The danger of using metallic plate and screw fixation in the young.
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Biomedical subjects
Publications and source records attributed to S M Joshi.
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Colloid cyst of the third ventricle is a rare benign intracranial lesion, and familial cases are rarer still. They may be asymptomatic or present with symptoms of raised intracranial pressure, including sudden death. Surgical excision is curative. We report a 24 year old pregnant woman with familial colloid cyst, who presented with headaches and suffered a cardiorespiratory arrest. Early computed tomography scan of the brain is advised in patients with a family history of third ventricular colloid cyst presenting to the accident and emergency department with headache.
The objective of the study was to highlight the diagnostic challenge of this elusive rare disease. A retrospective study of non-tuberculous spinal epidural abscesses (SEA) was carried out in Southern General Hospital, Glasgow, University Hospital of Wales, Cardiff, and Morriston Hospital, Swansea, from 1990 to 2000. Thirty-nine patients, consisting of 20 females and 19 males, with an age range from 20 to 85 years (mean: 61.1) were identified. Thirty-eight had localized back/neck pain. Eighteen were apyrexial. Twenty-nine demonstrated neurological deficit. All patients had raised inflammatory markers and gadolinium-enhanced magnetic resonance imaging (MRI) was diagnostic in 34. The most commonly identified organism was Staphylococcus aureus. All underwent surgical decompression, of which 13 required stabilization. Three died, seven lacked sphincter control and nine had motor deficit at the end of 1 year. It was concluded that fever is not mandatory for the diagnosis of SEA. Patients with localized back/neck pain and raised inflammatory markers need urgent MRI.
Purified retrovirus Gag proteins or Gag protein fragments are able to assemble into virus-like particles (VLPs) in vitro in the presence of RNA. We have examined the role of nucleic acid and of the NC domain in assembly of VLPs from a Rous sarcoma virus (RSV) Gag protein and have characterized these VLPs using transmission electron microscopy (TEM), scanning TEM (STEM), and cryoelectron microscopy (cryo-EM). RNAs of diverse sizes, single-stranded DNA oligonucleotides as small as 22 nucleotides, double-stranded DNA, and heparin all promoted efficient assembly. The percentages of nucleic acid by mass, in the VLPs varied from 5 to 8%. The mean mass of VLPs, as determined by STEM, was 6.5 x 10(7) Da for both RNA-containing and DNA oligonucleotide-containing particles, corresponding to a stoichiometry of about 1,200 protein molecules per VLP, slightly lower than the 1,500 Gag molecules estimated previously for infectious RSV. By cryo-EM, the VLPs showed the characteristic morphology of immature retroviruses, with discernible regions of high density corresponding to the two domains of the CA protein. In spherically averaged density distributions, the mean radial distance to the density corresponding to the C-terminal domain of CA was 33 nm, considerably smaller than that of equivalent human immunodeficiency virus type 1 particles. Deletions of the distal portion of NC, including the second Zn-binding motif, had little effect on assembly, but deletions including the charged residues between the two Zn-binding motifs abrogated assembly. Mutation of the cysteine and histidine residues in the first Zn-binding motif to alanine did not affect assembly, but mutation of the basic residues between the two Zn-binding motifs, or of the basic residues in the N-terminal portion of NC, abrogated assembly. Together, these findings establish VLPs as a good model for immature virions and establish a foundation for dissection of the interactions that lead to assembly.
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Purified retrovirus Gag proteins can assemble in vitro into virus-like particles (VLPs) in the presence of RNA. It was shown previously that a Rous sarcoma virus Gag protein missing only the protease domain forms spherical particles resembling immature virions lacking a membrane but that a similar protein missing the p10 domain forms tubular particles. Thus, p10 plays a role in spherical particle formation. To further study this shape-determining function, we dissected the p10 domain by mutagenesis and examined VLPs assembled within Escherichia coli or assembled in vitro from purified proteins. The results identified a minimal contiguous segment of 25 amino acid residues at the C terminus of p10 that is sufficient to restore efficient spherical assembly to a p10 deletion mutant. Random and site-directed mutations were introduced into this segment of polypeptide, and the shapes of particles formed in E. coli were examined in crude extracts by electron microscopy. Three phenotypes were observed: tubular morphology, spherical morphology, or no regular structure. While the particle morphology visualized in crude extracts generally was the same as that visualized for purified proteins, some tubular mutants scored as spherical when tested as purified proteins, suggesting that a cellular factor may also play a role in shape determination. We also examined the assembly properties of smaller Gag proteins consisting of the capsid protein-nucleocapsid protein (CA-NC) domains with short N-terminal extensions or deletions. Addition of one or three residues allowed CA-NC to form spheres instead of tubes in vitro, but the efficiency of assembly was extremely low. Deletion of the N-terminal residue(s) abrogated assembly. Taken together, these results imply that the N terminus of CA and the adjacent upstream 25 residues play an important role in the polymerization of the Gag protein.
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A retrospective study of 57 surgically-managed brain abscesses at the Neurosurgical Unit, Bir Hospital during a 6-year period from October 1990 is presented. Detailed hospital case notes could be traced in only 37 cases, consisting of 25 males and 12 females with age range from 5 months to 60 years. Cryptogenic abscess was the commonest category followed by abscess caused by chronic ear infection. The diagnosis was made with enhanced computed tomography (CT) in all the cases. Positive bacteriology was found in only nine cases. The treatment consisted of 6 weeks of intensive intravenous antibiotics and emergency surgical drainage of the abscess. Five out of the total cases died (13.5%). These patients were all in an extremely poor condition at the time of presentation. All the survivors made a good recovery. With timely CT diagnosis, surgical drainage and antibiotics, good results can be achieved even in a developing country.
Effective ex vivo purging techniques can decrease the likelihood of infusing bone marrow contaminated with leukemic cells during autologous transplantation. In preliminary studies, OL(1)p53, a 20-mer phosphorothioate oligonucleotide directed against p53 mRNA, decreased the number of acute myelogenous leukemia (AML) cells in vitro, suggesting a possible role for OL(1)p53 in purging bone marrow harvests of leukemia cells. To demonstrate that OL(1)p53 was nontoxic to hematopoietic progenitor cells, normal bone marrow cells were incubated with 10 microM OL(1)p53 for 36 h, and hematopoietic progenitor cell survival was determined by in vitro colony assays. OL(1)p53 had no toxic effect on the growth of either myeloid (CFU-GM) or erythroid (BFU-E) progenitor cells. OL(1)p53 was then used to ex vivo purge bone marrow harvests from nine patients with either AML or myelodysplastic syndrome (MDS). Bone marrow cells were incubated with 10 microM OL(1)p53 for 36 h before transplantation. The median times posttransplantation for the patient to recover an absolute neutrophil count greater than 0.5 x 10(9)/L and a platelet transfusion independence were 30 days and 56 days, respectively. Incubation of bone marrow cells with OL(1)p53 had no detrimental effect on the growth of hematopoietic progenitor cells, and transplantation of autologous bone marrow cells treated with the phosphorothioate oligonucleotide, OL(1)p53, resulted in successful recovery of circulating neutrophils following high-dose therapy in patients with AML or MDS. The data show that OL(1)p53 can be used safely to purge autologous bone marrow harvests from patients with leukemia.
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Brain abscesses were studied in 47 patients. Thirty-four (72%) of them were between 5-15 years and 9 were infants. Otogenic source (34%) was the commonest predisposing factor, followed by scalp and face infection (21.3%) and congenital cyanotic heart disease (12.8%). Twenty (42%) patients had multiple abscesses. Supratentorial abscesses were commonest (75.9%). Predominant clinical features were fever (87.2%), raised intracranial tension (78.7%) and altered sensorium (53.2%). A total of 38.3% presented with focal neurological deficit and 34% were admitted in Grade III or IV coma. Diagnosis of abscess and monitoring of its evolution was done principally by CT scanning. Causative organisms were isolated in 54.8% of cases and Staphylococci, Proteus and Pseudomonas were the common pathogens. Therapy was most often a combination of surgical aspiration with or without excision in addition to antimicrobial therapy. The overall mortality in our series was 44.7%. Bad prognostic factors were Grade III/IV of coma at admission, age below 2 years and multiple abscesses.
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