Biomedical subjects

M S Chan

Publications and source records attributed to M S Chan.

At least 37 records · Page 2Linked to original sources

PubMed1998

Epifil: a dynamic model of infection and disease in lymphatic filariasis.

The lack of a quantitative framework that describes the dynamic relationships between infection and morbidity has constrained efforts aimed at the community-level control of lymphatic filariasis. In this paper, we describe the development and validation of EPIFIL, a dynamic model of filariasis infection intensity and chronic disease. Infection dynamics are modeled using the well established immigration-death formulation, incorporating the acquisition of immunity to infective larvae over time. The dynamics of disease (lymphodema and hydrocele) are modeled as a catalytic function of a variety of factors, including worm load and the impact of immunopathological responses. The model was parameterized using age-stratified data collected from a Bancroftian filariasis endemic area in Pondicherry in southern India. The fitted parameters suggest that a relatively simple model including only acquired immunity to infection and irreversible progression to disease can satisfactorily explain the observed infection and disease patterns. Disease progression is assumed to be a consequence of worm induced damage and to occur at a high rate for hydrocele and a low rate for lymphodema. This suggests that immunopathology involvement may not be a necessary component of observed age-disease profiles. These findings support a central role for worm burden in the initiation and progression of chronic filarial disease.

Adolescent↗

PubMed1997

The global burden of intestinal nematode infections--fifty years on.

Fifty years after Stoll published his 'This Wormy World' article, the global prevalence of infections with intestinal nematodes remains virtually unchanged. The main species involved are Ascaris lumbricoides, Trichuris trichiura and hookworms, and there are now approximately one billion infections with each of these, worldwide. Given these large numbers, Man-Suen Chan here focuses on attempting to quantify the disease burden caused by these infections, using a recently formulated method of calculating disability-adjusted life years (DALYs). Using a mathematical model, it is estimated that approximately 70% of this burden can be prevented in high-prevalence communities by treating schoolchildren alone. Programmes targeted at schoolchildren have been shown to be extremely cost-effective, and hence this provides a realistic approach for combating these infections in the future.

Journal Article↗

PubMed1997

Human schistosomiasis: potential long-term consequences of vaccination programmes.

Fields trials of new schistosomiasis vaccines are anticipated within the next few years, but there remains great uncertainty regarding the optimal design of vaccination programmes. Mathematical models are used here to explore the potential long-term consequences of vaccination, assuming that the vaccines provide partial protection for a limited period. The analysis suggests that vaccines acting to reduce infection rates or egg output will have a similar impact on levels of infection, that this impact may be highly sensitive to the duration as well as the degree of protection, that it may take several decades for the full impact to become apparent, and that one consequence will be peak levels of infection occurring in older age classes. In terms of lowering levels of infection there may be advantages in delaying vaccination until children reach school age, especially if the vaccine gives short-lived protection, or to repeat vaccination. The short-term advantages can be greatly increased by combining the introduction of a vaccination programme with initial mass chemotherapy. Continuous combined vaccination and chemotherapy programmes may also be more effective than either intervention alone. More research is needed on the consequences of vaccinating previously vaccinated, infected, and infected and treated individuals and the importance of natural boosting of vaccine-induced immunity.

Adolescent↗

PubMed1997

Morbidity and mortality due to ascariasis: re-estimation and sensitivity analysis of global numbers at risk.

This paper presents estimates of the global numbers of people at risk from morbidity related to infection with Ascaris lumbricoides and the numbers of deaths from this infection. Morbidity is classified into 4 types: deficits in growth and fitness which are contemporaneous with infection, or permanent, overt acute illness of mild to moderate severity, and complications involving hospitalization. The estimation of morbidity is based on theoretical models of parasite distributions developed in previous papers. A sensitivity analysis is carried out in which parameters of the model are varied using a Latin hypercube sampling technique. The results estimate approximately 1300 million infections globally with 59 million at risk of some morbidity. The estimate for acute illness is 12 million cases per year with approximately 10,000 deaths. Most morbidity is in children. Sensitivity analysis suggests that infection estimates will not vary greatly with changes in parameter values but that morbidity estimates may be highly variable.

Adolescent↗

PubMed1997

Transmission patterns and the epidemiology of hookworm infection.

BACKGROUND: This paper presents a suite of models of hookworm transmission dynamics which vary the mixing patterns and rates of contamination and infection between children and adults. In this context mixing refers to the degree of epidemiological communication between children and adults, for example, whether adults are likely to get infected from infective material passed by children. METHODS: Three models are described which represent random mixing, no mixing and restricted mixing respectively. Child, adult and population targeted chemotherapy programmes are examined and compared between these models. Data from a hookworm control programme in Zimbabwe were analysed with respect to their fit to the various models. RESULTS: The analysis suggests that some mixing does occur and that in this study location, the sites where adults deposit faeces are more likely to lead to subsequent contamination than the sites children use. CONCLUSIONS: Mixing patterns may have a profound effect on transmission dynamics and should be considered in relation to design of control programmes.

Adult↗

PubMed1997

A logical approach to hepatocellular carcinoma presenting with jaundice.

OBJECTIVE: This prospective cohort study on patients with hepatocellular carcinoma (HCC) presenting with jaundice emphasized the importance of differentiating patients with hepatic insufficiency from patients with obstructive jaundice caused by tumor. SUMMARY BACKGROUND DATA: There are little data in the medical literature on the management of patients with HCC presenting with jaundice. Experience has accumulated mainly from case reports and retrospective studies. METHODS: Data were collected prospectively on 2095 patients with HCC seen over a 12-year period. All patients were investigated with blood tests, abdominal ultrasound, and chest radiography. Endoscopic retrograde cholangiopancreatography-percutaneous transhepatic cholangiography, computed tomography and hepatic angiography were carried out in selected patients. RESULTS: Of the 530 patients who had clinically detectable jaundice, 481 had jaundice due to hepatic insufficiency and 49 patients had obstructive jaundice. Patients with hepatic insufficiency had extremely poor prognosis, and 90% of them died within 10 weeks of first presentation. "Curative" resection, however, was possible in 9 of 49 patients with obstructive jaundice, and histologic analysis showed resectional margin involvement by tumor in 1 patient. In addition, 35 patients were treated with biliary stents to relieve the obstructive jaundice. Supportive treatment only was given to five patients who were considered too terminally ill. The overall survival of patients with HCC with obstructive jaundice was similar to those patients who presented with no clinical detectable jaundice and was much better than those with jaundice due to hepatic insufficiency (log-rank test, p < 0.001). CONCLUSIONS: The prognosis of patients with HCC who presented with jaundice due to hepatic insufficiency was dismal. It is important to identify the patients who had obstructive jaundice because with proper treatment, good palliation and occasional cure are possible.

Adult↗

PubMed1997

Spontaneous intracranial hemorrhage: which patients need diagnostic cerebral angiography? A prospective study of 206 cases and review of the literature.

BACKGROUND AND PURPOSE: In spontaneous intracerebral hemorrhage (ICH), the site, age of the patients, and preexisting hypertension are important factors in determining the possibility of finding an underlying vascular abnormality by cerebral angiography. To what extent these three factors affect the indication for angiography remains controversial. A prospective study was carried out to correlate the angiographic findings with these three factors. METHODS: Two hundred six consecutive spontaneous ICH cases with an age range from 5 to 79 years (median, 45) were investigated with CT and cerebral angiography over a 3-year period (April 1993 through March 1996). Exclusion criteria were (1) poor surgical risk or severely neurologically disabled patients, (2) refusal of angiography, (3) patients in whom severe coagulopathy accounted for the hemorrhage, (4) bleeding into tumor, or (5) subarachnoid hemorrhage-predominant cases. RESULTS: Angiographic yield (the frequency of positive angiography in a defined patient group) was significantly higher in patients (1) at or below the median age of 45 than those above (53/105, 50%, versus 18/101, 18%; P < .001) and (2) without preexisting hypertension than those with (64/145, 44%, versus 5/58, 9%; P < .001). The correlation of age and preexisting hypertension to angiographic yield was independent (logistic regression coefficients -0.056 and -1.59 and SE 0.12 and 0.515, respectively, both P < .001). In patients of the younger age group without preexisting hypertension, angiographic yield was 48% in putaminal, thalamic, or posterior fossa ICH and 65% in lobar ICH. In the older hypertensive patients, the yields were 0% and 10%, respectively. However, in patients with isolated intraventricular hemorrhage, most were normotensive and the yield was high in both age groups (67% versus 63%). CONCLUSION: Diagnostic cerebral angiography should be considered for all spontaneous ICH patients except those over 45 years old with preexisting hypertension in thalamic, putaminal, or posterior fossa hemorrhage.

Adolescent↗

PubMed1996

Cloning of m-fluorophenylalanine-resistant gene and mutational analysis of feedback-resistant prephenate dehydratase from Corynebacterium glutamicum.

Corynebacterium glutamicum was mutated by nitrosoguanidine and five m-fluorophenylalanine (mFP)-resistant mutants were isolated. The mutants were resistant to phenylalanine-mediated feedback inhibition of the prephenate dehydratase activity. Cloning and characterization of the mFP-resistant gene revealed that mutant prephenate dehydratase, encoded by the phe A gene, confers the mFP-resistant phenotype upon C. glutamicum. To determine the amino acid residues to which variation may result in the feedback resistance of prephenate dehydratase, the phe A gene was modified by site-directed mutagenesis and the activities of mutant enzymes were assayed in the presence of phenylalanine. The data indicated that Arg-202 and Gly-224 located at the C-terminal region of prephenate dehydratase were important residues regarding the feedback resistance. Variations of these residues rendered the enzyme insensitive to phenylalanine inhibition. The results also suggested that Gly-224 may reside at the entrance of phenylalanine-binding pocket.

Amino Acid Sequence↗

PubMed1996

Dynamic aspects of morbidity and acquired immunity in schistosomiasis control.

In schistosomiasis control, rational planning of chemotherapy programmes is complicated by the dynamic interactions between treatment and levels of acquired immunity and morbidity in the community. In this paper, mathematical models that address the development of acquired immunity and the prevalence of morbidity are incorporated within an age-structured transmission framework to explore some of the dynamic complexities of long-term chemotherapy programmes. As well as illustrating some of the potential problems inherent in predicting the consequences of control measures, the model provides insights into the dynamics of schistosomiasis transmission and the parameters that need to be measured to further improve the design of community-based control programmes.

Humans↗

PubMed1996

The consequences of uncertainty for the prediction of the effects of schistosomiasis control programmes.

Progress in the development of schistosomiasis models for use in control programmes is limited by the considerable uncertainty in many of the biological parameters. In this paper, this problem is addressed by a comprehensive sensitivity analysis of a schistosomiasis model using the Latin Hypercube method. Fifty simulations with different parameter contributions are run for 50 years with treatment during the first 20 years and reinfection thereafter. The analysis shows only a relatively small divergence between simulations during the chemotherapy treatment programme but considerable divergence in reinfection levels after treatment is stopped. A skewed distribution of outcomes was seen with most simulations showing effective control and a few where control had less impact. The most important uncertainty source was due to the unknown levels of acquired immunity and also uncertainty in the true worm burden. In particular, the strength of the immune response was most important in determining whether control was effective with higher immunity leading to less effective control. Among those simulations in which control was not very effective, those in which the mean worm burden was high showed the least effective control. Since both these are areas of genuine uncertainty, it is proposed that uncertainty analysis should be an integral part of any projection of control programmes.

Humans↗

PubMed1996

Cerebral venous oxygen saturation monitoring: is dominant jugular bulb cannulation good enough?

Venous oxygen saturation at the clinically dominant jugular bulb (SjO2) and that at the confluence of the cerebral sinuses (SccsO2) were compared by direct simultaneous blood sampling of 13 severely head injured patients. The side of dominant jugular bulb (JB) was determined by neck compression test. The right side was chosen if the test was equivocal. In effect, the right side was cannulated in all cases. Subsequent angiography showed that two of the 13 cases were left side dominant. In all, 176 pairs of blood samples were analysed. Correspondence rates (the difference between each pair of blood samples being less than 4% of oxygen saturation) for individual case were good (80-100%) in nine cases including one case with left side dominance. Correspondence rates were moderate in two cases (50 and 56%); the differences were not clinically significant. In the remaining two cases, including one with left side dominance, the correspondence rates were poor (0 and 4%, respectively); SccsO2 was always lower than SjO2; median differences were 13.4 and 23.1%. Ischemia in the cerebral hemispheres would have been underestimated if management were based on SjO2. Monitoring at the dominant JB accurately reflected the global and hemispheric cerebral oxygenation in 11/13 of cases. Monitoring at the non-dominant JB is not recommended.

Adolescent↗

PubMed1996

Histopathology of post-embolized meningiomas.

Although embolization of meningiomas has been performed for many years as a preoperative adjunct to reduce tumor vascularity and facilitate surgical excision, little has been written about the features of the histological artefacts introduced by the process. In particular, the fact that it may produce tumor necrosis may potentially cause confusion with atypical or malignant meningiomas. In this study, 25 meningeal tumors of different histological subtypes, all of which had been previously embolized, were reviewed histologically as well as with immunostaining for the MIBI antigen and proliferating cell nuclear antigen (PCNA). Necrosis, in the form of confluent necrosis as well as micronecrosis, was the most common feature (48%). Other characteristic features included florid ischemic changes (16%), intravascular Ivalon particles (24%), and fibrinoid necrosis of vascular walls (12%). Histological changes showed no obvious relationship with the interval between embolization and surgery. There was an increase in MIB1 and PCNA labelling indices in those tumor exhibiting necrotic foci, but it did not seem to have any prognostic significance. We believe pathologists should be familiar with the histological changes induced by embolization in meningiomas so that an erroneous diagnosis of a high-grade lesion will not be made.

Adult↗

PubMed1996

Hepatic haemangioendothelioma presenting with early heart failure in a newborn: treatment with hepatic artery embolization and interferon.

We report our management of a newborn presenting in utero with congestive heart failure secondary to a giant hepatic haemangioendothelioma. Control of heart failure was achieved by transcatheter hepatic artery embolization, and rapid regression of the tumor was observed after a course of alpha 1 interferon. The combination of hepatic artery embolization and interferon may be a useful approach in the management of this rare, potentially fatal condition.

Antineoplastic Agents↗

PubMed1996

Dynamic models of schistosomiasis morbidity.

Previous attempts to assess the health impact of schistosomiasis control programs on community morbidity have been limited by a lack of a theoretical framework that describes the dynamic relationships between infection and morbidity. In this paper, a model of schistosomal morbidity is developed and parameterized. Morbidity is divided into that due to current heavy infection, and early and late stages of chronic disease. The model was parameterized using data showing resolution of disease after treatment, correlations between prevalence of disease and intensity of infection and using age-morbidity profiles. The fitted parameters suggest that early manifestations of disease such as hepatomegaly in Schistosoma mansoni and S. japonicum infections would resolve relatively quickly following treatment whereas later forms of disease such as liver fibrosis resolve very slowly or not at all. Similar general conclusions were obtained with data on early and late forms of urinary tract morbidity in S. haematobium.

Adolescent↗

PubMed1995

Radiation pneumonitis after selective internal radiation treatment with intraarterial 90yttrium-microspheres for inoperable hepatic tumors.

PURPOSE: To investigate the clinical, histopathological, and radiological features of radiation pneumonitis arising as a complication of selective internal radiation treatment for liver tumors. To correlate the development of radiation pneumonitis with the degree of lung shunting as assessed by 99mTechnetium-labeled macroaggregated albumin (Tc-MAA) scan. METHODS AND MATERIALS: Five out of 80 patients who had inoperable hepatic tumors and underwent treatment with intraarterial 90Yttrium- (90Y)-microspheres, developed progressive restrictive ventilatory dysfunction without an infective or cardiovascular cause. Histopathological evidence of a pneumonitis and the presence of microspheres in the lung tissue suggested a diagnosis of radiation pneumonitis. The clinical course, radiological and histopathological findings, percentage tumor shunting to the lungs (lung shunting, as predicted by gamma camera scanning after intraarterial Tc-MAA), and the estimated radiation dose to the lungs were analyzed. In an attempt to reduce pulmonary shunting of the microspheres, three patients received partial hepatic embolization with inert particles before selective internal radiation therapy. RESULTS: In the five patients who developed radiation pneumonitis, lung shunting percentages (as predicted by Tc-MAA scan) ranged from 13.1 to 45.6% (median 23.7%). The estimated whole lung radiation dose ranged from 10.43 Gy to 36.44 Gy (median 25.04 Gy). Among 75 patients who did not develop radiation pneumonitis, the percentage lung shunting ranged from less than 1% to 15% (median 6%). Nine patients had lung shunting greater than 13% and five of them developed radiation pneumonitis, whereas this developed in none of those in whom shunting was below 13%. The onset of radiation pneumonitis ranged from 1 to 6 months after internal radiation treatment. All five patients exhibited characteristic plain radiographic and computerized tomographic changes comprising extensive consolidation with well-defined lateral margins. Clinical improvement after corticosteroid treatment was seen in two patients. Three patients died from respiratory failure and two from other causes. Partial hepatic arterial embolization reduced the degree of lung shunting to less than 13%, but did not prevent the development of radiation pneumonitis. CONCLUSION: Radiation pneumonitis may become a complication after intraarterial 90Y-microspheres treatment when lung shunting, as assessed by Tc-MAA scan, is high (above 13%). Prescribed activity of 90Y and lung shunting of Tc-MAA should be considered together before giving selective internal radiation (SIR) therapy for hepatic tumors, and preferably avoided if the lung shunting is above 13%.

Adult↗

PubMed1995

The practicality and sustainability of vaccination as an approach to parasite control.

The development of a successful vaccine depends not only on the production of the vaccine itself, but also on the design pf the vaccination programme. This involves a better understanding of the epidemiology of the disease to be controlled, the delivery system to be used and the costs involved. This review focuses on current understanding of parasite population dynamics and epidemiology, and on the logistic experience gained from immunization programmes using existing viral and bacterial vaccines. The feasibility and sustainability of any new vaccine would greatly benefit from research into epidemiology and health systems which are conducted in parallel, rather than sequential to, vaccine development.

Animals↗

PubMed1995

The development of an age structured model for schistosomiasis transmission dynamics and control and its validation for Schistosoma mansoni.

Mathematical models are potentially useful tools to aid in the design of control programmes for parasitic diseases. In this paper, a fully age structured epidemiological model of human schistosomiasis is developed and parameterized, and used to predict trends in infection prevalence, intensity and prevalence of heavy infections over age and time during several rounds of mass and age targeted treatment. The model is validated against data from a Schistosoma mansoni control programme in Kenya.

Adolescent↗

PubMed1995

Massive lingual swelling following palatoplasty. An unusual cause of upper airway obstruction.

We report a case of upper airway obstruction as a result of delayed massive lingual swelling following routine cleft palate repair in an otherwise healthy 12-month-old girl. We believe that ischaemia and venous congestion were the causes of macroglossia, after prolonged use of the Digman Dott tongue retractor. In any difficult and lengthy repair, we recommend the prophylactic insertion of a nasopharyngeal airway under direct vision by the surgeons after surgery to prevent potential upper airway obstruction.

Acute Disease↗