Agarwal Sk

Efficacy of GM-CSF as an Adjuvant to Hepatitis B Vaccination in Patients with Chronic Renal Failure—Results of a Prospective, Randomized Trial

Background. Chronic renal failure patients on hemodialysis are at an increased risk of acquiring hepatitis B infection. Hence vaccination against hepatitis B assumes great importance in these patients. However, the response to hepatitis B vaccination is poor, even when 4 double doses (40 µg) of the vaccine are given. This study was conducted to determine the efficacy of GM-CSF as an adjuvant to hepatitis B vaccine in CRF patients. Methods. CRF patients including both hemodialysis (HD) and non-dialysis (ND) patients were randomized to receive either placebo or a single injection of GM-CSF (in varying doses of 50 µg, 100 µg, 150 µg) a day prior to the 1st dose of recombinant hepatitis B vaccine (40 µg). Three more doses of the vaccine were given at 1, 2, and 6 months. The anti-HBs antibody titres were measured by ELISA at 3 and 7 months. Patients having antibody titres less than 10 IU/L were considered non-responders. The response rate and mean antibody titers were compared between the control (I) and GM-CSF (II) groups. Results. In group I, 31 and 27 patients were available for evaluation at 3 and 7 months respectively. In group II, 33 and 28 patients could be evaluated at the same time points. Within the control group (group I), the response rate in hemodialysis patients (63.6%) was lower as compared to non-dialysis patients (81.2%). The response rate in group II was higher than that in group I at both 3 months as well as 7 months (78.1% vs. 62.3% and 89.3% vs. 74.1%, p = ns). The best response rates in group II were observed when GM-CSF was used in a dose of 150 µg (90.9% at 3 months and 100% at 7 months). The mean antibody titers were also found to be higher in the group II as compared to group I (409.6 vs. 243.9 IU/L, p = 0.01). Conclusion. The results of this randomized, prospective study suggest that: 1. Patients with chronic renal failure should be vaccinated for hepatitis B as chronic renal insufficiency is established. 2. GM-CSF is an effective adjuvant to hepatitis B vaccine in these patients especially when a priming dose of 150 µg is used prior to 1st dose of hepatitis B vaccination.

Effect of improvement in anemia on electroneurophysiological markers (P300) of cognitive dysfunction in chronic kidney disease

Our aim is to study the effect of improvement in anemia on event‐related potentials (ERPs; P300) as markers of cognitive dysfunction in predialysis and dialysis patients of chronic kidney disease (CKD). Thirty anemic patients of CKD (hemoglobin [Hb]<9 g%), 15 in the predialysis group (Group A), and 15 patients on biweekly hemodialysis (Group B) were recruited for the study. Patients of uremic encephalopathy, dyselectrolytemia, and those with hearing problems were excluded. Both groups were given recombinant human erythropoietin (rhuEPO) 100 IU/kg biweekly for 6 weeks by the subcutaneous route. No intervention was performed in the third control group (Group C), which consisted of 30 normal healthy volunteers. The improvement in Hb was assessed every 2 weeks, and the amplitude and latency of the P300 component of the ERPs were studied before initiating treatment and after 6 weeks of rhuEPO administration. There was a significant increase in Hb in both the study groups without any significant alteration in kidney functions. A significant reduction in P300 latency was noted in both the study groups after intervention. Similarly, the amplitude of P300 also increased in both study groups, but attained statistical significance for the dialysis group only. No significant changes were observed in the control group. Administration of EPO in patients of anemia with CKD resulted in a significant improvement in the electrophysiological markers of cognitive function in the form of increased amplitudes and decreased latencies of P300 in both predialysis and dialysis patients.

Antihypertensive and Antioxidant Action of Amlodipine and Vitamin C in Patients of Essential Hypertension

The etiology of essential hypertension includes increased oxidative stress. The role of antihypertensive drug amlodipine as an antioxidant and the benefit of addition of vitamin C, an antioxidant to antihypertensive therapy were studied. Forty male patients of essential hypertension were randomly divided into two groups and treated with 5 mg amlodipine. In addition one group also received 1000 mg vitamin C (as two 500 mg tablets) once daily for three months. Although blood pressure decreased in both groups, the systolic blood pressure in patients given vitamin C was less (126.4 ± 7.47) compared to the other group (130.9 ± 7.27). A decrease in malondialdehyde, an increase in erythrocyte sodium-potassium adenosine triphosphatase (Na+ K+ ATPase) and an increase in the superoxide dismutase levels were observed in both groups. The increase in SOD was statistically more in the patients given vitamin C in addition to amlodipine (0.1717 ± 0.0150 compared to 0.152 ± 0.0219 units/100 ml assay). In spite of the known antihypertensive, antioxidant activity, similarity in correcting endothelial dysfunction independently, giving the two drugs together and early introduction of vitamin C perhaps decreases oxidative stress and augments the antioxidant status. This may prevent further vascular damage due to oxidative stress, leading to a better prognosis in essential hypertension patients.

Unusual complications of heroin abuse: transverse myelitis, rhabdomyolysis, compartment syndrome, and ARF.

Introduction. Heroin overdose can cause various rare neurological complications like spongiform leukoencephalopathy, seizures, stroke, toxic amblyopia, transverse myelopathy, mononeuropathy, plexopathy, acute inflammatory demyelinating polyradiculoneuropathy, rhabdomyolysis, compartment syndrome, fibrosing myopathy, and acute bacterial myopathy. We report here the simultaneous presentation of multiple complications of heroin toxicity. Case report. A young heroin addict was found unarousable lying in the lotus posture. Examination showed quadriplegia and left leg gangrene. He subsequently developed heroin-induced transverse myelitis, rhabdomyolysis, left leg compartment syndrome, and myoglobin-induced acute renal failure. Discussion. This case leads us to consider a common linked or systemic mechanism of injury rather than a local mechanism when multiple simultaneous organ failure occurs complicating heroin abuse.

Psoriatic Nephropathy—Does an Entity Exist?

Psoriasis is an immune-mediated chronic inflammatory disorder of the skin. Association with kidney disease has been debated for a long time. Secondary renal amyloidosis in psoriatic arthropathy and drug-induced renal lesions secondary to methotrexate or cyclosporine are accepted accompaniments of psoriasis. IgA nephropathy is also known to occur in psoriatics. We report three interesting cases of renal involvement in long-standing established psoriasis on topical therapy alone. The patients presented with hypertension, significant proteinuria, hypoalbuminemia, and dyslipidemia. Kidney biopsies revealed “mesangioproliferative glomerulonephritis with IgA nephropathy,” “focal proliferative glomerulonephritis,” and “membranous glomerulonephropathy.” The former two had marked active urinary sediment. Patients improved on prednisolone and angiotensin-converting enzyme inhibitors. Contrary to the belief that renal involvement in psoriasis is coincidental, we propose that kidney disease may be a common accompaniment of psoriasis, which may be labeled as “psoriatic nephropathy” or “psoriatic kidney disease.” The exact mechanism of this entity is yet to be elucidated.

Total dose infusion iron dextran therapy in predialysis chronic renal failure patients.

Background: Intravenous iron therapy is now the standard modality of iron supplementation in hemodialysis patients, but its role in predialysis chronic renal failure patients is less well established. The efficacy and safety of intravenous iron dextran as a total dose infusion in predialysis chronic renal failure patients, not receiving erythropoietin was assessed in this study. Methods: Fifty-six predialysis chronic renal failure patients with anemia, not receiving erythropoietin were included in the study, after obtaining informed consent. Hemoglobin, serum creatinine, creatinine clearance rate and serum ferritin were assessed in all the patients at baseline. Iron dextran in a dose of 1 g dissolved in 500 mL normal saline was administered to all patients as a total dose infusion over 6 h after a prior test dose. Patients were kept in hospital under observation for at least 24 h. All the parameters were repeated in all the patients at 12 weeks and in 21 patients at 1 year. Results: The mean hemoglobin (g/dL) in the patients at baseline and at 12 weeks was 8.28 ± 0.57 and 9.22 ± 0.44 respectively (p<0.001). The mean serum ferritin (ng/mL) increased from 29.73 ± 9.38 at baseline to 218.43 ± 15.66 at 12 weeks (p< 0.00001). The mean ferritin value in the 21 patients at 1 year was 136.5 ± 23.4 (p<0.01). There were no major adverse events and only minor side effects were observed in 4.9% patients. Conclusion: Iron dextran as a total dose infusion corrects anemia in predialysis patients and is an effective method to replenish iron stores. The effect on serum ferritin are evident even at 1 year after the total dose infusion.

Duplication cyst of oesophagus: a case report.

Duplication of the oesophagus is the second most common duplication of the gastrointestinal tract. Children with oesophageal duplication cyst usually present with dysphagia or as asymptomatic thoracic mass found o incidental chest x‐ray. We report a case of oesophageal duplication cyst that presented with inspiratory stridor and dyspnoea in a 6 month old boy. Bronchoscopy revealed an external compression on the trachea. Duplication cyst arising from the oesophagus was suggested on CT and MRI. The cyst was surgically excised with resolution of symptoms.

Acute demyelinating encephalitis after jequirity pea ingestion (Abrus precatorius)

Introduction. Castor and jequirity beans are uncommon causes of poisoning. The more common but less severe castor poisoning is well described, but jequirity bean (Abrus Precatorius) poisoning is rare. The toxicity is attributed to toxalbumins (ricin and abrin) that act by inhibiting protein synthesis. Their use as agents of biological warfare, mechanisms of action, and clinical features of poisoning are summarized. Case Report. A 30-year-old previously healthy female presented with bloody diarrhea and deep coma following ingestion of 3–4 seeds of a plant called ‘ratti.’ Investigations, including an MRI brain scan, showed evidence of acute demyelinating encephalitis. The patient died three days later due to progressive central nervous system depression. Discussion. This is a previously unreported manifestation of jequirity bean poisoning. Demyelination is immune-mediated, andAbrus is a well-known immuno-modulator and stimulator. A possible immunological pathogenic mechanism is hypothesized.

Blood, bone marrow and splenic lymphocyte subset profiles in Indian visceral leishmaniasis

We examined the lymphocyte subsets in peripheral blood, bone marrow and spleen of 11 patients with acute visceral leishmaniasis (VL) and 9 with chronic VL before and after 8 weeks of antileishmanial therapy. On admission, the CD4 cell count was depressed in the peripheral blood of acute and chronic VL cases as compared to the value in 10 normal control subjects. In contrast, CD4 cell counts were higher in the bone marrow in acute and chronic cases, and in splenic aspirates of chronic cases only, compared to normal values. The peripheral blood CD8 cell count, while normal in acute cases, was uniformly low in chronic cases. Counts of CD8 cells were also low in bone marrow of acute and chronic cases, as well as in splenic aspirates of chronic cases only. All these differences were significant (P < 0.05). After treatment, the CD4 cell count in the peripheral blood increased, but decreased in bone marrow and splenic aspirates. The CD8 cell count remained unaltered in the peripheral blood but increased significantly (P < 0.05) in bone marrow and spleen. The results suggest that in VL the peripheral blood picture may not reveal the actual T cell subset profile in the reticuloendothelial system. The changes in CD8 cell counts in the bone marrow and spleen seem to be independent, and are probably influenced by antileishmanial therapy.

Ataxia and deafness in a young male: an unusual aetiology.

We report here a case of 18 year old male with tremors of hands, deafness, tendency to fall while walking, drowsiness and double vision of total duration 1(1/2) years. He had internuclear ophthalmoplegia, broken saccades, hypertonia and hyperreflexia of all four limbs, intention tremors, signs of gait and limb ataxia. Pupillary reactions and fundus examination were normal and signs of meningeal irritation or sensory neurological deficit were absent. MRI head and cervical spine with gadolinium enhancement revealed demyelination as evident from multiple oblong foci isointense on T1-weighted images and hyperintense on T2-weighted and fluid attenuated inversion recovery sequences in corpus callosum, sub-cortical white matter, right thalamus, pons and periaqueductal region of midbrain. Ill-defined linear hyperintense signals were observed in cervical spinal cord. No skeletal abnormality was noted in the skull or cervical spine. Oligoclonal bands were present in the cerebrospinal fluid. Brainstem auditory evoked potentials were abnormal, although visual evoked potentials were in normal range. A diagnosis of primary progressive multiple sclerosis (PPMS) was made fulfilling the revised criteria as laid down. In view of its presentation, it is a unique case of PPMS from India.