Cutaneous lymphosarcoma in a sugar glider.
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Biomedical subjects
Publications and source records attributed to R Miller.
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Syngeneic mice receiving adoptively transferred enriched B cells or splenocytes pulsed in vitro with polyclonal anti-idiotypic antibodies (anti-Ids) against anti-CVB3 virus antibodies developed coxsackievirus B3 antigen-binding and virus-neutralizing antibodies during a 30-day period, in addition to overt expression of autoimmune myocarditis. Adoptive transfer of anti-Id pulsed T cells resulted in delayed appearance and transient expression of antiviral antibodies, and antiviral antibodies were marginal to absent in syngeneic animals receiving anti-Id pulsed macrophage populations. Proliferation analysis of recipient splenocytes indicated lack of proliferative capacity in response to monoclonal or polyclonal anti-Ids and only marginal proliferative capacity in response to coxsackievirus B3 virus antigen(s). In vitro assessment of delayed hypersensitivity in recipient animals demonstrated some specific immunity to anti-Ids in recipients receiving splenocytes or T cells. Anti-Ids expressing mimicry for heart-associated and/or viral antigen(s) interacting with B cells or other accessory cells suggest an autoantibody or anti-Id triggering of B-cell-mediated mechanisms involved in the development of myocarditis.
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OBJECTIVE: To investigate outpatients' use of, and satisfaction with social care services in an HIV unit. DESIGN: Survey of patients with HIV infection using self administered questionnaire. SETTING: Outpatient HIV clinics at the Royal Free Hospital, London, March-April 1991. MAIN OUTCOME MEASURES: Patients' social circumstances, use or intended use of social care services and satisfaction with social care services. RESULTS: The greatest demand was for counselling about coping with HIV (38% of respondents), available medical treatment (24%), counselling for the HIV test (33%), psychological support for emotional (24%) or relationship problems (16%), advice about housing (24%) and financial matters (20%). In general, the use of social care services by men and women was similar. Twice as many men, however, sought help with payment of domestic bills, compared with women. Women were more likely to seek advice about financial benefits, obtaining sterile injecting equipment and discuss sleep and relationship problems. Thirty eight percent of patients were unemployed. Overall, 84% thought the service was good or excellent. Although less than 40% of patients currently used any one service, 60% thought they would use these services in the future. CONCLUSION: The greatest demand for social care services was for coping with HIV, housing and financial matters, and HIV test counselling. More than half the patients stated that they would probably need social care services in future.
OBJECTIVE: To evaluate completeness of reporting of cases of AIDS to the Communicable Disease Surveillance Centre (CDSC) between 1982-1991. SETTING: Southside of the Bloomsbury and Islington District Health Authority. DESIGN: Reconciliation exercise with CDSC of cases reported with those known to have received treatment in the district from 1982 to March 1990. Case note review of unreported cases and follow-up at March 1991. MAIN OUTCOME MEASURES: Delayed and non-reporting of cases. RESULTS: Cumulatively 13% (46/351) of patients whose initial AIDS illness was diagnosed in the District remained unreported by March 1991. Non-reporting increased from 9% (2/23) of cases diagnosed prior to 1985 to 28% (26/92) of cases diagnosed between 1989 and 1990. After September 1987 the proportion of patients with a diagnosis of Pneumocystis carinii pneumonia or Kaposi's sarcoma was significantly higher in the reported group than in the non-reported group: 78% (124/158) v 51% (24/49) p < 0.001. Nine of 19 (47%) cases of AIDS transferring their care into the district had not been reported by their previous District Health Authority. CONCLUSIONS: Within the district non-reporting of cases of AIDS has risen over time as the numbers of patients treated has increased. The physician must be aware of the full AIDS case definition for surveillance purposes and the implications of non-reporting for the allocation of special "ring-fenced" resources for AIDS care. Adequate investment in information and reporting systems would seem essential.
Balanced continuous flow resection has been offered as the best form of irrigation in uroendoscopy. Although it will keep the bladder pressure low, using flow visualization techniques it has been demonstrated that it does not fulfil the requirements of an irrigating fluid when used in a confined environment such as the prostatic urethra. The outflowing irrigating fluid has been shown to be taken directly from the inflowing jet ('steal effect') thereby reducing the effectiveness of the irrigating jet on the working area of the resectoscope.
The inotropic state of the myocardium can be enhanced via an increase in cell Ca2+ loading or in myofilament responsiveness to Ca2+. Although different pharmacological agents combine these properties, no presently available drug acts predominantly as a myofilament sensitizer in situ. We have investigated the effects and the mechanism of action of novel diazinone derivatives, EMD 54622, EMD 53998, and EMD 54650 (developed by E. Merck, Darmstadt), on guinea pig myocardial preparations. Force- and ATPase-pCa relations in skinned fibers show differing potencies of these agents on myofilament sensitization: EMD 54622 greater than EMD 53998 much greater than EMD 54650. This is in contrast to their relative potencies to inhibit isolated myocardial phosphodiesterase III: EMD 54650 greater than EMD 53998 greater than EMD 54622. In isolated hearts studied at constant coronary flow, each of the three diazinone derivatives had a positive inotropic effect. In enzymatically dissociated left ventricular myocytes loaded with the Ca2+ probe indo-1, the positive inotropic effect of EMD 54622 occurred with no change in the amplitude of the cytosolic [Ca2+] (Cai) transient. In contrast, both EMD 53998 and EMD 54650 enhanced Cai transient and twitch contraction amplitudes. Length-indo-1 fluorescence relations were analyzed to determine the effects of the three substances on myofilament responsiveness to Ca2+. EMD 54622 enhanced and EMD 54650 had no effect on myofilament responsiveness to Ca2+. Less uniform results were obtained with EMD 53998 (in two of five cells the myofilament responsiveness to Ca2+ was increased, whereas in three other cells it was unaltered). Our results indicate that structural changes in the diazinone molecule shift the mechanism of action for the positive inotropic effect of the diazinone derivatives in the intact cell from a predominant myofilament sensitization (EMD 54622) to an enhancement in cell Ca2+ loading and an augmentation in the Cai transient (EMD 54650).
The debate over health care reform in the United States has drawn Canada under the microscope. Canada's health care system is frequently offered as a model for American national health insurance. Curiously absent from this policy discussion is any talk about the relative out-of-pocket costs of alternative models. In this paper, we provide data on these costs for American and Canadian elderly for medical, hospital, and ambulatory pharmaceutical use. Despite the fact that the elderly in America are generally viewed as facing fewer problems with access and out-of-pocket costs than younger Americans, their direct costs far exceed those of their Canadian counterparts. We also present data suggesting that, despite these greater costs, rates of growth in use of these services by American elderly have followed roughly the same pattern as those found in Canada. If Uncle Sam retired north of the border, being old and sick would also mean being wealthier and happier.
Despite intensive investigation into the cause of cerebral vasospasm (focal ischemic deficit) after subarachnoid hemorrhage, the morbidity and mortality associated with this condition remain high. Various studies have shown levels of catecholamine in plasma and cerebrospinal fluid (CSF) to be increased in subarachnoid hemorrhage, and it is possible that these vasoactive substances play an important role in the subsequent vasospasm. In an attempt to elucidate this possibility, the study presented here was undertaken to investigate the relationship between catecholamine levels in plasma and CSF and focal ischemic deficit (FID); the rupture of aneurysms on blood vessels supplying the hypothalamus as compared with the rupture of aneurysms on blood vessels supplying other areas of the brain; and the clinical outcome of the patients. Concentrations of adrenaline and noradrenaline in plasma and CSF samples obtained from 21 patients who had suffered aneurysmal subarachnoid hemorrhage were determined by a radioenzymatic technique. Significantly higher levels of adrenaline were found at the time of surgery in the CSF of patients with FID. A similar trend, though not statistically significant, was also observed for plasma. Patients with a rupture of aneurysms on blood vessels supplying the hypothalamus showed a tendency towards higher catecholamine levels in plasma and CSF. Subjects with a bad clinical outcome (i.e., those who were severely disabled or had died) had significantly higher levels of catecholamine in plasma than did those with a good clinical outcome (i.e., those with moderate or no disability). Further detailed analysis of the interrelationships showed that, within the group of patients with FID, those with rupture of aneurysms on blood vessels supplying the hypothalamus had significantly higher catecholamine levels in plasma than did those with rupture of aneurysms on other cerebral vessels. Furthermore, in the group of patients with rupture of aneurysms on blood vessels supplying the hypothalamus, those with a bad clinical outcome had significantly higher catecholamine levels in plasma than did those with a good clinical outcome. These findings lend support to the possibility that damage to the hypothalamus and subsequent elevations in catecholamine levels may be associated with FID and poor clinical outcome.
A 1% (W/V) formulation of Niclosamide (2', 5-Dichloro-4-nitrosalicylanilide) (TAP) was tested on Cebus apella monkeys as a topical prophylactic against schistosomiasis mansoni. Two experiments were conducted using the same formulation. In the first experiment, the TAP provided complete protection against schistosomiasis for 3 days. Of the 4 monkeys treated with TAP 7 days before exposure to Schistosoma mansoni cercariae, 2 were completely protected. The remaining 2 monkeys of the 7 day treatment group had a 78% or greater reduction in adult worm burdens when compared to the placebo treated monkeys. The second experiment was designed to determine the time between day 3 and 7 when the TAP no longer provided complete protection. However, all of the TAP treated monkeys in this experiment were completely protected, even the monkeys treated 7 days earlier. In both experiments, all monkeys used as infection controls and those receiving only the placebo became infected and showed typical experimental schistosomiasis. These results demonstrate that the TAP could provide fast acting, short-term protection to people who must enter cercariae infested water.
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Elevated maternal serum alpha-fetoprotein (MSAFP) levels have been associated with an increased incidence of both placental sonolucencies and pregnancy complications. We designed a prospective study to test the hypothesis that the presence of these sonolucencies or a positive maternal Kleihauer-Betke stain would be associated with an elevated risk of obstetric complications. We enrolled 95 women with singleton pregnancies, elevated MSAFP, and no evidence of fetal anomalies on second-trimester ultrasound evaluation. Placental sonolucencies were documented at the time of ultrasound examination, and a maternal Kleihauer-Betke stain for fetal cells was obtained on the same day. Complications of pregnancy included fetal growth retardation, preterm delivery, late vaginal bleeding (at or after the 20th week of gestation), and fetal death. Women with elevated MSAFP had an increased incidence of placental sonolucencies, positive maternal Kleihauer-Betke stains, first-trimester vaginal bleeding, late vaginal bleeding, preterm delivery, fetal growth retardation, and fetal death compared with controls. Thirty-nine of 95 women with elevated MSAFP (41.1%) had at least one complication. In women with elevated levels, neither the presence of placental sonolucencies nor a positive Kleihauer-Betke stain correlated with first-trimester vaginal bleeding, the MSAFP level, or an increased risk of pregnancy complications. First-trimester vaginal bleeding was associated with an increased risk of preterm delivery in subjects with elevated MSAFP.
The effect of a clinical pharmacokinetic consultation program for theophylline on the outcomes of pediatric patients with asthma was studied. The program was established in 1989 at a pediatric asthma clinic. For each patient visit, a clinical pharmacist recorded demographic, clinical, and medication-related information and counseled the parents. When an adjustment in the theophylline dosage was indicated, the pharmacist calculated the appropriate dosage using population pharmacokinetic values. If the pediatrician requested a measurement of the serum theophylline concentration, the time when the blood sample was drawn relative to the last dose was recorded, an average serum theophylline concentration at steady state and individualized pharmacokinetic values were calculated, and the dosage was adjusted accordingly. Patient data were compared among three stages: (1) the month before and the month of entry into the program, (2) months 5 and 6 after entry, and (3) months 11 and 12 after entry. A total of 44 patients were studied during each of stages 1 and 2, and 29 patients were reviewed during stage 3. There was a significant improvement in wheezing from stage 1 to stage 2 and in exercise tolerance and nocturnal coughing from stage 1 to stage 2 and stage 1 to stage 3. Forced expiratory volume in one second improved significantly from stage 1 to stage 2, and there was a significant reduction in the necessity for hospital visits for the treatment of exacerbations of asthma between stages 1 and 2. The daily weight-adjusted dose of theophylline increased significantly after the program began. Asthmatic children taking theophylline had improvements in outcome variables after pharmacokinetic consultation and medication counseling were initiated.
There is concern that children with chronic conditions are less likely to be enrolled in managed care systems and that they may not receive optimal care. We studied the relationship between enrollment in an Independent Practice Association (IPA) plan and utilization of ambulatory services among children in a suburban pediatric practice with one mild chronic condition--those receiving hyposensitization therapy for allergic diseases. Ambulatory utilization by IPA patients (N = 102) was determined by medical chart review for one year before and one year after each patient switched from Blue Cross to IPA coverage. Blue Cross hyposensitization patients (N = 57) matched for age served as controls. Patients receiving hyposensitization were more likely to have enrolled in an IPA than those not receiving hyposensitization (70% vs 45%, p < .001). Before enrollment pre-IPA patients had 41% fewer well-child care (WCC) visits than Blue Cross patients (p < .01); both underutilized WCC visits according to established guidelines. Controlling for age and baseline utilization, we found a significant increase in WCC and acute care visits after IPA enrollment (p < .05), but no change in hyposensitization visits or referrals. In this setting, there was no evidence for reduced access to ambulatory services but rather evidence for improved utilization of primary care.
Three interlaboratory round-robin studies (RR1, RR2, and RR3) were conducted to identify a serum-based reference material that would aid in the standardization of direct ion-selective electrode (ISE) measurements of sodium and potassium. Ultrafiltered frozen serum reference materials requiring no reconstitution reduced between-laboratory variability (the largest source of imprecision) more than did other reference materials. ISE values for RR3 were normalized by the use of two points at the extremes of the clinical range for sodium (i.e., 120 and 160 mmol/L), with values assigned by the flame atomic emission spectrometry (FAES) Reference Method. This FAES normalization of ISE raw values remarkably improved all sources of variability and unified the results from seven different direct ISE analyzers to the FAES Reference Method value. Subsequently, a three-tiered, fresh-frozen human serum reference material was produced to the specifications developed in RR1-RR3, was assigned certified values for sodium and potassium by Definitive Methods at the National Institute of Standards and Technology (NIST), and was made available in 1990 to the clinical laboratory community as a Standard Reference Material (SRM); it is now identified as SRM 956. Albeit retrospectively, we show how applying an FAES normalization step identical to that used in RR4/5 to the ISE data for SRM 956 after the NIST Definitive Method values were known, consistently moved the ISE results for RR3 closer to the true value for Na+ and K+.
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In response to reports of discrepant in vitro assays of high-purity concentrates, a double-blind crossover study of in vivo recovery and half-life of two brands of monoclonal-antibody-purified factor VIII concentrates (Monoclate and Hemofil-M) was performed in 23 patients with hemophilia A. In vivo recoveries were close to values predicted from the labelled unitage when plasma samples were assayed by a one-stage method. When a two-stage assay was used, lower recoveries were calculated and the recovery with Hemofil-M was slightly but significantly lower than that with Monoclate. The concentrates were re-assayed in vitro by the two-stage method. Monoclate (which is assayed by the manufacturer using a two-stage method) contained 97% of the labelled potency and Hemofil-M (which is assayed by the manufacturer using a one-stage method) contained 81% of the labelled potency. Differences in in vitro and in vivo assay methods contribute to disparities between expected and observed factor VIII recovery. Clearance of Hemofil-M was significantly faster than that of Monoclate, but volume of distribution at the steady state, mean residence time, and plasma half-disappearance times of the two concentrates were not significantly different.
The greatest risk factor for cancer is aging. Human cancer incidence increases exponentially with advancing age. Cancer growth rate and potential for metastatic spread may be influenced by age-specific change in host response. Because cancer and aging are, thus, inextricably linked, the American Cancer Society should encourage submission of research proposals that address the mechanisms of aging and how aging alters cancer development.