The authors estimated the incidence rates of cholera and death between 1985 and 1988 for 32,642 age- and sex-eligible persons who did not participate in a randomized, placebo-controlled field trial of killed oral cholera vaccines in rural Bangladesh. As compared with 20,744 placebo recipients, the relative risk of cholera for all nonparticipants, adjusted for potentially confounding demographic variables, was 1.20 (95% confidence interval (CI) 1.03-1.41); this adjusted relative risk reflected elevated adjusted relative risks in nonparticipants who were medically ineligible (RR = 1.65; 95% CI 1.22-2.22) or refused to participate (RR = 1.19; 95% CI 1.01-1.41), but not in persons absent at the time of vaccination (RR = 1.00; 95% CI 0.78-1.28). The adjusted relative risk of death was also elevated in nonparticipants as compared with placebo recipients (RR = 1.28; 95% CI 1.10-1.48), with the same pattern of adjusted relative risks for different categories of nonparticipants: for ineligible subjects, 2.64 (95% CI 2.12-3.29); for refusers, 1.20 (95% CI 1.02-1.41); and for absentees, 0.95 (95% CI 0.75-1.22). The authors concluded that nonparticipation was associated with clinically cogent adverse health outcomes, but that the magnitude of these associations varied according to the reason for nonparticipation. These findings underscore the caution required in assessing vaccine efficacy with controls who are not vaccinated because of choices made by patients or vaccinators.

Administration, Oral↗

PubMed1992

Changing disease patterns in AIDS.

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Acquired Immunodeficiency Syndrome↗

PubMed1992

Ubiquitous soluble Mg(2+)-ATPase complex. A structural study.

We have performed a detailed structural analysis of the soluble Mg(2+)-ATPase complex purified from Xenopus laevis ovary, which is an abundant and ubiquitous homo-oligomeric protein complex located in the nucleus and in the cytoplasm, belonging to a novel multigene-family of putative Mg(2+)-ATPases. Enzyme activity staining after non-denaturing polyacrylamide gel electrophoresis revealed that Mg(2+)-ATPase activity of the native protein is dependent on oligomerization and could not be detected in dissociated subunits. For the native protein a sedimentation coefficient of 15.3 S and a corresponding relative molecular mass of 612,000 was determined by analytical ultracentrifugation and a relative molecular mass of 590,000 was estimated from scanning transmission electron microscopy, supporting our previous conclusion that the oligomer comprises six 97,000 Mr subunits. Conventional electron microscopy of negatively stained specimens revealed the Mg(2+)-ATPase complex to be a hexagonal molecule in its favoured "end-on" projection and a double-banded molecule in its "side-on" projection (approx. 12 nm diameter; approx. 9 nm height). In addition, dimerized complexes could be observed in negatively stained specimens, yielding pronounced hexameric images and four-banded images in their end-on and side-on orientations, respectively (approx. 12 nm diameter; approx. 18.5 nm height). Two-dimensional (2D = mono-molecular) crystals have been produced from the dimerized complexes by the negative staining carbon film technique. Hexagonal crystals with a p6 plane group symmetry were obtained from molecules in their end-on orientation and longitudinal arrays with a p2 symmetry from complexes in their side-on orientation. A low-resolution molecular model of the native protein, derived from averages of these two 2D crystals, is presented. From our results we propose oligomerization as an inherent structural principle of organization for this whole newly defined Mg(2+)-ATPase multigene-family, that includes such seemingly diverse functionally defined proteins as mammalian and yeast "vesicle fusion" and "peroxisome assembly" proteins and the product of the yeast cell cycle gene CDC48.

Animals↗

PubMed1992

The use of adjuvant therapy in patients treated with conservative surgery and radiotherapy.

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Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Quaternary and subunit structure of Calliphora arylphorin as deduced from electron microscopy, electrophoresis, and sequence similarities with arthropod hemocyanin.

Arylphorin was purified from larvae of the blowfly Calliphora vicina and studied in its oligomeric form and after dissociation at pH 9.6 into native subunits. In accordance with earlier literature, it was electrophoretically shown to be a 500 kDa hexamer (1 x 6) consisting of 78 kDa polypeptides (= subunits). Electron micrographs of negatively stained hexamers show a characteristic curvilinear, equilateral triangle of 12 nm in diameter (top view) and a rectangle measuring 10 x 12 nm (side view). Alternatively, particles in the top view orientation exhibit a roughly circular shape 12 nm in diameter. Crossed immunoelectrophoresis revealed the presence of a major subunit type; the nature of a very minor and a third immunologically separated component remains unclear. A novel 2 x 6 arylphorin particle was detected and isolated. It comprises less than 10% of the total arylphorin material and shows a long, narrow interhexamer bridge in the electron microscope. An arylphorin dissociation intermediate identified as a trimer (1/2 x 6) was isolated; its possible quaternary structure is discussed on the basis of electron micrographs. The epitope of monoclonal antibody Ec-7 directed against tarantula (Eurypelma californicum) hemocyanin subunit d and also reactive to Calliphora arylphorin was traced to a highly conserved peptide of 27 amino acids localized in the center of the protein. The primary structure of Calliphora arylphorin as published in our preceding paper (Naumann and Scheller 1991) is compared in detail to the sequences of spider and spiny lobster hemocyanin. This revealed a basic framework of 103 strictly conserved amino acids. Isofunctional exchanges are proposed for another 76 positions. On the basis of these similarities, and the published three-dimensional model of spiny lobster hemocyanin, a detailed model of the quaternary structure of Calliphora arylphorin is presented. A second larval storage protein previously termed protein II was purified from Calliphora hemolymph. It was demonstrated to be a 500 kDa hexamer of 83 kDa subunits. In the electron microscope it shows a cubic view 9 nm in length with a large central hole and a rectangular view (9 x 10 nm) with a large central cavity. A morphologically very similar hemolymph protein was detected in Drosophila melanogaster larvae. From its structural appearance it is uncertain whether protein II belongs to the hemocyanin superfamily or not.

Amino Acid Sequence↗

PubMed1992

Electron microscopy of a double helical tubular filament in keyhole limpet (Megathura crenulata) hemolymph.

A approximately 25 nm hollow double helical filament has been detected ultrastructurally in the cell-free supernatant from hemolymph of the keyhole limpet Megathura crenulata (Gastropoda: Prosobranchia: Fissurellidae). Subsequently, much higher concentrations of this material were found in the cell pellet from hemolymph. Both negative staining and thin sectioning have been performed in an attempt to obtain a preliminary structural characterization of this new filament. It is proposed that the filaments are released or secreted from blood hemocytes in response to bleeding, but it has not been possible to define absolutely an intracellular organelle containing this material. It is shown that the hollow filaments, which have fine fibrillar surface extensions, are readily distinguishable from collagen fibrils and from tubular (multi-decameric) keyhole limpet hemocyanin (KLH).

Actin Cytoskeleton↗

PubMed1992

Increased gut parasympathetic activity and chronic diarrhoea in a patient with the acquired immunodeficiency syndrome.

A 25-year-old homosexual man with a 2-year history of watery diarrhoea and a 20 kg weight loss is described. He had been diagnosed HIV-1 antibody positive 6 years previously. Investigations excluded opportunist pathogens and other known causes of diarrhoea. A range of anti-diarrhoeal medication had been unsuccessful. Plasma levels of gastrointestinal and pancreatic peptides were normal and treatment with the somatostatin analogue, octreotide, which inhibits release of pancreatic/gut peptides, did not provide any benefit. Cardiovascular autonomic function tests revealed blunted pressor responses but no other abnormalities. Gastric emptying studies with a technetium labelled meal indicated rapid gastric emptying time. This was slowed by the anticholinergic drug, atropine. This suggested increased parasympathetic activity to the gut. He was, therefore, treated with the anti-cholinergic agent, propantheline bromide, which reduced the frequency and volume of stools. He put on weight and has remained well since. This case highlights the diagnostic challenge in HIV-associated chronic diarrhoea, the case for investigations of autonomic function, and the need for a therapeutic trial of anticholinergic drugs, when other measures have failed.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Cryptococcal meningitis in AIDS occurring despite systemic antifungal therapy.

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Acquired Immunodeficiency Syndrome↗

PubMed1992

Final report of the phase I trial of continuous infusion etanidazole (SR 2508): a Radiation Therapy Oncology Group study.

Seventy-eight patients have been treated on a Phase I trial using continuous infusion etanidazole while undergoing brachytherapy for locally advanced tumors. There were two sequential schemata, the first treated 63 patients with doses ranging from 8-23 g/m2 over 48 hr and the second treated 15 patients with doses ranging from 20-23 g/m2 over 96 hr. The tumor sites were: brain (n = 42), cervix (n = 22), and breast (n = 14). Patients received a loading dose of etanidazole of 2 g/m2 followed by a continuous infusion for a total of 48 or 96 hr while radioactive implants were in place. Of the 63 patients in the 48-hr study, 52 were entered at doses of less than or equal to 21 g/m2 and there were no definite neuropathies but two patients with the cramping/arthralgia syndrome. Of the 11 patients entered at 22-23 g/m2, 1 patient had symptoms of peripheral neuropathy (Grade II) and 6 had the cramping/arthralgia syndrome. This is a new syndrome, distinct from the peripheral neuropathy, characterized by transient alterations in sensations consisting of cramping, arthralgias, or tingling that resolved completely at intervals varying from a few hours to about 1 week post-treatment. The cramping/arthralgia syndrome limited dose escalation; therefore, the maximum tolerated dose over 48 hr was determined to be 20-21 g/m2. The 96-hr infusion was limited to patients with recurrent gliomas undergoing stereotactic implantation. To date, 15 patients have been treated with doses of 20-23 g/m2. No toxicity was encountered at doses less than or equal to 22 g/m2. At 23 g/m2, one patient developed Grade III neuropathy and three patients had mild cramping/arthralgia syndrome, for whom the drug was discontinued. Therefore, it appears the maximum tolerated dose at 96 hr will be approximately 23 g/m2, which is 10-15% higher than for the 48-hr infusion.

Brachytherapy↗

PubMed1992

Long-term radiation complications following conservative surgery (CS) and radiation therapy (RT) in patients with early stage breast cancer.

The frequency of brachial plexopathy, rib fracture, tissue necrosis, pericarditis, and second non-breast malignancies occurring in the treatment field among 1624 patients with early stage breast cancer treated with conservative surgery and radiation therapy at the Joint Center for Radiation Therapy between 1968 and 1985 is reported. The median follow-up time for survivors was 79 months (range 5-233 months). Brachial plexopathy was related to the use of a third field, the use of chemotherapy and the total dose to the axilla. Brachial plexopathy developed in 20 of 1117 women (1.8%) who received supraclavicular irradiation with or without axillary irradiation. The median time to its occurrence was 10.5 months (range 1.5-77 mo), and the majority (80%) of cases completely resolved. Among patients treated with a three-field technique, the incidence of brachial plexopathy was 1.3% (13/991) in patients treated with a dose to the axilla of less than or equal to 50 Gy, compared with 5.6% (7/126) in women treated with an axillary dose of greater than 50 Gy. The incidence of brachial plexopathy was 4.5% (15/330) among patients receiving chemotherapy, compared with 0.6% (5/787) when chemotherapy was not used (p less than 0.0001). Rib fracture was seen in 29 patients (1.8%), at a median time of 12 months following treatment (range 1-57). In all cases, the rib fracture healed without intervention. The incidence of rib fracture was 2.2% (28/1300) among patients treated on a 4 MV linear accelerator, compared with 0.4% (1/276) for patients treated on a 6 or 8 MV machine (p = 0.05). Of patients treated on a 4 MV machine, 0.4% (1/279) developed a rib fracture when a whole breast dose of 45 Gy or less was given, 1.4% (10/725) after receiving between 45 and 50 Gy, and 5.7% (17/296) following 50 Gy or higher. Tissue necrosis requiring surgical correction developed in three patients (0.18%) 22, 25, and 114 months after treatment. Presumed pericarditis (requiring hospitalization) was seen in 0.4% of women (3/831) who received radiation therapy to the left breast 2, 2, and 11 months after the start of treatment. Three women (0.18%) developed sarcomas in the treatments field at 72, 107, and 110 months, for a 10-year actuarial rate of 0.8%. Two of these sarcomas developed in areas of probable match-line overlap. One patient (0.06%) developed an in-field basal cell carcinoma at 42 months. In conclusion, the risk of significant complications following conservative surgery and radiation therapy for early stage breast cancer is low.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1992

Are cosmetic results following conservative surgery and radiation therapy for early breast cancer dependent on technique?

To assess the cosmetic results in relation to treatment technique, we retrospectively reviewed the results for 1159 Stage I-II breast cancer patients treated with conservative surgery and radiotherapy between 1970-1985. All patients underwent gross excision followed by radiation therapy including an implant or electron beam boost. The total dose to the primary site was greater than or equal to 60 Gy. Because of technical modifications introduced over time after 1981, the population was divided arbitrarily into two cohorts: 504 patients treated through 1981 and 655 treated between 1982-1985. Median follow-up time for surviving patients in the two cohorts were 107 months and 67 months, respectively. Cosmetic outcome was evaluated by the examining physician and scored as excellent, good, fair or poor. Excellent results at 5 years were scored in 59% of early cohort patients and 74% of the latter cohort (p = 0.002). Acceptable results (either good or excellent) were seen in 84% and 94%, respectively (p = 0.02). In the latter cohort, the likelihood of achieving an excellent result, but not an acceptable result, was significantly related to the volume of resected breast tissue and the use of chemotherapy. The number of fields (three-field technique, provided that fields are precisely matched, compared to tangents only) and boost type (implant vs electrons) did not influence the cosmetic outcome. We conclude that our current technique using breast RT to 45-46 Gy and a boost to the primary site of 16-18 Gy is associated with a high likelihood of acceptable cosmetic results and that this likelihood is not diminished by the use of adjuvant chemotherapy, a large breast resection, the use of a third field, or boost type.

Brachytherapy↗

PubMed1992

Low carbon monoxide transfer factor (TLCO) in HIV-infected patients without lung disease.

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Adult↗

PubMed1992

Age differences in genetic and environmental influences for health from the Swedish Adoption/Twin Study of Aging.

This cross-sectional study explored the etiology of variability in self-reported health. The sample comprises adult twins participating in the Swedish Adoption/Twin Study of Aging and includes identical (MZ) and fraternal (DZ) twin pairs who have been reared together or reared apart. Two different components of overall health status are analyzed: an index of chronic health problems and self-rated health. Height and weight were included to assess the representativeness of the twin data. Individual differences increased across age for both measures of health, and there were significant age differences in the genetic and environmental etiologies of this variation. Genetic variance showed a twofold increase for chronic illness up until age 70. Environmental influences during adulthood appear important later in life. For self-rated health, genetic effects were important in the older age groups; however, the increase in total variation is predominantly due to unique environmental influences.

Adoption↗