In vitro biomechanical testing of different configurations of acrylic external skeletal fixator constructs.

OBJECTIVE: To evaluate the in vitro biomechanical properties of four different configurations of acrylic external skeletal fixator constructs. MATERIALS AND METHODS: Simulated bone constructs were prepared using two segments of 20 mm ultra-high-density polyethylene rods with a gap of 5 mm. The full pins (1.5 mm) were passed through the proximal and distal segments of ultra-high-density polyethylene rods, in the same plane, parallel to each other in configuration U, and were crossed in the M1, M2 and C configurations at a 90° angle to each other. Configuration U was a single bilateral uniplanar construct, M1 was a double orthogonal bilateral construct, M2 was a double orthogonal bilateral construct with proximal and distal connecting articulations, and C was a double orthogonal bilateral construct with proximal and distal circumferential articulations. Temporary scaffolds of different external skeletal fixator configurations were constructed using commercially available polyvinyl chloride pipes (20 mm) connected and secured to the fixation pins at a fixed distance from the rods. Acrylic powder (polymer) mixed with liquid (monomer) was poured into the pipes and allowed to solidify to form the side bars and rings. The external skeletal fixator constructs were then subjected to axial compression, cranio-caudal three-point bending and torsion (n = 4 each) using a universal testing machine. Mechanical parameters, namely stress, strain, modulus of elasticity, stiffness and bending moment of fixator constructs, were determined from load-displacement curves. RESULTS: Configuration U was the weakest and configuration C was the strongest under all the testing modes. Under compression, the M1, M2 and C configurations were similar. Under bending, a significant difference was observed among the uniplanar, multiplanar and circular configurations with no difference between M1 and M2. However, under torsion, all the external skeletal fixator configurations differed significantly. CLINICAL SIGNIFICANCE: The freeform external skeletal fixator using acrylic as a replacement for a metallic bar may be useful to treat bone fractures and luxations in small animals, as it is mechanically strong, lightweight, economical, and pins can be passed from any direction depending upon the clinical situation.

Novel NaPi-IIc mutations causing HHRH and idiopathic hypercalciuria in several unrelated families: long-term follow-up in one kindred.

Homozygous and compound heterozygous mutations in SLC34A3, the gene encoding the sodium-dependent co-transporter NaPi-IIc, cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate-wasting resulting in hypophosphatemia, elevated 1,25(OH)(2) vitamin D levels, hypercalciuria, rickets/osteomalacia, and frequently kidney stones or nephrocalcinosis. Similar albeit less severe biochemical changes are also observed in heterozygous carriers, which are furthermore indistinguishable from those encountered in idiopathic hypercalciuria (IH). We now searched for SLC34A3 mutations (exons and introns) in two previously not reported HHRH kindreds, which resulted in the identification of three novel mutations. The affected members of kindred A were compound heterozygous for two different mutations, c.1046_47del and the intronic mutation c.560+23_561-42del, while the index case in kindred B was homozygous for the nonsense SLC34A3 mutation c.1764C>G (p.Y588X). The patient in kindred C was diagnosed with IH because of bilateral medullary nephrocalcinosis, suppressed PTH levels, and hypercalciuria; she was found to have a novel heterozygous c.1571_1880del mutation. The HHRH patients in kindred A were treated for up to 7years with oral phosphate, which led to reversal of hypophosphatemia, hypercalciuria, and prevention or healing of the mild bone abnormalities. PTH levels were normal throughout the observation period, while 1,25(OH)(2) vitamin D levels remained elevated and may thus be helpful for assessing treatment efficacy and patient compliance in HHRH.

Dietary modifications alone do not improve bone mineral density in children with idiopathic hypercalciuria.

Prior cross-sectional studies have demonstrated an association between hypercalciuria and low bone mineral density (BMD) in children and adults. However, the natural history of BMD in children with hypercalciuria and its response to therapy has not been evaluated. The objective of this retrospective study was to determine the change over time in lumbar (L1 - L4) BMD Z-score measured on sequential DXA scans in 19 children with hypercalciuria treated with dietary recommendations without (n = 12, Group A) and with citrate (n = 7, Group B). The mean lumbar bone density Z-score/year decreased in Group A (-0.11 ±/0.41) indicating that children with hypercalciuria lose L1 - L4 BMD over time. In contrast, the L1 - L4 BMD Zscore/ year increased in Group B (0.19 ± 0.38) suggesting that pharmacologic therapy may reverse this trend. Similarly 75% of patients in Group A, but only 29% patients in Group B had a decrease in L1 - L4 BMD. There was a definite, although not significant, trend towards improved mean bone mineral density Z-score per year and a lower percentage of patients with a decreased Z-score in hypercalciuric children treated with potassium citrate. Our findings suggest the possibility that dietary recommendations alone is not adequate as the bone mineral density of children with hypercalciuria will decrease over time, potentially increasing the risk for osteoporosis as an adult.

A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector.

A therapeutic CMV vaccine incorporating an antigenic repertoire capable of eliciting a cellular immune response has yet to be successfully implemented for patients who already have acquired an infection. To address this problem, we have developed a vaccine candidate derived from modified vaccinia Ankara (MVA) that expresses three immunodominant antigens (pp65, IE1, IE2) from CMV. The novelty of this vaccine is the fusion of two adjacent exons from the immediate-early region of CMV, their successful expression in MVA, and robust immunogenicity in both primary and memory response models. Evaluation of the immunogenicity of the viral vaccine in mouse models shows that it can stimulate primary immunity against all three antigens in both the CD4(+) and CD8(+) T cell subsets. Evaluation of human PBMC from healthy CMV-positive donors or patients within 6 months of receiving hematopoietic cell transplant shows robust stimulation of existing CMV-specific CD4(+) and CD8(+) T cell subsets.

Cell-cycle regulatory proteins in the podocyte in collapsing glomerulopathy in children.

Podocyte is a terminally committed cell in G1 arrest of cell cycle, and is unable to overcome G1/S transition phase in children with minimal change disease (MCD) and classic focal segmental glomerulosclerosis (FSGS), in contrast to dysregulated proliferative phenotype of idiopathic collapsing glomerulopathy (CGN) in adults. Forty-two kidney biopsies, MCD (14), FSGS (12), CGN (4), and normal (CON) (12), were evaluated by immunohistochemistry using dual staining for expression of p27, p21, and p57, and cyclins D and A, in podocytes of children with CGN. On light microscopy, all podocytes expressed p27, whereas p21 and p57 expression was seen in a portion of podocytes in normal kidney biopsies. Cyclin D was expressed in a small percentage of podocytes. Cyclin A expression was absent in normal biopsies. The staining for p27 decreased significantly, in order, from normal (100%) to MCD (45.8%) to CGN (24.2%) to FSGS (16.6%). p21 staining was significantly decreased from normal (69.8%) to CGN (15.5%) to MCD (2.2%) to FSGS (0.6%), and the difference between CGN and MCD and FSGS was also significant. There was no significant difference in staining of p57. Cyclin D staining was significantly increased in CGN (26.8%) compared to normal (7.2%), MCD (1.6%), and FSGS (0.0%), and the difference between CGN and MCD and FSGS was also significant. De novo cyclin A staining was only observed in children with CGN. Thus, p27 and p21 but not p57 was decreased in CGN, as in FSGS when compared to normal. Both cyclins D and A staining were increased in CGN. The staining pattern in CGN would suggest that podocyte is able to overcome G1/S transition phase, and has a proliferative phenotype. We propose, based on the significant contrast observed in podocytes injury response between CGN (proliferative) and classic FSGS (non-proliferative), that CGN not be considered as a morphological variant of FSGS.

Perforator stroke after elective stenting of symptomatic intracranial stenosis.

OBJECTIVE: To study the frequency, clinical course, and functional outcome of perforator stroke (PS) resulting from elective stenting of symptomatic intracranial stenosis. METHODS: Between September 2001 and November 2004, 169 consecutive patients with 181 symptomatic intracranial stenoses underwent stenting procedure at our institute. The preoperative perforator infarct adjacent to the stenotic segment (PIAS) on MRI was evaluated blindly. Patients who developed PS after stenting were enrolled. Each patient was assessed by an experienced stroke neurologist by neurologic examination and NIH Stroke Scale score every day until discharge and at day 30, and by modified Rankin Scale (mRS) score at the end of the first, third, and sixth month, and then at intervals of 6 months. RESULTS: PS frequency was 3.0% (5/169 patients). The patients with preoperative PIAS had a higher frequency of PS and PS exacerbation, resulting from intracranial stenting (8.2%, 4/49), vs patients without preoperative PIAS (0.8%, 1/120; p = 0.031). Four PSs occurred during the procedure and one 10 hours after stenting. Four PSs reached the maximum deficit almost at once, and one after 2 hours from onset. All five patients were functionally independent (mRS

Widespread electromyographic abnormalities in patients with monomelic amyotrophy: a detailed EMG study.

OBJECTIVE: To evaluate subclinical electromyographic changes in unaffected muscles of the patients with monomelic amyotrophy (MMA). PATIENTS AND METHODS: 35 patients of MMA with single limb atrophy (30 patients with upper limb involvement and 5 patients with lower limb involvement) were studied at All India Institute of Medical Sciences, New Dellhi, from September 2000 to September 2002. All the patients were evaluated clinically, by detailed three limb electromyography (EMG) and by MRI scan of the spine to rule out other disorders. RESULTS: The mean age of 35 male patients was 24.17 (+/-6.8) years and the mean duration of illness was 3.64 (+/-2.7) years. Patients with upper limb involvement had segmental pattern of atrophy, predominantly distal or proximal. EMG revealed evidence of subclinical diffuse chronic reinnervative changes. All the patients (100%) had bilateral chronic reinnervative changes and 50% had chronic reinnervative changes in three limbs. CONCLUSIONS: Patients with clinically single limb MMA were found to have evidence of widespread chronic reinnervative changes on EMG.

Quantitative thermal sensory testing in patients with monomelic amyotrophy.

BACKGROUND: Quantitative thermal sensory testing (QST) is a non-invasive method to assess somatic small fibre dysfunction, which is not evaluated with routine nerve conduction studies (NCS). Monomelic amyotrophy (MMA), is a pure motor disorder with no sensory abnormalities on routine NCS, and has not been evaluated using QST. AIMS AND OBJECTIVE: Present study aimed to evaluate somatic small fibre involvement in MMA patients. Forty patients with MMA with no sensory abnormalities or routine NCS were evaluated using QST for thresholds of cold sensation (CS), warm sensation (WS), cold pain (CP) and warm pain (WP), using method of limits. These were compared with 40 age-matched controls. RESULTS: No abnormalities in thresholds for CS, WS, CP and WP were found in MMA group as compared to controls. CONCLUSION: QST thus failed to demonstrate any abnormality. Hence we conclude that MMA is a pure motor disorder, with no involvement of somatic small sensory fibres (A delta and C).

Threshold intensity and central motor conduction time in patients with monomelic amyotrophy: a transcranial magnetic stimulation evaluation.

OBJECTIVE: To determine the Cortical threshold intensity (TI) and central motor conduction time (CMCT) in patients with monomelic amyotrophy (MMA). METHODS: TI and CMCT were evaluated by means of transcranial magnetic stimulation in 18 patients of MMA and 12 healthy controls at the clinical neurophysiology laboratory, department of neurology, All India Institute of Medical Sciences, New Delhi. RESULTS: The mean age of patients was 23.6 (SD 6. 7) years and of controls was 24.3 (SD 3.2) years (p > 0. 05). The mean TI in patients was 60.83% (SD 11.28) on ipsilateral and 60% (11.5%) on contralateral cortex stimulation. In controls, the mean TI was 66.67% (SD 11.5) on one side and 65% (11.87%) on contralateral cortex stimulation. There was no significant difference in the TI between these two groups (p > 0.05). The mean CMCT in patients was 8.3 (SD 1. 7) ms on ipsilateral and 9.4 (SD 1.6) ms on contralateral cortex stimulation (p > 0.05). In controls CMCT was 8.3 (SD 1.8) ms on one side and 8.6 (SD 1.4) ms on contralateral cortex stimulation. Upper limit of normal CMCT was 12.7 ms. CONCLUSIONS: As compared to controls there was no significant abnormality in TI and CMCT was normal in all except two patients where it was marginally prolonged. This could be because of excessive loss of anterior horn cells.

Myasthenic crisis: a retrospective study.

BACKGROUND AND OBJECTIVE: Myasthenic crisis (MC) is one of the important and common complications in the natural history of myasthenia gravis (MG). MC can be precipitated by multiple factors including deficiency or excess of the acetylcholinesterase inhibitors (AChEI). Any episode of MC is an emergency requiring aggressive therapy. We studied the demographic, clinical and treatment-related characteristics of patients who developed MC. MATERIALS AND METHODS: A retrospective study was conducted in patients with MC admitted during a 31-month period from February 1999 to August 2001, at a tertiary care center in India. RESULTS: Eleven patients (9.69% of the total 114 patients with MG) were admitted with 12 episodes of MC. Mean age at presentation was 39.83 + 13.18 years with male predominance. Seven patients had undergone thymectomy previously; of which 2 had postoperative MC. Six patients had thymoma. Steroid or cholinesterase inhibitor withdrawal and infections were the commonest precipitating factors for MC. Patients required ventilatory support for median 14 days. They responded to low volume of plasma exchange (PE) (mean 854 ml / day with mean 6.5 cycles per patient). CONCLUSIONS: This report highlights that the subset of Indian patients with MG who are at risk to develop MC belong to the 3rd and 4th decade, have bulbar symptoms at presentation and are associated with thymoma. Patients with MC should have judicious drug adjustments under supervision and should be treated aggressively during impending MC.

Inhibition of nitrification in soil by metal diethyldithiocarbamates.

Nitrification acts as a key process in determining fertilizer use efficiency by crops as well as nitrogen losses from soils. Metal dithiocarbamates in addition to their pesticidal properties can also inhibit biological oxidation of ammonium(nitrification) in soil. Metal [M = V(III), Cr(III), Mn(II), Fe(III), Ni(II), Cu(II), Zn(II) and Co(II)] diethyldithiocarbamates (DEDTC) were synthesized by the reaction of sodium diethyldithiocarbamate with metal chloride in dichloromethane/water mixture. These metal diethyldithiocarbamates were screened for their ability to inhibit nitrification at different concentrations( 10 microg/g soil, 50 microg/g soil and 100 microg/g soil). With increasing concentration of the complex, capacity to retard nitrification increased but the extent of increase varied for different metals. At 100 microg/g soil, different complexes showed nitrification inhibition from 22.36% to 46.45% . Among the diethyldithiocarbamates tested, Zn(DEDTC)2 proved to be the most effective nitrification inhibitor at 100 microg/g soil. Manganese, iron and chromium diethyldithiocarbamates also proved to be effective nitrification inhibitors than the others at 100 microg/g soil. The order of percent nitrification inhibition in soil by metal diethyldithiocarbamates was: Zn(II) > Mn(II) > Fe(III) > Cr(III) > V(III) > Co(II) > Ni(II) > Cu(II).

Asymptomatic spinal arachnoiditis in patients with tuberculous meningitis.

Spinal arachnoiditis is one of the common and disabling complication of tuberculous meningitis (TBM). We focused on early diagnosis of spinal arachnoiditis by spinal MRI in asymptomatic patients in whom neurological examination was normal. We studied 16 patients with a diagnosis of probable or highly probable TBM with symptoms for less than 1 month; three had radiological evidence of spinal arachnoiditis. High cerebrospinal fluid protein appeared to be a risk factor for development of spinal arachnoiditis. MRI is sensitive to detect early spinal arachnoiditis. Earlier diagnosis may be helpful in management of spinal arachnoiditis in TBM.

Hepatocyte dysfunction and hepatic encephalopathy in Plasmodium falciparum malaria.

BACKGROUND: According to the WHO, signs of hepatic dysfunction are unusual, and hepatic encephalopathy is never seen in malaria. However, in recent years, isolated cases have been reported from different parts of world. AIM: To identify the evidence for hepatocyte dysfunction and/or encephalopathy in jaundiced patients with falciparum malaria. DESIGN: Prospective observational study. METHODS: We studied 86 adult patients of both sexes who had malaria with jaundice (serum bilirubin > 3 mg%). The main outcome measures were: flapping tremor, deranged psychometric test, level of consciousness, serum bilirubin level, serum aspartate transaminase (AST) and alanine transaminase (ALT) levels, blood ammonia level, viral markers for hepatitis, ultrasonography of liver and gall bladder and electroencephalography (EEG). RESULTS: The range of serum bilirubin was 3-48.2 mg% (mean +/- SD 10.44 +/- 8.71 mg%). The ranges of AST and ALT levels were 40-1120 IU/l (294.47 +/- 250.67 IU/l) and 40-1245 IU/l (371.12 +/- 296.76 IU/l), respectively. Evidence of hepatic encephalopathy was seen in 15 patients. Asterexis was observed in 9 patients, impaired psychometric tests in 12 and altered mental state in 13. Arterial blood ammonia level was 120-427 meq/l (310 +/- 98.39 meq/l). EEG findings included presence of large bilateral synchronous slow waves, pseudo burst suppression and triphasic waves. Four patients died due to multiple organ dysfunction; the others made rapid recoveries. DISCUSSION: There is strong evidence of hepatocyte dysfunction and hepatic encephalopathy in some of these patients, with no obvious non-malarial explanation. Current guidelines may need to be revised.

Pulmonary manifestations in brucellosis: a report on seven cases from Bikaner (north-west India).

OBJECTIVES: Pulmonary manifestations of Brucellosis are rare. We came across seven patients with predominant symptomatology of pulmonary involvement amongst 98 patients of active brucellosis seen in last four years. MATERIAL AND METHODS: The study is related to patients of brucellosis whose principal presenting features were related to respiratory symptom (cough, expectoration, pain in chest and breathlessness) along with fever and other constitutional symptoms. It included seven patients amongst 98 patients of active brucellosis seen during June 1996 to Feb. 2000 at PBM Hospital Bikaner. Diagnosis was confirmed by demonstration of the raised brucella agglutination titre of 1:320 or more in the serum. All patients were treated with rifampicin 900 mg daily and doxycyclin 100 mg twice daily for six week. The treatment was extended for another four weeks in two patients because of persistence of skiagram abnormalities. RESULT: Three patients had abnormality in skiagram chest in the form of pleural effusion, multiple paranchymal opacities and pneumonia. The skiagram chest was normal in remaining four patients. The response of treatment started with 10-15 days and all the patients became symptom-free at the end of six weeks except one patient. Skiagram chest at this time was normal in patients of pleural effusion but there was persistence of haziness and few opacities in other two patients. Follow up skiagram chest at the end of six months and twelve months was normal in all patients except calcified opacity in one patient. There was no evidence of relapse in any patient at the end of one year follow up. Liver function tests remained within normal range and no drug toxicity was observed. CONCLUSION: Pulmonary manifestations of brucellosis are rare. Treatment with rifampicin and doxycylin showed marked clinical and radiological improvement. All patients were completely disease-free at the end of one year follow up.

Sodium valproate in the management of painful neuropathy in type 2 diabetes - a randomized placebo controlled study.

OBJECTIVE: To study the effectiveness and safety aspects of sodium valproate in the management of painful neuropathy in patients of type 2 diabetes mellitus. MATERIAL AND METHODS: A randomized double-blind placebo controlled trial of sodium valproate was done in type 2 diabetic patients to assess its efficacy and safety in the management of painful neuropathy. We screened 60 patients but eight patients could not complete the study; hence, the present study was done on 52 patients. Each patient was assessed by clinical examination, pain score by short form of the McGill pain questionnaire (SF-MPQ) and electrophysiological examination, which included motor and sensory nerve conduction velocity, amplitude and H-reflex initially and at the end of 1 month of treatment. RESULTS: Significant improvement was noticed in the pain score of patients receiving sodium valproate in comparison to patients receiving placebo at the end of 1 month (P < 0.05). The changes in electrophysiological data were not significant. The drug was well tolerated by all patients except one who developed a raised aspartate transaminase (AST)/alanine transaminase (ALT) level after 15 days of treatment. CONCLUSION: Sodium valproate is a well-tolerated drug and provides significant subjective improvement in painful diabetic neuropathy. These data provide a basis for future trials of longer duration in a larger group of patients.