The Role of Delirium and Other Risk Factors on Mortality in Elderly Patients with Critical Limb Ischemia Undergoing Major Lower Limb Amputation.

BACKGROUND: Delirium in patients with critical limb ischemia (CLI) is associated with increased mortality. The main goal of this study was to investigate the association between delirium and mortality in patients undergoing major lower limb amputation for CLI. In addition, other risk factors associated with mortality were analyzed. METHODS: An observational cohort study was conducted including all patients aged ≥70 years with CLI undergoing a major lower limb amputation between January 2014 and July 2017. Delirium was scored using the Delirium Observation Screening Score in combination with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Risk factors for mortality were analyzed by calculating hazard ratios using a Cox proportional hazards model. RESULTS: In total, 95 patients were included; of which, 29 (31%) patients developed a delirium during admission. Delirium was not associated with an increased risk of mortality (hazard ratio [HR] = 0.84; 95 % confidence interval [CI]: 0.51-1.73; P = 0.84). Variables independently associated with an increased risk of mortality were age (HR 1.1; 95% CI 1.0-1.1), cardiac history (HR 3.3; 95% CI 1.8-6.1), current smoking (HR 2.9; 95% CI 1.6-5.5), preoperative anemia (HR 2.8; 95% CI 1.1-7.2), and living in a nursing home (HR 2.2; 95% CI 1.1-4.4). CONCLUSION: Delirium was not associated with an increased mortality risk in elderly patients with CLI undergoing a major lower limb amputation. Factors related to an increased mortality risk were age, cardiac history, current smoking, preoperative anemia, and living in a nursing home.

A randomized controlled trial of single-class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy: final 96-week results from the FREE study.

OBJECTIVES: The aim of the study was to test the antiviral efficacy of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen, with potential beneficial metabolic effects, as maintenance therapy after induction with dual NRTIs and a boosted protease inhibitor (PI). METHODS: An open-label, noninferiority study was carried out. Antiretroviral therapy (ART)-naïve patients with CD4 count ≤ 350 cells/µL and HIV-1 RNA >30000 copies/mL (n=207) were treated with zidovudine/lamivudine and lopinavir/ritonavir. After achieving HIV-1 RNA <50 copies/mL on two consecutive occasions between weeks 12 and 24 after baseline, 120 patients (baseline: median HIV-1 RNA 5.19 log10 copies/mL; median CD4 count 180 cells/µL) were randomized to receive abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) (n=61) or to continue the PI-based ART (n=59). RESULTS: For the proportions of patients (intention-to-treat; missing=failure) with HIV-1 RNA <400 copies/mL (PI group, 66%; ABC/3TC/ZDV group, 71%) and <50 copies/mL (PI group, 63%; ABC/3TC/ZDV group, 62%) at 96 weeks, switching to ABC/3TC/ZDV was noninferior compared with continuing the PI regimen; the difference in failure rate (ABC/3TC/ZDV minus PI) was -4.4 percentage points [95% confidence interval (CI) -21.0 to +12.3 percentage points] and +0.4 percentage points (95% CI -16.9 to +17.7 percentage points), respectively. In the per protocol analysis, the difference in virological failure for HIV-1 RNA >400 copies/mL (0 of 39 patients in the PI group and two of 45 patients in the NRTI group) and for HIV-1 RNA >50 copies/mL (two of 39 and three of 45 patients, respectively) was +4.4 percentage points (95% CI -2.1 to +11.0 percentage points) and +1.5 percentage points (95% CI -8.6 to +11.7 percentage points), respectively, also showing noninferiority. Serum lipids significantly improved in the NRTI group, but not in the PI arm. CONCLUSIONS: A single-class NRTI regimen after successful induction with standard ART had similar antiviral efficacy compared to continuation of a PI-based regimen at 96 weeks after baseline, with improved serum lipids.

One decade of point-prevalence surveys for carriage of extended-spectrum beta-lactamase-producing enterobacterales: whole genome sequencing based prevalence and genetic characterization in a large Dutch teaching hospital from 2013 to 2022.

OBJECTIVES: To determine the prevalence, trends, and potential nosocomial transmission events of the hidden reservoir of rectal carriage of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E). METHODS: From 2013 to 2022, yearly point prevalence surveys were conducted in a large Dutch teaching hospital. On the day of the survey, all admitted patients were screened for ESBL-E rectal carriage using peri-anal swabs and a consistent and sensitive selective culturing method. All Enterobacterales phenotypically suspected of ESBL production were analysed using whole genome sequencing for ESBL gene detection and clonal relatedness analysis. RESULTS: On average, the ESBL-E prevalence was 4.6% (188/4,119 patients), ranging from 2.1 to 6.6% per year. The ESBL-prevalence decreased on average 5.5% per year. After time trend correction, the prevalence in 2016 and 2020 was lower compared to the other year. Among the ESBL-E, Escherichia coli (80%) and CTX-M genes (85%) predominated. Potential nosocomial transmission events could be found in 5.9% (11/188) of the ESBL-E carriers. CONCLUSIONS: The ESBL-E rectal carriage prevalence among hospitalized patients was 4.6% with a downward trend from 2013 to 2022. The decrease in ESBL-E prevalence in 2020 could have been due to the COVID-19 pandemic and subsequent countrywide measures as no nosocomial transmission events were detected in 2020. However, the persistently low ESBL-E prevalences in 2021 and 2022 suggest that the decline in ESBL-E prevalence goes beyond the COVID-19 pandemic, indicating that overall ESBL-E carriage rates are declining over time. Continuous monitoring of ESBL-E prevalence and transmission rates can aid infection control policy to keep antibiotic resistance rates in hospitals low.

Determining host suitability of pecan for stored-product insects.

A no-choice test was performed to determine survival and reproductive capacity of stored-product insect pests on pecan, Carya illinoensis (Wangenheim) Koch. Insects used were Indianmeal moth, Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae); sawtoothed grain beetle, Oryzaephilus surinamensis (L.) (Coleoptera: Cucujidae); red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae); lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae); and rusty grain beetle, Cryptolestes ferrugineus (Stephens) (Coleoptera: Laemophloeidae). Fifty adults of each beetle species or 10 reproductive pairs of P. interpunctella adults were placed in 0.5-liter containers with either whole-shell pecans, cracked-shell pecans, randomly selected in-shell pecans, pecan nutmeats, cracked wheat, or glass beads and held at 28 degrees C, 60-70% relative humidity, and 16:8 (L:D) photoperiod for 2, 4, 6, and 8 wk. Four replications of each insect-diet-interval combination were performed. Larvae of P. interpunctella, O. surinamensis, T. castaneum, C. ferrugineus, and adult P. interpunctella and O. surinamensis developed on cracked and nutmeat pecan diets. R. dominica did not complete reproduction on pecans. Knowledge that these pests can reproduce on stored pecan will assist pecan growers, accumulators, and storage facilities in preventing insect outbreaks on their product.

Occult Fractures in Children with a Radiographic Fat Pad Sign of the Elbow: A Meta-Analysis of 10 Published Studies.

BACKGROUND: A radiographic fat pad sign after an elbow injury in children may indicate an occult fracture. Different incidences and locations of occult fractures have been reported. The primary objective of this meta-analysis was to assess the overall rate of occult fractures in children with a positive fat pad sign from the data of original studies. Secondary objectives were to assess the fracture types and to identify risk factors for sustaining an occult fracture. METHODS: A systematic literature search of the Embase, MEDLINE, and Cochrane databases was performed according to PRISMA guidelines. Studies on pediatric populations with a positive fat pad sign identified using a lateral elbow radiograph and with follow-up imaging were included in this meta-analysis. Included studies were assessed for risk of bias with use of the MINORS (Methodological Index for NOn-Randomized Studies) instrument. RESULTS: Ten studies with a total of 250 patients, of whom 104 had an occult fracture, were included. Accounting for heterogeneity between the studies, the overall occult fracture rate was 44.6% (95% confidence interval: 30.4% to 59.7%). The most common fracture locations were the supracondylar humerus (43%), proximal ulna (19%), proximal radius (17%), and lateral humeral condyle (14%). Definitions of a positive pad fad sign were not uniform among studies, and the follow-up imaging modality also varied (radiography, magnetic resonance imaging, or computed tomography). The average MINORS score was 10.1 for the 7 noncomparative studies and 18.7 for the 3 comparative studies, with both averages classified as moderate quality. We were not able to identify risk factors for an occult fracture in the presence of a positive fat pad sign. CONCLUSIONS: The occult fracture rate was 44.6% in pediatric elbow injuries with a positive fat pad sign. Supracondylar humeral fractures were the most frequently encountered type. The findings of this meta-analysis underline the potential clinical relevance of a positive fat pad sign in children and denote the opportunity for future studies to create evidence-based guidelines. LEVEL OF EVIDENCE: Level II. See Instructions for Authors for a complete description of levels of evidence.

Evaluation of A-V impulse technology as a treatment for oedema following polytetrafluoroethylene femoropopliteal surgery in a randomised controlled trial.

OBJECTIVE: To investigate the efficacy of A-V impulse technology (A-V) for oedema prevention and treatment following PTFE femoropopliteal surgery. DESIGN: Prospective randomized clinical trial. MATERIALS: 36 patients undergoing PTFE femoropopliteal bypass reconstructions, either being treated postoperatively with a compression stocking (CS) (Group-1, n = 19) or with A-V (Group-2, n = 17). METHODS: Patients in treatment group-1 used a CS postoperatively during 1 week day and night, patients in group-2 were treated with A-V postoperatively at night during one week. The lower leg circumference was measured preoperatively and at five postoperative time points. RESULTS: Limb circumference has increased postoperatively on day 1 (CS 1.5%/A-V 1.4%), on day 4 (5.7%/6.3%), on day 7 (6.6%/6.1%), on day 14 (7.9%/7.7%) and on day 90 (5.8%/5.2%). Differences between treatment groups were not significant. A re-operation gives a significant 3.9% increase in circumference as compared to a first operation (95% CI: 1.5-6.4%; p = 0.002). CONCLUSION: No significant differences were found in the extent of developed edema between the groups following PTFE femoropopliteal bypass surgery. A redo peripheral bypass operation results in significantly more postoperative oedema than a first-time performed bypass operation.

Puberty induction in Turner syndrome: results of oestrogen treatment on development of secondary sexual characteristics, uterine dimensions and serum hormone levels.

BACKGROUND: Besides short stature, gonadal dysgenesis leading to a lack of oestrogen is one of the main characteristics of Turner syndrome (TS). In most TS girls, puberty is induced with exogenous oestrogens. OBJECTIVE: To describe the pubertal development and uterine dimensions achieved by low-dose 17beta-oestradiol (17beta-E2) orally started at an appropriate age. Additionally, to determine whether serum hormone levels aid evaluation of pubertal progression. DESIGN: In 56 TS girls, we prospectively studied pubertal stage, serum E2, LH, FSH, SHBG and oestrone (E1), starting oestrogen treatment with a low-dose 17beta-E2 (5 microg/kg/day) during GH treatment at mean (SD) age 12.7 (0.7) years. Hormone levels were measured at start, 3 months after start and after increasing 17beta-E2 dosage. Uterine dimensions were measured in 39 TS women at age 19.9 (2.2) years. RESULTS: Although breast and pubic hair development were similar to that in normal Dutch girls up to Tanner stage B5 and P5, respectively, breast development was 2 years later. Before oestrogen therapy, E2 levels were comparable to those in prepubertal girls. With a 17beta-E2 dose of 5 microg/kg/day, these levels increased significantly, becoming comparable to normal late pubertal or adult concentrations, whereas SHBG levels were unchanged. At the adult 17beta-E2 dose, SHBG had increased significantly. Uterus shape was juvenile in four (10.2%), cylindrical in four and mature-adult shaped in 31 (79.5%) of TS patients. CONCLUSIONS: During GH treatment in TS girls, normal breast development up to B5 can be mimicked, with just a 2-year delay. In a clinical setting, serum hormone levels provide no additional information for evaluating pubertal progression. After age-appropriate pubertal induction, uterine dimensions in women aged nearly 20 years were subnormal. It remains unclear whether this was related to E2 dosage, timing or duration, or factors related to TS.

Spine radiographs to improve the identification of women at high risk for fractures.

SUMMARY: In women older than 60 years with clinical risk factors for osteoporosis but without osteoporosis based on bone mineral density (T-score >or= -2.5), a systematic survey with X-rays of the spine identified previously unknown vertebral deformities in 21% of women. INTRODUCTION: This study determines the prevalence of vertebral deformities in elderly women with clinical risk factors for osteoporosis but with BMD values above the threshold for osteoporosis (T-score >or= -2.5). METHODS: Bisphosphonate naïve women older than 60 years attending 35 general practices in the Netherlands with >or=2 clinical risk factors for osteoporosis were invited for BMD measurement (DXA). In women with T-score >or= -2.5 at both spine and the hips, lateral radiographs of the thoracic and lumbar spine were performed. RESULTS: Of 631 women with a DXA measurement, 187 (30%) had osteoporosis (T-score < -2.5 at the spine or the hip). Of the remaining 444 women with T-score >or= -2.5 at both spine and hip, 387 had additional spine radiographs, of whom 80 (21%) had at least one vertebral deformity. CONCLUSION: In elderly women with clinical risk factors for osteoporosis but BMD T-score >or= -2.5, addition of spine radiographs identified vertebral deformities in 21% (95% CI: 17-25). Since these women are at risk of future fractures, antiosteoporotic treatment should be considered.

Delayed- and immediate-type reactions in the atopy patch test with food allergens in young children with atopic dermatitis.

In recent years, the atopy patch test (APT) has been suggested as an addition in the allergological work-up of children with atopic dermatitis (AD) and suspected food allergy. We initiated a prospective clinical study in children with AD younger than 3 yr, to evaluate the additional clinical value of the APT next to our own standardized allergological work-up in case of a suspected food allergy. One hundred and thirty-five children were included in the study. They were tested using the skin application food test (SAFT), the APT and measurement of specific IgE. The allergens used in the skin tests were freshly prepared food stuffs and included commercially available cow's milk (CM), the egg white of a hard boiled hen's egg and mashed peanuts in a saline solution. Allergy was defined using a flowchart incorporating the results from the SAFT, oral challenges (OCs) and elimination and (re)introduction periods. To determine the additional value of the APT next to the SAFT, we analyzed the SAFT negative patients per allergen and used an exact binary logistic analysis to evaluate the simultaneous effects of the APT and measurement of specific IgE, calculating mutually adjusted odds ratios (ORs) for positive APTs and specific IgE levels above 0.70 U/l. We found clinically relevant food allergies in 23% (egg white) to 28% (CM and peanut) of our study population. Positive SAFT reactions were observed in 14% (peanut), 16% (egg white) and 21% (CM) of our patient population. Next to the SAFT, we did not observe a significant additional value of the APT for the diagnosis of CM or egg white allergy, but we did find a significant additional value for the diagnosis of peanut allergy (OR = 11.56; p < 0.005, 2-sided). In clinical practice this statistically significant value does not exclude the need for OC and controlled elimination and (re)introduction periods due to the presence of false-negative as well as false-positive results in the APT. In conclusion, we could not find enough support for the current addition of the APT to our standardized allergological work-up in young children below the age of 3 yr with AD and suspected food allergy. At the moment the additional value of the classical delayed-type APT next to the SAFT seems to be very limited at best in this study population and does not justify the time-consuming nature of the skin test.

Efficacy of venlafaxine compared with tricyclic antidepressants in depressive disorder: a meta-analysis.

With respect to the pharmacological characteristic, venlafaxine is comparable with tricyclic antidepressants (TCAs), and venlafaxine might be comparable in efficacy. We performed a systematic review investigating the relative efficacy and tolerability of venlafaxine compared with TCAs (imipramine, clomipramine, amitriptyline, nortriptyline and desipramine). Relevant double-blind randomised trials were identified from systematic searches of electronic databases. An exact analysis of the estimated odds ratios of response of the TCA relative to venlafaxine showed no overall significance of treatment effect (P = 0.38). The odds ratios were not homogenous across studies (P = 0.0213). The average dose of venlafaxine was 103.5 mg/day and for the TCA 106.1 mg/day. An exact analysis of the estimated odds ratios of the withdrawals and side effects in the trials with a TCA relative to venlafaxine showed no overall significance of withdrawal. From our review, no significant difference in treatment effect between low dose of both venlafaxine and the TCAs could be found. In our opinion, because of the heterogeneity of the odds ratios, one cannot conclude that they are of equal efficacy.

Serum tryptase and SCORMA (SCORing MAstocytosis) Index as disease severity parameters in childhood and adult cutaneous mastocytosis.

BACKGROUND: Skin lesions are the predominant clinical feature of the commonest form of mastocytosis. Mastocytosis is classified according to World Health Organization criteria. Determination of the levels of mast-cell mediators or their metabolites reflects the mast-cell burden. The extent of cutaneous mastocytosis can be assessed clinically using a scoring system (SCORing MAstocytosis; SCORMA Index) that we have developed. OBJECTIVE: Serum tryptase levels were compared with the SCORMA Index in a large group of paediatric and adult patients to investigate whether there was any correlation between the two. METHODS: The SCORMA Index in 64 patients (31 children and 33 adults) was compared with serum tryptase levels. The results of the first visit at which SCORMA and tryptase were evaluated were analysed. RESULTS: There was a positive correlation between the SCORMA Index and serum tryptase levels, indicating the value of the SCORMA Index in the assessment of mastocytosis with skin involvement. CONCLUSION: The results of this study showed that the SCORMA Index is a useful tool for evaluating the severity of cutaneous mastocytosis. The correlation between the SCORMA Index and serum tryptase levels underlines the benefit of the SCORMA Index as a clinical tool. Repeated SCORMA Index measurements can provide a rapid impression of changes in the clinical state of mastocytosis. This is particularly relevant in children, because taking blood samples from this group is much more difficult. The well-established methods for evaluation of disease severity may be expanded by the rapid SCORMA Index method.

[Symptoms of depression in strict Calvinist patients and in patients without religious affiliations: a comparison]. / Symptomen bij een depressie; bevindelijk gereformeerde versus niet-kerkelijke patiënten.

BACKGROUND: Culture can have a considerable influence on the way in which a depression is experienced, expressed or presented. Strict Calvinists or reformed pietists form an orthodox protestant cultural minority in the Netherlands. This orthodox wing of the Dutch Reformed Churches places a strong emphasis on personal religious experience of God's work of conversion. It is possible that symptoms of depression in this group differ somewhat from such symptoms in nonaffiliated depressed patients. AIM: To determine whether depressive symptoms in strict Calvinistic patients differ from those in non-affiliated patients. METHOD: Seventy depressed adult Dutch nationals receiving treatment as outpatients under the mental health service were asked to fill in a depression self-scoring list (Beck Depression Inventory II (bdi-ii)). A comparison was made between the total scores and scores of symptom clusters of strict Calvinists and the corresponding scores of non-affiliated patients. results The strict Calvinists had a lower total score than the non-affiliated patients on the bdi-ii and their scores were particularly lower for the symptom clusters suicidality and restrictions in functioning. CONCLUSION: Strict Calvinists differed from the non-affiliated patients in the way in which they presented on a depression self scoring list during depression. Perhaps strict Calvinists have less chance of being diagnosed and treated at an early stage because they conceal their depression and struggle on for a longer time. The study shows that insight into the religious background of Dutch national patients can be important for accurate psychiatric diagnostics.

[Beta-blockers and electroconvulsive therapy: a review]. / Prevention of post-discharge suicide: an inventory.

BACKGROUND: When patients with cardiovascular disorders undergo electroconvulsive therapy (ect) they sometimes have to be treated for tachycardia and high blood pressure. AIM: To describe the effects of beta-blockers on seizure duration and cardiovascular variables in patients undergoing ect. METHOD: Search for studies in Medline, with the keywords 'beta-adrenergic blocking agents' and 'electroconvulsive therapy'. Only articles based on randomised placebo-controlled investigations were included. results The search strategy produced 21 articles. These were assessed by all authors. Esmolol was the drug administered in most of the trials. Since seizure duration can influence the therapeutic effect of ect it is advisable to use bilateral electrode placement in patients with cardiovascular risk factors and to administer esmolol prior to seizure induction. CONCLUSION: The beta-blocker of choice for use during ect seems to be esmolol; it can shorten seizure duration, although the effect is probably dose-dependent. Esmolol is also the drug of choice in ect sessions for patients without cardiovascular risk factors but who develop prolonged hypertension or tachycardia. A possible alternative is labetalol, but its longer half-life is a disadvantage, particularly if it is administered in a high dose. So far, experience with landiolol is limited, but its short half-life, greater cardioselectivity and higher potency mean that it could be a promising alternative.

[Comparison of the effectiveness of two treatment strategies in inpatients with a depressive disorder. A double-blind study of imipramine followed by lithium addition versus fluvoxamine followed by lithium addition]. / De vergelijking van de effectiviteit van twee behandelingsstrategieën bij opgenomen patiënten met een depressieve stoornis. Een dubbelblind onderzoek met imipramine versusfluvoxamine, gevolgd door lithiumadditie.

BACKGROUND: There is still uncertainty regarding the best treatment optionfor depressed inpatients and the best strategy to follow if patient response is insufficient. AIM: To compare the efficacy of imipramine and fluvoxamine in depressed inpatients who subsequently received lithium supplement in case of poor response. METHOD: After a drug-free period and four days of placebo use, patients were randomised either to imipramine or to fluvoxamine (phase 1); the antidepressant dosage was fixed according to a predetermined plasma level. The efficacy of the antidepressant was evaluated four weeks after the predetermined plasma level had been attained. If patient response was inadequate, the antidepressant was augmented with lithium (phase 2). Patient response to the lithium addition was evaluated three weeks after an adequate lithium level had been attained. RESULTS: The study involved 138 inpatients. At the end of phase 1, imipramine was found to be superior tofluvoxamine according to the Clinical Global Impression of Improvement. Remission was achieved by 6 (23%) patients on imipramine and by 10 (15%) patients on fluvoxamine; this difference was not statistically significant. At the end of phase 2, 41 (9%) patients on imipramine and 27 (40%) patients on fluvoxamine achieved remission, this significant difference demonstrating the superiority of the imipramine strategy. CONCLUSION: Imipramine with subsequent lithium addition is superior to a similar strategy with fluvoxamine.

von Willebrand factor and development of diabetic nephropathy in IDDM.

We tested the hypothesis that dysfunction of vascular endothelium, indicated by an increase in plasma level of von Willebrand factor (vWF), is present in patients with insulin-dependent diabetes mellitus (IDDM) who develop diabetic nephropathy (DN). DN was classified as absent (urinary albumin excretion [UAE] rate less than 15 microgram/min), incipient (UAE rate 15-200 micrograms/min), or clinical (UAE rate greater than 200 micrograms/min). We followed a cohort of 59 patients for a median of 3 yr. At baseline, 52 patients had no DN, 6 had incipient DN, and 1 had clinical DN. At follow-up, 38 patients had no DN (group 1). Incipient DN had developed in 14 patients and worsened in 3 patients. Clinical DN had worsened in 1 patient. Together, these 18 patients comprised group 2. A decrease in UAE was observed in the remaining three patients with incipient DN at baseline (group 3). In group 1, vWF--measured by immunoelectrophoresis and expressed as a percentage of normal--increased slightly (median 10%, range -43 to 145, P = 0.009). In group 2, vWF increased in all patients (median 80%, range 14 to 206 [corrected], P = 0.0002 vs. baseline and group 1). In group 3, vWF decreased (median -19%, range -44 to -18). After correction for possible confounders, i.e., age, varying duration of follow-up, and initial level of vWF, the difference in vWF change between groups 1 and 2 remained significant (P = 0.009). Poor glycemic control at baseline, estimated by glycosylated hemoglobin, was a significant predictor of increases in vWF in both group 1 and groups 1 and 2 combined.(ABSTRACT TRUNCATED AT 250 WORDS)

Mast cell distribution in normal adult skin.

AIMS: To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. METHODS: Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults. RESULTS: There was an uneven distribution of MCs in different body sites using the anti-tryptase monoclonal antibody technique. Numbers of MCs on the trunk, upper arm, and upper leg were similar, but were significantly different from those found on the lower leg and forearm. Two distinct groups were formed--proximal and distal. There were 77.0 MCs/mm2 at proximal body sites and 108.2 MCs/mm2 at distal sites. Adjusted for the adjacent diagnosis and age, this difference was consistent. The numbers of MCs in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders were not different from those in the control group. Differences in the numbers of MCs between the distal and the proximal body sites must be considered when MCs are counted for a reliable diagnosis of mastocytosis. A pilot study in patients with mastocytosis underlined the variation in the numbers of MCs in mastocytosis and normal skin, but showed a considerable overlap. The observed numbers of MCs in adults cannot be extrapolated to children. CONCLUSIONS: MC numbers varied significantly between proximal and distal body sites and these differences must be considered when MCs are counted for a reliable diagnosis of mastocytosis. There was a considerable overlap between the numbers of MCs in mastocytosis and normal skin.

Effects of 24R,25-dihydroxyvitamin D3 in combination with 1 alpha-hydroxyvitamin D3 in predialysis renal insufficiency: biochemistry and histomorphometry of cancellous bone.

The effect of combined administration of 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3) and 1 alpha-hydroxyvitamin D3 (1 alpha-(OH)D3) was studied in 24 non-dialyzed patients with chronic renal insufficiency (CRI), matched pairwise as to age, sex, and creatinine clearance (Cr.cl). Low Ca intake had been supplemented beforehand. Then, 1 alpha-(OH)D3 (mean dose 0.55 micrograms daily) was given orally to all patients for 3 months (T0 to T3). Subsequently, patients were assigned randomly to 6 months further treatment either with 1 alpha-(OH)D3 alone (Group A) or with 1 alpha-(OH)D3 plus a high dosage of 24,25-(OH)2D3 (50 micrograms orally, twice weekly) (Group B). Histomorphometry was performed at T0, T3, and T9. In both groups iPTH was equally suppressed, into the lower normal range. Whereas in Group A, serum Ca rose steadily and Cr.cl declined, in Group B both parameters levelled off between T6 and T9. At T9, in Group A the elevated resorption and osteoid indices had normalized markedly, but osteoblasts (Ob.Pm) and mineralizing boundaries (M.Bd) were depressed considerably between T3 and T9. In contrast, in Group B, preservation of Ob.Pm and improved mineralizing activity were observed (M.Bd at T9 > T3 > T0). Resorption indices hardly changed. In the patients with high Ob.Pm at T0, cancellous bone area increased significantly. This was not observed in Group A. Thus, in Group B, osteoblast recruitment appeared maintained and M.Bd appeared normalized. Decline of remodeling toward an adynamic state with an increased risk of hypercalcemia appeared prevented.

Cytogenetic, molecular genetic and pathological analyses in 126 meningiomas.

In a series of 126 meningiomas, tumor and patient characteristics were investigated and statistically analyzed. A combined cytogenetic and molecular genetic approach was used to study chromosomal abnormalities and loss of markers on chromosome 22q. This approach was successfully applied to 93 meningiomas. In 66 cases, complete or partial loss of chromosome 22 was observed and in at least 12 of them this chromosome was involved in structural aberrations. In addition to chromosome 22 changes, chromosomes 1, 6, 11, 13, 14, 18, 19, X, and Y were also frequently involved in structural and numerical aberrations. Statistical analysis revealed a significant association between the number of chromosomal abnormalities and tumor grade. Complex karyotypes predominated in the group of grade II/III meningiomas. Furthermore, other variables showed statistically (or marginally statistically) significant differences. Meningiomas from the convexity were more often grade II/III, displayed predominantly (partial) loss of chromosome 22 and had complex karyotypes more often. These features were frequently found in meningiomas from males. Base meningiomas, on the other hand, occurred more often in females; they were usually grade I, showed loss of (parts of) chromosome 22 less often and displayed fewer additional chromosomal abnormalities.

Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension.

We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week. Compared with placebo, 24-hour ambulatory blood pressure did not change with the 1-mg dose, and it fell (mean and 95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the 25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg dose. Heart rate did not change during either dose. With the 25-mg dose, the antihypertensive effect was attenuated during the second half of the recording, and with the 100-mg dose, it was maintained for 24 hours. Baseline values of renin and the antihypertensive response to the 25- and 100-mg doses were well correlated (r = .68, P < .01). Renin did not change with the 1-mg dose, but it rose threefold to fourfold with the 25-mg dose and fourfold to fivefold with the 100-mg dose 4 to 6 hours after administration. With the 100-mg dose, renin was still elevated twofold 24 hours after dosing. The changes in renin induced by the AT1 receptor antagonist were associated with parallel increments in angiotensin I and angiotensin II. Aldosterone, despite AT1 receptor blockade, did not fall.(ABSTRACT TRUNCATED AT 250 WORDS)

Seasonal variations in binding of 3H-paroxetine to blood platelets in healthy volunteers: indications for a gender difference.

Binding of paroxetine to blood platelet membranes was studied longitudinally in 20 healthy volunteers (11 men and 9 women) in order to determine seasonal and gender variations. Blood samples were obtained in September, December, March, and June, and repeated in September. A significant seasonal variation in the maximal number of binding sites (Bmax) was found. Men were found to have significantly lower (Bmax) values than women. Although the pattern of seasonal variation was not identical in men and women, no significant differences were detected. The affinity constant (KD) of paroxetine binding showed a significant seasonal variation. Men were found to have a significantly higher KD (lower affinity) than women. The pattern of seasonal variation was identical in men and women. These data support the evidence indicating a substantial seasonal effect on the serotonergic system, and show that in paroxetine binding studies, groups of subjects should be matched for season and gender.