AU)

Multiple forms of alkaline phosphatase in plasma of hemodialysis patients.

We used quantitative assays to measure the activity of the bone, liver, and intestinal forms of alkaline phosphatase in plasma in 75 patients with endstage chronic renal failure undergoing hemodialysis. The results were correlated with radiological and other biochemical indices of bone disease and with biochemical indices of liver disease. The total activity of alkaline phosphatase in plasma increased in 28 patients. In 10 of these patients, nine of whom had increased activity of gamma-glutamyltransferase in plasma, the increase in total activity of alkaline phosphatase was from the liver isoenzyme alone (nine patients) or from the liver and bone isoenzymes together (one patient). Intestinal alkaline phosphatase in plasma, although greater than 23 U/L in eight patients, was solely responsible for the increase in total alkaline phosphatase in one patient (who had normal gamma-glutamyltransferase). Bone alkaline phosphatase in plasma was increased in 25 patients, seven of whom had normal total alkaline phosphatase, and was closely correlated (r = 0.78) with osteocalcin concentration in plasma, which was increased in a much greater proportion of patients (99%). Both total and bone alkaline phosphatase were correlated with parathyrin in plasma (r = 0.46 and 0.50, respectively) and with osteocalcin (r = 0.60 and 0.78, respectively). Osteocalcin and bone alkaline phosphatase, but not parathyrin, decreased with age, implying that the skeletal response to parathyrin may be age dependent. In patients with increased total alkaline phosphatase undergoing hemodialysis, the concurrent measurement of gamma-glutamyltransferase may help identify whether the enzyme increase originates from the liver or bone, but this approach wrongly identified the source of the increase in three of 28 patients. Therefore, we recommend a separate measurement of the bone isoenzyme of alkaline phosphatase.

Alkaline phosphatase isoenzymes in plasma in hyperthyroidism.

Alkaline phosphatase (ALP; EC 3.1.3.1) isoenzymes were measured in the plasma of 63 untreated hyperthyroid patients (the hyperthyroid group), 58 treated hyperthyroid patients, and 100 blood donors. Total, liver, and bone ALP activities were significantly higher in the hyperthyroid group than in the treated hyperthyroid group or the blood donors. Bone ALP was more frequently and more markedly abnormal than liver ALP. Intestinal ALP did not differ significantly between the groups. The hyperthyroid patient group had significantly higher plasma calcium concentrations and lower serum parathyrin concentrations than those of the treated hyperthyroid group.

Plasma alkaline phosphatase isoenzymes in diabetes mellitus.

Alkaline phosphatase (ALP) isoenzymes were measured in type 1 diabetics, type 2 diabetics and in a non-diabetic control group. Within the diabetics and the control group, intestinal ALP activity was significantly higher in BO secretors than A secretors or ABO non-secretors. There was no difference in intestinal ALP activity between type 1 and type 2 diabetics but the diabetics had a significantly higher activity of this isoenzyme than the corresponding blood group/secretor status category of the control group. Liver ALP was significantly higher in the diabetics compared with the control group. Bone ALP showed no significant difference between the diabetics and the control group.

Clinical implications of labile HbA1 as assayed by the electrophoretic method.

The labile fraction of glycosylated haemoglobin (HbA1) was detected using an agar gel electrophoretic method; complete removal of this fraction was obtained by prior incubation of blood for 4 h in isotonic sodium chloride solution at 37 degrees C. Intra-individual variation in pre- and post-incubation HbA1 measurements was considerable, but no greater than would be predicted from methodological imprecision (within-plate CV = 2.8%, between-plate CV = 4.1%). In blood from 13 diabetics with a wide spectrum of glycaemic control, mean labile HbA1 was only 5% of total HbA1 (range -4.4% to + 15.6%); the size of the labile fraction was proportional to total HbA1 and plasma glucose concentrations. Sodium chloride incubation did not affect clinically appropriate classification of results. It is concluded that total HbA1 is adequate for clinical purposes. The colorimetric method was found to be less convenient and less precise.

Variability in pK'1 of human plasma.

(1) Results were presented of an investigation of the relationship between ionic strength and PK'1 (negative logarithmic form of the apparent overall first dissociation constant of carbonic acid in plasma) in separated human plasma at constant PCO2. (2) Ionic strength was varied by adding dry NaCl to diluted aliquots of plasma from six healthy people and dry NaCl plus dry NaHCO3 to diluted aliquots of plasma from six other healthy people. pK'1 was determined from simultaneous measurements of pH and PCO2, and measurements of TCO2. Values for solubility factor for CO2 (s) were corrected for differences in plasma water and in Na concentration. All plasmas were equilibrated at 37 degrees C in a tonometer with a constant gas mixture (5% CO2, 12% O2, 83% N2). Precision of pK'1 determinations averaged 0.003. pK'1 was also determined on fresh undiluted healthy plasma, similarly tonometered. (3) We report (a) considerable variability in pK'1 of fresh undiluted healthy plasma (from 6.0197 to 6.1217); and also in extrapolated values for pK'1 at a notional zero ionic strength (6.179 to 6.325); (b) that variation in plasma ionic strength alters pK'1; (c) that change in plasma bicarbonate [HCO3]p can also change pK'1; (d) that change in pK'1, changes measured pH. (4) Implications are discussed.