Characteristics of recovery of adrenocortical function after treatment for Cushing's syndrome due to pituitary or adrenal adenomas

OBJECTIVE: Surgical cure of Cushing's syndrome (CS) is followed by adrenocortical insufficiency, which may be long-lasting. The aim was to elucidate recovery of adrenocortical function, defined as a normal cortisol response to ACTH stimulation, and the relation to ACTH in patients cured for CS due to pituitary Cushing's disease (CD) or adrenal (AA) adenomas. DESIGN: A retrospective study including 32 patients considered surgically cured for CS (18 CD, 14 AA). RESULTS: Twelve (67%) patients with CD recovered within median 24 months (range 7 months-4(1)/(2) years) whereas six did not recover within 3-12 years. Plasma ACTH (p-ACTH) at time of recovery was not different from p-ACTH in patients not recovering (P = 0.9). Eleven (79%) patients with AA recovered within 24 months (10 months-4 years) whereas three did not recover within 4-10 years. p-ACTH at time of recovery was higher compared to patients not recovering (P < 0.04). No differences were observed comparing CD and AA patients concerning preoperative 24-h urinary free cortisol (UFC) excretion, postoperative unstimulated s-cortisol or recovery time. By contrast, p-ACTH measured at time of recovery was higher in AA compared to CD (median 12.3 vs. 4.6 pmol/l) (P < 0.001), whereas plasma dehydroepiandrosterone sulfate (p-DHEAS) was lower in AA compared to CD (median 300 vs. 1500 nmol/l) (P = 0.02). CONCLUSION: Recovery of secondary adrenal insufficiency is a slow process in both CD and AA. ACTH measured at time of recovery was significantly higher and DHEAS significantly lower in patients with AA compared to CD, which may suggest different mechanisms of the recovery process and different set points in the glucocorticoid feedback inhibition of ACTH secretion.     

Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function

Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate, mobilization of intracellular Ca2+, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation (see accompanying report). A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, 7 out of 10 known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC- gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC- delta 1 > PLC-beta 4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.     

Possible effect of secretor locus on plasma concentration of factor VIII and von Willebrand factor

A significant fraction (30%) of the genetically determined variance in plasma concentration of the von Willebrand factor antigen (vWf:Ag) has been shown to be related to ABH determinants. Individuals with blood group O, who have the highest amounts of blood group H substance, have the lowest concentration of vWf:Ag. The Lewis substances, Le(a) and Le(b), are biochemically closely related to the ABH substances as both can be produced from the same precursor substance. We studied the effect of the presence of the Lewis antigens on the plasma concentration of vWf:Ag and factor VIII antigen (VIII:Ag) in 323 individuals of different ABO groups from a series of twins and in 58 blood donors of blood group O. Among persons belonging to blood group O, those with the Le(a) antigen had a higher concentration of both vWf:Ag and VIII:Ag than individuals lacking Le(a). Le(a+b-) people are nonsecretors and Le(a-b+) people are secretors of ABH substance. Thus, the lowest concentration of vWf:Ag and VIII:Ag was found in group O secretors. The effect is most likely due to an effect of the secretor locus. This finding may be of importance for the detection of carriers of hemophilia A and for the diagnosis of type I von Willebrand disease.     

The Fit for Delivery study: rationale for the recommendations and test‐retest reliability of a dietary score measuring adherence to 10 specific recommendations for prevention of excessive weight gain during pregnancy

Aiming at preventing excessive weight gain during pregnancy, 10 specific dietary recommendations are given to pregnant women in the intervention arm of the Norwegian Fit for Delivery (FFD) study. This paper presents the rationale and test‐retest reliability of the food frequency questionnaire (FFQ) and a dietary score measuring adherence to the recommendations. The study is part of the ongoing FFD study, a randomised, controlled, intervention study in nulliparous pregnant women. A 43‐item FFQ was developed for the FFD study. A dietary score was constructed from 10 subscales corresponding to the 10 dietary recommendations. Adding the subscales yielded a score from 0 to 10 with increasing score indicating healthier dietary behaviour. The score was divided into tertiles, grouping participants into low, medium and high adherence to the dietary recommendations. Pregnant women attending ultrasound screening at about week 19 of pregnancy were asked to complete the FFQ twice, 2 weeks apart. Of 154 pregnant women completing the first questionnaire, 106 (69%) completed the form on both occasions and was included in the study. The test‐retest correlations of the score and subscales were r = 0.68 and r = 0.56–0.84, respectively (both P ≤ 0.001). There was 68% test‐retest correct classification of the score and 70–87% of the subscales. In conclusion, acceptable test‐retest reliability of the FFQ and the dietary score was found. The score will be used in the FFD study to measure adherence to the dietary recommendations throughout pregnancy and in the following year post‐partum.     

Fate of the rectum after colectomy and ileostomy for Crohn's colitis

Eighty-four patients had colectomy with ileostomy and oversewing of the rectum for Crohn's colitis. Seventy-two patients were operated on because of intractable disease, colitis in combination with rectal fistulas, and toxic megacolon. The operative mortality was 6 percent, and neither emergency surgery nor treatment with steroids correlated with operative morbidity. After a median 7.7 years of follow-up, 25 ileorectal anastomoses had been undertaken, 16 of which were successful. Twenty-nine proctectomies were performed; the resulting 10-year cumulative risk of proctectomy was 50 percent. While the risk of proctectomy was significantly less among patients with a normal rectum at colectomy compared with patients with proctitis, the initial macroscopic degree of proctitis did not correlate with the risk of subsequent proctectomy. The 5-year cumulative ileal resection rate in 29 patients with a rectum in situ but out of circuit was 29 percent. The possibility of a future ileorectal anastomosis should still be considered in patients with proctocolitis.     

Screening for risk of violence using service users’ self‐perceptions: A prospective study from an acute mental health unit

Service users’ self‐perception of risk has rarely been emphasized in violence risk assessments. A recent review pointed to the importance of a multidisciplinary approach, because different perspectives may provide a deeper and improved understanding of risk assessment. The aim of this study was to investigate service users’ perceptions of their own risk of committing violence, using a self‐report risk scale, to determine the feasibility and efficacy of this potential violence risk marker during acute mental health hospitalization. All service users admitted to a psychiatric emergency hospital in Norway during one calendar year were included (N = 512). Nearly 80% self‐reported no risk or low risk; only seven (1.4%) reported moderate risk or high risk. Service users who reported moderate risk, high risk, don't know, or won't answer were more likely to be violent (OR = 4.65, 95% CI = 2.79–7.74) compared with those who reported no risk or low risk. There was a significant gender interaction with higher OR for women on both univariate and multivariate analyses. Although the OR was higher for women, women's violence rate (11.0%) was almost half that of men (21.8%). For women, sensitivity and specificity were 0.55 and 0.88, respectively; corresponding values for men were 0.40 and 0.80. Inclusion of self‐perception of violence risk is the first step towards service users’ collaborative involvement in violence prediction; these results indicate that self‐perception can contribute to violence risk assessments in acute mental health settings. Findings also indicate that there are gender differences in these assessments.     

A qualitative study of clinical reasoning in physiotherapy with preterm infants and their parents: Action and interaction

Background: Physiotherapists (PTs) in primary health care provide services to preterm infants and their parents after hospital discharge. The service should be collaborative and individualized to meet the family’s needs. In this study, we analyze pediatric PTs’ collaborative work in the clinical setting and investigate the PTs’ emerging clinical reasoning (CR) in interaction with the infant and parent(s).

Methods: The study is based on observations of 20 physical therapy sessions and 20 interviews with PTs. We performed a systematic content analysis informed by enactive theory regarding the interactions and co-creation of meaning.

Results and Discussion: CR emerged in reciprocity with the PTs’ interaction with the infant and parent(s). Based on the sensitivity to the infant’s motor abilities and signs of engagement as well as the parents’ need of support and education, the PTs individualized and reasoned about their therapeutic approach. This interactional CR was vulnerable: infant disengagement, parent expectations, and PT preoccupations could obfuscate interactions and hamper CR.

Conclusion: Through mutuality and engagement with the infant and parent(s), the PTs allow the autonomy of interaction to emerge and shape the translation of CR into successful therapeutic actions and learning together with the infant and parent(s).     

Lesion-Specific and Vessel-Related Determinants of Fractional Flow Reserve Beyond Coronary Artery Stenosis

Objectives

The aims of the present study were: 1) to investigate the contribution of the extent of luminal stenosis and other lesion composition-related factors in predicting invasive fractional flow reserve (FFR); and 2) to explore the distribution of various combinations of morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR.

Reduced Mortality After Oral Polio Vaccination and Increased Mortality After Diphtheria-tetanus-pertussis Vaccination in Children in a Low-income Setting

PurposeThe diphtheria-tetanus-pertussis vaccine (DTP) and oral polio vaccine (OPV) were introduced in children 3 of 5 months of age in 1981–1983 in Bandim, in the capital of Guinea-Bissau. Because DTP has been linked to deleterious nonspecific effects (NSEs) and OPV to beneficial NSEs, we followed up this cohort to 3 years of age and examined the effects of DTP with OPV on all-cause mortality and the interactions of DTP and OPV with the measles vaccine (MV).MethodsDTP and OPV were offered at 3 monthly community weighing sessions. Vaccination groups were defined by the last vaccine received. We compared overall mortality for different groups in Cox proportional hazards regression models, reporting hazards ratios (HRs) with 95% CIs.FindingsThe study cohort included 1491 children born in Bandim from December 1980 to December 1983. From 3 to 35 months of age, with censoring for MV, children vaccinated with DTP and/or OPV had higher mortality than both unvaccinated children (HR = l.66; 95% CI, 1.03–2.69) and OPV-only vaccinated children (HR = 2.81; 95% CI, 1.02–7.69); DTP-only vaccinated children had higher mortality than OPV-only vaccinated children (HR = 3.38; 95% CI, 1.15-–9.93). In the age group of 3–8 months, before MV is administered, DTP-only vaccination was associated with a higher mortality than DTP with OPV (HR = 3.38; 95% CI, 1.59–7.20). Between 9 and 35 months of age, when MV is given, DTP-vaccinated and MV-unvaccinated children had higher mortality (HR = 2.76; 95% CI, 1.36–5.59) than children who had received MV after DTP, and among children who received DTP with MV or after MV, DTP-only vaccination was associated with a higher mortality than DTP with OPV (HR = 6.25; 95% CI, 2.55–15.37).ImplicationsBecause the 2 vaccines had differential effects and the healthiest children were vaccinated first, selection biases are unlikely to explain the estimated impact on child survival. OPV had beneficial NSEs, and administration of OPV with DTP may have reduced the negative effects of DTP.