Everolimus-associated Acute Kidney Injury in Patients with Metastatic Breast Cancer.

Recently, everolimus (Evl) has been introduced in the management of hormone receptor-positive metastatic breast cancer, in combination with aromatase inhibitors. Evl-induced acute kidney injury has hitherto been described in other malignancies, especially renal cell cancer, but only once before in a patient with breast cancer. We describe two cases of Evl-associated nephrotoxicity in patients with breast cancer, one of whom underwent a renal biopsy showing acute tubular necrosis. Both our patients improved after withdrawal of the offending agent and have normal renal functions on follow-up.

Can a urine dipstick test be used to assess smoking status in patients undergoing planned orthopaedic surgery? a prospective cohort study.

AIMS: Smoking is associated with post-operative complications but smokers often under-report the amount they smoke. Our objective was to determine whether a urine dipstick test could be used as a substitute for quantitative cotinine assays to determine smoking status in patients. PATIENTS AND METHODS: Between September 2013 and July 2014 we conducted a prospective cohort study in which 127 consecutive patients undergoing a planned foot and ankle arthrodesis or osteotomy were included. Patients self-reported their smoking status and were classified as: 'never smoked' (61 patients), 'ex-smoker' (46 patients), or 'current smoker' (20 patients). Urine samples were analysed with cotinine assays and cotinine dipstick tests. RESULTS: There was a high degree of concordance between dipstick and assay results (Kappa coefficient = 0.842, p < 0.001). Compared with the quantitative assay, the dipstick had a sensitivity of 88.9% and a specificity of 97.3%. Patients claiming to have stopped smoking just before surgery had the highest rate of disagreement between reported smoking status and urine testing. CONCLUSION: Urine cotinine dipstick testing is cheap, fast, reliable, and easy to use. It may be used in place of a quantitative assay as a screening tool for detecting patients who may be smoking. A positive test may be used as a trigger for further assessment and counselling. Cite this article: Bone Joint J 2016;98-B:1418-24.

The relationship between spinopelvic measurements and patient-reported outcome scores in patients with multiple myeloma of the spine.

AIMS: Patients with multiple myeloma (MM) develop deposits in the spine which may lead to vertebral compression fractures (VCFs). Our aim was to establish which spinopelvic parameters are associated with the greatest disability in patients with spinal myeloma and VCFs. PATIENTS AND METHODS: We performed a retrospective cross-sectional review of 148 consecutive patients (87 male, 61 female) with spinal myeloma and analysed correlations between spinopelvic parameters and patient-reported outcome scores. The mean age of the patients was 65.5 years (37 to 91) and the mean number of vertebrae involved was 3.7 (1 to 15). RESULTS: The thoracolumbar region was most commonly affected (109 patients, 73.6%), and was the site of most posterior vertebral wall defects (47 patients, 31.8%). Poorer Oswestry Disability Index scores correlated with an increased sagittal vertical axis (p = 0.006), an increased number of VCFs (p = 0.035) and sternal involvement (p = 0.012). Poorer EuroQol visual analogue scale scores correlated with posterior vertebral wall defects in the thoracolumbar region (p = 0.012). The sagittal vertical axis increased with the number of fractures and kyphosis in the thoracolumbar (p = 0.009) and lumbar (p < 0.001) regions. CONCLUSIONS: In MM, patients with VCFs have poorer clinical scores at presentation in the presence of sagittal imbalance. Outcome is particularly affected by multiple fractures in the thoracolumbar and lumbar regions and by failure to prevent kyphosis. Patients with MM should be screened for spinal lesions early. Cite this article: Bone Joint J 2016;98-B:1234-9.

Profile of gynecologic malignancies reported at a tertiary care center in India over the past decade: comparative evaluation with international data.

OBJECTIVE: Comprehensive statistics on gynecologic malignancies reported from India are deficient. This study was performed to ascertain the profile of gynecologic cancers reported at our center regarding incidence, histologic subtypes, frequency of involvement at various sites and stage at presentation. We endeavored to compare our data with gynecologic cancers reported at other national and international centers. MATERIALS AND METHODS: Retrospective review of records of gynecologic cancers obtained from Departments of Pathology and Gynecology, at a tertiary care center, Delhi from January 2000 to December 2009 was performed. Comparison with international data was performed using Fishcher's exact test and chi square tests. RESULTS: A total of 1315 gynecologic cancers were reported. Cervical malignancies were the commonest at our center as compared to uterine malignancies in data from Surveillance, Epidemiology, and End Results (SEER) Program of United States and European Union. All malignancies except cervical cancers affected a younger age group at our center than in the US population. Cervical cancer presented at a relatively more advanced stage, ovarian cancers at more localized stages, whereas uterine cancers presented at similar stages as compared to Western data. CONCLUSIONS: Our registry presents composite data from North India. Higher age and advanced stage at presentation of cervical cancers suggests lacunae in screening programs available. Ovarian malignancies were more localized at presentation than in the Western population for which environmental or genetic factors may be causative.

Functional colonic obstruction in an adult as a presenting feature of thymoma.

Functional colonic obstruction is a colonic motility disorder with a number of causes. One cause is myenteric ganglionitis, which may result from paraneoplastic processes. We present the case of a previously healthy 53-year-old man who presented with a week's history of functional colonic obstruction. A transverse loop colostomy failed to resolve his symptoms and he subsequently underwent an extended right hemicolectomy. Histology demonstrated lymphocytic myenteric ganglionitis that was felt to be of paraneoplastic origin. The patient later developed bilateral ptosis and was diagnosed with ocular myasthenia gravis. Further investigation revealed the presence of a thymoma that was resected, resulting in an improvement to his symptoms. We present this case and a review of the literature to illustrate the importance of seeking out a paraneoplastic cause for functional colonic obstruction in adults as early resection of the tumour may help alleviate symptoms and avoid bowel surgery.

Identification and molecular characterization of acyl-CoA synthetase in human erythrocytes and erythroid precursors.

Full-length cDNA species encoding two forms of acyl-CoA synthetase from a K-562 human erythroleukaemic cell line were cloned, sequenced and expressed. The first form, named long-chain acyl-CoA synthetase 5 (LACS5), was found to be a novel, unreported, human acyl-CoA synthetase with high similarity to rat brain ACS2 (91% identical). The second form (66% identical with LACS5) was 97% identical with human liver LACS1. The LACS5 gene encodes a highly expressed 2.9 kb mRNA transcript in human haemopoietic stem cells from cord blood, bone marrow, reticulocytes and fetal blood cells derived from fetal liver. An additional 6.3 kb transcript is also found in these erythrocyte precursors; 2.9 and 9.6 kb transcripts of LACS5 are found in human brain, but transcripts are virtually absent from human heart, kidney, liver, lung, pancreas, spleen and skeletal muscle. The 78 kDa expressed LACS5 protein used the long-chain fatty acids palmitic acid, oleic acid and arachidonic acid as substrates. Antibodies directed against LACS5 cross-reacted with erythrocyte membranes. We conclude that early erythrocyte precursors express at least two different forms of acyl-CoA synthetase and that LACS5 is present in mature erythrocyte plasma membranes.

Identification of differentially expressed mRNAs in human fetal liver across gestation.

Differential gene expression, with its precise start and stop times, is believed to be critical for the programmed development of new cells and tissues. Within the developing fetus, one tissue of particular interest is fetal liver. This organ undergoes rapid changes in the pathway toward liver development in utero since it is also the major site of hematopoiesis, until bone marrow hematopoiesis predominates. Believing that patterns would emerge from the bi-weekly large-scale inspection of expressed genes in the fetal liver, we employed differential display reverse transcription-polymerase chain reaction (DDRT-PCR) as ourprimary inspection tool. Using DDRT-PCR, we isolated cDNAs differentially expressed throughout fetal liver development and in adult liver. We displayed approximately 25 000 cDNAs from 10 and 24 week fetal liver and adult liver. From this initial screen, we determined that approximately 0.1-1% of the mRNA population undergoes expression changes. We extracted, purified and sequenced 25 differentially displayed cDNA bands. Fourteen cDNAs had similarities to known genes, while 11 cDNAs were not similar to any characterized gene. The differentially expressed cDNAs from known genes present in fetal liver include alpha-fetoprotein, stem cell factor, erythroid alpha-spectrin, 2,3-bisphosphoglycerate mutase, insulin-like growth factor-2, porphobilinogen deaminase and Mac30. The differentially expressed cDNAs present in adult liver but not in 10 week fetal liver were nicotinamide deaminase, human fibrinogen-related protein and alpha-acid glycoprotein. The majority of differentially expressed genes found during this effort appear to be turned on during organogenesis, however, some genes were found that are apparently turned off completely.

Autosomal dominant polycystic kidney disease: observations from a university hospital in saudi arabia.

Thirty cases of autosomal dominant polycystic kidney disease (ADPKD) seen at King Fahd Hospital of the University, Al-Khobar over a period of eight years, were analysed with respect to clinical features, laboratory investigations, radiological findings, complications and outcome. There were 13 males and 17 females with a mean age of 45 yrs + 10.1 (range 16-65 years). There was positive family history of renal disease in 17 cases. At the time of presentation, 27 cases had abdominal pain. The other features noted were hematuria (20 cases), polyuria (10 cases), urinary tract infection (22 cases), headache (9 cases), uremia (7 cases) and nephrolithiasis (5 cases). Bilaterally palpable kidneys were present in all cases. Hypertension (17 cases) was the next common clinical finding. Other clinical features noted were hepatomegaly (5 cases) and mitral valve prolapse (5 cases). Twenty-one patients had cysts in liver and five had cysts in spleen. Varying degrees of renal failure were seen in 15 cases. Six (20%) patients progressed to end stage renal disease during the period of observation.

Outcome of patients with pre-existing hepatitis B virus infection following renal transplant.

Twenty four patients who were HBsAg positive prior to renal transplantation were studied with respect to their hepatic and renal outcome. The kidneys in all patients were obtained from living related donors. The standard immunosuppressive therapy consisted of azathioprine and prednisolone. Post-renal transplant follow-up varied from 32-86 months (mean 55 +/- 9). Renal functions, liver functions, HBsAg and HBsAb status was closely monitored during follow-up. One patient developed acute hepatitis four months after transplantation; this resolved in 10 weeks. Four patients showed transient elevations of liver enzymes. The results of liver biopsy in 16 cases revealed, normal histology (8), virus in hepatocytes (5), and acute hepatitis (3). None of the patients had evidence of chronic liver disease. Two patients died due to chronic rejection/chronic renal failure and two patients died due to septicaemia. Five living patients have mild to moderate chronic rejection. It was concluded that pre-existing HBsAg carrier state in transplant patients had no deteriorating effect on the liver. The mortality was related to chronic rejection and septicaemia.

Identification of chromophore binding domains of yeast DNA photolyase.

Photolyases contain two chromophores, flavin plus either methenyltetrahydrofolate (MTHF) or 8-OH-5-deazaflavin (HDF). Amino acid sequence comparison reveals that all photolyases sequenced to date have extensive sequence homology in the carboxyl-terminal half; in the amino-terminal region the folate and deazaflavin class enzymes are more homologous to other members of the same class. This modular arrangement of sequence homologies suggests that the amino-terminal half of photolyase is involved in MTHF or HDF binding whereas the carboxyl-terminal half carries the flavin binding site. In this study we attempted to identify such structural domains of yeast photolyase by partial proteolysis and gene fusion techniques. Partial digestion with chymotrypsin yielded an amino-terminal 34-kDa fragment containing tightly bound MTHF and a carboxyl-terminal 20-kDa polypeptide which lacked chromophore or DNA binding activity. However, a fusion protein carrying the carboxyl-terminal 275 amino acids of yeast photolyase bound specifically to FAD but not to MTHF or DNA. We conclude that the amino-terminal half of yeast photolyase constitutes the folate binding domain and that the carboxyl-terminal half carries the flavin binding site.

The effect of serum from patients of chronic renal failure on colony forming units (CFU-S) in mice.

Repopulating ability of mouse bone marrow stem cells, treated with pre-dialysis, post-dialysis and control sera was assessed by colony forming units (CFU-S). Significant lower colony counts were observed in pre-dialysis group as compared to control group. There was an improvement in the colony counts when the cells were treated with post-dialysis sera. The study suggests the presence of inhibitor/s of CFU-S in the uraemic sera which is/are partially removed by haemodialysis.

Emergency treatment with ketoconazole in disseminated intravascular coagulation due to metastatic prostatic carcinoma.

We report the use of ketoconazole to control disseminated intravascular coagulation due to prostatic carcinoma. Clinical improvement in the condition of the patient was noted in 48 hours and coagulation profile became normal in 10 days.

Incidence of reflux nephropathy (RN) in ESRD and effect of nephrectomy in RN on blood pressure and haematocrit following renal transplantation.

One hundred and fifty cases of end stage renal disease (ESRD) on pretransplant workup showed vesicoureteric reflux (VUR) in 21 (14%). Of these, 15 were primary reflux nephropathy (PRN) whereas 6 were secondary VUR. All patients in PRN group showed grade III to IV reflux while secondary VUR ranged between grade I to II. In the PRN group 38.5% had severe, 23% moderate and 23% mild hypertension; 53.3% were nonoliguric and 46.7% were oliguric. Mean plasma renin activity (PRA) was 6.6 and 2.85 ng/ml/hr in PRN and secondary VUR groups respectively. All cases of PRN and 2 from secondary VUR underwent nephrectomy and a month later renal transplantation. Following surgery blood pressure normalised without therapy in 50% and another 50% required lesser drugs in comparison to age matched non nephrectomised controls who showed hypertension in 100% cases, 60% requiring 3 to 4 drugs combination (p less than 0.05). Risk of low haematocrit in nephrectomised patients was insignificant.