Peripheral blood progenitor cell transplantation in lymphoma and leukemia using a single apheresis

Myeloablative treatment and peripheral blood progenitor cell (PBPC) transplantation are increasingly used for lymphomas and leukemias. We have sought to optimize conditions for priming, collection, and engraftment of the leukapheresis product. Fifty-four consecutive adult patients were eligible, 31 with high-grade non-Hodgkin's lymphoma of poor prognosis, 12 with Hodgkin's disease in chemosensitive relapse, and 11 with poor prognosis acute lymphoblastic leukemia. Filgrastim was administered after routine chemotherapy with VAPEC-B or HiCCOM to mobilize PBPC. A rapidly increasing white blood cell count was used to predict the time of peak PBPC release and plan leukapheresis. Forty- five patients underwent leukapheresis. A median of 14 L of blood was processed at a single apheresis. A median of 2.4 x 10(8)/kg mononuclear cells (MNCs), 1.04 x 10(6)/kg granulocyte-macrophage colony-forming cells (GM-CFCs), and 10.6 x 10(6)/kg CD34+ cells were obtained. Slightly fewer MNCs were obtained from the heavily pretreated Hodgkin's disease group. There were no other significant differences in the size or composition of the leukapheresis harvest in the three patient groups. Forty patients underwent high-dose therapy and PBPC transplantation. Filgrastim was administered by daily subcutaneous injection until the absolute neutrophil count was > or = 1 x 10(9)/L for 2 consecutive days. Rapid and sustained hematopoietic engraftment occurred in all patients. The median time to achieve a neutrophil count > or = 0.5 x 10(9)/L was 9 days (range, 8 to 16 days); to achieve a platelet count > or = 20 x 10(9)/L was 10 days (range, 6 to 88 days); and to achieve a platelet count > or = 50 x 10(9)/L was 15.5 days (range, 10 to 100 days). Neutrophil recovery was faster than that of a historical control group treated with autologous bone marrow transplantation and filgrastim, but platelet recovery times were halved in the PBPC group. There was no secondary engraftment failure. Requirements for blood and platelet transfusions, antibiotic use, and parenteral nutrition were similar in the three patient groups. The median number of days in the hospital was 13 (range, 10 to 55) in the PBPC patients, compared with 19 (range, 14 to 51) in the historical controls. Leukapheresis yields (MNC, GM-CFC, and CD34+ cell numbers) were not useful for predicting the times to engraftment. We have shown that sufficient PBPC for transplantation can be obtained at a single leukapheresis after mobilization with routine chemotherapy and filgrastim in patients with non-Hodgkin's lymphoma, Hodgkin's disease, and acute lymphoblastic leukemia, even those heavily pretreated.(ABSTRACT TRUNCATED AT 400 WORDS)     

The maternal Mediterranean dietary pattern is associated with a reduced risk of spina bifida in the offspring

Objective  The objective of this study was to test the hypothesis whether a maternal dietary pattern is associated with the risk of spina bifida (SB) in the offspring.
Design  Case–control study.
Setting  Eight clinic sites in the Netherlands, 1999–2001.
Sample  A total of 50 mothers of children with SB and 81 control mothers.
Methods  Maternal food intakes were obtained by food frequency questionnaires at the standardised study moment of 14 months after the birth of the index child. Principal component factor analysis (PCA) and reduced rank regression (RRR) were used to identify dietary patterns.
Main outcome measures  Maternal biomarkers were used as response measures in the RRR analysis and composed of serum and red blood cell (RBC) folate, serum vitamin B12 and total plasma homocysteine. The strength of the use of the dietary pattern in association with SB risk was estimated by odds ratios and 95% CI with the highest quartiles of the dietary pattern as reference.
Results  A predominantly Mediterranean dietary pattern was identified by both PCA and RRR. Those dietary patterns were highly correlated ( r = 0.51, P < 0.001) and characterised by joint intakes of fruit, vegetables, vegetable oil, alcohol, fish, legumes and cereals and low intakes of potatoes and sweets. We observed a significantly increased risk of SB offspring in mothers with a weak use of the Mediterranean dietary pattern, OR 2.7 (95% CI 1.2–6.1) and OR 3.5 (95% CI 1.5–7.9). The Mediterranean dietary pattern was correlated with higher levels of serum and RBC folate, serum vitamin B12 and lower plasma homocysteine.
Conclusion  The Mediterranean dietary pattern seems to be associated with reduction in the risk of offspring being affected by SB.     

Example of somatic mosaicism in a series of de novo neurofibromatosis type 1 cases due to a maternally derived deletion

Neurofibromatosis type 1 (NF1), affecting primarily the growth of neural crest-derived tissues, is one of the most common autosomal dominant genetic disorders with an unusually high spontaneous mutation rate. In four cases of sporadic NF1, demonstrated by hemizygosity to have a deletion involving the NF1 gene, we were able to assign the deletion event to the maternally derived chromosome. One of these individuals was determined to be a somatic mosaic for NF1, as a trace of the maternally derived haplotype was detected at the NF1 locus. This indicated a postzygotic, as opposed to gametic, deletion event. It may be that somatic mosaicism is more common in NF1 than has hitherto been appreciated and may responsible in part for the high mutation rate in this disorder. In addition, it is suggested that the mechanism(s) of gene deletion is subject to a parent of origin effect, being more frequent on the maternally derived chromosome. This is in contrast to the other types of mutations which, in sporadic NF1, have been found to occur preferentially on the paternally derived chromosome. Hum Mutat 9:452–457, 1997 © 1997 Wiley-Liss, Inc.     

Abdominal compartment syndrome caused by tension pneumoperitoneum in a scuba diver

Abdominal compartment syndrome is a surgical emergency caused by a raised intra-abdominal pressure, which may lead to respiratory, cardiovascular and renal compromise. It is most commonly seen in post-operative and trauma patients and it has a variety of causes. Tension pneumoperitoneum (TP) is a rare cause of abdominal compartment syndrome most often seen after gastrointestinal endoscopy with perforation.We present the case of a fit 52-year-old experienced female diver who developed TP and shock following a routine training dive to 27m. Following accidental inhalation of water, she had an unstaged ascent and, on reaching the surface, developed severe acute abdominal pain and distension. She was brought to our emergency department by air ambulance for assessment. Clinical and radiological examination revealed a shocked patient with dramatic free intra-abdominal gas and signs of abdominal compartment syndrome, which was treated with needle decompression. Symptoms and signs resolved quickly with no need for further surgical intervention. TP is a surgical emergency where surgery can be avoided with prompt diagnosis and treatment.     

Antihypertensive Medication Prescribing Patterns in a University Teaching Hospital

J Clin Hypertens (Greenwich) Treatment of hypertension among hospitalized patients represents an opportunity to improve blood pressure recognition and treatment. To address this issue, the authors examined patterns of antihypertensive medication prescribing among 5668 hypertensive inpatients. Outcomes were treatment with any antihypertensive medication and treatment with first-line therapy, defined as angiotensin-converting enzyme inhibitors, β-blockers, thiazide diuretics, or calcium channel blockers. Logistic regression models adjusting for age, sex, race, length of stay, service line, and comorbidity were used for all comparisons. The multivariate-adjusted odds ratios for treatment were higher for men (1.4, P<.001), older patients (2.5 for age older than 80 vs 1.0 for age younger than 40; P<.001), non-white race (1.2 vs 1.0 for white race; P<.004), and generalist service line (1.4 vs 1.0 for all other services; P<.001). Multivariate-adjusted odds ratios for receiving first-line agents were higher for older patients and generalist service line. Among surgical patients, receipt of medical consultation was only marginally associated with higher odds of antihypertensive or first-line treatment after adjustment for relevant clinical variables. Demographic factors and service line appear to play a major role in determining the likelihood of inpatient hypertension treatment. Understanding and addressing these disparities has the potential to incrementally improve hypertension control rates in the population.