Therapeutic leukocytapheresis for improvement in respiratory function in a woman with hyperleukocytosis and mantle cell lymphoma with a circulating small lymphocyte phenotype

Mantle cell lymphoma is an aggressive malignant B‐cell disorder that often presents with a leukemic picture. Circulating lymphoma cell morphology may vary from small round mature‐appearing lymphocytes resembling the lymphocytes of chronic lymphocytic leukemia to large prolymphocytoid or blastoid cells. Rare reports of hyperleukocytosis with leukostasis, treated with leukocytapheresis, are described in patients with prolymphocytoid or blastoid morphology. We report an 88 year old woman with mantle cell lymphoma, hyperleukocytosis (WBC > 400 × 10³/µL) with severe respiratory compromise but without interstitial or alveolar infiltrates on radiograph or computerized tomography of the chest. She was afebrile and had no central nervous system signs. Circulating lymphoma cell morphology was predominantly of the small lymphocyte type. A two‐whole‐blood‐volume leukocytapheresis reduced her WBC from 465 to 221 × 10³/µL in 150 min. Her respiratory rate decreased from 28/min to 18/min and her arterial oxygen saturation (SpO₂) rose from 91% to 97% on 6 L/min of oxygen by nasal cannula. Severe breathlessness before the procedure abated completely by the end of the procedure. Respiratory compromise may occur in mantle cell lymphoma with hyperleukocytosis with a mature lymphoma cell phenotype, even without a clear picture of leukostasis. Although the ultimate survival of the patient depends on treatment with chemotherapy, leukocytapheresis for alleviation of symptoms may be warranted and should be considered. Respiratory status and response to leukocytapheresis should be documented with physiological measurements. J. Clin. Apheresis 31:398–402, 2016. © 2015 Wiley Periodicals, Inc.     

Presence of calcitonin-like peptide in rat milk: possible physiological role in regulation of neonatal prolactin secretion

Previous results have shown that salmon calcitonin (sCT), a peptide in rat brain and pituitary gland, inhibits basal and TRH-stimulated PRL release and reduces PRL mRNA levels in isolated anterior pituitary cells of adult rats in culture. Rat milk contains a variety of neuropeptides and hormones, some of which are absorbed in bioactive form to exert endocrine influences in the developing offspring. The present studies were undertaken to investigate whether a CT-like peptide is present in rat milk. Circulating PRL levels in neonatal rats are low, and there is an abrupt increase in the basal secretion of this hormone at weaning. A second objective was to examine whether CT plays a role in the regulation of PRL secretion in neonatal animals. A sensitive and specific RIA for sCT was developed and used to assay rat milk on various days of lactation for sCT-like immunoreactivity. sCT-like activity was present in the water-soluble (infranatant) fraction of milk throughout lactation in concentrations as high as 1589 pg/ml. There were no statistically significant differences in immunoreactive levels of the peptide in milk samples from different days of lactation. sCT-like immunoreactivity in rat milk infranatant coeluted with synthetic sCT on reverse phase HPLC, and these HPLC fractions inhibited basal PRL release when added to cultures of anterior pituitary cells. This inhibition of PRL release by the sCT-immunoreactive HPLC fractions was comparable to that exerted by equivalent concentrations of synthetic sCT. Newborn rats were injected sc with 10 microliters normal rabbit serum or anti-sCT serum from the day of birth until postpartum day 10. The rats were killed on day 11, and their sera were analyzed for PRL. Anti-sCT-injected rats showed a significant increase in serum PRL levels compared to those in untreated or normal serum-treated rats. These results demonstrate that a CT-like peptide, which is a potent inhibitor of PRL release, is present in rat milk throughout lactation, and that passive immunization with a highly specific anti-sCT serum leads to an increase in serum PRL levels in neonatal rats. CT, possibly of milk origin, may be a physiologically relevant PRL-inhibiting factor during the neonatal period.     

Role of transesophageal echocardiography in the clinical management of a patient with a giant coronary artery aneurysm

Transthoracic echocardiography (TTE) has substantial limitations for the study of abnormalities of the coronary tree. Transesophageal echocardiography (TEE) allows a more complete examination of the coronary arteries, particularly the proximal segments. This report describes the use of TEE after cardiac catheterization in the clinical management of a patient with unstable angina. While angiography first showed the giant aneurysm of the left circumflex coronary artery, TEE, by revealing an active thrombus of the lumen, prompted an immediate surgical resolution.     

New norms for a new generation: cognitive performance in the framingham offspring cohort

A previous publication presented normative data on neuropsychological tests stratified by age, gender, and education based on the Original Cohort of the Framingham Heart Study. Many contemporary investigations include subject samples with higher levels of education, a factor known to affect cognitive performance. Secular change in education prompted the reexamination of norms in the children of the Original Cohort. The study population consisted of 853 men and 988 women from the Offspring Study, free of clinical neurological disease, who underwent a neuropsychological examination, which included tests given to their parents in 1974 to 1976 as well as additional newer tests to provide a more comprehensive battery. The Offspring population overall was more evenly distributed by gender and better educated. Their performance on cognitive tests was superior to that of the Original Cohort. Multivariable analyses revealed that more years of education explained only a part of the cohort differences. These findings suggest that continued surveillance of each generation is necessary to document the impact that unique social and economic variables have on cognitive function. Here, the authors provide updated normative data.     

A Hybrid Markov Chain–von Mises Density Model for the Drug-Dosing Interval and Drug Holiday Distributions

Lack of adherence is a frequent cause of hospitalizations, but its effects on dosing patterns have not been extensively investigated. The purpose of this work was to critically evaluate a novel pharmacometric model for deriving the relationships of adherence to dosing patterns and the dosing interval distribution. The hybrid, stochastic model combines a Markov chain process with the von Mises distribution. The model was challenged with electronic medication monitoring data from 207 hypertension patients and against 5-year persistence data. The model estimates distributions of dosing runs, drug holidays, and dosing intervals. Drug holidays, which can vary between individuals with the same adherence, were characterized by the patient cooperativity index parameter. The drug holiday and dosing run distributions deviate markedly from normality. The dosing interval distribution exhibits complex patterns of multimodality and can be long-tailed. Dosing patterns are an important but under recognized covariate for explaining within-individual variance in drug concentrations.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-014-9713-5) contains supplementary material, which is available to authorized users.KEY WORDS: adherence, circular distribution, compliance, dosing patterns, runs     

Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses.

BACKGROUND: Cardiac resynchronization therapy (CRT) for congestive heart failure patients with delayed left ventricular (LV) conduction is clinically beneficial in approximately 70% of patients. Unresolved issues include patient selection, lead placement, and efficacy of LV pacing alone. Being an electrical approach, detailed electrical information during CRT is critical to resolving these issues. However, electrical data from patients have been limited because of the requirement for invasive mapping. OBJECTIVES: The purpose of this study was to provide observations and insights on the variable electrophysiologic responses of the heart to CRT using electrocardiographic imaging (ECGI). METHODS: ECGI is a novel modality for noninvasive epicardial mapping. ECGI was conducted in eight patients undergoing CRT during native rhythm and various pacing modes. RESULTS: In native rhythm (six patients), ventricular activation was heterogeneous, with latest activation in the lateral LV base in three patients and in the anterolateral, midlateral, or inferior LV in the remainder of patients. Anterior LV was susceptible to block and slow conduction. Right ventricular pacing improved electrical synchrony in two of six patients. LV pacing in three of four patients involved fusion with intrinsic excitation resulting in electrical resynchronization similar to biventricular pacing. Although generally electrical synchrony improved significantly with biventricular pacing, it was not always accompanied by clinical benefit. CONCLUSION: Results suggest that (1) when accompanied by fusion, LV pacing alone can be as effective as biventricular pacing for electrical resynchronization; (2) right ventricular pacing is not effective for resynchronization; and (3) efficacy of CRT depends strongly on the patient-specific electrophysiologic substrate.     

Divergent outcomes of gut microbiota alteration upon use of spectrum antibiotics in high sugar diet-induced diabetes in rats

Background: A sugar rich diet induces inflammation and insulin resistance (IR) mainly through gut microbiota alteration. Gut dysbiosis increases lipopolysaccharide (LPS) and reduces propionate and butyrate levels to impair the insulin signalling cascades by different molecular pathways, which progresses into IR. The present study was designed to investigate the effect of spectrum specific antibiotics on the modulation of gut microbiota and its signalling pathways to prevent diet-induced diabetes. Methods: Healthy male Wistar rats were divided into a non-diabetic group with a control diet (CD), a diabetic group with a high sucrose diet (HSD) and two antibiotic fed groups (linezolid and cefdinir; administered by oral gavage) along HSD. Physiological, biochemical, inflammatory and microbiome parameters were examined. Results: Cefdinir administration in HSD rats reduced fasting glucose, serum triglyceride, and cholesterol levels compared to HSD alone. In addition, cefdinir reduced serum LPS by decreasing the population of Gram-negative phyla, that is, Bacteroidetes and Proteobacteria in the fecal content. Furthermore, cefdinir treatment decreased hepatic/ileal/colonic Tlr4, Nlr1, and Nf-κB at the mRNA level. Moreover, cefdinir-treated rats had shown increased fecal butyrate and propionate and reduced acetate levels compared to HSD alone. Cefdinir treatment also induced ileal/colonic Gpr43 and Glut4 at the mRNA level after 12 weeks of administration. Conclusions: Taken together, these data suggest that administration of a Gram-negative spectrum antibiotic, that is, cefdinir, has modulated the gut microbiota, and reduced serum LPS and triglycerides, which prevented the progression of IR and inflammation in HSD rats.

A sugar rich diet induces inflammation and insulin resistance (IR) mainly through gut microbiota alteration.