The syndrome of thrombosis, thrombocytopenia, and recurrent spontaneous abortions associated with antiphospholipid antibodies: Hughes syndrome

aPL-associated thrombosis (Hughes syndrome) is widely recognized as a major cause of organ damage in autoimmune diseases. Beginning with the first symposium in 1984, international aPL symposia have facilitated research on aPL antibodies, and the clinical standardization of aPL tests. It is hoped that the present symposium will continue this tradition, because much remains to be learnt about the origin and pathogenicity of aPL antibodies. In addition, new insights are needed for more effective therapies to be developed.     

Analysis of the factors influencing the quality of life of patients with advanced or recurrent breast cancer

To investigate the factors influencing the quality of life (QOL) of Japanese patients with advanced or recurrent breast cancer, a newly developed QOL questionnaire, "The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs" (QOL-ACD), was answered by 23 patients, and a multiple regression analysis was performed. The demographic and medical factors relating to the overall QOL score and to the four categories of the QOL-ACD, namely (1) activity, (2) physical condition, (3) psychological condition, and (4) social relationships, were analyzed. The results indicated that skin metastasis, a heavier body weight, and bone metastasis had a strong negative influence on the overall QOL scroe, whereas endocrine therapy, the existence of a primary lesion, and more extensive first surgery had a strong positive influence on it. With regard to the analysis of the four categories, endocrine therapy was found to be positively related to all four categories. The multiple correlation coefficient (R) between the estimated overall QOL score and the observed overall QOL score was about 0.77. The results of this analysis showed that endocrine therapy can improve the QOL of patients with advanced or recurrent breast cancer, and that the QOL-ACD questionnaire could prove extremely useful for predicting the QOL of individual patients and for aiding clinicians in deciding on the most appropriate type of therapy for each patient.     

Splenic vein thrombosis with pancytopenia and fever: antiphospholipid antibody syndrome

Antiphospholipid antibody syndrome (APS) is now recognized as one of the most important causes of hypercoagulability. The most common site for venous thrombosis in APS is deep venous thrombosis of the lower extremities. Other sites of venous thrombosis include retinal veins, renal veins, and hepatic veins. The authors report a case of splenic vein thrombosis disclosing antiphospholipid syndrome in which also the cytolytic effect of aPL may play a role of "cofactor" in the genesis of thrombosis through the release of thromboplastin from the lysis of red cells, granulocytes and platelets, making them vulnerable to clearance by splenic macrophages. Important considerations are stressed about differential diagnosis, etiopathogenetic factors, therapy and follow-up of the patient.     

Nailfold capillary microscopy in patients with antiphospholipid syndrome

In this paper we tried to define the capillaroscopic pattern of anti phospholipid syndrome able to differentiate between the primary (PAPS) and the systemic lupus erythematosus-associated form (SLE-APS) and to be a predictive marker of thrombotic manifestations. Eight PAPS and five SLE-APS patients were studied. In each patient the evaluation was based on anti cardiolipin antibody levels, nailfold capillaroscopy, retinal fluorangiography and transcranial doppler sonography. Statistical analysis has been performed using chi 2 analysis. Morphological alterations of capillary loops, venular visibility and sludging of blood were often observed in both groups. While we found in higher prevalence a variability of capillary loop length in PAPS patients, the SLE-APL group significantly differed for the presence of microhaemorrhages (p < 0.001). When we evaluated the clinical history, a marked microcirculatory damage was related with the occurrence of thrombotic manifestations in the PAPS patients. Anti cardiolipin antibody levels, retinal fluorangiography and transcranial doppler sonography did not correlate with clinical history in either group. In conclusion, nailfold capillaroscopy can be usefully employed in the differentiation between primary and SLE-associated anti phospholipid syndrome, and it can help to identify the patients at higher risk of thrombotic disease.     

Severe motor weakness associated with lumbar spinal stenosis. A retrospective study of a series of 61 patients

PURPOSE OF THE STUDY: Severe motor weakness is a rather infrequent symptom in the course of lumbar stenosis. The objectives of this study are three fold: describe the motor deficit, evaluate the prognosis factors and determine the type of stenosis the most likely to be complicated by motor loss. MATERIAL AND METHODS: 61 consecutive patients with a mean age of 63 years, operated on for a lumbar stenosis and with a severe motor deficit have been retrospectively studied. The mean follow-up was 38 months. The overall functional result was evaluated according to a rating scale, specially developed in our unit for the follow-up of lumbar stenosis. The motor capacity was rated from 0 (complete paralysis) to 5 (normal strength). According to that scale the motor weakness was rated as 0, 11 times as 1, 11 times, as 2, 11 times and as 3, 28 times. The deficit was unilateral in 79 per cent of cases and multiradicular in 58 per cent of patients. Sphincter abnormalities were also present in 9 cases. In 9 out of 10 patients the motor deficit was in the L5 territory. Stenosis was extended to 3 levels in 30 cases and was focal in the remaining cases. Degenerative spondylolishthesis was disclosed in 20 patients. In 3 out of 4 cases decompression was performed after 3 weeks of motor weakness and within 3 weeks in the remaining cases. RESULTS: According to our rating scale the overall results were considered excellent in 29 cases, good in 21 cases and fair in the 11 remaining cases. There was no complication, and no postoperative worsening of the deficit was observed. Regression of motor weakness was complete 22 times, partial 29 times and null 10 times. In the eleven complete deficits with a 0 cotation one receded completely, 7 receded partially and no improvement was noted in the 3 remaining cases. 6 out of the 9 patients with sphincter abnormalities recovered completely. In this study favourable prognosis parameters were as follows: age under 62 years, monoradicular deficit, stenosis at one level and association with a discal herniation. In contrast, severity of the initial motor weakness, association with sphincter abnormalities, presence or not of degenerative spondylolisthesis, or of a complete block on the myelogram were not influential variables. Chances of recovery were statistically diminished when decompression was performed after 6 weeks. DISCUSSION AND CONCLUSION: No study dealing specifically with the postoperative outcome of motor deficit caused by lumbar stenosis has been published. However the rate of motor recovery (complete or partial) disclosed in our series is comparable with that found in other series dealing more generally with the overall post-surgery outcome. At our last follow-up, 82 per cent of our patients were considered as having an excellent or good result. It can be concluded that the existence of a motor deficit is not a major pejorative factor of the overall final functional result. Motor weakness is more frequently observed in elderly patients, in cases with degenerative spondylolisthesis, or when a discal herniation is associated with a bony compression. Chances of recovery are better, when the deficit is monoradicular, when the stenosis is focal, or associated with a discal herniation and when the patient is relatively young.     

Risk factors influencing the outcome of portal and mesenteric vein thrombosis

BACKGROUND/AIMS: This study analyzes risk factors that influence the course and outcome of portal and superior mesenteric vein thrombosis (PMVT). METHODOLOGY: We retrospectively reviewed 45 patients who were admitted to our institution over a 17-year period with a diagnosis of PMVT. Patients were classified according to three etiological groups, namely: cirrhosis (47%), pancreatitis (22%), and other causes (33%), with 1 patient belonging to two different groups. RESULTS: Over the course of the disease, rupture of gastric or esophageal varices was more frequent (p<0.005) in cirrhotics (75%) than non-cirrhotics (17%). Sclerotherapy was always the first treatment for variceal bleeding, with a success rate of 73% but a rate of recurrence of 56%. Surgical procedures were performed on 22% of patients. Actuarial survival was 43% at 5 years, but survival was significantly increased for idiopathic cases (p=0.005) and decreased in the presence of cirrhosis (p<0.001), malignancy (p<0.0001) or hematemesis (p<0.005). Gastrointestinal bleeding and terminal malignancies were responsible for 50% of deaths. CONCLUSIONS: Cirrhotic patients experience a detrimental outcome with an increased risk of gastrointestinal bleeding, which is the first cause of mortality in PMVT. Non-cirrhotic patients, especially idiopathic cases, enjoy a longer survival rate and seldom bleed, which allows for the use of anticoagulative therapy.     

Adolescents who attempt suicide: A retrospective clinical chart review of hospitalized patients.

In a review of pediatric hospital admissions over 4 years, we identified 173 adolescents who had attempted suicide. Of these individuals, 104 (60.1%) were female and 69 (39.9%) were male. The age range was 10–20 years, with approximately 60% of the population being 17–20 years old. The three characteristics most often exhibited by an adolescent in the year prior to the attempt were alcohol use, drug use, and rebellion toward authority. Only 10% of the attempters were reported to have come from a harmonious family. Depression, impulsivity, and anger were the most predominant personality characteristics reported. The suicide attempts were usually precipitated by conflicts with a significant person, either a parent or a boy- or girlfriend, and were accomplished by drug overdose. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Primary antiphospholipid syndrome with recurrent transient ischemic attacks: report of a case and its successful treatment

A 35-year-old woman was admitted to our hospital with complaints of a two-year history of recurrent, daily episodes of transient ischemic attacks; the symptoms consisted of scotoma of her left eye, vertical diplopia, and paresthesia of her right arm. The presence of lupus anticoagulants and anticardiolipin antibodies led to the diagnosis of antiphospholipid syndrome (APS). After thrombotest values had decreased to 30% (international normalized ratio: 1.5) with warfarin, her symptoms did not recur. This suggests that anticoagulant therapy is effective for the prevention of recurrence of ischemic events complicated by primary APS, even when they occur repeatedly.     

Molecular and clinical study of 61 Angelman syndrome patients

This is the first study of of posttraumatic stress symptoms in parents (24 mothers and one father) of children with burns. The purpose of the study was to determine what factors relate to parental posttraumatic stress disorder (PTSD). Because the sample is all mothers, except for one father, the conclusions are about mothers. Through use of the Structured Clinical Interview for DSM-III-R, symptoms were determined as occurring from the time of the burn injury until 1 month before the interview (past), 1 month before the interview only (present), or from the date of the burn trauma up to and including 1 month before the interview (past and present). By Structural Clinical Interview criteria, 52% of the mothers had past PTSD, with four (31%) of those mothers having present PTSD symptoms. Eleven mothers and the one father reported neither past nor present PTSD. Multiple regression analysis revealed that larger burns were more strongly related to present PTSD symptoms than were proximity, social support, or perceived stress. Additional findings indicated that mothers with more than one child burned and those mothers who were burned themselves met diagnostic criteria for PTSD. Implications are that posttraumatic stress symptoms can be disruptive to a mother feeling capable of caring for her child with burns after the injury. Individual and group therapy during and after a child's hospitalization may be useful for mothers to reduce stress and to develop better coping skills.     

Do patients with antiphospholipid syndrome have autoantibodies to beta 2-glycoprotein I?

High positive anticardiolipin antibody tests have been associated with recurrent thrombosis and pregnancy loss. Although these antibodies were believed to bind negatively charged phospholipids, recent reports have suggested that a serum protein, beta 2-glycoprotein I (beta 2-GPI), may be the true antigen for these antibodies. To resolve this issue, we compared binding of 75 anticardiolipin-positive and 71 anticardiolipin-negative serum samples from patients with rheumatic diseases to beta 2-GPI by using an enzyme-linked immunosorbent assay (ELISA). Serum samples from 30 healthy blood donors and 10 laboratory personnel were used as normal controls. We found no difference in binding between the three groups of serum samples. In addition, when binding to beta 2-GPI coated plates was compared with binding to ELISA plates without beta 2-GPI (blank), no difference was observed. Finally, binding of anticardiolipin-positive serum samples to plates coated with cardiolipin-beta 2-GPI mixture varied directly with the cardiolipin concentrations. Based on these findings, we conclude that anticardiolipin-positive serum samples do not bind beta 2-GPI.     

IgG from patients with antiphospholipid syndrome binds to platelets without induction of platelet activation

The clinical manifestations of the antiphospholipid syndrome (APLS) include arterial and venous thrombosis, thrombocytopenia and fetal loss, but the pathogenic mechanisms remain unclear. It has been hypothesized that platelet activation by autoantibody may be a pathogenic mechanism. We studied IgG binding, microparticle (mp) formation and P-selectin expression by flow cytometry in normal platelets after incubation in serum from 11 patients with antiphospholipid antibodies and that from 10 normal healthy subjects. Levels of platelet-associated IgG were significantly higher after incubation in patient sera (mean 17.2, range 2.0-75.0%) compared with normal sera (mean 2.0, range 1.2-3.7%, P<0.05). Incubation of normal platelets in serum led to increased microparticle formation (P<0.01) and P-selectin expression (P < 0.05), compared with unstimulated platelets. There was no significant difference, however, between microparticle formation nor P-Selectin expression induced by patient serum (mp 3.0 (1.6-5.0)%; P-selectin 8.0 (4.0-16.6)%) versus normal serum (mp 3.2 (2.1-4.5)%; P-selectin 10.1 (4.0-15.6); median (range)). Pre-activation of platelets with sub-threshold ADP concentrations or thrombin receptor activator peptide resulted in a small increase in microparticle formation, but there was still no significant difference between the effects of patient and control sera. Despite the presence of platelet membrane binding IgG in serum from 5/11 patients with antiphospholipid antibodies, there was no evidence for associated enhanced platelet-activating ability. This study supports antiplatelet reactivity in antiphospholipid syndrome, but not a direct platelet-activating role for platelet-directed autoantibodies.     

A recurrent missense mutation in the KAL gene in patients with X-linked Kallmann's syndrome

Kallmann's syndrome (KS) is defined by the association of hypogonadotropic hypogonadism and anosmia or hyposmia. Segregation analysis in familial cases has demonstrated diverse inheritance patterns, suggesting the existence of several genes regulating GnRH secretion. Genetic defects have been demonstrated in the KAL gene, located on the Xp22.3 region, explaining the X-linked form of the disease. We report molecular findings regarding the KAL gene in 12 unrelated males with X-linked KS. PCR of the 14 exons of the KAL gene was performed on genomic DNA. PCR products of all exons were purified and sequenced. Genetic defects in the KAL gene were found in 7 patients. One exhibits a deletion from exon 3 to exon 5. Six individuals present a previously unidentified missense mutation in exon 11, consisting of a G to A substitution at codon 514 (GAA to AAA). In the remaining 5 individuals, no mutations were observed. We also found three different polymorphic changes. The first one, in exon 2, had not been reported previously. The other two were located at exons 11 and 12. The deletion described, comprises only part (exon 5) of the coding region of the first fibronectin type III-like repeat of the KAL protein. The rest of the deletion comprises part of the conserved cysteine-rich N-terminal region that corresponds to the whey acidic protein motif. The same missense mutation was found in 6 of the 12 patients, indicating the possibility that it derived from a common ancestor or suggesting the presence of a hot spot in this region of the gene.     

Alterations of lymphocyte subsets in patients with recurrent fetal wastage positive for antiphospholipid antibodies treated with Chinese herbal medicine

The delay technique is an established method of enhancing flap survival. This investigation attempts to determine which of two delay techniques results in the best delay effect by measuring their relative abilities to capture adjacent vascular territories in a rat model. A dorsal flap based on the iliac branch of the iliolumbar artery with a captured random zone corresponding to the axial territory of the lateral thoracic artery was used in the evaluation. Sprague-Dawley rats (350-400 g) were randomly assigned into three groups. Group I was the control group. In group II, the circumferential borders of the animal's dorsum were incised without undermining and the dominant pedicle of the lateral thoracic flap was divided. In group III, the medial and lateral borders of the flap were incised and undermined as a bipedicled flap, violating the musculocutaneous perforators. The dominant pedicle of the lateral thoracic artery was also divided. Group III had the greatest survival with only 9% of flap area necrosis compared to 28% and 21% for groups I and II, respectively. These differences were statistically significant. The results suggest that musculocutaneous perforators provide a substantial vascular source to the tissue at risk and should be considered in selecting a delay technique.     

Vertebral artery injury during anterior decompression of the cervical spine. A retrospective review of ten patients

Ten patients who suffered iatrogenic injury to a vertebral artery during anterior cervical decompression were reviewed to assess the mechanisms of injury, their operative management, and the subsequent outcome. All had been undergoing a partial vertebral body resection for spondylitic radiculopathy or myelopathy (4), tumour (2), ossification of the posterior longitudinal ligament (1), nonunion of a fracture (2), or osteomyelitis (1). The use of an air drill had been responsible for most injuries. The final control of haemorrhage had been by tamponade (3), direct exposure and electrocoagulation (1), transosseous suture (2), open suture (1), or open placement of a haemostatic clip (3). Five patients had postoperative neurological deficits, but most of them resolved. We found direct arterial exposure and control to be safe, quick and reliable. Careful use of the air drill, particularly in pathologically weakened bone, as in infection or tumour, is essential. Arterial injury is best avoided by a thorough knowledge of the anatomical relationships of the artery, the spinal canal, and the vertebral body.     

The clinical syndrome associated with antiphospholipid antibodies. A diagnosis to be confirmed after a long follow-up

A clinical case of syndrome of antiphospholipid antibodies is reported. The patient is a 10-year-old girl with thrombophlebitis of the right leg associated with the presence of lupus-like anticoagulant antibodies. No secondary pathologies were found. It is not possible, anyway, to make a definitive differential diagnosis between primary and secondary forms of syndrome of antiphospholipid antibodies because of intermediate situations where antiphospholipid antibodies are associated with 2 or 3 ARA criteria for the diagnosis of lupus (lupus-like syndrome). A long term follow-up is therefore necessary.