Biomedical subjects
Publications and source records attributed to M E O'Brien.
Anaphylactic reactions to platinum compounds are well recognised, but uncommon. These vary from true type I reactions to direct histamine release due to nonimmunological mechanisms. We present 6 cases to illustrate this--5 due to cisplatin and a report of this occurring with carboplatin--with a near fatal outcome in 3 of the cases.
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It is well known that certain genes in the HLA-D region confer increased susceptibility to insulin-dependent diabetes mellitus (IDDM). Previous studies have documented an increased risk associated with the HLA-DR beta chain alleles, DR3 and DR4, and the DQ beta chain allele DQB1*0302 (formerly DQw8). Since DQ alpha is also polymorphic and has been strongly implicated as the primary IDDM susceptibility locus in other races, we wanted to assess the contribution of DQ alpha to IDDM in Caucasians. This information would enable us to define more precisely the class II association with IDDM as well as gain insight into issues of cis versus trans association of DQ heterodimers in this disease. To this end, the DQ alpha genotype was determined for a large group of diabetic and normal Caucasian individuals who had been HLA-DQ beta and HLA-DR typed previously. Using the polymerase chain reaction and a set of twelve oligonucleotide probes, we determined the DQ alpha genotype of 323 patients with IDDM and 182 normal subjects. We found that certain DQ alpha alleles are decreased in the diabetic population compared with normal subjects (i.e. DQA1*0102 and *0103), while others are significantly increased in patients with IDDM (i.e. DQA1*0301 and *0501). In addition, certain combinations of DQ alpha alleles are associated with increased susceptibility to disease (i.e. DQA1*0301, *0501). These results parallel our findings at the DQ beta locus; however, because of the various associations between DQ alpha and DQ beta chains, the risks conferred by DQ alpha are generally lower than those at DQ beta. Moreover, our data indicate that, in Caucasians, no single DQ alpha allele accounts for the highest degree of susceptibility to IDDM as in other races, although DQ alpha analysis may be informative in a few cases. When done in combination, however, oligonucleotide analyses at both DQ alpha and DQ beta complement each other and provide a more complete assessment of the HLA-associated component of disease susceptibility in IDDM.
A survey of 34 first-time federal grantees about the satisfying and stressful experiences related to administration and non-scientific aspects of their projects resulted in four major categories of satisfaction (Personal-Social, Material-Career, Impact on School and University, Clinical) and seven categories of stress (Budget, Personnel, Equipment, Access to subjects, Fatigue, Inadequate administrative and peer support, and the Grant cycle itself). Satisfiers were more enduring and profound than the stressors, and their effects often reached beyond the investigator to the university, clinical site and profession. Useful information for new investigators and doctoral students was identified.
Although Freund's adjuvant has been used for decades as an immune enhancer in rabbits, adverse physiologic side effects have prompted the search for more suitable alternatives. We used osteocalcin, a bovine bone protein (M.W. 5,800), as the test antigen to evaluate four adjuvant regimens: a) primary inoculation with complete Freund's adjuvant (CFA) followed by three boosts with incomplete Freund's adjuvant (IFA), b) four serial inoculations with RIBI MPL+TDM+CWS adjuvant, c) four serial inoculations with TiterMax #R-1, and d) primary inoculation (only) with TiterMax #R-1. The antibody yield associated with the CFA/IFA regimen (mean OD = 2.152) was at least sixfold that of either TiterMax (mean OD = 0.358) or RIBI (mean OD = 0.239) multiple injection regimens. No antibody response was observed after the single injection of TiterMax antigen emulsion. Maximal antibody production occurred rapidly in response to Freund's adjuvant (day 31) as compared with TiterMax (day 74) and RIBI (day 66).
The introduction of a serious life-threatening illness such as end stage renal disease (ESRD) is an added stress dimension to the already enormous demands placed on the contemporary family system. The purpose of the present study was to identify qualitatively and describe selected aspects of psychosocial adaptation among the families of ESRD patients experiencing four primary modes of dialytic therapy: incenter hemodialysis, home dialysis, continuous ambulatory peritoneal dialysis (CAPD), and continuous cyclic peritoneal dialysis (CCPD). Five family coping styles emerged from content analysis of the data collected from 50 family members at four time periods. These styles have been labelled: Remote Family Style, Enfolded Family Style, Altered Family Style, Distressed Family Style, and Receptive Family Style.
Glycoproteins from normal and malignant human cervix were studied using an organ culture system and compared by gel electrophoresis and autoradiography. Five glycoproteins of 178 kDa, 95 kDa, 93 kDa, 82 kDa and 38 kDa and 1 glycolipid (46 kDa) were detected more frequently in squamous carcinomas. Certain glycoproteins were shown to be oncofoetal and some had affinity for Concanavalin A (Con A). The 82 kDa glycoprotein was present in 16/17 squamous carcinomas but in only 1/13 normal cervices. This band represented a glycoprotein containing glucosamine, mannose, small quantities of methionine and no fucose. These preliminary results suggest that these glycoproteins and in particular the 82-kDa glycoprotein are worthy of further investigation and characterisation.
The combination of mitozantrone and prednimustine has been reported to elicit response rates of around 50% in patients with advanced breast cancer. In the present trial, either three or nine courses of this combination were given to previously untreated patients with advanced breast cancer. Mitozantrone was given at 12 mg/m2 on day 1 and prednimustine was given orally at 130 mg/m2 on days 1-5; treatment was repeated every 4 weeks. A total of 34 patients were treated; the performance status was 0-1 in 29 subjects and 2 in 5 cases. Locoregional disease only was present in 13 patients; 9 showed lung involvement; 8, liver; 3, bone; and 1, stomach involvement. A total of 10 subjects had received no prior hormone therapy. The median disease-free interval from the time of initial diagnosis was 24 months (range, 0-144 months). In all 14/23 patients exhibited an oestrogen receptor level of greater than 20 fmol. Grade 1 nausea and vomiting occurred in 16 patients and that of grade 2-3, in 11 subjects; nausea was prolonged for greater than 10 days in 7 cases. Grade 4 neutropenia occurred in 2 patients. The response rate was 21% (95% confidence interval, 8%-38%). The combination of mitozantrone and oral prednimustine is toxic and displays low activity.
The natural history of low grade lymphoma and the influence of a 'no initial treatment' policy on survival were studied retrospectively in a group of 153 patients with stage II-IV low grade non-Hodgkin's lymphoma. The median follow-up was 85 months (range 45-229 months) and median survival of 50 months (range 14-220 months). Favourable outcome was significantly associated with the absence of B symptoms and a centroblastic/centrocytic (cb/cc) diffuse and follicular histological subtype and was inversely associated with increasing age. No significant differences in survival were found according to patient gender, site or stage of disease or whether the patients were participants in a clinical trial. Importantly, there was no survival disadvantage amongst the 56 patients who were initially untreated compared to those receiving other treatment modalities: initially untreated patients had a median survival of 75 months; 56 per cent were alive at 5 years and the median treatment free interval was 33 months. This favourable outcome persisted even after adjustment for other important prognostic variables. Further studies are needed to identify the characteristics of those patients with indolent disease in whom treatment may be deferred without adversely affecting survival.
Fifty-five patients who had relapsed or progressed from chemotherapy for advanced disease were treated with mitomycin C and 5-FU on a 6 weekly regimen. After a median of 2 cycles of therapy the overall response rate was 12% with no complete responses. Significant leucopenia but no thrombocytopenia was seen and despite the low overall response rate the regimen was tolerable and did produce responses in patients primarily resistant to Adriamycin combination chemotherapy. Low overall activity indicates the need for more effective second line treatment.
Compliance with the therapeutic regimen is a critical and frequently confusing concept both for chronic renal failure patients and for care-givers. A panel group of maintenance dialysis patients was followed over a period of 9 years to identify the variables associated with positive or negative compliance behavior. Individual patient changes in adherence to the therapeutic regimen over time were also examined. Significant differences related to social support, especially when the demographic variable of education was controlled, were found. Serendipitous and surprising results were also documented when compliance behavior was evaluated in relation to patient mortality. From the analysis of quantitative and qualitative data, a typology of "ritual" versus "reasoned" compliance was derived.
A retrospective case-control study was carried out on 230 patients with multiple sclerosis (MS) and 230 controls matched for year of birth and sex. The geographical distribution of residence of MS patients and controls was similar. Two peak ages of onset of MS were observed among woman patients (20-24, 30-34 years). There was no difference in histories of infectious diseases and autoimmune diseases between the two groups. A greater number of hairdressers was noticed among the patient group (p less than 0.05) and three patients (no control) had had professional contact with pathology specimens.
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High dose metoclopramide is an effective anti-emetic for use with cisplatin containing chemotherapy regimens but can cause extrapyramidal reactions. Lorazepam and dexamethasone are increasingly being used to alleviate chemotherapy induced emesis. This trial has assessed the contribution of high dose metoclopramide to anti-emetic control when given with dexamethasone and lorazepam. Eight-one patients receiving chemotherapy, mainly for gynaecological malignancy, entered a randomised double blind cross-over trial comparing dexamethasone and lorazepam with or without a 24 h metoclopramide infusion. This was followed by oral dexamethasone with or without oral metoclopramide for three further days depending on the initial randomisation. Sixty-one patients were fully evaluable. Fifty-five received cisplatin containing regimens and six non-cisplatin regimens. There was a significant reduction in the number of episodes of vomiting during the first 24 h in patients receiving the metoclopramide combination (P = 0.0001). On first exposure to chemotherapy 45% of patients receiving dexamethasone, lorazepam and high dose metoclopramide had no vomiting while 67% had two episodes or less ('major control'). This compared to 11% total control and 25% major control in those receiving dexamethasone, lorazepam and placebo. The control of nausea in the first 24 h was also improved (P = 0.0001). There was no difference in the degree of nausea or vomiting during the following three weeks between those receiving oral dexamethasone alone and those receiving dexamethasone and metoclopramide. Both groups showed a significant increase in nausea in the three weeks following the second course of treatment when compared to the first (P = 0.0007). Extrapyramidal reactions were recorded in 11.5% of patients receiving metoclopramide. More patients stated a preference for the metoclopramide combination although this was not statistically significant (chi 2(1) = 0.29, P = 0.59). In conclusion the combination of dexamethasone and lorazepam can give major control of emesis in 25% of patients receiving very emetogenic chemotherapy. The addition of metoclopramide increases this to 67% on first exposure to chemotherapy, but at the expense of extrapyramidal reactions in 11.5%.
The compound p-mercuribenzenefulfonate was found to affect the self-association behavior of both spectrin and actin. The reagent brings about the depolymerization of F-actin, as judged from the decrease in the fluorescence of an attached pyrene label, with a second-order rate constant an order of magnitude less than that for the disruption of isolated erythrocyte cytoskeletons. Therefore, it is unlikely that the depolymerization of actin is the rate-determining step in the mercurial-dependent disruption of the erythrocyte cytoskeleton. Low reagent concentrations caused an initial rapid dissociation of spectrin tetramers at a rate comparable with that of cytoskeleton disruption. Prolonged incubation, or higher reagent concentrations, resulted in subsequent aggregation of spectrin. The reagent also prevented the interaction between spectrin and actin, presumably through its depolymerization of actin and its effects on spectrin. The early event in the disruption of isolated erythrocyte cytoskeletons by p-mercuribenzenesulfonate thus appears to be the dissociation of spectrin oligomers. Subsequent depolymerization of actin brought about by the reagent then results in total disruption of the cytoskeleton.
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Two patients are reported with coexisting adenocarcinomas of pancreas and breast. One represents synchronous neoplasms, the other metachronous tumors diagnosed 7 years apart. The significance of these findings is discussed, including possible carcinogenic dietary factors common to both neoplasms. The potential problems associated with the histologic diagnosis of such coexisting tumors are stressed.