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Biomedical subjects

D Powell

Publications and source records attributed to D Powell.

At least 37 records · Page 2Linked to original sources

Dose-response and failure pattern for bulky or barrel-shaped stage IB cervical cancer treated by combined photon irradiation and extrafascial hysterectomy.

From 1975 to 1987, 80 patients with bulky or barrel-shaped Stage IB cervical cancer were treated with preoperative irradiation and Cs-137 intracavitary implant therapy, before a planned extrafascial abdominal hysterectomy, using a consistent treatment policy. Of the hysterectomy specimens obtained, 37% were positive histologically at 89 +/- 2.3 days after the start of radiotherapy and at 4 to 6 weeks after the completion of radiation therapy. Sixty-three percent were negative after a total external and internal cervix irradiation dose of 9642 cGy at point T. The average point A dose contributed by intracavitary therapy was 2104 cGy. The survival rate at 5 years was 84%: At 10 years the survival rate was 78%. The failure pattern was analyzed for patients who had positive and negative specimens. The patients with positive specimens failed pelvically or pelvically and distantly. Patients with negative specimens failed in extrapelvic or distant metastatic sites. Preoperative radiotherapy led to excellent local and pelvic control of tumor, and the failures became predominantly distant metastases. The combined radiosurgical therapy was tolerated well and allowed surgical staging of disease. This permitted earlier and selective consideration of adjunctive therapy (i.e., paraaortic irradiation, chemotherapy, or chemoradiotherapy). The dose-response data give insight into the effects of photon radiotherapy on bulky or barrel Stage IB cervical cancers and correlate histologic status with failure pattern, outcome, and long-term survival.

Adult

An outbreak of paratyphoid fever in the UK associated with a fish-and-chip shop.

An outbreak of Salmonella paratyphi B infection in the UK associated with a fish-and-chip shop is reported. The source of infection for the first three cases was believed to be a food handler who was infected overseas 6 years earlier. His wife whose faeces and urine were originally culture negative continued to run the shop but subsequently her faeces became positive on one occasion. She was considered to have been the source of two further cases, and secondary household spread of infection from these two cases resulted in one symptomatic and two asymptomatic infections. A second household contact of the proprietor also became a faecal excretor 2 months later. We recommend that food handlers living in households or in intimate contact with cases or carriers of S. paratyphi B should be put off work until all household contacts cease excreting the organism.

Adolescent

Selective infection of human CD4+ cells by simian immunodeficiency virus: productive infection associated with envelope glycoprotein-induced fusion.

Simian immunodeficiency virus (SIV) and human immunodeficiency virus share the property of tropism for CD4-bearing cells. Infection is initiated by a high-affinity interaction between CD4 and conserved domains on the viral envelope glycoprotein. In this report, we demonstrated that SIV had a restricted host range among human CD4+ cells when compared with human immunodeficiency virus type 1 or type 2. This restricted tropism was associated with the inability of the SIV envelope glycoprotein to induce membrane fusion in cells not susceptible to productive exogenous infection by SIV. We conclude that the major route of SIV entry into CD4+ cells is by envelope-mediated direct fusion with the cell and that additional envelope-cell interactions after CD4 binding are required for productive infection.

Antigens, Surface

Retrospective study of early postoperative convulsions after intracranial surgery with isoflurane or enflurane anaesthesia.

Retrospective analysis of the case records of 383 patients undergoing elective intracranial surgery showed that, in the first 24 h after surgery, 13.9% of patients receiving low concentrations (0.4-1 MAC) of isoflurane had one or more convulsions after operation, compared with 8% receiving enflurane (0.4-1 MAC). Controlled ventilation was required as part of the therapy for convulsions in 4.9% of the isoflurane group and 3.6% of the enflurane group. These differences between the groups were not statistically significant.

Anesthesia, Inhalation

Effect of insecticidal ear tags on populations of lice (Damalinia ovis) infesting sheep.

Polymer matrix ear tags containing 13.7% w/w tetrachlorvinphos or 8.5% w/w cypermethrin were applied to Merino wethers infested with lice and carrying two months wool. The cypermethrin tags reduced louse numbers by a maximum of 89% in comparison to controls at 16 weeks after treatment and by 85% at the conclusion of the experiment 38 weeks after application. Lice were not eradicated from any sheep. The number of lice counted on sheep treated with tetrachlorvinphos-impregnated tags was not significantly different from controls.

Analysis of Variance

Insulin-like growth factor binding proteins from cultured human fibroblasts. Characterization and hormonal regulation.

Specific, high affinity insulin-like growth factor (IGF) binding proteins are secreted by human fibroblasts in culture. By multiple criteria, the species of IGF binding proteins produced by human fibroblasts are distinct from the HepG2/amniotic fluid IGF binding protein, but share many characteristics with the growth hormone-dependent IGF binding protein forms predominant in normal adult human plasma. Treatment of cultured human fibroblasts with growth hormone produced an increase in IGF binding protein activity in the medium, while addition of glucocorticoids markedly diminished IGF binding activity. Insulin, epidermal growth factor, platelet-derived growth factor, and progesterone had no effect on IGF binding activity in fibroblast media. In comparison, HepG2 IGF binding activity was enhanced by progesterone, decreased by insulin, and unaffected by growth hormone or glucocorticoid treatment. Five molecular forms of IGF binding proteins were identified by Western ligand blots in human fibroblast conditioned medium, with Mr = 41,500, 37,000, 32,000, 28,000, and 23,000. In human fibroblast conditioned medium, the Mr = 41,500 and 37,000 IGF binding protein species were abundant, as in normal human plasma, with a major Mr = 23,000 form which was a minor component in plasma.

Animals

Efficacy of brachytherapy with californium-252 neutrons versus cesium-137 photons for eradication of bulky localized cervical cancer: single-institution study.

A fast-neutron-emitting radioisotope, 252Cf, is being tested in clinical trials of neutron brachytherapy for cervical cancer. The efficacy for histological eradication of bulky stage IB cervical tumors (mean diameter, approximately 6 cm) using combined radiation and surgery was studied in 65 patients treated with 137Cs or 252Cf before surgery during 1983-1986. Forty-four patients were treated with 137Cs and 21 were treated with 252Cf at equivalent doses of radiation. Fifteen of the 44 specimens (34%) were positive after 137Cs therapy. Only one of the 21 specimens was positive after 252Cf therapy (P = .025), and that patient was treated in a delayed schedule 21 days after the start of external-beam irradiation rather than early in the course. 252Cf therapy required a much lower radiation dose and shorter treatment time. The study compared tumor destruction of an identically staged human cervical tumor in situ by direct histological means, using 252Cf neutron therapy or conventional photon therapy at an identical and equivalent dose adjusted by a relative biological effectiveness of 6.0 for 252Cf.

Adult

Group-specific, major histocompatibility complex class I-restricted cytotoxic responses to human immunodeficiency virus 1 (HIV-1) envelope proteins by cloned peripheral blood T cells from an HIV-1-infected individual.

Freshly separated unfractionated peripheral blood mononuclear cells (PBMC) and cloned cell lines from a healthy human immunodeficiency virus 1 (HIV-1)-seropositive individual were examined for cytotoxic responses to HIV proteins expressed by recombinant vaccinia viruses. It was found that freshly isolated PBMC recognize variant envelope proteins of HIV-1 but not a more distantly related envelope protein derived from the simian immunodeficiency virus (SIVmac). Although the effector cells were predominantly CD8+, both MHC-matched and -unmatched target cells were lysed. Cytotoxic T lymphocyte (CTL) clones were found to lyse cells expressing HIV-1 envelope or reverse transcriptase. In contrast to the cytotoxic response detected with PBMC, the cloned CTLs were major histocompatibility complex (MHC) class I restricted. Our finding that a cloned CTL line lysed cells expressing highly divergent HIV envelopes strongly suggested that a conserved epitope was recognized. Identification of these shared epitopes may assist in designing a vaccine for HIV-1 that could stimulate MHC-restricted cytotoxic responses.

Acquired Immunodeficiency Syndrome

Regulation of two nested proteins from gene 49 (recombination endonuclease VII) and of a lambda RexA-like protein of bacteriophage T4.

Phage T4 gene 49, encoding recombination endonuclease VII, specifies, by initiation from an AUG and an internal GUG codon, two in-frame overlapping peptides (of 18 and 12 kD). The gene is transcribed early and late, albeit from different promoters. The sequence predicts that in long early transcripts, initiated far upstream of the coding sequence, the Shine-Dalgarno sequence of the first ribosome binding site can be sequestered in a hairpin and/or cleaved. These processes might reduce initiation from the first AUG and facilitate initiation of the 12-kD peptide from the internal GUG. The potential of this hairpin to participate in Y structures or cruciforms suggests possible autoregulation. Shorter, more stable late transcripts initiated from a late promoter immediately upstream of the first ribosome binding site cannot form this hairpin. More efficient translation of the longer 18-kD gene 49 peptide from these late transcripts accounts for the strong dependence of endonuclease VII activity on late gene expression. An ORF downstream from gene 49 can be translated from a motA-dependent transcript that starts inside gene 49 as well as from the gene 49 transcripts. Its initiation codon overlaps the stop codon of gene 49, suggesting some coupling of translation. The deduced protein resembles, among others, the RexA protein of phage lambda. Possible implications for T4 recombination and for the interference of lambda lysogens with T4 gene 49 and rII mutants are discussed.

Amino Acid Sequence

Specimen histology after one or two preoperative CF-252 implants for bulky stage IB cervical cancer.

Using hysterectomy specimens obtained 1 month after Cf-252 neutron brachytherapy plus fractionated radiotherapy, we determined the fraction of positive and negative specimens with neutron dose for bulky Stage IB cervical cancers. The specimens obtained and studied after an initial Cf-252 insertion when the sources were newer and less decayed were more frequently negative for histological evidence of cancer than after the sources had decayed and 2 insertions were needed. After two insertions to deliver a therapeutic dose preoperatively the specimens were more frequently positive. When a larger initial dose was delivered to the tumor a larger proportion of negative specimens was noted. The size of neutron dose fraction was important to local tumor clearance and to rendering the specimens negative as well as schedule in use.

Brachytherapy

Intrauterine herpes simplex virus infections.

Neonatal herpes simplex virus (HSV) infection is usually acquired at birth, although a few infants have had findings suggestive of intrauterine infection. We describe 13 babies who had clinical manifestations of intrauterine HSV infection, including skin lesions and scars at birth (12), chorioretinitis (eight), microcephaly (seven), hydranencephaly (five), and microphthalmia (two). All infants had combinations of these defects. Infection was proved by viral isolation in each case; all isolates were HSV-2. Two infants died during the first week of life; 10 of the surviving infants had severe neurologic sequelae, and one infant was blind. Four mothers experienced an apparent primary genital HSV infection, and one had recurrent infection, at varying times during gestation. The remaining women denied a history of symptoms of genital HSV infection. These findings indicate that intrauterine HSV infection can occur as a consequence of either primary or recurrent maternal infection and has severe consequences for the fetus.

Abnormalities, Multiple

Chronic paroxysmal hemicrania in a South African black. A case report.

A 35-year-old black man with a 4-year continuous history of multiple paroxysms of unilateral temporal and ocular pain is reported. Multiple (that is, 15-20) attacks occurred in 24 h. There were no symptom-free periods. Mild exophthalmos, marked sweating, nasal congestion, and lacrimation were present on the affected side. There was no response to ergot preparations, steroids, or lithium but dramatic and sustained relief with indomethacin.

Adult

Biological and biochemical characterization of a cloned Leu-3- cell surviving infection with the acquired immune deficiency syndrome retrovirus.

Leu-3- cells that survive infection with the acquired immune deficiency syndrome (AIDS) retrovirus can be induced with IUdR to express infectious virus. A cellular clone (8E5), isolated by limiting dilution of a mass culture of survivor cells, was found to contain a single, integrated provirus that was constitutively expressed. Although IUdR treatment of 8E5 cells failed to induce infectious virus, cocultivation with Leu-3+ cells generated the characteristic syncytia associated with acute AIDS retrovirus infection. The single integrated copy of proviral DNA directs the synthesis of all major viral structural proteins except p64, as monitored by immunoblotting. The relationship of the 8E5 clone to viral latency and persistence is discussed.

Acquired Immunodeficiency Syndrome

Isolation and characterization of the alpha 1-antitrypsin gene of mice.

We have characterized a genomic clone of the mouse equivalent of alpha1-antitrypsin (alpha1-antiprotease) a gene that is expressed in liver. There are at least three other genomic sequences similar to the gene expressed in mouse liver and all appear to be located on chromosome 12. The duplicated regions might include genes that are also expressed in the liver and/or in other tissues. Comparison of the sequences of the mouse alpha1-antitrypsin sequence expressed in liver with sequences of alpha1-antitrypsins from other mammals reveals great homology in the coding regions, particularly in the amino acids at the active site, including the neighboring methionine and serine thought to play a key role in the protease inhibition.

Animals

Bone and mineral metabolism and chronic alcohol abuse.

Studies of bone and mineral metabolism were made in 22 patients with chronic alcohol abuse and varying degrees of liver damage. None of the patients had clinical evidence of metabolic bone disease, but quantitative bone histology showed that six had osteoporosis, three osteomalacia, and two osteoporosis and osteomalacia combined. Trabecular bone volume (TBV) tended to be reduced in relation to age, and there was histological evidence of reduced bone formation particularly among the patients with osteoporosis. Multivariate analysis of the relevant variables showed that the major determinants of age-adjusted trabecular bone volume were the serum concentration of albumin and the dietary calcium. The presence of osteoporosis was related to the state of liver function and the type of alcohol habitually consumed, and was a particular feature of patients with severe liver disease and those who only drank spirits. Six patients (five with osteoporosis) had biochemical evidence of hyperparathyroidism, but none showed histological evidence of increased bone resorption or of osteitis fibrosa. In four patients the development of hyperparathyroidism was probably related to underlying magnesium deficiency. Serum calcidiol tended to be reduced and was directly related to the state of liver function; four patients had reduced or low normal serum concentrations of calcitriol. In only three patients could the development of osteomalacia be related to vitamin D deficiency; in two patients the cause of the osteomalacia was obscure. Significant changes in bone structure and mass appear to be common among heavy drinkers even in the absence of clinical metabolic bone disease. These skeletal abnormalities are likely to be relevant to the increased fracture risk associated with heavy drinking.

Adult

Peritonitis in children undergoing continuous ambulatory peritoneal dialysis.

During a four-year period there were 77 episodes and 15 recurrences of peritonitis in 30 children treated with continuous ambulatory peritoneal dialysis for periods of one to 39 months (mean, 15.3 months). The incidence was one episode per 6.0 patient-months. Organisms cultured included Staphylococcus epidermidis (17 episodes), Staphylococcus aureus (15 episodes), and fungi (four episodes). Special culture techniques were needed to ensure a high yield of positive cultures. Peritonitis was usually treated with intraperitoneal administration of cefazolin sodium, and 61% of the episodes were treated at home. There was one death, from Candida peritonitis, and catheters were removed in 11 children because of resistant or recurrent peritonitis (eight cases) or fungal peritonitis (three cases). Peritonitis rates were highest in children who had difficulty performing bag changes aseptically but who could not be transferred to hemodialysis and in hospitalized patients.

Adolescent