Ear-related problems among children attending the paediatric and otorhinolaryngology out-patients clinics of the University of Nigeria Teaching Hospital,Enugu

BackgroundEar related diseases are commonly seen in clinics worldwide especially among children. They are associated with significant morbidity and frequent hospital visits. Limited data exists regarding the burden of ear disease among Nigerian children.ObjectiveTo determine the prevalence of ear-related problems among children presenting at the Paediatric and Otorhinolaryngology clinics of the University of Nigeria Teaching Hospital, Enugu.ResultsThree thousand and twenty-one children were seen during the study period. Out of these, 248 children (8.2%) presented with ear-related problems. Chronic otitis media (30.5%), acute otitis media (29.9%), cerumen auris (11.3%), otitis externa (10.1%), hearing impairment (7.3%) and foreign body in the ear (5.7%) were the most commonly diagnosed ear-related problems.ConclusionEar-related problems among children presenting at the UNTH Enugu were not uncommon. However, otitis media was the most commonly diagnosed ailment affecting the ears in children.     

Comparative effects of nisoldipine, nifedipine and bepridil on experimental pulmonary hypertension

Calcium channel blockers sometimes reduce pulmonary vascular resistance (PVR) in patients with pulmonary hypertension. This study compares the pulmonary vasodilator effect of two new calcium channel blockers, nisoldipine and bepridil, to that of nifedipine in three groups of anesthetized dogs (n = 8 for each group). In each group the normoxic hemodynamics were recorded before and after low, medium and high doses of the respective agents given i.v. In addition, the effect of these doses on the pulmonary pressor responses to hypoxia and prostaglandin F2 alpha (PGF 2 alpha) was measured. During normoxia all doses of bepridil caused brief increases in cardiac output. However, during the hypoxic and PGF 2 alpha challenges cardiac output fell and PVR rose above predrug responses, rather than being reduced. Nisoldipine produced a sustained increase in cardiac output throughout the experiment. During hypoxia, at high dose, it decreased pulmonary arterial pressure, unlike the two other agents. However, in common with them, nisoldipine also caused systemic hypotension. After medium and high dose nisoldipine and after high dose nifedipine, PVR remained close to normoxic control levels during both hypoxic and PGF 2 alpha challenges. Both medium dose nisoldipine (5 X 10(-8) M/kg) and high dose nifedipine (5 X 10(-7) M/kg) reduced hypoxic PVR by 39% of the untreated hypoxic value. Although nisoldipine is more effective in reducing pulmonary hypertension than nifedipine or bepridil, it also causes marked systemic hypotension. This lack of specificity may limit the therapeutic potential of this agent when given i.v.     

MRI assessment of aortic flow in patients with pulmonary arterial hypertension in response to exercise

Background

While primarily a right heart disease, pulmonary arterial hypertension (PAH) can impact left heart function and aortic flow through a shifted interventricular septum from right ventricular pressure overload and reduced left ventricular preload, among other mechanisms. In this study, we used phase contrast (PC) MRI and a modest exercise challenge to examine the effects of PAH on systemic circulation. While exercise challenges are typically performed with ultrasound in the clinic, MRI exercise studies allow for more reproducible image alignment, more accurate flow quantification, and improved tissue contrast.

Methods

Six PAH patients and fifteen healthy controls (8 older age-matched, 7 younger) exercised in the magnet bore with an MRI-compatible exercise device that allowed for scanning immediately following cessation of exercise. PC scans were performed in the ascending aorta during a breath hold immediately after modest exercise to non-invasively measure stroke volume (SV), cardiac output (CO), aortic peak systolic flow (PSF), and aortic wall stiffness via relative area change (RAC).

Results

Images following exercise showed mild blurring, but were high enough quality to allow for segmentation of the aorta. While SV was approximately 30% lower in PAH patients (SV_PAH,rest?=?67?±?16?mL; SV_PAH,stress?=?90?±?42?mL) than age-matched controls (SV_,older,rest?=?93?±?16?mL; SV_older,stress?=?133?±?40?mL) at both rest and following exercise, CO was similar for both groups following exercise (CO_PAH,stress?=?10.8?±?5.7?L/min; CO_older,stress?=?11.8?±?5.0?L/min). This was achieved through a compensatory increase in heart rate in the PAH subjects (74% increase as compared to 29% in age-matched controls). The PAH subjects also demonstrated reduced aortic peak systolic flow relative to the healthy controls (PSF_PAH,_rest?=?309?±?52?mL/s; PSF_older,_rest?=?416?±?114?mL/s; PSF_PAH,_stress?=?388?±?113?mL/s; PSF_older,_stress?=?462?±?176?mL/s). PAH patients and older controls demonstrated stiffer aortic walls when compared to younger controls (RAC_PAH,rest?=?0.15?±?0.05; RAC_older,rest?=?0.17?±?0.05; RAC_young,rest?=?0.28?±?0.08).

Conclusions

PC MRI following a modest exercise challenge was capable of detecting differences in left heart dynamics likely induced from PAH. These results demonstrated that PAH can have a significant influence on systemic flow, even when the patient has no prior left heart disease. Image quantification following exercise could likely be improved in future studies through the implementation of free-breathing or real-time MRI acquisitions.

Trial registration

Retrospectively registered on 02/26/2018 (TRN:NCT03523910).

     

Preparation and successful engraftment of purified CD34+ bone marrow progenitor cells in patients with non-Hodgkin's lymphoma

From September 1992 to January 1994, we evaluated the use of the CEPRATE SC stem cell concentrator (CellPro, Inc, Bothell, WA) to select CD34+ cells from the bone marrow (BM) of 25 patients with non-Hodgkin's lymphoma in complete remission. This system uses the biotinylated 12.8 IgM MoAb to select CD34+ cells. Cells are retained on an avidin column and detached by agitation. Fifteen patients have been transplanted with the CD34+ purified fraction. The CD34+ purified fraction of the 25 processed BMs contained a median of 0.54% of the original nucleated cells in a volume of 5 to 10 mL. The median concentration of CD34+ cells was 49% (range, 12% to 80%), and the median enrichment of CD34+ cells was 33-fold (range, 9- to 85-fold). This selected CD34+ fraction retained 60% (range, 15% to 95%) of late granulocyte-macrophage colony- forming units (CFU-GM), 55% (range, 12% to 99%) of early CFU-GM, and 31% (range, 2% to 100%) erythroid burst-forming units (BFU-E) corresponding to median enrichments of 22-fold (range, 1- to 71-fold), 19-fold (range, 2- to 58-fold), and 14-fold (range, 2- to 200-fold), respectively. There was a correlation between immune phenotypes and progenitor cells. In the initial buffy-coat fractions, the percentage of CD34+ cells was correlated to the cloning efficiency of both late CFU-GM (P < .05) and early CFU-GM (P < .001). In the final selected fraction, there was a correlation between the percentage of CD34+/CD33- and the cloning efficiency of early CFU-GM (P < .05) and between the percentage of CD34+/CD33+ and the cloning efficiency of late CFU-GM (P < .05). Lymphoma cells positive for t(14; 18) were found by polymerase chain reaction in 9 of 14 buffy coats tested before CD34+ cell purification. In 8 cases, the CD34(+)-selected fraction was found to be negative, and the CD34- fraction was found to be positive. After cryopreservation, the recoveries of progenitor cells in the CD34(+)- purified fraction were 79% for late CFU-GM, 71% for early CFU-GM, and 73% for BFU-E. The 15 patients transplanted with the concentrated CD34+ fraction received a median dose of 1 x 10(6) CD34+ cells/kg (range, 0.3 to 2.96) and 10.62 x 10(4) early CFU-GM/kg (range, 0.92 to 25.55). Median days to recovery to 0.5 x 10(9)/L neutrophils and 50 x 10(9)/L platelets were days 15 (range, 10 to 33) and 23 (range, 11 to 68), respectively.(ABSTRACT TRUNCATED AT 400 WORDS)     

"Maximal" drug therapy is not necessarily optimal in chronic angina pectoris

Beta-adrenergic blocking agents, nitrates and calcium channel antagonists are effective in treating angina pectoris, but much remains unknown about how they act in combination. Consequently, treadmill exercise was used to assess the relative efficacy of nifedipine or isosorbide dinitrate, or both, in 19 patients with stable angina receiving propranolol. Propranolol therapy was continued and either placebo, nifedipine (20 mg), isosorbide dinitrate (20 mg) or both drugs were given randomly 1 1/2 hours before exercise in a double-blind trial. In 16 patients who completed the protocol, heart rate at rest during propranolol therapy was 53.7 +/- 1.9 beats/min (mean +/- standard error of the mean); it increased 4.6 +/- 1.2 beats/min with the addition of nifedipine (p less than 0.01), but was unchanged with isosorbide dinitrate or both combined. Compared with values during treatment with propranolol alone, systolic blood pressure at rest decreased with each vasodilator individually and when combined. Rate-pressure product at maximal exercise was the same with all combinations. Exercise duration was 467 +/- 50 seconds with propranolol, increased to 556 +/- 47 seconds with isosorbide dinitrate (p less than 0.05) and to 636 +/- 50 seconds with nifedipine (p less than 0.001). Exercise duration with all three drugs was 597 +/- 47 seconds (p less than 0.01 compared with propranolol alone). The improvement with nifedipine was greater than with isosorbide dinitrate (p less than 0.05) but exercise duration was not significantly different with the combination of these drugs than when either drug was used alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amifostine improves the antileukemic therapeutic index of mafosfamide: implications for bone marrow purging

One of the principal challenges of cancer chemotherapy is the relative inability of most anticancer drugs to distinguish between normal and neoplastic tissues. Consequently, a broad range of toxicities are experienced by patients, especially myelosuppression. Amifostine, a phosphorylated aminothiol, increases the selectivity of specific anticancer drugs for neoplastic cells by protecting normal tissues. One potential application of this protector is during bone marrow purging to selectively remove contaminating cancer cells. This study took normal or leukemic marrow from human subjects and evaluated the ability of amifostine to selectively protect normal bone marrow progenitor cells versus leukemic progenitor cells from the cytotoxic effect of mafosfamide. The dose response of mafosfamide amifostine on leukemia colony-forming units or normal marrow progenitor cells was determined and the LD95 was calculated. Amifostine pretreatment resulted in a statistically significant protection of granulocyte-macrophage colony- forming units and erythroid blast-forming units from the toxicity of mafosfamide (P = .031). Thus, amifostine protection of normal marrow progenitor cells allows a higher LD95 concentration of mafosfamide to be used in ex vivo purging. In contrast, amifostine pretreatment increased the cytotoxicity of mafosfamide on the fresh human leukemia progenitor cells (P = .006). The dual effect of amifostine protection of normal marrow progenitor cells coupled with amifostine-induced sensitization of the leukemia cells increases the possible cell-kill of leukemic stem cells. With amifostine pretreatment, at the LD95 concentrations of mafosfamide for marrow progenitor cells, there was an estimated 6 log increase in cell-kill of the leukemia cells. This selective cell-kill offers the potential for lowering the incidence of leukemic relapse, while preserving more normal stem cells for autologous transplantation.