Outcome of primary antiphospholipid syndrome in childhood

The objective of this paper is to investigate the long-term outcome of primary antiphospholipid syndrome (APS) in the paediatric age. The features of unselected patients with primary APS who had disease onset before the age of 16 years were retrospectively analysed in three Italian referralcentres. Clinical and laboratory manifestations were assessed to establish whether, at the end of follow-up, the final diagnosis was still primary APS or whether they had developed definite SLE or lupus-like syndrome. Fourteen patients, nine boys and five girls, who had the presenting clinical manifestation of APS between three and 13 years of age (median nine years) and were followed for two to 16 years (median six years). Six patients presented with deep vein thrombosis, five with cerebral stroke, two with peripheral artery occlusion and onewith myocardial infarction. During follow-up, four patients had one or more recurrences of vascular thrombosis. At last observation, 10 patients could still be classified as having primary APS, two had developed SLE, one lupus-like syndrome and one Hodgkin's lymphoma. In conclusion; our analysis suggests that some children who present with the features of primary APS may progress to develop SLE or lupus-like syndrome.     

Prevalence and clinical significance of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

BACKGROUND: Antibodies against cyclic citrullinated peptide (anti-CCP) are considered to be specific for rheumatoid arthritis (RA). OBJECTIVE: To assess the clinical significance of anti-CCP in a cohort of patients with juvenile idiopathic arthritis (JIA). METHODS: Anti-CCP were tested by an enzyme linked immunosorbent assay (ELISA) in serum samples from 109 patients with JIA (30 boys, 79 girls), with a mean age of 8.7 years (range 0.6-20.3) and mean disease duration of 3.6 years (range 3 months to 15.6 years). As control groups, anti-CCP were also tested in sera of 30 healthy children, 25 patients with juvenile onset systemic lupus erythematosus (SLE), and 50 adult patients (30 with RA, 20 with SLE). RESULTS: Positive anti-CCP values were found in sera of two patients with JIA (2%), one with polyarthritis, and one with oligoarthritis. Statistical analysis showed that anti-CCP were not associated with the presence of antinuclear antibodies, raised erythrocyte sedimentation rate, or erosions. In the control groups, none of the patients with juvenile onset SLE and only one of 20 adults with SLE were positive for anti-CCP, but 19/30 (63%) adults with RA showed anti-CCP positivity. CONCLUSIONS: Anti-CCP can be detected in children with JIA, but are less frequently present than in adults with RA.     

Sezary cell morphology induced in peripheral blood lymphocytes: re- evaluation

In this study we examined the effect of mitogens and epidermal cells in inducing a Sezary cell morphology in normal peripheral blood lymphocytes. Peripheral blood mononuclear cells from six healthy volunteers were stimulated with the mitogens phytohemaglutinin and concanavalin A, and also cocultivated with human epidermal cell cultures. Incubation times with mitogens and epidermal cells were four days and stimulation of the lymphocytes by mitogens was confirmed by standard 3H-thymidine uptake. Standard transmission electron microscopy showed that in the mitogen-driven system 20% to 60% (33 +/- 15%) and in the epidermal cell-driven system 5% to 15% (8 +/- 4%) of the lymphoid cells exhibited mild to moderate indentation of the nuclei with nuclear contour indices (NCI) of 4.6 to 6.5 but no Sezary cells were observed (cells with NCI greater than 6.5 and up to 19.2). In the mitogen- stimulated preparation 2% to 5% (3 +/- 1%) of the lymphoid cells showed nuclear multilobulation resembling the cells seen in adult T cell lymphoma/leukemia. Incubation of mononuclear cells for longer periods of up to 4 weeks with mitogens and exogenous IL-2 resulted in no further morphologic changes. Using an indirect immunogold technique at the electron microscopic level, the cells showing nuclear indentation or lobulation were shown to bear both T helper (CD4) and T suppressor (CD8) cell phenotypes in a similar ratio to the total numbers of T helper and T suppressor cells present. Mitogens and epidermal cells are thus not able to induce a morphologic change to Sezary cells in normal peripheral blood lymphocytes.     

Electrovectorcardiographic study of negative T waves on precordial leads in arrhythmogenic right ventricular dysplasia: relationship with right ventricular volumes

In 24 cases of arrhythmogenic right ventricular (RV) dysplasia, the electrovectorcardiographic (ECG-VCG) behavior of T horizontal (wave and loop) was analyzed and the data compared with RV angiographic volumes. Arrhythmogenic RV dysplasia was diagnosed on the basis of echocardiographic and angiographic data in all subjects. At ECG, T wave was negative in V1 in nine subjects (37%), in V1-V2 in six (25%), in V1-V3 in two (8%), in V1-V4 in one (4%), in V1-V5 in two (8%), and in V1-V6 in four (16%). Nine subjects (37%) presented a bifid T wave in V2-V4. At VCG, T horizontal loop showed three morphologic characteristics: (1) counterclockwise rotation with a mean axis range of +15 degrees to -10 degrees (average, +5 degrees); (2) a figure-eight pattern with a mean axis range of +10 degrees to -40 degrees (average, -17 degrees); and (3) clockwise rotation with a mean axis range of -40 degrees to -110 degrees (average, -70 degrees). T wave changes seem to be primary and independent from QRS changes. RV and diastolic volumes ranged from 100 to 320 m1/m2 (average, 169 +/- 69). The extension of T wave negativity on precordial leads has a direct relationship with RV enlargement (r = 0.89, p less than 0.01). T changes are probably caused by dislocation of the left ventricle backwards secondary to RV dilatation, asynchronous RV repolarization, or intraparietal RV conduction defects.     

Clinical and diagnostic aspects of cystic insulinoma

Cystic endocrine tumors of the pancreas rarely occur, and only a few cases of cystic insulinoma have been reported to date. Diagnosis of insulinoma could be difficult if the functional activity is incomplete, possibly leading to blunted symptoms of hypoglycemia and failure in the laboratory to provide evidence of hyperinsulinemia. We report a clinical case of cystic insulinoma confirmed by histological examination after surgery, characterized by a high intracystic insulin concentration despite normal blood basal levels of the hormone. New diagnostic findings from dynamic tests and cystic fluid examination have been carefully focused on.     

Neonatal organization of the brain opioid systems controlling prolactin and luteinizing hormone secretion

It is known that the neural mechanisms which control PRL and gonadotropin secretion are different in male and female rats. The present experiments have been designed in order to analyze: 1) whether sexual differences exist in the responses of PRL and LH to the opioid antagonist naloxone; and 2) the mechanisms underlying these possible differences. To this purpose the responses of PRL and LH to the sc injection of either saline (0.5 ml) or naloxone (2.5 mg/kg) have been tested in the following four groups of animals: 1) normal male rats; 2) normal female rats; 3) female rats treated on the second day of life with 1.25 mg testosterone (androgenized female rats); and 4) male rats orchidectomized 2 days postnatally (demasculinized male rats). The naloxone challenge has been provided when the animals were 16, 26, and 60 days old; the animals were killed in the afternoon 20 min after treatment. The results obtained have shown that the acute injection of naloxone significantly decreases serum levels of PRL in normal males and in androgenized females at all ages considered. On the contrary, the opioid antagonist was always ineffective in normal females and in neonatally castrated males. The treatment of male rats with naloxone was without any effect on LH release before puberty (at 16 and 26 days of age), but induced a significant increase of serum LH titers after sexual maturation (60 days). In normal females, naloxone brought about a significant increase of serum LH only at 16 and 60 days (animals in estrus), but not at 26 days. Treatment with naloxone did not exert any significant effect on LH release in androgenized females and in deandrogenized males of any age. The present data suggest that, in the rat a sexual difference exists in the opiatergic control of PRL secretion; apparently, the central opioid systems which regulate PRL secretion develop towards a male pattern because of the presence of androgens in the neonatal period. On the contrary neonatal androgens do not seem to exert any important effect in directing the organization of the opiatergic mechanisms controlling LH release.     

Development of an instrument for the identification of frail older people as a target population for integrated care

Background

Primary care is increasingly interested in the identification of frailty, as it selects the target population for integrated care. However, instruments for the identification of frailty specifically validated for use in primary care are scarce. This study developed the Easycare Two-step Older persons Screening (Easycare-TOS), which provides a valid, efficient, and pragmatic screening procedure to identify frail older people.

Aim

This paper aims to describe the development of the Easycare-TOS and the data from the pilot studies.

Design and setting

Observational pilot study in seven academic GP practices in and around Nijmegen, The Netherlands.

Method

The Easycare-TOS was developed in a cyclic process with the input of stakeholders. In every cycle, the requirements were first defined, then translated into a prototype that was tested in a pilot study. The Easycare-TOS makes optimal use of prior knowledge of the GP, and the professionals’ appraisal is decisive in the frailty decision, instead of a cut-off score. Further, it considers aspects of frailty, as well as aspects of the care context of the patient.

Results

The pilot data have shown that after step 1, two-thirds of the patients do not need further assessment, because they are judged as not frail, based on prior knowledge of the GP. The overall prevalence of frailty in this pilot study is 24%. Most professionals who participated in the pilot studies considered the time investment acceptable and the method to be of added value.

Conclusion

The Easycare-TOS instrument meets the predefined efficiency, flexibility, and acceptability requirements for use as an identification instrument for frailty in primary care.     

Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.