Collagenofibrotic glomerulopathy- report of a rare renal disease with serial biopsies.

INTRODUCTION: Collagenofibrotic glomerulopathy or collagen type-III glomerulopathy is a rare glomerular disease characterised by the deposition of type III collagen fibres in the subendothelial space and mesangium of the glomerulus. CASE REPORT: Here, we present a case of collagenofibrotic glomerulopathy in a 49-year-old Indian female, the first to be reported from Singapore. Renal biopsy showed PAS (periodic acid-Schiff), silver and Congo red negative, amorphous extracellular material that expanded mesangial and subendothelial regions. Such materials were strongly positive for anti-collagen III immunofluorescent staining. Under electron microscopy, the mesangial and some subendothelial regions were greatly expanded by abundant collagen fibres which were different from normal collagen III fibres in both appearance and periodicity. DISCUSSION: The availability of past renal biopsies for reference offered insight into disease progression. From the initial diagnosis of focal segmental glomerulosclerosis to eventually collagenofibrotic glomerulopathy over a time span of more than 10 years, this case highlights the gradual accumulation of collagen fibres in the glomeruli before classical features are apparent. It also emphasises the importance of electron microscopy in the diagnosis of this disease.

Nerve Injury After Surgical Excision of Mandibular Third Molars Under Local Anesthesia: An Audit.

BACKGROUND: Injury of the inferior alveolar nerve (IAN) sustained during surgical removal of an impacted lower third molar may cause paresthesia of the lower lip, chin, lower gingivae and anterior teeth. Lingual nerve (LN) injuries may result in ipsilateral paresthesia of the anterior two thirds of the tongue, mucosa of floor of mouth and lingual gingivae. A close anatomic relationship between the roots of the third molar and mandibular canal places the IAN at risk of damage. PURPOSE: The primary aim of this retrospective audit was to ascertain the incidence of IAN and LN damage after mandibular third molar surgery in National Dental Centre Singapore. A secondary aim was to identify the contributory factors for the risk of IAN and LN nerve injury on the basis of the data collected. METHODS: This retrospective audit included 1276 mandibular third molar surgical removals performed in the local anesthesia operating theatre (LAOT) at the National Dental Centre Singapore (NDCS) from April to December 2013. Data included patient details, clinical characteristics, and 1 week postoperative presence/absence of sensory alteration as reported by the patient. RESULTS: Summary of results- Out of 1276 third molar sites audited, 8 (0.62%) sites had altered sensation of the IAN and 1 (0.078%) had altered sensation of the LN at 1 week postoperative review. CONCLUSION: The incidence of IAN injury (0.62%) and lingual Nerve injury (0.08%) after one week from surgery in our audit was low compared to similar studies. This retrospective audit did not show any correlation of nerve injury to age, gender, race, site, angulation of tooth, grade of operator, removal of bone or tooth division. There was no single radiological sign associated with paresthesia, although the most common radiological signs were interruption of the canal line and darkening of the roots.

Using a checklist to assess if a child undergoing MRI needs general anaesthesia.

AIM: To assess if a child-assessment checklist covering tasks children are expected to perform during magnetic resonance imaging (MRI) can determine whether the child requires general anaesthesia (GA) during MRI. MATERIALS AND METHODS: In this institute review board approved study, children who underwent MRI from September 2016 to June 2017 at KK Women's and Children's Hospital were assessed using a checklist by a research assistant before their examination. During this project, the checklist had no influence on whether the MRI was performed under GA or not. The checklist consisted of five items rated on a binary scale assessing the child's behaviour. Binary logistic regression was performed separately on the overall sample and for a subset of younger children to identify variables associated with the requirement for GA. RESULTS: The mean age of the overall sample (798 children) and the subset of children <8 years (124 children) were 11.7±3.7 and 5.5±1.3 years, respectively. In both groups, children who required GA were significantly younger than those who did not (p<0.001). No gender differences were observed. Children who required GA scored higher on the checklist compared to those who did not in both groups (p<0.001). The diagnostic accuracy of the checklist was found to be good (area under the curve [AUC]=0.97 for both groups), with a suggested cut-off score of 4. Intraclass correlation coefficient of the ratings by two independent individuals was 0.78. CONCLUSION: The child assessment checklist was useful in identifying GA requirement in children undergoing MRI and can be administered by non-medical staff with good inter-rater reliability.

Impact of elective caesarean section on neonatal retrieval in Western Australia during a 12-year period.

OBJECTIVE: To determine whether 2006 Australian national guidance to delay elective caesarean section until 39 weeks' gestation would reduce the need for neonatal retrieval for respiratory compromise following elective caesarean. STUDY DESIGN: This is a retrospective cohort study comparing infants born by elective caesarean section who required retrieval for respiratory distress in Western Australia before and after the national guidance (2003-2006 vs. 2008-2014). RESULTS: The proportion of infants born by elective caesarean section who required retrieval for respiratory distress was reduced in the later cohort (0.77% (153/19 780) vs. 0.55% (227/40 875); p = 0.0012). The diagnosis of surfactant-deficient lung disease amongst retrieved infants was also reduced (26% (40/153) vs. 17.4% (40/227); p = 0.04). CONCLUSION: A reduction in the proportion of elective caesarean sections before 39 weeks in Western Australia was associated with a reduction in retrieval for respiratory compromise related to surfactant deficiency in infants born by elective caesarean section.

Early morbidity associated with fasciotomies for acute compartment syndrome in children.

PURPOSE: Acute compartment syndrome (ACS) requires urgent fasciotomy to decompress the relevant muscle compartment/s prior to onset of irreversible myonecrosis and nerve injury. A fasciotomy is not a benign procedure. This study aims to describe and quantify early morbidity directly associated with fasciotomies for ACS in children. METHODS: Clinical charts of 104 children who underwent 112 fasciotomies over a 13-year period at a tertiary children's hospital were reviewed. The following were analyzed: ACS aetiology, fasciotomy site, number of subsequent procedures, method of wound closure, short-term complications and length of hospital stay. RESULTS: Short-term complications included wound infections (6.7%) and the need for blood transfusion (7.7%). Median number of additional operations for wound closure was two (0 to 10) and median inpatient stay was 12 days (3 to 63; SD 11.7). After three unsuccessful attempts at primary closure, likelihood of needing skin grafting for coverage exceeded 80%. Analyses showed that fasciotomy-wound infections were associated with higher risk for four or more closure procedures. Number of procedures required for wound closure correlated with longer inpatient stay as did ACS associated with non-orthopaedic causes. CONCLUSION: Fasciotomy is associated with significant early morbidity, the need for multiple closure operations, and prolonged hospital stay. The decision for fasciotomy needs careful consideration to avoid unnecessary fasciotomies, without increasing the risk of permanent injury from missed or delayed diagnosis. Skin grafting should be considered after three unsuccessful closure attempts. Less invasive tests or continuous monitoring (for high-risk patients) for compartment syndrome may help reduce unnecessary fasciotomies. LEVEL OF EVIDENCE: Level IV, Case series.

The impact of non-motor symptoms on the quality of life of Parkinson's disease patients: a longitudinal study.

BACKGROUND AND PURPOSE: Non-motor symptoms (NMSs) are common amongst patients with Parkinson's disease (PD); however, little is known about their influence on the health-related quality of life (QoL) over a defined follow-up period. The study was aimed to establish the impact of NMSs on the QoL of patients with PD over a 2-year follow-up period. METHOD: A total of 227 newly referred PD patients were prospectively recruited between 2013 and 2014. The Non-Motor Symptoms Scale was used to evaluate NMSs burden whilst QoL was assessed with the Parkinson's Disease Questionnaire-39 items. Motor disabilities were assessed using the Part III (motor) Unified Parkinson's Disease Rating Scale (UPDRSm). RESULTS: The mean age was 64.37 (10.18) years; 59.9% were males and a majority (89.0%) were ethnic Chinese. Almost 65% were unemployed and 84.6% had attained no more than secondary level of education. In the univariate analysis, total NMSs burden, age, gender, subsequent visit, Hoehn and Yahr staging, disease duration and UPDRSm score were individually predictive of change in the Parkinson's Disease Questionnaire Summary Index score from baseline to follow-up visit. However, in the multivariate analysis, total NMSs burden significantly predicted the QoL scores whilst motor scores did not. Specifically, NMS domains 2 (sleep/fatigue), 3 (mood/apathy) and 5 (attention/memory) were most significantly predictive of QoL change. CONCLUSION: Unlike motor disabilities, NMSs burden, in particular sleep, mood and attention, have a significant impact on the QoL of PD patients over a 2-year follow-up period.

Sustained release of ganciclovir from poly(lactide-co-glycolide) microspheres.

Biodegradable poly(lactide-co-glycolide) microspheres loaded with ganciclovir were produced using the emulsification/solvent evaporation technique. The effects of drug-to-polymer ratio and dispersion time on the drug content in the microspheres were investigated. The release rate of the drug was studied for 20 weeks in a phosphate buffered solution of pH 7 at 37 degrees C. Data revealed that lower drug content was obtained with increasing drug-to-polymer ratio and decreasing dispersion time. The release of the drug followed a triphasic release pattern, i.e. an initial burst, a diffusive phase and a second burst. The initial burst occurred within the first 2 days of immersion. After the burst, the release was by diffusion for up to 13 weeks, followed by another burst release, which signals the onset of bulk degradation of the polymer. Gel permeation chromatography (GPC), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and ultraviolet spectroscopy (UV) were used to follow the hydrolytic degradation and drug release rate of the microspheres.

Epstein-Barr virus-associated T-cell lymphoma in solid organ transplant recipients.

Post-transplantation lymphoproliferative diseases (PTLDs) are a heterogenous group of lymphoid proliferative disorders occurring in transplant patients. Most PTLDs are B-cell in origin; T-cell PTLDs are seldom reported, and EBV-associated T-cell PTLDs are rare. The first case of a T-cell, non-EBV-associated PTLD was first described in a renal allograft recipient in 1987. A total of 40 cases of T-cell PTLDs in solid organ transplant recipients have been reported. However, so far only 16 cases of EBV-associated T-cell PTLDs have been reported in the literature. The sites of occurrence of EBV-associated T-cell PTLDs were in the gastrointestinal tract, lungs, bone marrow, skin, liver and spleen. The pathogenesis of EBV-associated T-cell PTLD is uncertain; it is speculated that the EBV may infect a subset of T-cells that express the CD21 receptor. The present treatment of EBV-associated T-cell PTLD consists of surgical removal, reduction or withdrawal of immunosuppression and/or radiotherapy and chemotherapy. The prognosis is uncertain, and the 1-year survival for patients who were followed up for 1 year was 50%.

Acute renal failure from hemoglobinuric and interstitial nephritis secondary to iodine and mefenamic acid.

Mefenamic acid ingestion, usually in excess and over prolonged period is known to produce interstitial nephritis, or less commonly papillary necrosis, with acute renal failure. However, it is not dose-dependent for the induction of tubulointerstitial damage. Excess iodine ingestion is known to produce toxicity and possible death, but acute renal failure is rare. There is evidence from clinical and experimental data that iodine has toxic effect on tubular epithelial cells. Iodine has not been documented to produce red cell hemolysis and hemoglobinuria. We present a unique case of acute renal failure from hemoglobinuric and acute interstitial nephritis secondary to suicidal ingestion of potassium iodide solution and also ingestion of a few mefenamic acid tablets. These agents led to potentiation of the renal injury from hemoglobinuric tubulopathy, probably from the iodine, and renal dysfunction from alteration of renal perfusion by selective COX-1 inhibition of prostaglandin production, and induction of acute interstitial nephritis from mefenamic acid, leading to acute renal failure which was reversible by hemodialysis and supportive therapy.

Acute renal failure from myoglobinuria secondary to myositis from severe falciparum malaria.

Renal disease is a common complication in malaria infection. In acute falciparum malaria renal involvement is usually mild, but in severe disease acute renal failure is a major problem. Acute renal failure has been attributed to ischaemic tubular necrosis from hypovolaemia resulting from vasodilatation due to endothelial injury. Though myositis is recorded as a common manifestation in falciparum malaria, only 1 case with myositis and myoglobinuria with acute renal failure has been documented; but no renal biopsy was performed in the patient. In the present study we examined the case of a 17-year-old man with severe falciparum malaria with myositis and myoglobinuria who developed acute renal failure requiring dialysis. Muscle biopsy revealed severe myositis with macrophages and T lymphocytes including CD4+ cells. The kidney biopsy showed scanty T cells and macrophages in the glomeruli which were only mildly hypercellular. The renal tubules showed myoglobin casts in the lumen and foci of interstitial inflammatory cells, including macrophages and T lymphocytes but no CD4+ cells. Rhabdomyolysis induced by macrophages and T cells with myoglobinuria and acute renal failure is a problem in severe falciparum malaria infection.

Once-daily intraperitoneal gentamicin is effective therapy for gram-negative CAPD peritonitis.

OBJECTIVE: To report our 3-year experience with the use of once-daily intraperitoneal (IP) gentamicin in the treatment of gram-negative continuous ambulatory peritoneal dialysis (CAPD) peritonitis. DESIGN: A prospective cohort study in prevalent CAPD patients. SETTING: A tertiary care institution. PATIENTS: All CAPD patients who presented with new episodes of peritonitis were studied. At presentation with peritonitis, IP vancomycin and gentamicin were administered as empirical therapy. IP gentamicin was given at a single daily dose of 40 mg/2 L in the overnight bag. The antimicrobial agents were reviewed when the culture results became available. Intraperitoneal ceftazidime was added for the treatment of pseudomonas peritonitis. MAIN OUTCOME MEASURES: Results of microbiological cultures and clinical outcomes of peritonitis were analyzed. RESULTS: Over a 36-month period, 190 episodes of peritonitis were recorded, of which 62/190 episodes (32.6%) isolated gram-negative organisms. The gram-negative organisms isolated were Escherichia coli, 15/62 episodes (24.1%); Pseudomonas aeruginosa, 12/62 episodes (19.4%); Acinetobacter spp, 12/62 episodes (19.4%); Klebsiella spp, 10/62 episodes (16.1%); and others, 13/62 episodes (21.0%). The overall treatment success rate was 66.1%. The treatment success rates were 74.0% if pseudomonas infections were excluded, 76.1% if gentamicin-resistant pathogens were excluded, and 80.5% if both pseudomonas infections and gentamicin-resistant pathogens were excluded. CONCLUSIONS: Once-daily IP gentamicin appears to be effective in the treatment of gram-negative CAPD peritonitis.

Peptic ulcer and gastritis in uraemia, with particular reference to the effect of Helicobacter pylori infection.

AIMS: To determine: (i) the prevalence of histological gastritis and peptic ulcer; and (ii) the clinical features of peptic ulcer, in patients with end-stage renal failure. METHODS: Upper endoscopy was performed by a single observer in 268 patients with end-stage renal failure over a 6-year period. Gastric histology and Helicobacter pylori status were studied in 40 consecutive subjects in whom there were no contraindications for gastric biopsy and who had not used antibacterial drugs in the preceding 4 weeks. As there are only limited data for healthy volunteers in Singapore, 33 age-, sex- and race-matched patients with functional dyspepsia from an earlier drug trial and 18 healthy volunteers who were not age-matched were used as controls. The clinical features of 43 consecutive uraemic patients with peptic ulcer were compared with those of 118 consecutive non-uraemic peptic ulcer patients seen by the same author. RESULTS: Among uraemic patients, histological gastritis was less common, compared with healthy volunteers and functional dyspepsia patients. Helicobacter pylori infection as assessed by histology was also less common among uraemic patients compared with functional dyspepsia patients, but the difference was not statistically significant on serological assessment. Uraemic patients with ulcer had an equal sex ratio, in contrast to a male preponderance among peptic ulcer patients with normal renal function. Uraemic patients with ulcer were more likely to be pain-free, to present with haemorrhage, to have multiple ulcers and postbulbar duodenal ulcers, but were less likely to have H. pylori infection. Among uraemic subjects, the prevalence of H. pylori infection was similar whether or not peptic ulcer was present. CONCLUSIONS: The prevalence of histological gastritis was lower in uraemic patients when compared with patients with functional dyspepsia and healthy volunteers. Peptic ulcers in uraemic subjects have different clinical characteristics from peptic ulcer in non-uraemic subjects.

Psychosocial and psychiatric morbidity in patients on CAPD.

Continuous ambulatory peritoneal dialysis (CAPD) is an important mode of therapy for patients with end-stage renal disease. Although techniques and patient survival rates have improved, the psychosocial rehabilitation of Asian CAPD patients has not been studied. The aim of this study is to measure the extent of psychosocial and psychiatric morbidity in a sample of Asian CAPD patients. Patients from the outpatient CAPD facility affiliated with a tertiary care hospital were randomly selected and enrolled in the study. Demographic and clinical data were collected. Psychosocial and psychiatric assessments using the Hospital Anxiety and Depression Scale and coping style questionnaires were performed by a trained psychiatrist. The patients' most bother-some symptoms and specific worries were noted. Thirty of 105 stable CAPD patients (mean age 54.2 +/- 14.1 years, M:F 1:2, mean duration on CAPD 22.3 +/- 8.3 months) were studied. Twenty-one patients were married. Twenty-two patients were uneducated, 19 were unemployed, and 9 were homemakers. Based on the Hospital Anxiety and Depression scales, 50% of the patients were identified as cases of anxiety and 13% as depression. Although 93% of the patients accepted their illness, 46% of the patients were in a state of despair and hopelessness. Pruritus was the most frequent complaint (40%), followed by dietary restrictions (23%). The main worries were financial in 83% of patients, sexual dysfunction in 73%, and unemployment in 67%. In conclusion, Asian CAPD patients have a high degree of undetected psychosocial and psychiatric morbidity. These issues need to be addressed to provide adequate psychosocial rehabilitation.

Paracetamol and its metabolites in saliva and plasma in chronic dialysis patients.

1. Many pharmacokinetic studies on paracetamol are based on saliva paracetamol concentrations. The utility of saliva in patients with chronic renal failure is unclear. In this study, concentrations of saliva and plasma paracetamol and its major metabolites, sulphate and glucuronide conjugates were determined at 0.5, 1, 2 and 3 h after the ingestion of 1 g paracetamol in 20 patients with endstage renal failure. Ten haemodialysis patients were studied on a non-haemodialysis day and during a haemodialysis session. The other 10 patients were on chronic ambulatory peritoneal dialysis. 2. The plasma paracetamol concentrations attained in all groups were not different from those reported previously in healthy subjects. Mean +/- s.d. plasma paracetamol concentrations at 0.5 h in haemodialysis patients on a non-haemodialysis day, during haemodialysis and in those on chronic ambulatory peritoneal dialysis were 15.3 +/- 8.2, 21.5 +/- 10.9 and 18.2 +/- 12.3 micrograms ml-1 respectively. 3. The saliva paracetamol concentrations were highly variable and unpredictable. Saliva paracetamol concentrations at 1, 2 and 3 h after ingestion in the haemodialysis group during haemodialysis were 31.5 +/- 20.1, 14.1 +/- 10.4 and 7.3 +/- 3.8 micrograms ml-1 respectively, significantly (P < 0.05; paired t-test) higher than the corresponding plasma paracetamol concentrations which were 11.0 +/- 2.8, 6.5 +/- 2.8 and 3.2 +/- 0.9 micrograms ml-1 respectively. 4. Correlation coefficients between saliva and plasma paracetamol concentrations in haemodialysis patients on a non-haemodialysis day and during haemodialysis and in chronic ambulatory peritoneal dialysis patients were poor; r = 0.58 (P < 0.0002); r = 0.40 (P < 0.02); and r = 0.13 (P = 0.49) respectively. 5. Three hours after paracetamol ingestion, plasma paracetamol, sulphate and glucuronide concentrations were significantly (P < 0.05) reduced in haemodialysis patients during haemodialysis when compared with the same patients on a non-haemodialysis day (paired t-test) and to the chronic ambulatory peritoneal dialysis group (Kruskal-Wallis ANOVA) except for plasma glucuronide. This indicates the effective removal of paracetamol and metabolites by haemodialysis. In contrast, chronic ambulatory peritoneal dialysis seemed to remove glucuronide only. 6. In the light of the poor correlation between saliva and plasma paracetamol in dialysis patients in this study, we would like to caution against using saliva paracetamol concentrations for pharmacokinetic studies in this group of patients.