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Biomedical subjects

S Russell

Publications and source records attributed to S Russell.

At least 19 recordsLinked to original sources

Management of mitochondrial disease on an intensive care unit.

Patients with mitochondrial disease may present to the Intensive Care Unit (ICU) with a variety of neurological and general medical disorders. Eleven patients were admitted to a neurological ICU between 1970 and 1992 because of respiratory insufficiency, status epilepticus and/or metabolic encephalopathy associated with mitochondrial disease. Respiratory impairment occurred in eight patients and was associated with nocturnal hypoventilation due to respiratory muscle weakness, aspiration due to bulbar weakness and abnormalities of central control leading to a reduced CO2 drive, irregular respiratory patterns and sleep apnoea. Seven patients received continuous respiratory support during the acute illness; three were subsequently weaned to domiciliary ventilation, and four died. Five patients had stroke-like episodes, which in two were recurrent. Four patients developed tonic-clonic grand mal epilepsy associated with myoclonic fits (2 patients), absences (2), focal fits (1) and status epilepticus (2). Encephalopathy was associated with recurrent lactic acidosis (2 patients), cardiac failure (2), hyponatraemia (2), renal abnormalities (3) and complete heart block (1). Although rare, mitochondrial disease should be considered in any patient with unexplained respiratory failure, intractable epilepsy, lactic acidosis or recurrent stroke.

Acidosis, Lactic

Soemmering's ring support for posterior chamber intraocular lens implantation during penetrating keratoplasty. Changing trends in bullous keratopathy.

BACKGROUND: Changing trends in cataract extractions have resulted in a new category of bullous keratopathy: corneal decompensation after complicated extracapsular cataract extraction. These cases of bullous keratopathy are associated with rupture of the posterior capsule, vitreous loss, and significant intraocular inflammation at the time of the original complicated extracapsular cataract extraction. METHODS: The authors reviewed 14 consecutive cases of penetrating keratoplasty for bullous keratopathy in which posterior chamber intraocular lens implantation was supported by remnants of the posterior capsule and/or Soemmering's ring without suture fixation. All 14 patients had a history of complicated extracapsular cataract extraction with capsule rupture and vitreous loss. RESULTS: All 14 patients had clear, compact grafts without migration of the intraocular lens with a mean follow-up of 12.1 months. Vision improved in 93% of cases, and there was no significant worsening of glaucoma. CONCLUSIONS: Pseudophakic bullous keratopathy after traumatic extracapsular cataract extraction with an anterior chamber intraocular lens and aphakic bullous keratopathy after traumatic extracapsular cataract extraction are two relatively new clinical entities that present new intraocular lens management options. Bullous keratopathy after complicated extracapsular cataract extraction should be recognized as a distinct clinical entity. Intraocular lens implantation into the ciliary sulcus with Soemmering's ring and peripheral capsular support provide the advantages of a posterior chamber intraocular lens without the risk of iris or scleral sutures. The authors predict that bullous keratopathy associated with traumatic extracapsular cataract extraction will become one of the more common indications for penetrating keratoplasty.

Adolescent

Bone marrow transplantation in children using closely matched related and unrelated donors.

Seventeen bone marrow transplants were undertaken on 15 patients with leukemia or aplastic anemia using marrow from closely matched (phenotypic or five out of six HLA-A, B and DR antigen matched related and unrelated) donors. Donors were siblings (four), parents (seven), aunt (one), great aunt (one) or matched unrelated (two). When compared with transplants using matched sibling donors, survival was not different (51.4 +/- 13.4% vs. 48.1 +/- 9.6%; p = 0.87) but transplant-related complications and morbidity were higher as follows: graft-versus-host disease (GVHD) (87% vs. 15%; p less than 0.001), interstitial pneumonitis (59% vs. 14%; p less than 0.003), days in hospital (51 vs. 26; p less than 0.001), and chronic transplant related morbidity 50% vs. 11%; p + 0.033). The age of donors who were closely matched was significantly greater than that of their recipients (29.7 +/- 13.9 years vs. 8.1 +/- 3.1 years; p less than 0.001) and was associated with poorer transplant outcome. Median transplant-related complication-free survival for patients receiving transplants from age non-disparate donors was 53 months (range 18-86 months) compared with 12 months (range 2-42 months) for age disparate donors (p = 0.028). Transplants from closely matched donors were undertaken in the ratio of one to every three matched donors, indicating the importance of this source of marrow in a transplant program.

Adult

Site-directed recombination in the genome of transgenic tobacco.

The plant genome responds to the bacteriophage P1-derived loxP-Cre site-specific recombination system. Recombination took place at loxP sites stably integrated in the tobacco genome, indicating that the Cre recombinase protein, expressed by a chimeric gene also stably resident in the genome, was able to enter the nucleus and to locate a specific 34 bp DNA sequence. An excisional recombination event was monitored by the acquisition of kanamycin resistance, which resulted from the loss of a polyadenylation signal sequence that interrupted a chimeric neomycin phosphotransferase II gene. Molecular analysis confirmed that the excision had occurred. Recombination occurred when plants with the integrated loxP construction were stably re-transformed with a chimeric cre gene and when plants with the introduced loxP construction were cross-bred with those carrying the chimeric cre gene. As assayed phenotypically, site-specific recombination could be detected in 50%-100% of the plants containing both elements of the system. Kanamycin resistance was detected at 2-3 weeks after re-transformation and in the first leaf of hybrid seedlings. This demonstration of the effectiveness of the loxP-Cre system in plants provides the basis for development of this system for such purposes as directing site-specific integration and regulation of gene expression.

Blotting, Northern

Gender differences in retrieval from long-term memory following acute intoxication with ethanol.

The present study investigated the effects of ethanol on retrieval from long-term memory by using a set of cognitive decision tasks. Male and female subjects were administered either 0.0 or 1.0 milliliter of ethanol per kilogram of body weight, and then asked to make physical, lexical, and semantic decisions about pairs of words. In general, intoxicated subjects responded significantly slower than sober subjects on all decision types. In addition, female subjects demonstrated greater performance deficits than males when intoxicated. The results suggested that the reduction in speed was not due to a simple slowing of motor responses. Rather the ethanol induced memory deficits may result from the slowing of cognitive operations that impair the efficiency of working memory. Several reasons were proposed for the observed difference in reaction to intoxication between male and female subjects, including neuroendocrine processes and cognitive differences.

Adult

Recombinant interleukin-2 (rIL-2) given intrasplenically and intravenously for advanced malignant melanoma. A phase I and II study.

Recombinant interleukin-2 (rIL-2) was used to treat 31 patients with progressing metastatic malignant melanoma. Only three patients had disease confined to non-visceral sites; the median number of organ sites involved was four. The first dose of rIL-2 was given intrasplenically (to stimulate cytotoxic cells in high concentration) via a femoral artery catheter, and four further i.v. doses were given over 6 days. A total of three courses at 21-day intervals was planned. Doses were escalated in 15 patients from 1 x 10(6) to 16.4 x 10(4) Cetus units m-2. The maximum tolerated dose (11.0 x 10(6) U m-2) was used in the other 16 patients. Of the 71 courses, severe but transient toxicity requiring interruption of rIL-2 or additional care occurred on three courses (dyspnoea) and 15 from hypotension, but the patients' performance status improved. Four patients had partial tumour responses although in only one patient did response occur in all sites of disease. However, responses occurred in visceral sites and six patients are alive at 9-16 months. IL-2 is of use in advanced melanoma and does not need complicated ICU facilities.

Adult

Characterization of the adenovirus proteinase: substrate specificity.

Peptides were synthesized based on the cleavage sites in the adenovirus type 2 proteins pVI and pVII. The synthetic peptides were incubated with disrupted, purified adenovirus as a source of proteinase and specific cleavages were monitored by fast protein liquid chromatography and amino acid analysis. Using this approach it was established that all the peptides cleaved were of the form M(L)XGX decreases G or M(L)XGG decreases X. Thus we have shown that the adenoviral proteinase recognizes a specific secondary structure formed by a sequence of at least five amino acids, the main determinants of specificity being two and four residues to the N-terminal side of the bond cleaved. We were able to examine the relevant structural features of the peptide substrates by utilizing the CHEM-X molecular modelling package. Using our consensus sequence we were able to predict the cleavage sites in the viral proteins pVIII, pre-terminal protein (pTP), 11K and IIIa. Octapeptides containing the predicted sites in pVIII and the pTP were synthesized and shown to be cleaved by the proteinase.

Adenoviruses, Human

Nursing mosaic.

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Humans

Mutation of a protein kinase C phosphorylation site in the erbB protein of avian erythroblastosis virus.

Tumor promoter-stimulated phosphorylation of threonine 98 of the erbB protein of avian erythroblastosis virus (AEV) correlates with inhibition of erbB-dependent mitogenesis. To more clearly define the role of phosphorylation of this residue in regulation of the activity of the erbB protein, we have constructed erbB mutations which encode alanine (Ala-98), tyrosine (Tyr-98), or serine (Ser-98) at position 98. The biosynthesis and stability of the three mutant proteins were similar to those of the wild-type erbB protein, and all three retained the ability to transform chicken embryo fibroblasts. Treatment of transformed CEF with 12-tetradecanoylphorbol-13-acetate (TPA) stimulated incorporation of 32Pi into wild-type and mutant erbB proteins and resulted in a slight decrease in the electrophoretic mobilities of all the erbB proteins. Tryptic maps of erbB phosphopeptides showed no endogenous or TPA-stimulated phosphorylation of alanine 98 or tyrosine 98 in cells transformed by the Ala-98 and Tyr-98 mutants. Analysis of tryptic phosphopeptides by high-pressure liquid chromatography revealed that TPA treatment of cells stimulated phosphorylation of other sites of the erbB protein in addition to threonine 98. A high endogenous level of phosphorylation of serine 98 of the Ser-98 mutant protein was found, and TPA treatment of cells did not result in further phosphorylation of this residue. Cells transformed by wild-type and mutant AEV were equally sensitive to TPA-dependent inhibition of growth in soft agar and TPA-dependent inhibition of [3H]thymidine incorporation. TPA treatment inhibited tyrosine phosphorylation to a similar extent in cells transformed by wild-type or Ala-98 AEV. These data indicate that phosphorylation of threonine 98 of the erbB protein is not responsible for TPA-dependent inhibition of growth of AEV-transformed cells or TPA-induced inhibition of erbB-dependent tyrosine phosphorylation. TPA-stimulated phosphorylation of the erbB protein at other sites may mediate these effects. The data also show that subtle changes in a phosphorylation site (i.e., changing threonine to serine) can drastically alter recognition by protein kinases.

Alpharetrovirus

Comparison of the efficacy of naproxen sodium and dihydrocodeine tartrate in the treatment of post-operative pain.

A single-blind, parallel study was carried out in 54 patients with post-operative pain after minor orthopaedic procedures to compare the efficacy and tolerance of naproxen sodium and dihydrocodeine tartrate. Patients were allocated at random to receive oral treatment as soon as analgesia became necessary with an initial dose of either 550 mg naproxen sodium or 30 mg dihydrocodeine tartrate, then doses of 275 mg and 30 mg, respectively, when required up to a maximum of 5 doses per day for 3 days. Assessments were made of pain severity and pain relief 2 and 4 hours after the first dose and at the end of each day. The results indicated that naproxen sodium gave statistically significantly greater pain relief than dihydrocodeine tartrate after the first dose. Both treatments were well tolerated and few side-effects were reported. Three patients in each group were withdrawn due to lack of efficacy (combined with adverse effects in 1 naproxen sodium patient), and 1 patient in each group was withdrawn because of side-effects.

Administration, Oral

Calcified cytoid bodies in acquired immunodeficiency syndrome.

The postmortem histopathologic findings of eyes from two patients with acquired immunodeficiency syndrome (AIDS) are presented. Both patients had succumbed to multiple opportunistic infections. All of the eyes demonstrated calcified cotton-wool patches of the retina. To date, there have been no prior descriptions of calcification of cotton-wool spots (CWS). The pathophysiologic mechanisms unique to AIDS that allow some of these CWSs to calcify have yet to be determined.

Acquired Immunodeficiency Syndrome