Mild gentamicin nephrotoxicity reduces the progression of chronic adriamycin nephrosis

SUMMARY: The effect of mild acute tubular injury on the progression of tubulointerstitial fibrosis was studied in pair-fed uninephrectomized male Wistar rats with established adriamycin nephrosis ( n = 34). Rats were stratified into three groups according to endogenous creatinine clearance (CrCl), proteinuria (Upr) and body weight (BW): (i) group 1 (Fe, n = 12) received a single intraperitoneal injection of ferric nitrilotriacetate (5 mg Fe/kg BW); (ii) group 2 (G, n = 10) three daily subcutaneous injections of gentamicin (60 mg/kg BW) and; (iii) group 3 (C, n = 12) saline injections. Serial CrCl (day 2, day 5, weeks 2, 4, 6 and 8) and renal histology (week 8) were examined following administration of nephrotoxin. CrCl was reduced on d2 (Fe: 0.78 ± 0.23 mL/min; mean ± SD) and day 5 (G: 0.91 ± 0.36 mL/min) as compared with C (1.22 ± 0.12 mL/min; P <0.05). There was no change in the serum creatinine and functional recovery occurred by d5 (Fe) and week 2 (G). Upr decreased transiently in G at week 2 (G: 482 ± 208 mg/day vs C: 716 ± 233; P = 0.05) despite similar food intake, baseline Upr and CrCl. At week 8, CrCl in Fe (0.84 ± 0.40 mL/min) was similar to C (0.84 ± 0.58 mL/min), whereas in G it remained stable (1.27 ± 0.39 mL/min; P <0.05). By morphometric analysis, mean relative interstitial volume (RIV) and glomerulosclerosis (GS) in Fe (RIV: 28.5 ± 13.4%; GS: 10.3 ± 12.3%) was no different to C (RIV: 24.5 ± 12.5%; GS: 20.9 ± 20.0%), whereas both parameters were reduced in G (RIV: 14.1 ± 8.1%; GS: 4.0 ± 4.8%; P <0.05). Mild gentamicin nephrotoxicity therefore reduced the progression of adriamycin nephrosis. the mechanism of this finding is unclear, but it may relate to altered glomerular and tubular cell handling of protein.     

Diabetes mellitus and hearing loss

A prospective hearing survey was performed in a sample of 102 diabetic patients. The hearing data were compared with the hearing thresholds of three control population groups. A significant difference was found in the average hearing thresholds between the diabetic patients and all of the three control populations. Diabetic patients have worse hearing threshold levels especially at low and mid frequencies (P < 0.001). There was also a correlation between the duration of diabetes and hearing loss. No significant correlation was found between the different stages of diabetic retinopathy and the degree of hearing loss.     

HOSPITAL READMISSION IN STROKE SURVIVORS ONE YEAR VERSUS THREE YEARS AFTER DISCHARGE FROM INPATIENT REHABILITATION: PREVALENCE AND ASSOCIATIONS IN AN ASIAN COHORT

ObjectiveTo examine the prevalence and risk factors for readmission after inpatient rehabilitation in stroke survivors, in a developed multi-ethnic Southeast Asian country.MethodsA retrospective cohort study of 1,235 stroke survivors who completed inpatient rehabilitation in a tertiary rehabilitation centre.ResultsA total of 296 (24.0%) patients with stroke were readmitted within the first year, and 87 (7.0%) patients were readmitted 1–3 years after stroke. Significant risk factors for readmission of patients in the first year post-stroke were older age (p = 0.027), lower admission Functional Independence Measure (FIM) motor (p = 0.001) and cognition scores (p = 0.025), a Charlson Comorbidity Index (CCI) ≥1 (p < 0.001) and the presence of at least one medical complication during initial hospitalization (p < 0.001), while FIM gain was found to be protective (p < 0.001). Looking at readmission after 1 year post-stroke, a CCI ≥1 (p < 0.001) and the presence of medical complications during initial hospitalization (p < 0.001) were risk factors for readmission, while FIM gain (p = 0.001) was protective. Common causes for readmission include recurrent stroke and falls.ConclusionThere is a high readmission rate in stroke survivors, even after the first year post-stroke. Interventions, such as fall risk assessments, vaccinations, meticulous catheter care, intensified secondary risk factors interventions and continued post-discharge rehabilitation, may hold promise for reducing readmission rates.LAY ABSTRACTReadmission of stroke patients results in high morbidity and healthcare costs. Although many studies have examined readmission of stroke survivors in the first year post-stroke, there is a scarcity of studies into readmission after the first year post-stroke, and the effect of rehabilitation on these patients. This study investigated 1,235 patients 3 years post-stroke rehabilitation. Of these patients, 296 (24.0%) were readmitted within the first year, and 87 (7.0%) were readmitted 1–3 years post-stroke. Significant risk factors for readmission included older age, lower functional scores on admission, presence of chronic medical conditions and medical complications during their initial hospital stay. However, functional improvement during inpatient rehabilitation was associated with a reduced readmission rate. This study demonstrates that there is a high readmission rate even after the first year post-stroke. It also highlights the importance of rehabilitation in reducing readmission in stroke survivors.Key words: patient readmission, stroke rehabilitation, stroke, cerebral haemorrhage, risk factors, treatment outcome

Patients with stroke admitted to inpatient rehabilitation often have significant neurological dysfunction, resulting in a high risk of readmission for acute care after discharge. Hospital readmissions may indicate unresolved problems, quality of immediate post-hospital care, or a high degree of morbidity, and have a significant impact on healthcare costs (1). Studies also report a relatively high readmission rate between 30 days and 1 year post-stroke. Ottenbacher et al. reported a 30-day readmission rate of 12.7% after discharge from inpatient rehabilitation, based on Centers for Medicare & Medicaid Services data (2), while Zhong et al. reported a pooled 1-year hospital readmission rate of 42.5% in a meta-analysis of patients with stroke in general (1). However, there are few studies investigating the readmission rate of patients with stroke more than one year after discharge from inpatient rehabilitation.Various risk factors linked to readmission within the first year have been identified in various studies and systemic reviews, including older age, previous history of stroke and cardiovascular disease, diabetes mellitus, length of acute hospitalization and complications during acute stay, compared with control groups who were not readmitted (1–5). Less is known about the long-term risk factors for stroke survivors who survive the first year after stroke without any readmissions, and if these risk factors are different from those previously mentioned. Although a non-white ethnicity has been suggested as a risk factor for readmission (3), this finding may not be applicable to other non-Western populations with different socioeconomic demographics. Several studies have also identified infections, cardiovascular causes, and recurrent stroke as leading causes for readmission within one year after discharge, although it is uncertain if these findings are applicable for readmissions beyond 1 year post-event (1).While pre-stroke and post-rehabilitation functional scores have also been increasingly recognized as significant predictors of readmission (6, 7), this requires further validation, as many of these studies are based on billing or administrative databases, and questions on the reliability, accuracy and completeness of these data remain (8). It is also unclear if functional gains during rehabilitation have a sustained effect on readmission rates beyond 1 year post-stroke.The aim of this study is to examine the prevalence and risk factors for readmission after inpatient rehabilitation in stroke survivors, within 1 year vs 1–3 years post-stroke, in a developed multi-ethnic Southeast Asian country.     

Clinically relevant drug interactions between anticancer drugs and psychotropic agents

YAP K.Y.‐L., TAY W.L., CHUI W.K. & CHAN A. (2011) European Journal of Cancer Care 20 , 6–32
Clinically relevant drug interactions between anticancer drugs and psychotropic agents Drug interactions are commonly seen in the treatment of cancer patients. Psychotropics are often indicated for these patients since they may also suffer from pre‐existing psychological disorders or experience insomnia and anxiety associated with cancer therapy. Thus, the risk of anticancer drug (ACD)‐psychotropic drug–drug interactions (DDIs) is high. Drug interactions were compiled from the British National Formulary (53rd edn), Lexi‐Comp's Drug Information Handbook (15th edn), Micromedex® (v5.1), Hansten & Horn's Drug Interactions (2000) and Drug Interaction Facts (2008 edn). Product information of the individual drugs, as well as documented literature on ACD‐psychotropic interactions from PubMed and other databases was also incorporated. This paper identifies clinically important ACD‐psychotropic DDIs that are frequently observed. Pharmacokinetic DDIs were observed for tyrosine kinase inhibitors, corticosteroids and antimicrotubule agents due to their inhibitory or inductive effects on cytochrome P450 isoenzymes. Pharmacodynamic DDIs were identified for thalidomide with central nervous system depressants, procarbazine with antidepressants, myelosuppressive ACDs with clozapine and anthracyclines with QT‐prolonging psychotropics. Clinicians should be vigilant when psychotropics are prescribed concurrently with ACDs. Close monitoring of plasma drug levels should be carried out to avoid toxicity in the patient, as well as to ensure adequate chemotherapeutic and psychotropic coverage.     

Tissue macrophage response in human papillomavirus infection and cervical intraepithelial neoplasia

Summary. Tissue macrophages in the uterine cervix were studied immunocytochemically with monoclonal antibody (MoAb) 3.9 which reacts with the majority of macrophages, and Ell which is specific for the C3b receptor, CR1. Samples from five normal women, six with human papillomavirus (HPV) infection and 10 with cervical intraepithelial neoplasia (CIN) were tested. A small population of MoAb 3.9 positive and only occasional MoAb Ell positive macrophages were found in the normal cervix. In HPV infection and CIN there was a significant infiltration of MoAb 3.9 positive and MoAb Ell positive macrophages in both the epithelium and the stroma. The pattern of infiltration in these groups of women suggests that these macrophages were most likely to be functioning as the first line of defence against the spread of the virus infection, either through a direct anti-virus mechanism or non-specific phagocytosis.     

Pathogenesis of Duchenne muscular dystrophy: The calcium hypothesis revisited

Rapid advances in the molecular genetics of Duchenne muscular dystrophy (DMD) and the discovery and localization of the gene product dystrophin has brought new hope that successful treatment for this disease may not be too far away. Dystrophin has been postulated to have a mechanical function, helping to resist stress associated with muscle contraction. The presence of dystrophin in low concentrations in muscle cells, its expression in nervous tissue and the observation that hypercontraction of the sarcomeres precedes membrane rupture make the hypothesis unlikely. On the basis of an analogy with a cytoskeletal protein ankyrin, which is associated with the sodium/potassium adenosine triphosphatase (ATPase) in the kidney, it is possible that dystrophin deficiency leads initially to an increased but inefficient calcium-ATPase activity, which pumps calcium out of the cell. Partial failure of the pump would result in intracellular accumulation of calcium, hypercontractions of the sarcomeres, rupture of the cell membrane, massive influx of calcium and cell necrosis.     

Papuloerythroderma of Ofuji: a report of three cases and review of the literature

Papuloerythroderma of Ofuji is a rare, distinctive entity featuring widespread erythematous, flattopped papules, with a striking sparing of body folds (the so-called‘deck-chair’sign), and peripheral eosinophilia. We report three elderly men who showed the typical features of this disease, and who responded to corticosteroid therapy. Immunohistochemical studies with anti-S-100 and UCHL-1 (CD45 RO) antibodies indicated the presence of abundant dendritic cells and mature T cells in the dermis. In addition, one patient had concomitant tinea corporis. Treatment with griseofulvin alone resulted in clearing of the fungal infection and improvement of his papuloerythroderma, and worsening of his papuloerythroderma occurred when the tinea relapsed.     

Left Ventricular Mechanical Assist Devices and Cardiac Device Interactions: An Observational Case Series

Background: Nonpulsatile left ventricular assist devices (LVADs) are increasingly used for treatment of refractory heart failure. A majority of such patients have implanted cardiac devices, namely implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy-pacemaker (CRT-P) or cardiac resynchronization therapy-defibrillator (CRT-D) devices. However, potential interactions between LVADs and cardiac devices in this category of patients remain unknown.
Methods: We reviewed case records and device logs of 15 patients with ICDs or CRT-P or CRT-D devices who subsequently had implantation of a VentrAssist LVAD (Ventracor Ltd., Chatswood, Australia) as destination therapy or bridge to heart transplantation. Pacemaker and ICD lead parameters before and after LVAD implant were compared. In addition, ventricular tachyarrhythmia event logs and potential electromagnetic interference reports were evaluated.
Results: Right ventricular (RV) sensing decreased in the first 6 months post-LVAD. Mean R-wave amplitude preimplant was 10.9 ± 5.25 mV compared with 7.2 ± 3.4 mV during follow-up (P = 0.02). RV impedance also decreased from 642 ± 240 ohms at baseline to 580 ± 212 ohms at follow-up (P = 0.007). There was a significant increase in RV stimulation threshold following implantation of the LVAD from 0.8 ± 0.6 V at baseline to 1.4 ± 1.0 V in the first 6 months postimplant (P = 0.01). A marked increase in ventricular tachyarrhythmia burden was observed in three patients. One patient displayed electromagnetic interference between the LVAD and defibrillator, resulting in inappropriate defibrillation therapy.
Conclusions: LVADs have a definite impact on cardiac devices in respect with alteration of lead parameters, ventricular tachyarrhythmias, and electromagnetic interference.     

Photodermatoses in a Singapore skin referral centre

The inducing or exacerbating effect of sunlight on skin diseases is often not appreciated in tropical countries, perhaps because of the perennial presence of sunlight, and a retrospective review of photodermatoses seen in a referral skin clinic was therefore carried out. The photodermatoses seen were secondary photoaggravation of primary skin diseases (32·2%), systemic drug photo-sensitivity (11·3%), polymorphic tight eruption (13%), chronic actinic dermatitis (5·3%), solar urticaria (5·3%), actinic prurigo (4%), photoallergic contact dermatitis (2·6%), porphyria (1·3%) and xeroderma pigmentosum (1·3%). Compared with the results of Western studies, there were more photoaggravated underlying skin diseases and systemic drug photosensitivity, and fewer idiopathic photodermatoses and photoallergic contact dermatitis; the common photoallergens were chlorpromazine, promethazine and musk ambrette, very similar to those seen in the West.     

Predictive factors for the resolution of childhood otitis media with effusion following initial surgical treatment

A prospective study of outcome after treatment for glue ear was performed in a sample of 143 children aged between 1 and 11 years. The resolution or recurrence of effusion following initial surgery was analysed in relation to six potentially relevant factors. Multivariate analysis showed that resolution of effusion was statistically more frequent in ears found to have a dry tap at surgery, children with a history of atopy, those who underwent adenoidectomy and it was related to the age of the child at operation. Older children had a better prognosis. Univariate analysis suggested that girls have a significantly better outcome than boys, but this was not confirmed in multivariate analysis. The results suggest that there should be a longer period of observation in atopic individuals and older children. Furthermore, the study showed that ears with dry taps should not be treated with ventilation tubes.