Acquired homozygosity of the rearranged bcr allele during the acute leukemic phase of a patient with Ph-negative chronic myeloid leukemia

A 45-year-old male patient with Ph-negative chronic myeloid leukemia (CML) had rearranged bcr-3' and bcr-5' gene regions in Southern blot studies when leukemia was diagnosed. During development of terminal blast crisis, successive blood samples showed a progressive decrease in the amount of germline bcr DNA and its complete loss by full blast crisis. There were also increased amounts of rearranged bcr DNA consistent with acquired homozygosity. A similar result was obtained with an IgV lambda probe and indicated homozygosity of a significant part of chromosome 22. The bcr-abl gene complex behaves as a somatic dominant in CML, and we suggest that its acquired homozygosity is a mechanism of bcr-abl amplification similar to duplication of the Ph chromosome commonly found in the blast crisis of CML.     

Use of porcine factor VIII in the treatment of patients with acquired hemophilia

Data have been collected from 47 centers in Europe and North America on the treatment with porcine factor VIII concentrate of 74 acute bleeding episodes in 65 patients with acquired hemophilia. The median initial anti-human factor VIII auto-antibody inhibitor level was 38 Bethesda unit (BU)/mL (range 1.2 to 1,024) whereas that against porcine was 1 BU/mL (range 0 to 15). The mean initial dose of porcine factor VIII infused was 84 IU/kg, which increased the plasma factor VIII:C activity by 0.85 IU/mL. Therapy was continued for a mean of 8.5 days during which time the average number of infusions was 11. Objective clinical responses were rated as good or excellent in 78% of recipients. Side effects were uncommon; only one patient experienced a severe anaphylactic reaction necessitating the discontinuation of porcine FVIII therapy. After therapy, no increase in the median level of anti- human FVIII or anti-porcine antibody was noted in the group as a whole, although 13 patients showed individual increases in either anti-human or anti-porcine antibody levels or both of more than 10 BU/mL. Of the 7 patients who subsequently rebled, 5 were successfully re-treated and 2 did not respond to further porcine factor VIII treatment. Porcine factor VIII is safe and clinically effective treatment for bleeding episodes associated with acquired hemophilia and should be considered as first-line therapy for patients whose acquired anti-factor VIII:C antibody cross-reacts with porcine factor VIII:C at low levels.     

Electrophysiologic demonstration of bilateral anomalous pathways in a patient with Wolff-Parkinson-White syndrome (type B preexcitation).

Pre- and postoperative electrophysiologic studies are described that were suggestive of two (right- and left-sided) anomalous atrioventricular (A-V) connections in a patient with type B Wolff-Parkinson-White syndrome and intractable arrhythmias, who underwent epicardial mapping and successful surgical ablation of the right-sided anomalous pathway. The presence of the right-sided anomalous pathway capable of both antegrade and retrograde conduction was suggested by the following observations: (1) Type B preexcitation on the surface electro-cardiogram; (2) maximal preexcitation and minimal stimulus-delta with low lateral right atrial pacing; (3) epicardial mapping of the atria and ventricles; and (4) disappearance of ventricular preexcitation after surgical ablation of the right-sided anomalous pathway. The presence of an additional left-sided anomalous pathway capable of only retrograde conduction (concealed on the surface electrocardiogram) was sugg-sted by the following observations: (1) Left to right retrograde atrial activation sequence during reentrant tachycardia and ventricular pacing at rapid rates and with coupled ventricular pacing postoperatively; (2) spontaneous conversion of wide ORS tachycardia utilizing the anomalous pathway for antegrade conduction to narrow QRS tachycardia with significant slowing in rate; and (3) smooth antegrade A-V nodal conduction curves with echo zone postoperatively. The demonstration of bilateral anomalous pathway in patients with preexcitation has important electrophysiologic and surgical implications.     

The acute-phase protein PTX3 is an essential mediator of glial scar formation and resolution of brain edema after ischemic injury

Acute-phase proteins (APPs) are key effectors of the immune response and are routinely used as biomarkers in cerebrovascular diseases, but their role during brain inflammation remains largely unknown. Elevated circulating levels of the acute-phase protein pentraxin-3 (PTX3) are associated with worse outcome in stroke patients. Here we show that PTX3 is expressed in neurons and glia in response to cerebral ischemia, and that the proinflammatory cytokine interleukin-1 (IL-1) is a key driver of PTX3 expression in the brain after experimental stroke. Gene deletion of PTX3 had no significant effects on acute ischemic brain injury. In contrast, the absence of PTX3 strongly compromised blood–brain barrier integrity and resolution of brain edema during recovery after ischemic injury. Compromised resolution of brain edema in PTX3-deficient mice was associated with impaired glial scar formation and alterations in scar-associated extracellular matrix production. Our results suggest that PTX3 expression induced by proinflammatory signals after ischemic brain injury is a critical effector of edema resolution and glial scar formation. This highlights the potential role for inflammatory molecules in brain recovery after injury and identifies APPs, in particular PTX3, as important targets in ischemic stroke and possibly other brain inflammatory disorders.     

Recombinant tissue plasminogen activator enhances microglial cell recruitment after stroke in mice

The effect of recombinant human tissue plasminogen activator (rtPA) on neuroinflammation after stroke remains largely unknown. Here, we tested the effect of rtPA on expression of cellular adhesion molecules, chemokines, and cytokines, and compared those with levels of inflammatory cell recruitment, brain injury, and mortality over 3 days after transient middle cerebral artery occlusion (MCAO) in mice. Mortality was dramatically increased after rtPA treatment compared with saline treatment during the first day of reperfusion. Among the animals that survived, rtPA significantly increased CCL3 expression, microglia recruitment, and cerebral infarction 6 hours after MCAO. In contrast, the extent of neutrophils and macrophages infiltration in the brain was similar in both saline- and rtPA-treated animals. Recombinant human tissue plasminogen activator induced Il1b and Tnf expression, 6 and 72 hours after MCAO, respectively, and dramatically reduced interleukin 6 (IL-6) level 24 hours after reperfusion. A dose response study confirmed the effect of rtPA on CCL3 and Il1b expressions. The effect was similar at the doses of 1 and 10 mg/kg. In conclusion, we report for the first time that rtPA amplified microglia recruitment early after stroke in association with a rapid CCL3 production. This early response may take part in the higher susceptibility of rtPA-treated animals to reperfusion injury.     

Breastfeeding Shows a Protective Trend toward Adolescents with Higher Abdominal Adiposity

ObjectiveThe question of whether breastfeeding has a protective effect against the development of overweight or obesity later in life remains controversial, especially during adolescence. The objective was to assess the relationship between breastfeeding and adolescents’ body composition.MethodsThe HELENA study is a cross-sectional study involving 3,528 adolescents from 10 European cities. The outcome measures were body weight and height, subscapular skinfolds as well as waist circumferences. Breastfeeding, smoking status, and parental socioeconomic status were assessed by self-administered questionnaires. Dietary intake was recorded using two 24-hour recall surveys. Two adjustment approaches were used: i) covariance analysis adjusted for confounding factors (propensity score adjustment) and ii) multivariate quantile regression.ResultsAfter adjustment, no significant associations were observed between breastfeeding and body composition parameters (BMI Z-score; sum of skinfolds; waist-to-height ratio). An adjusted quantile regression analysis showed a non-significant trend for a protective effect of breastfeeding toward the highest percentiles of adiposity in boys but not in girls. This is of particular interest with respect to the superiority of the waist-to-height ratio over waist circumference and BMI for detecting cardiometabolic risk factors.ConclusionThis first European study, including a large set of factors influencing adolescents’ body composition, showed a non-significant trend toward a protective effect of breastfeeding on highest percentiles of adolescent''s abdominal adiposity.Key Words: Breastfeeding, Body composition, Adolescents, Waist-to-height ratio, BMI, Propensity score     

Results of Stent Supported Percutaneous Transluminal Coronary Angioplasty in Octogenarians With Coronary Artery Disease

Between January 1995 and July 1998, percutaneous transluminal coronary angioplasty was performed on 27 lesions in 24 octogenarians. Half of the patients were African American. Women comprised 67% of the study group. Patients with unstable angina and myocardial infarction constituted 54% of the cohort. Two-thirds of the patients (83%) had single vessel disease with predominant class A and B lesion complexity of the angioplasty site. Acute success rate was 92%. Stents were successfully placed in 11 subjects (46%). None had acute myocardial infarction, emergency coronary artery bypass surgery, or stroke as a complication of the procedure. One patient presenting with acute myocardial infarction complicated by cardiogenic shock, died. Significant bleeding complications requiring blood transfusions occurred in 17% of patients. Of the patients, 23 (96%) were discharged in a clinically stable condition. Follow up during a two year period was completed in 21 patients (88%). One patient died of cancer. Four subjects (19%) underwent repeat percutaneous transluminal coronary angioplasty. One other patient had recurrent chest pain requiring multiple hospitalizations. The remaining 16 patients (76%) remained free of recurrence of angina. We concluded that percutaneous transluminal coronary angioplasty with stent placement can be performed in octogenarians with a high rate of clinical and angiographic success with an acceptable range of morbidity and mortality, and favorable long term (two year) outcome.     

Ageing appearance in China: biophysical profile of facial skin and its relationship to perceived age

Background Perceived age is important to women and is a primary driver for topical product use and facial cosmetic surgery. Changes in facial features and biophysical skin parameters with chronological age and their associations with perceived age have not been described in Asian populations. Objective To investigate the relationship between biophysical properties of the skin, visual features of skin ageing and perceived facial age in Chinese women. Methods Facial photographs were collected of 250 Chinese women, aged 25–70 years in Shanghai, China. The perceived facial age was determined and related to the chronological age for each participant and to a range of visual assessments of skin appearance and objective biophysical measurements of the skin. The profile of changes in these parameters with age was investigated together with the differences in those parameters for women judged to look younger than their chronological age and those judged to look older than their chronological age. Results Large discrepancies in perceived age (up to 29 years) were found in women of the same chronological age. Each objective skin measure and visual assessment parameter had a stronger correlation with perceived age than with chronological age. The strongest relationships to perceived age were for wrinkles and hyperpigmentation. Skin colour, hydration and trans‐epidermal water loss (TEWL) had weaker associations with perceived age. Women judged to look older than their chronological age had significantly higher scores than those judged to look younger for coarse wrinkles and hyperpigmentation across all age groups. The appearance differences between these groups were evident in composite facial images of the same average chronological age. Conclusions We have identified the skin attributes which differ with perceived age in Chinese women. Perceived age is a better measure of the biological age of facial skin than is chronological age in this population.     

Adolescents with type 1 diabetes and risky behaviour

Aim: The aim of the student is to assess whether adolescents with type 1 diabetes mellitus (T1DM) in Italy differ from their healthy peers in regard to risky behaviour. Methods: Data were collected from 215 patients, aged 14 ± 2 years with a mean disease duration of 7 ± 5 years. The control group was comprised of 464 healthy adolescents recruited among high school students. Each patient completed an anonymous confidential questionnaire to determine the prevalence of sexual behaviour, alcohol and tobacco consumption, illicit drug use, and, among patients with diabetes and frequency of mismanagement related to diabetes care. Results: Compared with controls, subjects with diabetes showed a similar rate of sexual intercourse among males and lower rates among females (34.8% vs 35.5%, p NS and 29.4% vs 41.4%, p < 0.05, respectively). Males in the diabetes group reported a higher rate of tobacco use, whereas females showed similar or higher rates of use for every illicit drug studied. Among patients with diabetes, those who are engaged in risky behaviour showed a higher rate of treatment mismanagement (76% vs 34%, p < 0.01). Conclusion: Adolescents with T1DM are as likely as their healthy peers to engage in risky behaviour, indicating the potential benefit of anticipatory guidance concerning glycaemic control and increased risk of acute and chronic complications.