Efficacy and Feasibility of Allogeneic Hematopoietic Stem-Cell Transplantation in the Treatment of Refractory Acute Myeloid Leukemia

Background

Refractory acute myeloid leukemia (AML) includes AML includes failure of disease to respond to standard induction chemotherapy, relapse within 6 months after first CR, and 2 or more relapses. The outcome of these patients is usually very poor; only a small proportion can be rescued by allogenic hematopoietic stem-cell transplantation (allo-HSCT). The aim of this study was to evaluate the efficacy and feasibility of allo-HSCT in patients with refractory AML.

Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application

Background/aim  Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs.
Methods  Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N₂ cryosurgery (spray, two cycles, 10–20 s) and imiquimod was continued for additional 2–12 weeks (median, 4). The outcome after at least 18 months of follow-up (18–24 months) is currently reported.
Results  Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions  'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results.     

Increased salt retention and hypertension from non-steroidal agents in the elderly

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.      

Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Preparation of magnetic dye affinity adsorbent and its use in the removal of aluminium ions

Aluminium has recently been considered as a causative agent in dialysis encephalopathy, osteodystrophy, and anemia occuring in hemodialysis patients. The aim of this study is to prepare magnetic poly(2-hydroxyethylmethacrylate) (mPHEMA) adsorbent and to investigate it's useability for the removal of Al(III) ions from drinking and dialysis water. Magnetic PHEMA beads in a size range 80-120 microm were produced by a dispersion polymerization technique. Then Alizarin Red was covalenlty attached onto the mPHEMA beads. Al(III) adsorption from aqueous solutions was examined by batch system. mPHEMA beads were characterized by swelling tests, electron spin resonance (ESR), scanning electron microscopy (SEM), and elemental analysis. Important results obtained in this study are as follows: the swelling ratio of mPHEMA beads was 34%. The presence of magnetite in the polymeric structure was confirmed by ESR. The mPHEMA beads have a spherical shape and porous structure. Alizarin Red loading was 135.8 micromol g(-1) polymer. The maximum Al(III) adsorption was 722 micromol g(-1) polymer at pH 5.0. Non-specific Al(III) adsorption was about 23 micromol g(-1) polymer under the same conditions. High desorption ratios (98%) were achieved by using 0.1 M HNO3. It was possible to reuse the beads without significant loss of Al(III) adsorption capacity.     

Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions

Autosomal dominant cerebellar ataxia with progressive macular degeneration is caused by a CAG/glutamine repeat expansion in the SCA7 gene/protein. Neuronal intranuclear inclusions were detected in the brain of an early onset SCA7 case with the 1C2 antibody directed against an expanded polyglutamine domain. Nuclear inclusions were most frequent in the inferior olivary complex, a site of severe neuronal loss in SCA7. They were also observed in other brain regions, including the cerebral cortex, not considered to be affected in the disease. Using confocal microscopy we showed that some inclusions were ubiquitinated, but to varying degrees, ranging from <1% in the cerebral cortex to 60% in the inferior olive. In addition, we also observed cytoplasmic staining using the 1C2 antibody, particularly in the supramarginal gyrus, the hippocampus, the thalamus, the lateral geniculate body and the pontine nuclei. These data confirm that the presence of intranuclear inclusions in neurons is a common characteristic of disorders caused by CAG/polyglutamine expansions, but unlike what has been reported for Huntington's disease, SCA1 and SCA3/MJD, in SCA7 the inclusions were not restricted to the sites of severe neuronal loss.      

Mental health of adolescents associated with sexual and reproductive outcomes: a systematic review

ObjectiveTo systematically review the literature on the mental health of adolescents associated with sexual and reproductive outcomes, and compare the mental health outcomes with that of other age groups.MethodsWe searched seven databases for relevant peer-reviewed articles published between 1 January 2010 and 25 April 2019. Our inclusion criteria required that the study included age-disaggregated data on adolescents, and focused and assessed mental health outcomes associated with pregnancy or sexually transmitted infections. We extracted data on the specific health event, the mental health outcome and the method of measuring this, and comparisons with other age groups.FindingsAfter initially screening 10 818 articles by title and abstract, we included 96 articles in our review. We observed that a wide-ranging prevalence of mental ill-health has been reported for adolescents. However, most studies of mental health during pregnancy did not identify an increased risk of depression or other mental disorders among adolescents compared with other age groups. In contrast, the majority of studies conducted during the postpartum period identified an increased risk of depression in adolescents compared with other age groups. Three studies reported on mental health outcomes following abortion, with varying results. We found no studies of the effect of sexually transmitted infections on mental health among adolescents.ConclusionWe recommend that sexual and reproductive health services should be accessible to adolescents to address their needs and help to prevent any adverse mental health outcomes.     

Thyroid dysfunction after mantle irradiation of Hodgkin's disease patients

Thyroid dysfunction can develop in patients with Hodgkin's disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, lymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated.     

CT-Cephalometry—A study in Indian population

Determination of obstructive site in obstructive sleep apnoea (OSA) is of paramount importance is planning the management. Cephalometric evaluation of lateral X-rays when combined with clinical assessment and fibreoptic examination of the airway helps in locating the site of obstruction. The usual technique of cephalometry has been modified so as to give a better delineation of the soft tissues. Holding a 2mm card board in the mouth and using barium paste helped in more accurate calculations. Using our technique, various parameters have been quantified and a number of controls were studied and normal range derived. Further improvement in cephalometry has been done by using C.T. cephlometry topogram technique. A topogram is a scan done on a running table top cranio-caudally. Using the topogram technique 38 OSA patients were evaluated for all the parameters. The technique, its advantages over traditional cephalometry and the values obtained in the study are discussed in this paper.     

Comparison of randomized preemptive dexketoprofen trometamol or placebo tablets to prevent withdrawal movement caused by rocuronium injection

Rocuronium is a non-depolarizing neuromuscular blocking agent which is associated with injection pain and induces withdrawal movement of the injected hand or arm or generalized movements of the body after intravenous injection. The aim of this randomized study was to compare the efficacy of pretreatment with oral dexketoprofen trometamol (Arvelles^®; Group A) with placebo (Group P) without tourniquet to prevent the withdrawal response caused by rocuronium injection. The study cohort comprised 150 American Society of Anaesthesiologists class I–III patients aged 18–75 years who were scheduled to undergo elective surgery with general anesthesia. The patients response to rocuronium was graded using a 4-point scale [0 = no response; 1 = movement/withdrawal at the wrist only, 2 = movement/withdrawal involving the arm only (elbow/shoulder); 3 = generalized response]. The overall incidence of withdrawal movement after rocuronium injection was significantly lower in Group A (30.1 %) than in Group P (64.6 %) (p < 0.001). The incidence of score 0 withdrawal movements was higher in Group A (69.9 %) than in Group P (35.4 %), that of score 1 withdrawal movements was similar between groups (Group A 21.9 %; Group B 26.1 %) (p = 0.560) and that of score 2 withdrawal movements was lower in Group A (8.2 %) than in Group P (38.5 %) (p < 0.001). There were no score 3 withdrawal movements in either group (p > 0.05). These results demonstrate that the preemptive administration of dexketoprofen trometamol can attenuate the degree of withdrawal movements caused by the pain of the rocuronium injection.