Evaluation of Effect of Statins on Erythropoietin Resistance in Patients of Chronic Kidney Disease on Maintenance Haemodialysis.

METHODS: Thirty adult patients of end stage renal disease with erythropoietin hyporesponsiveness undergoing maintenance hemodialysis were included in the study. Patients were divided randomly into two groups of 15 patients each. Group A were given atorvastatin in a dose of 20 mg once daily for a period of 4 months along with erythropoietin 6000 IU S/C and IV iron 100mg twice weekly after each hemodialysis. Group B was given erythropoietin 6000 IU S/C and IV iron 100 mg twice weekly after each hemodialysis without addition of atorvastatin for 4 months. Hematological, renal parameters, inflammatory parameters such as erythrocyte sedimentation rate, highly sensitive C reactive protein, serum ferritin and erythropoietin resistance index were done at baseline and then two monthly intervals for 4 months. RESULTS: At the end of study, in group A hemoglobin and haematocrit significantly increased (p <0.001 for both) while HsCRP, ESR and erythropoietin resistance index decreased significantly (p=0.001, 0.001 and <0.001 respectively). In group B, the increase in hemoglobin and haematocrit were not statistically significant (p >0.05) similarly fall in HsCRP and ERI were also not significant statistically (p >0.05). The mean rise in hemoglobin between subsequent months was higher in group A as compared to group B which was statically significant. CONCLUSION: Statin can be used as an adjuvant to erythropoietin in management of anemia in patients of chronic kidney disease, who show hyporesponsiveness to increased doses of erythropoietin, by its anti-inflammatory properties.

Evaluation of Effect of Ascorbic Acid on Ferritin and Erythropoietin Resistance in Patients of Chronic Kidney Disease.

OBJECTIVE: This study was planned to evaluate the effect of short term intravenous ascorbic acid on reducing ferritin and erythropoietin resistance in patients of chronic kidney disease (CKD) on maintenance haemodialysis (MHD). METHODS: Forty adult patients [20 patients in group A with increased serum ferritin level (>500 ng/ml), transferrin saturation (TSAT) ≤20% and 20 patients in group B with normal serum ferritin level (<200 ng/ml), TSAT ≤20%] of end stage renal disease (ESRD) with erythropoietin hyporesponsiveness undergoing maintenance hemodialysis were included in the study. Group A was given intravenous (i.v.) ascorbic acid in a dose of 500 mg once a week after each 4 hours session of dialysis for 3 weeks in a month (total 1500 mg/month), for a period of 3 months along with erythropoietin 6000 IU subcutaneous (S/C) twice weekly without iron therapy. Group B was given erythropoietin (6000 IU S/C twice weekly after each hemodialysis) and intravenous (IV) iron 100 mg/week for 3 months. Hematological and renal investigations, erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (HsCRP), serum ferritin and TSAT were done at baseline and then one monthly intervals for three months whereas intact parathyroid hormone (iPTH) was measured at the start and end of the study. RESULTS: At the end of 3 months of study, in group A, Hemoglobin (Hb) and TSAT significantly increased while ferritin, HsCRP and erythropoietin resistance index (ERI) decreased significantly. In group B, the increase in Hb and TSAT were not significant statistically while ferritin increased significantly and fall in HsCRP and ERI were not significant statistically. The mean rise in Hb between subsequent months was higher in group A as compared to group B. CONCLUSIONS: Short term i.v ascorbic acid could be a new successful adjuvant in reducing ferritin and erythropoietin resistance and enhancing Hb and TSAT in CKD patients on MHD.

Insulinoma Presenting with Neuropsychiatric Symptoms.

An insulinoma is a rare pancreatic endocrine tumor which is typically a hypervascular, solitary small tumour. 90 % of tumors are benign and less than 2 cm in size. Some insulinomas are associated with MEN-1 syndrome. Some cases of insulinoma may present with neuropsychiatric symptoms and may be wrongly diagnosed as psychosis. We report a case of insulinoma in a 55 years old female who presented with episodes of abnormal behavior and altered sensorium. On detailed investigations she was diagnosed as a case of hyperinsulinemic hypoglycemia due to insulinoma (in her case MRI abdomen was normal) DOTANOC PET CT confirmed the insulinoma in body/tail of pancreas.

Cardiac Abscess with Ventricular Aneurysm Secondary to Old Myocardial Infarction.

Myocardial Abscess (MA) is a rare life threatening condition mostly occurring secondary to underlying infective endocarditis. But it can also be found secondary to septicemia with some unknown focus of sepsis in the body. Development of MA as a consequence of left ventricular aneurysm (LVA) secondary to myocardial infarction is very rare. We report the case of 56 year old male, who presented with high grade fever and leukocytosis. On detailed evaluation, he was found to have a myocardial abscess with underlying LVA.

Role of ACE and IL-1ß Gene Polymorphisms in Erythropoeitin Hyporesponsive Patients with Chronic Kidney Disease with Anemia.

BACKGROUND: Hyporesponse to erythropoietin is a common problem seen in around 5-10% of patients. Recently the focus from these remediable factors has been shifted to the non-modifiable innate factors i.e polymorphism of ACE and IL-1B gene and studies have shown that DD genotype and IL-1B CC genotype have lower erythropoietin requirement. The aim of our study was to evaluate the role of ACE and IL-1B gene polymorphisms in erythropoietin hyporesponse in CKD patients with anemia. METHODS: A total of 50 patients were selected. After taking pre-informed written consent, they were segregated into two groups, group A and B with 25 patients in each group. Group A included CKD stage III-IV patients and Group B included CKD stage V patients who were on regular maintenance. All patients were given erythroepoietin and response was monitored using erythropoietin resistance index (ERI). Genotyping of ACE and IL-1B genes were done and serum levels of ACE and IL-1B were measured. Mean values of ERI were compared between different genotype subgroups and analysed using binary regression analysis. RESULTS: The study group included 6 patients with diabetic nephropathy and out of these 4(66.6%) had DD genotype. On comparing the effect of ACE polymorphism on ERI levels it was seen that the mean ERI values in DD subgroup were significantly lower (16.97±5.35, 21.88±6.25, 22.69±8.35 at 1,3 and 5th month) as compared to ID (18.16±3.39, 24.17±3.66, 32.74±9.95 and II (20.73±5.17, 27.74±7.30, 41.08±13.83 U/Kg/g/dL). In the case of IL-1B the mean ERI values were lowest in the TT subgroup (16.46±4.45, 21.96±5.77,23.98±8.48) as compared to CC (19.49 ±5.62,25.46±7.07, 33.59±12.61) and CT (18.12±4.27,24.14±5.70, 31.89±13.83 U/Kg/g/dL). The mean serum values of ACE were in a decreasing trend i.e DD> ID> II (238.05 ± 52.46, 194.73±50.28 and 162.99±39.71 ng/ml, (p < 0.05). The mean serum values of IL1B in CC, CT and TT were 23.24±28.77, 18.32±16.25, 23.34±13.83 pg/ml (p>0.05). CONCLUSIONS: D allele positively affected the serum ACE level but there was no association between IL-1B genotype and its levels. ACE gene polymorphism has an important role in determining the response to EPO and progression of CKD. Pre-treatment screening for genotype may help in predicting the patients at risk and poor responders.

Evaluation of Effect of Vitamin D Deficiency on Anemia and Erythropoietin Hyporesponsiveness in Patients of Chronic Kidney Disease.

BACKGROUND: The role of vitamin D deficiency and inflammation levels in renal anemia has been documented. However, no study is available in India where the role of vitamin D supplementation in patients with hyporesponsiveness to increased doses of erythropoietin is available. Hence this study. MATERIAL AND METHODS: This study was conducted on 50 adult patients of CKD, on regular, twice weekly hemodialysis. It included 38 cases in group A with deficient serum vitamin D levels (<30 ng/ml) and 12 cases in group B with sufficient vitamin D levels (>30 ng/ml). Both groups of cases were receiving erythropoietin in a dose of 4000 I.U. subcutaneously twice weekly following dialysis and had failed to show rise in hemoglobin (Hb) >1gm/dl after one month, hence erythropoietin was increased to 6000 I.U. Group A was given additional vitamin D in a dose of 60000 I.U. orally, once a week for next three months along with erythropoietin 6000 I.U. where as Group B served as control. Hematological and renal parameters, ESR, high sensitivity C reactive protein (HsCRP) and serum ferritin were estimated at baseline and then at one monthly intervals for next four months. Parathyroid hormone (iPTH), serum B12, folic acid and vitamin D (25OHD3) were measured at the start and end of the study only. Erythropoietin resistance index (ERI) was calculated to evaluate dose response. RESULTS: Basal ERI, HsCRP and ESR and serum ferritin were raised in both the groups. At the end of four months, there was a significant increase in the Hb and hematocrit (Hct) (p<.001) and a significant fall in ERI, ESR, HsCRP, serum ferritin and iPTH (p<.001) in group A. Group B, also had a significant increase in the hemoglobin and hematocrit (p<.001) and decrease in ERI, ESR, HsCRP, serum ferritin and iPTH which was not significant. Basal vitamin D and ERI had a positive and insignificant correlation (r=0.05; p=0.756) in group A where as a negative and insignificant correlation was observed between them at the end of four months (r= -0.195; p >0.05). CONCLUSIONS: vitamin D play an important role in reducing inflammation and thereby in the cure of anemia in EPO hyporesponsive CKD patients and needs to be supplemented, if deficiency is found.

Gitelman Syndrome: Presenting During Pregnancy with Adverse Foetal Outcome.

Gitelman syndrome (GS) is a rare autosomal recessive salt-losing tubulopathy. The incidence of Gitelman syndrome is 25 cases in 1 million among western population. This patient presented with loose stool, vomiting and sudden onset quadriparesis. Investigations revealed hypokalaemia, metabolic acidosis, hypomagnesaemia, hypocalciuria, hypermagnesuria. Symptoms and hypokalemia improved after starting oral magnesium and potassium supplements. But the patient again presented with symptomatic hypokalemia and delivered a still born foetus with hydrocephalus. Patient was put on potassium sparing diuretics along with supplements and thereafter, has been asymptomatic. There have been very few case reports on Gitelman syndrome in pregnancy and most of them show favourable outcomes. This is a rare case report of a pregnant female with Gitelman syndrome with foetal loss.

Kallman Syndrome.

Kallman syndrome (KS) is a rare genetic disorder characterized clinically by failure to attain puberty or failure to fully complete it along with an absent or impaired sense of smell with absence of bilateral olfactory bulbi and sulci alongwith absent olfactory tracts. Only very few cases of Kallman syndrome have been reported in females in Indian population.

Families of Pseudohypoparathyroidism presenting as Seizure.

Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders characterized by variable insensitivity to parathyroid hormone. We describe two cases of 22 year male and 24 year female who have typical clinical features of Albright's hereditary osteodystrophy (AHO). Laboratory investigation revealed evidence of pseudohypoparathyroidism and skeletal survey showed shortening of the metacarpals and metatarsals.

Spectrum of renal disorders in a tertiary care hospital in Haryana.

INTRODUCTION: There is a paucity of data pertaining to spectrum of renal diseases in various parts of India. Available literature has emphasized more on specific clinical syndromes of renal diseases rather than over all spectrum. The present study highlights specimen of symptomatic renal disorders at a tertiary care hospital in Haryana and will find place for better resource management and planning. MATERIALS AND METHODS: It included 1806 patients either presenting for the first time to nephrology outpatient department of admitted between Jan 1996 - Dec 2001 to the institute. The study was retrospective for five years (1996-2000) and prospective for one year. Records of all these patients were analyzed and patients were grouped in different renal syndromes. RESULTS: Mean age of patients was (38.79 +/- 15.15 years) with male preponderance in all renal syndromes. Chronic renal failure (CRF) was the commonest presentation (56.02%). Nephrotic syndrome accounted for 22.36% whereas acute renal failure (ARF) was seen in 12.84%. Other presentations were acute nephritic syndrome (6.75%) and asymptomatic urinary abnormality (AUA) (0.99%). Chronic glomerulonephritis (CGN) (39.32%) and diabetic nephropathy (DN) (19.16%) were leading causes of CRF. Medical ARF accounted for 2/3rd of the cases of ARF and surgical etiology was seen in 1/5th of causes whereas obstetric cause was responsible for 1/7th of the cases. Minimal change disease (MCD) (33.33%) was the commonest cause of primary nephrotic syndrome followed by membranoproliferative glomeruolonephritis (MPGN). Secondary glomerular diseases were found in 21.28%. Post-streptococcal glomerulonephritis (PSGN) was the commonest cause of nephritic syndrome (37.70%). CONCLUSION: It is the first large study of its kind from a tertiary health care centre of Haryana. Male patients in their peak of life (3rd and 4th decade) were the major candidates requiring renal care with CRF as the commonest presentation and diabetic nephropathy as the second commonest cause of CRF after CGN. We need more Indian studies on spectrum of renal diseases for better available resource management.

Organophosphate induced delayed neuropathy.

A 19 year young male who consumed organophosphorous compound and required assisted mechanical ventilation for two weeks, later on developed delayed neuropathy is described.

Evaluation of enzymes in pyogenic and tuberculous meningitis.

OBJECTIVES: Lactic dehydrogenase (LDH), creatine kinase (CK) and gamma glutamyl transpeptidase (GGTP) were measured serially in cerebrospinal fluid (CSF) and serum in twenty five cases of meningitis and an equal number of age and sex matched healthy control subjects with an aim to find out their diagnostic and prognostic significance in cases of meningitis. METHODS: The enzymatic activity was measured serially (day 0, 4th and 7th) in cerebrospinal fluid (CSF) and serum in twenty-five cases of meningitis consisting of fifteen cases of pyogenic meningitis (PM) and ten of tuberculous meningitis (TBM) and an equal number of age and sex matched healthy control. The clinical details including the level of consciousness and neurological deficit were correlated with the enzymatic activity and prognosis. RESULTS: The levels of these enzymes were significantly elevated in all the cases of meningitis in serum as well as CSF as compared to control subjects. The activity was significantly higher in pyogenic than tuberculous meningitis (p<0.001) and it was higher in CSF than in serum (p<0.001). The maximum elevation in activity of GGTP and LDH were seen on the first day whereas CK was highest on 4th day and thereafter, the activity of all the enzymes declined in the majority of cases who had shown clinical improvement. However, in three cases of pyogenic and five cases of tuberculous meningitis, the enzymatic activity on subsequent estimation, increased serially. All these eight cases died. Further, the basal enzymatic activity in all these eight cases that died was higher as compared to those who survived. Of all the enzymes, CSF GGTP levels correlated best with the clinical picture. CONCLUSIONS: It is concluded that GGTP, CK and LDH were significantly elevated in cases of meningitis. It was not possible to differentiate the type of meningitis on the basis of enzymatic activity in any of them. However, it was possible to predict prognosis because higher basal activity and serial rise were associated with poor prognosis.

Comparison of oral versus intravenous iron therapy in predialysis patients of chronic renal failure receiving recombinant human erythropoietin.

OBJECTIVES: To compare oral versus intravenous iron in pre-dialysis patients of chronic renal failure (CRF) receiving recombinant human erythropoietin (rHuEPO). METHODS: The study was undertaken in 40 adult patients of chronic renal failure. The patients were randomly divided into two groups A and B of 20 patients each. Group A patients were given oral iron and group B patients were given intravenous iron. All patients in both groups were given recombinant human erythropoietin 2000 IU twice weekly subcutaneously. The study was carried for up to three months. Patients were monitored every month for renal parameters and haematological parameters which included haemoglobin, reticulocyte count and packed cell volume. Ferrokinetic studies were done at baseline and at three months. RESULTS: It was observed that haematological parameters showed significant statistical improvement in the intravenous iron group as compared to group A (oral iron group). The ferrokinetic studies revealed that serum iron, serum ferritin and transferrin saturation, decreased significantly in oral iron group, whereas significant increase was seen in group B (intravenous iron group). None of the patients developed any adverse effects because of erythropoietin or iron therapy. CONCLUSIONS: Concomitant use of intravenous iron is better than oral iron in CRF patients treated with rHuEPO. The intravenous route of iron administration may be a preferred route along with rHuEPO therapy, more so in the Indian context where prevalence of iron deficiency anaemia is fairly high.

Evaluation of role of acute intermittent peritoneal dialysis in resistant congestive heart failure.

AIMS AND OBJECTIVES: To evaluate the role of acute intermittent peritoneal dialysis (PD) in resistant congestive heart failure (CHF). MATERIAL AND METHODS: The study was conducted on 20 adult patients of resistant CHF. These patients were subjected to 12 cycles of acute intermittent hypertonic peritoneal dialysis. Improvement was monitored by clinical symptomatology, echocardiography, measurement of ultrafiltration and quantity of sodium transferred. RESULTS: There was improvement in clinical symptomatology. There was significance improvement in left ventricular (LV) function as evidenced by improvement in ejection fraction from a predialysis value of 43.35 +/- 16.73% to a post dialysis value of 53.55 +/- 14.53%. The ultrafiltration and quantity of sodium transferred was also significant. CONCLUSIONS: Acute intermittent hypertonic peritoneal dialysis is an effective and safe treatment modality in patients of resistant CEF. The patients subsequently respond well to medical therapy.

Characterization by single strand conformation polymorphism of mutations in the rpoB gene of rifampin-resistant Mycobacterium tuberculosis in strains from Vancouver, Mexico City and New Delhi.

OBJECTIVE: The study was conducted to evaluate usefulness of single strand conformation polymorphism (SSCP) over DNA sequencing in the diagnosis of rifampicin (Rif)-resistant tuberculosis. METHODS: Forty seven isolates of Mycobacterium tuberculosis (MTB) Rif-resistant and 25 Rif-sensitive were obtained from Vancouver, Mexico city and New Delhi and were analyzed by polymerase chain reaction (PCR) amplification of rpoB gene and the mutations were identified by DNA sequencing and SSCP. RESULTS: The mutations observed by DNA sequencing in 47 RIF-resistant isolates showed that the most common mutation among Vancouver isolates was in codon 526, Hist-->Arg and in Mexico isolates was in codon 531, Ser-Leu and New Delhi isolates was in codon 516, Asp-->Val. Using fluorescence based PCR-SSCP, it was possible to distinguish Rif-resistant isolates from Rif-sensitive isolates. CONCLUSION: DNA sequencing is a highly accurate method for the detection of mutations associated with drug resistance in tuberculosis but is more expensive and requires special equipment and personnel. SSCP is a simple, accurate method and suitable for analysis of large number of samples and the results are available in less than 72 hours.