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Biomedical subjects

S R Duncan

Publications and source records attributed to S R Duncan.

At least 37 records · Page 2Linked to original sources
PubMed1996

Pulmonary capillaritis and alveolar hemorrhage. Update on diagnosis and management.

Pulmonary vascular inflammatory disorders may involve all components of the pulmonary vasculature, including capillaries. The principal histopathologic features of pulmonary capillaritis include capillary wall necrosis with infiltration by neutrophils, interstitial erythrocytes, and/or hemosiderin, and interalveolar septal capillary occlusion by fibrin thrombi. Immune complex deposition is variably present. Patients often present clinically with diffuse alveolar hemorrhage, which is characterized by dyspnea and hemoptysis; diffuse, bilateral, alveolar infiltrates on chest radiograph; and anemia. Pulmonary capillaritis has been reported with variable frequency and severity as a manifestation of Wegener's granulomatosis, microscopic polyarteritis, systemic lupus erythematosus, Goodpasture's syndrome, idiopathic pulmonary renal syndrome, Behçet's syndrome, Henoch-Schönlein purpura, IgA nephropathy, antiphospholipid syndrome, progressive systemic sclerosis, and diphenylhydantoin use. In addition to history, physical examination, and routine laboratory studies, certain ancillary laboratory tests, such as antineutrophil cytoplasmic antibodies, antinuclear antibodies, and antiglomerular basement membrane antibodies, may help diagnose an underlying disease. Diagnosis of pulmonary capillaritis can be made by fiberoptic bronchoscopy with transbronchial biopsy, but thoracoscopic biopsy is often employed. Since many disorders can result in pulmonary capillaritis with diffuse alveolar hemorrhage, it is crucial for clinicians and pathologists to work together when attempting to identify an underlying disease. Therapy depends on the disorder that gave rise to the pulmonary capillaritis and usually includes corticosteroids and cyclophosphamide or azathioprine. Since most diseases that result in pulmonary capillaritis are treated with immunosuppression, infection must be excluded aggressively.

Anemia↗
PubMed1995

Infant mortality and famine: a study in historical epidemiology in northern England.

OBJECTIVE: To examine whether periodic variations in annual infant mortality were associated with malnutrition and the poor quality of the food supply available to the community. DESIGN: Retrospective study of historical epidemiology of infant mortality by time series analysis and family reconstitution of parish registers of burials and baptisms. SETTING: Penrith, Cumbria, England, 1557-1812. SUBJECTS: A total of 17,500 births during 1557-1812. RESULTS: This community in the Eden Valley, Cumbria, close to the Scottish borders, was living under marginal conditions with high mortality and low fertility. Clear oscillations in infant mortality synchronise with the oscillations in the wheat price index which is regarded as a measure of the availability of food to the community, and to pregnant and nursing mothers in particular. Input-output analysis showed that the relationship between the wheat price index (input) and infant mortality (output) was highly significant (p < 0.001). Events during the famine of 1623 have been analysed in detail: high wheat prices during pregnancy caused subsequent severe infant mortality but did not have indirect effects on the subsequent mortality of the surviving children over the age of 1 year. Non-stationary oscillations in neonatal and post neonatal mortality were strongly coherent (p < 0.001) with the wheat price index throughout the period. CONCLUSIONS: Infant mortality is particularly sensitive to famine and also to the quality of the food supply available to pregnant and nursing mothers. The lags between neonatal and post-neonatal mortalities and wheat prices, together with the analysis of the famine of 1623, support the hypothesis that neonatal mortality was related to malnutrition in pregnancy whereas post-neonatal mortality was primarily directly dependent on exogenous causes in the first year of life.

England↗
PubMed1995

Delivery and distribution of aerosolized cyclosporine in lung allograft recipients.

The aim of the present study was to identify factors determining the delivery to and distribution of aerosolized cyclosporine A (CSA) in the lungs of patients with severe pulmonary allograft rejection. Five such patients inhaled a previously characterized radioaerosol consisting of 4 to 6 cc of CSA (50 mg/ml) in ethanol mixed with technetium-99m (99mTc) bound to human serum albumin, generated by an AeroTech II nebulizer. The total dose of CSA depositing in the lungs was determined with a previously described inspiratory/expiratory mass-balance filter technique. Regional distribution of drug within the lungs was measured using a gamma camera. In addition, the following physiologic parameters were measured: regional volume and ventilation using xenon-133 (133Xe) equilibrium and 133Xe washout, respectively, and regional perfusion using intravenous 99mTc macroaggregates. The relationships between these parameters and regional drug deposition were assessed using linear regression analysis. The lung dose ranged from 20 to 53 mg (0.097 to 0.175 mg CSA deposited per milligram placed in nebulizer). In recipients of single-lung allografts, preferential drug deposition occurred either in the allograft (two patients) or in the native lung (one patient). Marked nonuniformities in regional distribution were also apparent in two double-lung allograft recipients. There was a weak but statistically significant correlation between regional drug deposition and regional ventilation, as measured by 133Xe washout (r = -0.542, p = 0.014), suggesting that although regional ventilation is important, it is not the only factor determining regional deposition in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Modelling the different smallpox epidemics in England.

Time series analysis has revealed two different patterns of smallpox epidemics in Britain in the seventeenth and eighteenth centuries: in large conurbations (exemplified by London) the disease was endemic whereas medium-sized rural towns (exemplified by Penrith, Cumbria) suffered from 5 year epidemics with no cases of smallpox in the inter-epidemic years. The oscillations (epidemics) persisted for over 150 years and it is suggested that both systems were pumped up by regular fluctuations in susceptibility (delta beta). Modelling suggests that: (i) the natural frequency of oscillations in large cities is two years and the system is pumped up by a 1 year, seasonal input; (ii) it takes five years to build up a pool of susceptibles in medium-sized towns by new births and epidemics are then triggered by a 5 year input. The equations represent a system that has two components, a basic linear element with the remainder of the system being nonlinear; modelling a progressive increase in delta beta in London illustrates theoretically how a predominantly linear response changes to a nonlinear response and ultimately to chaos. A variation in susceptibility is a theoretical condition for inducing chaos; the undriven system cannot become chaotic. Modelling populations of progressively increasing size/density and applying a 1 year or 5 year sinusoidal oscillation in delta beta illustrates the fundamental distinction in the response of medium-sized rural towns and large cities.

Child↗
PubMed1994

A comparison of ganciclovir and acyclovir to prevent cytomegalovirus after lung transplantation.

In an attempt to modify the sequelae of cytomegalovirus (CMV) infections after lung transplantation, 25 allograft recipients were randomized to either ganciclovir 5 mg/kg once a day 5 d/wk (Group G) or acyclovir 800 mg four times a day (Group A). All subjects received ganciclovir during postoperative Weeks 1 through 3, and they were then given either A or G regimens until Day 90. At termination of study enrollment, the cumulative incidence of all CMV infections (including seroconversions) was increased in Group A compared with that in Group G (75% versus 15%, p < 0.01), as was the incidence of overt CMV shedding and/or pneumonitis (50% versus 15%, p < 0.043). In comparison with those in Group G, subjects in Group A were also afflicted with an increased prevalence of obliterative bronchiolitis (OB) during the first year after transplantation (54% versus 17%, p < 0.033). Intravenous catheters for ganciclovir administration resulted in four complications among three of the subjects in Group G (23%). The short-term benefits of ganciclovir were ultimately limited, moreover, in that cumulative rates of CMV and prevalence of OB are now similar in both treatment groups after approximately 2 yr of observation. We conclude that prolonged ganciclovir prophylaxis decreases the early incidence of CMV and OB among lung transplant recipients, but these effects are of finite duration. Although CMV prevention appears to have considerable potential value in this population, definitive viral prophylaxis will require development of protracted or repeated treatment regimens, or longer-acting agents.

Acyclovir↗
PubMed1993

An hypothesis for the periodicity of smallpox epidemics as revealed by time series analysis.

Parish registers have been studied by time series analysis to detect smallpox epidemics in England during 1600-1800. Confirmatory evidence was provided by the seasonality of child mortality. A 5-year cycle in smallpox epidemics was detected in medium-sized, rural towns. Consideration of the mathematics of the dynamics of viral diseases suggests that the true interepidemic period where smallpox is endemic should be 2-3 years and it is concluded that, in the towns studied, the disease was not endemic but that the oscillations were established by 5-year cycles of periods of famine associated with high wheat prices. The cross-correlation function between the two cycles shows zero lag and the input-output function shows significant coherence. Another epidemic follows only when a sufficient density of susceptibles has been established by births, so that the cycles become phase-locked. It is predicted that smallpox (i) was endemic in London and other large cities, with 2-3 year epidemics, (ii) was epidemic with a 5-year oscillation in rural towns, (iii) did not reach epidemic proportions in scattered communities.

Birth Rate↗
PubMed1993

Recurrence of sarcoidosis in pulmonary allograft recipients.

Lung transplantation is a potentially curative therapy for the end-stage pulmonary sequelae of sarcoidosis. We reviewed the course of five lung allograft recipients with underlying sarcoidosis (S) at the University of Pittsburgh Medical Center and compared them with a control group (C) of 44 contemporaneous transplant recipients with other respiratory diseases. Sarcoid granulomata have developed in the allografts of 4 S, although these lesions have not yet been demonstrated to result in clinically significant abnormalities. In comparison with C, sarcoidosis patients had significantly greater mean grades of acute rejection during the first 3 months after transplantation (2.1 +/- 0.3 versus 1.6 +/- 0.1, S and C, respectively, p < 0.042) and larger proportions of lung biopsies showing more than mild acute rejection (40 versus 18%, p < 0.012) and lymphocytic bronchitis (30 versus 13%, p = 0.02), as well as a greater percentage of polymorphonuclear leukocytes in BAL returns (34.9 +/- 5.4 versus 19.0 +/- 1.6, p < 0.01). The two groups did not differ, however, in frequency of obliterative bronchiolitis, survival, or pulmonary function. We conclude that lung transplant recipients with underlying sarcoidosis are very likely to develop recurrent disease in the allograft and have more severe acute rejection responses, especially in the first weeks after transplantation. Pulmonary transplantation appears to be an efficacious therapy for end-stage sarcoidosis, but the long-term sequelae of the increased acute rejection and recurrent sarcoidosis in the allograft remain to be determined.

Adult↗
PubMed1993

The dynamics of smallpox epidemics in Britain, 1550-1800.

Time-series analysis, a valuable tool in studying population dynamics, has been used to determine the periodicity of smallpox epidemics during the seventeenth and eighteenth centuries in two contrasting representative situations: 1) London, a large city where smallpox was endemic, and 2) Penrith, a small rural town. The interepidemic period was found to be two years in London and five years in Penrith. Equations governing the dynamics of epidemics predict 1) a two-year periodicity and 2) that oscillatory epidemics die out quickly. It is suggested that epidemics were maintained by a periodic variation in susceptibility linked either to a five-year cycle of malnutrition or to an annual cycle. Computer modeling shows how the very different patterns of epidemics are related to population size and to the magnitude of the oscillation in susceptibility.

Disease Outbreaks↗
PubMed1992

Interstitial and airspace granulation tissue reactions in lung transplant recipients.

Twenty-three transbronchial and open-lung biopsies from patients who had received a lung allograft displayed fibromyxoid plugs of granulation tissue within airways, airspaces, and the interstitium in a patchy distribution. This granulation tissue-like reaction was identified in three clinicopathologic settings. First, 11 cases occurred with acute lung rejection, of which four cases had been partially treated with steroids for a previous rejection episode. Second, in seven cases the fibromyxoid tissue represented the healing phase of previously diagnosed diffuse alveolar damage resulting from preservation (harvest) injury to the allograft. Third, five cases were related to infection: herpes, Pseudomonas, Serratia, Staphylococcus, and Pneumocystis pneumonias. Although organizing pneumonia-like responses usually suggest an infectious episode, this reaction may be seen as a manifestation of acute lung rejection or ischemic lung injury.

Biopsy↗
PubMed1992

Ventilatory effects of clonidine alone and in the presence of alfentanil, in human volunteers.

Clonidine, an alpha 2-adrenergic agonist, can potentiate opioid-induced analgesia. In a double-blind placebo-controlled study in human volunteers, we sought to determine whether clonidine also potentiates opioid-induced respiratory depression. Hypercapnic ventilatory responses (minute ventilation, mean inspiratory flow rate, and mouth occlusion pressure) were measured in five healthy male volunteers on two separate occasions (with or without clonidine, approximately 3.5 micrograms.kg-1 orally) under the following conditions: baseline, 2 h after clonidine/placebo (alfentanil concentration of 0), and during computer-controlled alfentanil infusions to approximate plasma concentrations of 5, 10, 20, 40, and 80 ng.ml-1. Plasma alfentanil concentrations were measured before and after each rebreathing test, and clonidine concentrations were measured after each rebreathing test. The end-tidal CO2 (PET(CO2)) was measured continuously. Data were analyzed by repeated-measures analysis of variance. The PET(CO2) and measured concentrations of alfentanil were included as covariates, and a compound symmetry error analysis was assumed. Statistical significance was achieved when P less than 0.05. For minute ventilation, mean inspiratory flow rate, and mouth occlusion pressure there was a statistically significant relationship to the covariates of PET(CO2) and plasma alfentanil concentration. Clonidine, when compared to placebo, caused a small but significant depression of mean inspiratory flow rate. There was similarly a small, but statistically insignificant, depression of minute ventilation by clonidine. The mouth occlusion pressure was not affected by clonidine treatment. Clonidine treatment did not potentiate alfentanil-induced respiratory depression. Although the combination of an opioid and an alpha 2-adrenergic agonist may act synergistically for the analgesic response, there is no synergistic effect by this drug combination on respiratory depression.

Adult↗
PubMed1992

Morphine and hydromorphone epidural analgesia. A prospective, randomized comparison.

Because evidence from uncontrolled, unblinded studies suggested fewer side effects from epidural hydromorphone than from epidural morphine, we employed a randomized, blinded study design to compare the side effects of lumbar epidural morphine and hydromorphone in 55 adult, non-obstetric patients undergoing major surgical procedures. A bolus dose of epidural study drug was given at least 1 h prior to the conclusion of surgery, followed by a continuous infusion of the same drug for two postoperative days. Infusions were titrated to patient comfort. Visual analog scale (VAS) pain scores, VAS sedation scores, and subjective ratings of nausea and pruritus were assessed twice daily. The two treatments provided equivalent analgesia. Sedation scores and prevalence of nausea did not differ significantly between groups. Prevalence of pruritus, however, differed significantly on postoperative day 1, with moderate to severe pruritus reported by 44.4% of patients in the morphine group versus 11.5% in the hydromorphone group (P < .01). On post-operative day 2, reports of pruritus by patients receiving morphine remained higher than those among the hydromorphone-treated subjects, although this difference was no longer statistically significant (32% vs. 16.7%, P = .18). We conclude that lumbar epidural morphine and hydromorphone afford comparable analgesia, but the occurrence of moderate to severe pruritus on the first postoperative day is reduced by the use of hydromorphone.

Aged↗
PubMed1992

Detection of inspiratory resistive loads by heart-lung transplant recipients.

Human heart-lung transplantation recipients (HL) are models for the effects of selective lower respiratory tract denervation. We used a series resistor to examine thresholds of inspiratory flow resistance perception among 16 HL in comparison with 15 normal control subjects (C) and 12 heart transplant recipients (H). HL and C were closely age matched. H subjects were older and had mildly reduced lung volumes compared with the other groups. The perception threshold was defined as the added resistance (delta R) detected by subjects at 50% of random, blinded presentations. These delta R were subsequently expressed as a fraction of the airway resistance of the subject and baseline resistance of the apparatus (delta R/Raw + Rapparatus), otherwise known as the Weber fraction. The mean +/- SEM Weber fractions were nearly identical for HL and C (0.32 +/- 0.05 versus 0.34 +/- 0.05, respectively). The Weber fraction of H (0.74 +/- 0.17) was significantly greater than those of both other groups (p less than 0.05 by Kruskal-Wallis test). We conclude that lower respiratory tract afferents do not play a significant role in the perception of inspiratory resistive loads. The finding of an abnormally high Weber fraction in the heart transplant population remains unexplained but may be a function of age or restrictive pulmonary defects.

Adult↗
PubMed1992

Ganciclovir prophylaxis for cytomegalovirus infections in pulmonary allograft recipients.

Cytomegalovirus (CMV) is a substantial cause of morbidity in pulmonary allograft recipients. In an attempt to decrease the prevalence of this infection, we treated 13 recipients at risk for cytomegalovirus with 3 wk of intravenous ganciclovir (5 mg/kg twice a day for 14 days, starting 5 days after the procedure, followed by 1 wk of the drug at a dose of 5 mg/kg/day). Following the ganciclovir course, patients received oral acyclovir, 800 mg three times a day for at least 2 months more. CMV infections developed in 5 recipients (38%), and none of these episodes occurred during the ganciclovir therapy. Neither of the 2 deaths in this group could be attributed to CMV. In comparison, the prevalence of CMV in the preceding cohort of 11 transplant recipients who were administered acyclovir alone was 91% (p << 0.01 by log-rank test), and there were 3 deaths due to viral infections (p = 0.08 by Fisher's exact test). Groups were similar in terms of immunosuppression and renal function during treatment, and none of the recipients developed leukopenia. We conclude that ganciclovir prophylaxis is well tolerated and appears to have considerable efficacy for prevention of CMV infections in pulmonary transplant recipients.

Administration, Oral↗
PubMed1992

Sequelae of cytomegalovirus pulmonary infections in lung allograft recipients.

Indirect effects of cytomegalovirus (CMV) infections in lung transplant recipients (LTX) have not previously been described in detail. We compared spirometric results, development of chronic rejection, rates of respiratory superinfections, and mortality as long as 2 yr after transplantation, between 62 LTX who never developed CMV (CMV-) and 56 LTX with a history of CMV pulmonary infections (CMV+). Initial spirometric parameters were near identical for both groups, but determinations > or = 6 months after transplantation showed that expiratory flows of the CMV+ were significantly reduced. Actuarial prevalences of chronic allograft rejection (CR) at 2 yr were highest among CMV+ with biopsy-proved pneumonitis (74%) compared with 22% among CMV- (p < 0.038). Bacterial or fungal pneumonias developed in 58.9% of the CMV+, whereas the rate among CMV- was 38.7% (p < 0.05). Only 36% of LTX with CMV pneumonitis lived 2 yr compared with 70% survival for CMV- (p < 0.016). Ganciclovir treatment of CMV infections decreased rates of respiratory superinfections and improved survival of patients, but it did not appear to affect subsequent development of CR. We conclude that CMV pulmonary infections among LTX result in serious late sequelae and that current treatment is ineffectual for prevention of viral-associated CR in these patients.

Adult↗
PubMed1991

A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants; The City of Hope-Stanford-Syntex CMV Study Group.

BACKGROUND: Cytomegalovirus (CMV)-associated interstitial pneumonia is a major cause of death after allogeneic bone marrow transplantation. We conducted a controlled trial of ganciclovir in recipients of bone marrow transplants who had asymptomatic pulmonary CMV infection. We also sought to identify risk factors for the development of CMV interstitial pneumonia. METHODS: After bone marrow transplantation, 104 patients who had no evidence of respiratory disease underwent routine bronchoalveolar lavage on day 35. The 40 patients who had positive cultures for CMV were randomly assigned to either prophylactic ganciclovir or observation alone. Ganciclovir (5 mg per kilogram of body weight intravenously) was given twice daily for two weeks and then five times per week until day 120. RESULTS: Of the 20 culture-positive patients who received prophylactic ganciclovir, 5 (25 percent) died or had CMV pneumonia before day 120, as compared with 14 of the 20 culture-positive control patients (70 percent) who were not treated prophylactically (relative risk, 0.36; P = 0.01). No patient who received the full course of ganciclovir prophylaxis went on to have CMV interstitial pneumonia. Four patients treated with ganciclovir had maximal serum creatinine levels greater than or equal to 221 mumol per liter (2.5 mg per deciliter), as compared with none of the controls (P = 0.029). Of the 55 CMV-negative patients who could be evaluated, 12 (22 percent) had CMV pneumonia--a significantly lower rate than in the untreated CMV-positive control patients (relative risk, 0.33; P = 0.003). The strongest predictors of CMV pneumonia were a lavage-fluid culture that was positive for CMV and a CMV-positive blood culture, both from specimens obtained on day 35. CONCLUSION: In recipients of allogeneic bone marrow, asymptomatic CMV infection of the lung is a major risk factor for subsequent CMV interstitial pneumonia. Prophylactic ganciclovir is effective in preventing the development of CMV interstitial pneumonia in patients with asymptomatic infection.

Adolescent↗