Activated marrow-infiltrating lymphocytes effectively target plasma cells and their clonogenic precursors

A major limitation of adoptive immunotherapy is the availability of T cells specific for both terminally differentiated tumor cells and their clonogenic precursors. We show here that marrow-infiltrating lymphocytes (MILs) recognize myeloma cells after activation with anti-CD3/CD28 beads with higher frequency than activated peripheral blood lymphocytes from the same patients. Furthermore, activated MILs target both the terminally differentiated CD138+ plasma cells and the myeloma precursor as shown by profound inhibition in a tumor clonogenic assay. The presence of antigen in the marrow microenvironment seems to be important for the maintenance of tumor specificity. Taken together, these results highlight the intrinsic tumor specificity of MILs and describe a novel approach for the generation of tumor-specific T-cell populations suitable for adoptive immunotherapy of multiple myeloma.     

Variant carotid origin of left anterior inferior cerebellar artery mimicking infarct on angiography

A case is presented of a rare anterior inferior cerebellar artery variant, originating from the internal carotid artery. This mimicked a cerebellar infarct on vertebral angiography of a patient who presented with dysmetria and gait imbalance. It is important for the neuroradiologist and neurointerventionist to be aware of common and unusual cerebellar arterial anatomic variants to avoid incorrect diagnoses, as well as understand possible implications for surgery and interventional therapies.     

Ethical dilemma of recovering organs before donor death

Organ transplant has had a momentous effect in improving global health over the years. However, there exists a sizeable discrepancy between the supply and demand of organs, especially in developing countries, where lack of expertise, financial constraints, and inadequate transplant facilities have been obstacles. According to current practice, donors must be dead before unpaired vital organs can be recovered. Equal health warrants needs-based health care for everyone. Recovering viable organs from donors while they are alive, but with death inevitable, may be significant to persons on waiting lists. Future policies in organ transplantation must be made after thorough consideration of all aspects of donation and dealing with the inequalities of health care. These pose a challenge for medicolegal and ethical organizations.     

Alopecia areata in children

Objective: To determine the clinical presentations of alopecia areata in children as well as the frequency of associated disorders. Design: Cross-sectional study. Place and Duration of Study: Department of Dermatology, Ziauddin University Hospital, KDLB Campus, Karachi during the calendar years 2005 and 2006. Patients and Methods: Children of either gender suffering from alopecia areata, upto 15 years of age, who fulfilled the selection criteria were included in the study. Only freshly registered cases were studied. Severity of the disease was graded as mild, moderate and severe disease, and other clinical patterns including alopecia totalis, alopecia universalis and ophiasis. Hematological and biochemical profile was evaluated. Chi-square test was applied for statistical analysis in order to determine p-value using the percentages of variables. Results: One hundred and fourteen patients comprising 54 males (47%) and 60 females (53%), aged 4 upto 15 years, the mean age being 9.1 years, were enrolled. Family history of alopecia areata was positive in 11 patients (10%). Fifty nine patients (51%) were of age 6-10 years, 39 patients (35%), aged 11-15 years, and 16 (14%) were of age below 5 years. Mild alopecia areata (41%, p < 0.05) was the most common presentation followed by moderate disease (31%, p < 0.05), severe alopecia (17%, p < 0.05), alopecia totalis (7%, p < 0.05), alopecia universalis (2.7%, p=0.05) and ophiasis (1.7%, p=0.05). Nail changes were found in 40 patients (35%, p < 0.05). Definite evidence of atopy was obtained in 23 patients (20%, p< 0.05). The autoimmune disorders associated with alopecia areata included: hypothyroidism (4.3%), vitiligo (3.5%), psoriasis (1.8%), systemic lupus erythematosus (SLE 0.9%), hypoparathyroidism (0.9%) and diabetes mellitus (0.9%). Conclusion: The spectrum of childhood alopecia areata ranges from mild, moderate and severe alopecia, ultimately to alopecia totalis, alopecia universalis and ophiasis. Nail changes as well as atopy and autoimmune disorders are the associated disorders.     

Gender differences in serum leptin concentrations from umbilical cord blood of newborn infants born to nondiabetic, gestational diabetic and type-2 diabetic mothers

To investigate gender differences, if any, in leptin concentrations from umbilical cord blood of new born infants of mothers with type 2 diabetes mellitus (DM), gestational diabetes mellitus (GDM), and Non diabetic (ND) at delivery. Serum leptin concentrations were measured in 105 newborns (53 males and 52 females in the three groups). Blood was taken from the umbilical cord of the babies at delivery. Maternal anthropometric measurements were recorded within 48 hours after delivery. Pearson correlation coefficient was used to explore the relationship between serum leptin concentrations and anthropometric measures of the fetus and their mother. Both Serum leptin level and serum C-peptide was measured by chemiluminescence based ELISA. The median range of leptin concentration in cord blood was ND group: Male [13.91 (3.22 – 47.63)], Female [16.88 (2 – 43.65)]; GDM group: Male [32 (7 – 76.00)], Female [36.73 (4.80 – 81.20)]; DM group: Male [20.90 (2 –76.00)], Female [32 {2.58 – 80.67)]. Cord serum leptin levels correlated with birth weight(r=0.587, p=0.0001), ponderal index (PI) (r=.319, p=0.024)of the babies and body mass index (BMI) (r=−0.299, p=0.035) of their mothers but did not correlate with gestational age, cord serum C-peptide concentration or placental weight at delivery. Leptin concentrations were higher in the female fetus in comparison to the male fetus. Birth weight of the female fetuses were also higher than that of male fetus. We found that there are very strong associations between cord leptin concentrations at delivery and birth weight, ponderal index of the baby, body mass index of the mothers with Type 2 DM. We also found that high leptin levels could represent an important feedback modulator of substrate supply and subsequently for adipose tissue status during late gestation or adipose tissue is the major determinant of circulating leptin levels.     

Promoting Global Research Excellence in Severe Sepsis (PROGRESS): Lessons from an International Sepsis Registry

Abstract Background:   The PROGRESS Registry (Promoting Global Research Excellence in Severe Sepsis) was designed to provide comparative data reflecting everyday clinical practice, thereby allowing participating institutions to explore and benchmark medical interventions in severe sepsis. Materials and Methods:   PROGRESS was an international, noninterventional, prospective, observational registry collecting data that describe the management and outcomes of severe sepsis patients in intensive care units (ICUs). Patients were enrolled who had been diagnosed with severe sepsis (suspected or proven infection and ≥ 1 acute sepsis-induced organ dysfunction) at the participating institutions, where de-identified data were entered directly into a secured website. PROGRESS was governed by an independent international medical advisory board. Results:   PROGRESS took place in 276 ICUs in 37 countries, and 12,881 patients were identified as having severe sepsis. There was considerable variation among countries in enrollment levels, provision of standard treatment and supportive therapies, and ICU and hospital outcomes. Eight countries accounted for 65.2% of the enrolled patients. Males (59.3%) and Caucasian (48.6%) patients predominated the patient cohort. Diagnosis of severe sepsis was prior to ICU admission in 45.7% of patients, at ICU admission in 29.1% of patients, and after ICU admission in the remainder. Globally, ICU and hospital mortality rates were 39.2% and 49.6%, respectively. The mean length of ICU and hospital stay was 14.6 days and 28.2 days, respectively. Conclusions:   The PROGRESS international sepsis registry demonstrates that a large web-based sepsis registry is feasible. Wide variations in outcomes and use of sepsis therapies were observed between countries. These results also suggest that additional opportunities exist across countries to improve severe sepsis outcomes.