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Biomedical subjects

S M Graham

Publications and source records attributed to S M Graham.

At least 37 records · Page 2Linked to original sources
PubMed2001

Pulmonary disease in HIV-infected African children.

Childhood human immunodeficiency virus (HIV) infection is common in most regions of sub-Saharan Africa. Acute and chronic respiratory diseases are major causes of morbidity and mortality in HIV-infected children. They represent a significant added burden in a region where diagnostic capabilities are limited and management decisions are often made on the basis of clinical guidelines alone. Pneumocystis carinii pneumonia is now recognised as an important cause of acute severe pneumonia and death in HIV-infected infants. However, there are few data on incidence and aetiology for more treatable conditions such as bacterial pneumonia. The association of pulmonary tuberculosis and HIV infection is uncertain, and the diagnosis is further confused by the presence of lymphoid interstitial pneumonitis and other chronic HIV-related pulmonary disease. This article reviews the literature and highlights the urgent need for further research in order to improve clinical management and appropriate interventions.

AIDS-Related Opportunistic Infections↗
PubMed2001

Diagnosis of pulmonary tuberculosis in children in an HIV-endemic area, Malawi.

The diagnosis of pulmonary tuberculosis (PTB) in young children is particularly complex in resource-poor regions where HIV infection is common. This study examines the impact of HIV infection on diagnosis in children with suspected PTB attending Queen Elizabeth Central Hospital, Blantyre. A total of 110 children (4 months-14 years) were studied over a 4-month period. Clinical data were recorded and investigations included Mantoux test, chest X-ray, HIV status (HIV-PCR when younger than 18 months) and sputum, if available. Laryngeal swabs were compared with sputa or gastric aspirates in a subgroup of 60 children. All children were commenced on anti-TB therapy and followed for treatment response. Aware of the clinical overlap between HIV and TB infection, we used more limited criteria than recommended to allocate a final diagnosis following review of all data except HIV status. Final diagnosis included confirmed PTB (n = 8), probable PTB (n = 41), lymphocytic interstitial pneumonitis (n = 10), pulmonary Kaposi sarcoma (n = 3) and bronchiectasis (n = 5). Culture rates of M. tuberculosis were: five (27.8%) of 18 sputa, three (7.1%) of 42 gastric aspirates and four (6.6%) of 60 laryngeal swabs. The HIV infection rate was 70.6% overall and 57.8% in 45 children with confirmed or probable PTB. Although a positive contact history was more common in HIV-infected children, a final diagnosis of confirmed or probable PTB was less common than in HIV-uninfected children (36% vs 63%; p = 0.02). The Mantoux test was positive in 14 (19%) of 72 HIV-infected compared with 15 (50%) of 30 HIV-uninfected children (p < 0.01). A final diagnosis could not be made in 43 (39%) of the study children with suspected PTB, the majority of whom were HIV-infected. HIV-infected children had a significantly poorer response to TB treatment and higher lost-to-follow-up rates.

Adolescent↗
PubMed2000

Clinical presentation and outcome of Pneumocystis carinii pneumonia in Malawian children.

BACKGROUND: Necropsy studies from Africa have shown that Pneumocystis carinii pneumonia (PCP) is common in infants with HIV infection. We aimed to describe the rate, clinical presentation, and outcome of PCP in young Malawian children with acute severe pneumonia. METHODS: Children aged between 2 months and 5 years who were in hospital with a diagnosis of severe pneumonia were admitted to a study ward for clinical monitoring. We carried out blood culture, immunofluorescence on nasopharyngeal aspirate samples to test for PCP, polymerase chain reaction to detect HIV, and chest radiography. FINDINGS: 16 cases of PCP were identified among 150 children with radiologically confirmed severe pneumonia. All were HIV-positive and younger than 6 months. 21 children had bacterial pneumonia (including one who was also PCP positive) and 114 were not confirmed. The most common bacterial pathogens among children without PCP were Streptococcus pneumoniae (eight) and non-typhoidal salmonellae (seven). On admission, children with confirmed PCP had a lower mean age, body temperature, and oxygen saturation than children with bacterial pneumonia and were less likely to have a focal abnormality on auscultation. Oxygen requirements were much greater in children with PCP than those with bacterial pneumonias (96 of 105 hospital days vs 15 of 94, p<0.0001). Ten of 16 children with PCP and six of 21 with bacterial pneumonia died (relative risk 2.19 [95% CI 1.0-4.7]). The overall case-fatality rate of severe pneumonia was 22%. In addition to a strong association with PCP, a fatal outcome was significantly and independently associated with HIV infection (2.98 [1.1-7.9]) and with age under 6 months (2.76 [1.0-5.2]). INTERPRETATION: PCP is common and contributes to the high mortality from pneumonia in Malawian infants. Clinical features are helpful in diagnosis. The study highlights the impact of HIV infection and difficult issues of management in countries with few resources.

AIDS-Related Opportunistic Infections↗
PubMed2000

Geographic variation in allergic fungal rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) has a worldwide distribution. This survey of 20 otolaryngologic practices throughout the United States confirmed a variation in the frequency of AFRS relative to endoscopic sinus procedures performed for all other diagnoses. The highest incidence occurred in Memphis, Tennessee at 23%, with three other southern practices reporting a frequency of at least 10%. In the northern locations the frequency ranged from 0 to 4%. No correlation with mould counts was demonstrated, possibly because of incomplete mould data relative to most of the surgical locations.

Humans↗
PubMed2000

Urban/rural differences in prevalence and risk factors for intestinal helminth infection in southern Malawi.

Urbanization may increase the risk of human infection with intestinal helminths. A cross-sectional survey was conducted to investigate the prevalence, intensity and potential risk factors of acquiring such infection, among children aged 3-14 years in similar urban and rural communities in southern Malawi. Stool samples were collected from 553 children (273 urban and 280 rural). The overall prevalence of helminth infection was significantly higher in the urban subjects than in the rural (16.5% v. 3.6%; P < 0.001), mostly because of differences in the prevalence of Ascaris lumbricoides infection. Living in an urban community was associated with a significantly higher risk of infection [odds ratio (OR) = 5.3; 95% confidence interval (CI) = 2.6-12.1], even after controlling for potential confounding factors. In the urban community, risk factors included having pools of water/sewage around houses (OR = 3.0; CI = 1.4-6.5), not wearing shoes (OR = 7.1; CI = 2.7-19.2), not attending school (OR = 2.8; CI = 1.2-6.5), having mothers with 4-8 years of education (OR = 5.2; CI = 2.0-14.0), and having mothers below 35 years of age (OR = 4.09; CI = 1.39-16.28). In this part of Africa, efforts to reduce helminth infections may best be focused on reducing geohelminth burden in urban areas.

Adolescent↗
PubMed2000

Detection of pneumococcal capsular antigen in saliva of children with pneumonia.

The concentration of pneumococcal capsular antigen (PCA) in saliva was examined in 44 Thai children aged between 2 months and 2 years admitted with community-acquired pneumonia and in 52 healthy controls. None of the children with pneumonia had a positive blood culture. PCA was detected by latex agglutination in the saliva of 12/44 (27%) children with pneumonia compared with 9/52 (17%) of the controls. More cases than controls had a PCA titre > or = 10 (9/44 (20%) vs 1/52 (2%), p < 0.01). Three of the five cases with a saliva PCA titre > or = 1000 were urine PCA antigen-positive. The salivary PCA titres were higher, but not significantly, in children with heavier pneumococcal carriage. Quantitative measurement of PCA in the saliva may be valuable in helping to make an aetiological diagnosis in children with pneumonia.

Antigens, Bacterial↗
PubMed2000

Laryngeal cancer cost analysis: association of case-mix and treatment characteristics with medical charges.

OBJECTIVES: To examine the relationship of various pretreatment case-mix characteristics and treatment modalities with medical charges incurred during diagnosis, treatment, and 2-year follow-up for patients with laryngeal cancer. DESIGN: Retrospective chart review and billing record analysis. METHODS: The charts and billing records of patients diagnosed with laryngeal cancer at the University of Iowa Hospitals and Clinics (UIHC) between January 1, 1991 and December 31, 1994 were reviewed. The independent variables included various pretreatment patient-mix and tumor characteristics (age, AJCC TNM clinical stage, smoking history, ASA class, and comorbidity as defined by Kaplan-Feinstein grade) as well as type of treatment. The dependent variables included total physician, office, and university hospital-based charges incurred during the pretreatment evaluation and 0- to 3-, 3- to 12, and 12- to 24-month billing periods after the initiation of cancer-directed therapy. Total 1-year and 2-year charges were also evaluated. Univariate and multivariate analyses were used to investigate the relationships between dependent and independent variables and to develop models predictive of management charges during the individual and total billing periods. RESULTS: Pretreatment charges showed no significant associations (P < .05) with any of the independent variables. Multiple regression analyses indicated that comorbidity, stage, and initial treatment modality were significant variables in one or more of the models predicting charges incurred during the 0- to 3-month, 3- to 12-month, total 1-year, and total 2-year billing periods. The models yielded R2 values for the total 1- and 2-year billing periods of 0.5246 and 0.5055, respectively. CONCLUSIONS: This work supports continued study of measures that may result in earlier detection of laryngeal cancer as a potential means of reducing management charges. These results also indicate that a more accurate method of stratifying the disease severity of laryngeal cancer patients for reimbursement purposes would include measurements of the severity of the index disease as well as comorbid diseases.

Aged↗
PubMed2000

Functional magnetic resonance imaging using iron oxide particles in characterizing head and neck adenopathy.

OBJECTIVES: In lymph nodes harboring metastases the reticuloendothelial system is replaced by tumor cells and does not concentrate iron particles. This study assesses the value of contrast magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxide particles (Combidex, Advanced Magnetics, Inc., Cambridge, MA) to characterize and stage neck nodes. STUDY DESIGN: Prospective analysis of neck imaging by Combidex MRI, with correlation from pathological assessment of resected lymph nodes. METHODS: Nine patients underwent MRI and subsequent bilateral neck dissections (three), unilateral neck dissections (five) or fine-needle aspiration (one). Each case was evaluated for the number, location, MRI characteristics, and pathological assessment of lymph nodes. RESULTS: Forty-nine separate nodal levels were evaluated with both Combidex MRI and pathological assessment. The presence of metastatic nodal involvement among 45 levels was correctly assessed by the Combidex MRI (three false-negative results, one false-positive result; sensitivity, 84%; specificity, 97%). Analysis was possible for 101 of the individual lymph nodes identified by MRI that could be correlated with individual nodes pathologically examined. Combidex MRI assessment was correct for 99 nodes (one-false positive result, one false-negative result; sensitivity, 95%, specificity, 99%). Standard MRI interpretation without Combidex identified that 12 of 18 nodes (67%) that were greater than or equal to 10 mm (greatest dimension) contained tumor, whereas 9 of 83 nodes (ll%) that were less than 10 mm contained tumor. CONCLUSIONS: Combidex MRI provides functional information to characterize lymph nodes in the clinical staging of squamous cell carcinoma of the head and neck. The inability of MRI to identify small lymph nodes restricts the usefulness of this technique.

Adult↗
PubMed2000

Bacteremia in febrile Malawian children: clinical and microbiologic features.

BACKGROUND: There are no published data for the incidence or etiology of childhood bacteremia in Malawi. We describe the clinical and microbiologic features of children admitted to hospital from whom blood cultures yielded bacterial pathogens. METHODS: Any neonate or child admitted to the pediatric wards of the Queen Elizabeth Central Hospital had a blood culture taken in the event of fever without obvious clinical explanation. Clinical and microbiologic data were prospectively collected for children with a significant positive culture. RESULTS: Between September, 1996, and August, 1997, we processed 2,123 cultures. Of these, 365 (17.2%) grew a pathogen. Non-typhi salmonellae (NTS) and enteric Gram-negative bacilli constituted 67.4% of isolates, and Streptococcus pneumoniae constituted 16.4%. More than two-thirds of NTS episodes coincided with the peak malaria transmission season (January to June); 67% of bacteremic children were malnourished, 28% severely so. Patients with NTS bacteremia were significantly more likely to have coincident malaria and to have splenomegaly and anemia than children with other infecting organisms. The overall mortality was 38% but varied considerably according to age and nutritional status. Prior antibiotic use, coincident malaria or meningitis did not adversely affect outcome. In vitro resistance to the commonly available antibiotics ampicillin and trimethoprim-sulfamethoxazole was found in 76 and 71% of NTS isolates. Screening tests for penicillin resistance suggested a rate of 21% among pneumococci. CONCLUSIONS: Bacteremia is common in hospitalized Malawian children and has a high mortality. There are high rates of resistance to some of the commonly used antibacterial agents.

Adolescent↗
PubMed2000

Morbidity among human immunodeficiency virus-1-infected and -uninfected African children.

OBJECTIVE: To assess patterns of morbidity and associated factors in late infancy and early childhood among human immunodeficiency virus (HIV)-infected and -uninfected African children. DESIGN: Prospective study. SETTING: The Queen Elizabeth Central Hospital, Blantyre, Malawi. PARTICIPANTS: Children with known HIV status from an earlier perinatal intervention trial were enrolled during the first year of life and followed to approximately 36 months of age. OUTCOME MEASURES: Morbidity and mortality information was collected every 3 months by a questionnaire. A physical examination was conducted every 6 months. Blood to determine CD4(+) values was also collected. Age-adjusted and Kaplan-Meier analyses were performed to compare rates of morbidity and mortality among infected and uninfected children. RESULTS: Overall, 808 children (190 HIV-infected, 499 HIV-uninfected but born to infected mothers, and 119 born to HIV-uninfected mothers) were included in this study. Of these, 109 died during a median follow-up of 18 months. Rates of childhood immunizations were high among all children (eg, lowest was measles vaccination [87%] among HIV-infected children). Age-adjusted morbidity rates were significantly higher among HIV-infected than among HIV-uninfected children. HIV-infected children were more immunosuppressed than were uninfected children. By 3 years of age, 89% of the infected children died, 10% were in HIV disease category B or C, and only approximately 1% were without HIV symptoms. Among HIV-infected children, median survival after the first occurrence of acquired immunodeficiency syndrome-related conditions, such as splenomegaly, oral thrush, and developmental delay, was <10 months. These same conditions, in addition to frequent bouts of fever, were the main morbidity predictors of mortality. CONCLUSIONS: The frequency of diseases was high, and progression from asymptomatic or symptomatic HIV disease to death was rapid. Management strategies that effectively reduce morbidity for HIV-infected children are needed.

Acquired Immunodeficiency Syndrome↗
PubMed2000

The traveling salesman problem: a hierarchical model.

Our review of prior literature on spatial information processing in perception, attention, and memory indicates that these cognitive functions involve similar mechanisms based on a hierarchical architecture. The present study extends the application of hierarchical models to the area of problem solving. First, we report results of an experiment in which human subjects were tested on a Euclidean traveling salesman problem (TSP) with 6 to 30 cities. The subject's solutions were either optimal or near-optimal in length and were produced in a time that was, on average, a linear function of the number of cities. Next, the performance of the subjects is compared with that of five representative artificial intelligence and operations research algorithms, that produce approximate solutions for Euclidean problems. None of these algorithms was found to be an adequate psychological model. Finally, we present a new algorithm for solving the TSP, which is based on a hierarchical pyramid architecture. The performance of this new algorithm is quite similar to the performance of the subjects.

Algorithms↗
PubMed1999

Selective phosphitylation of the primary hydroxyl group in unprotected carbohydrates and nucleosides.

[reaction: see text] Carbohydrates and nucleosides containing a phosphate at the less-hindered primary hydroxyl group are often prepared using a protection/deprotection strategy. Herein we report that the phosphoramidite method can be used to selectively incorporate phosphorus at the primary hydroxyl group of O-unprotected carbohydrates and nucleosides; in situ oxidation of the resulting phosphite triester yields the phosphate triester.

Carbohydrates↗
PubMed1999

TC21 and Ras share indistinguishable transforming and differentiating activities.

Constitutively activated mutants of the Ras-related protein TC21/R-Ras2 cause tumorigenic transformation of NIH3T3 cells. However, unlike Ras, TC21 fails to bind to and activate the Raf-1 serine-threonine kinase. Thus, whereas Ras transformation is critically dependent on Raf-1 TC21 activity is promoted by activation of Raf-independent signaling pathways. In the present study, we have further compared the functions of Ras and TC21. First we determined the basis for the inability of TC21 to activate Raf-1. Whereas Ras can interact with the two distinct Ras-binding sequences in NH2-terminus of Raf-1, designated RBS1 and Raf-Cys, TC21 could only bind Raf-Cys. Thus, the inability of TC21 to bind to RBS1 may prevent it from promoting the translocation of Raf-1 to the plasma membrane. Second, we found that TC21 is an activator of the JNK and p38, but not ERK, mitogen-activated protein kinase cascades and that TC21 transforming activity was dependent on Rac function. Thus, like Ras, TC21 may activate a Rac/JNK pathway. Third, we determined if TC21 could cause the same biological consequences as Ras in three distinct cell types. Like Ras, activated TC21 caused transformation of RIE-1 rat intestinal epithelial cells and terminal differentiation of PC12 pheochromocytoma cells. Finally, activated TC21 blocked serum starvation-induced differentiation of C2 myoblasts, whereas dominant negative TC21 greatly accelerated this differentiation process. Therefore, TC21 and Ras share indistinguishable biological activities in all cell types that we have evaluated. These results support the importance of Raf-independent pathways in mediating the actions of Ras and TC21.

3T3 Cells↗
PubMed1999

The use of granulocyte colony stimulating factor to promote wound healing in a neutropenic patient after head and neck surgery.

BACKGROUND: Neutropenia and neutrophil dysfunction, in association with a variety of diseases, has been shown to play a role in poor wound healing. Wound breakdown with fistula formation in patients undergoing total laryngectomy results in significant morbidity and increased hospital stay. Although malnutrition, prior radiation, diabetes, and other diseases are recognized as factors predisposing patients with head and neck cancer to developing fistulas, neutrophil dysfunction should also be considered. Granulocyte colony stimulating factor (G-CSF) has been used successfully to treat neutropenia and neutrophil dysfunction. METHODS: This study was conducted as a case report. RESULTS: We present the first report of a neutropenic head and neck cancer patient with a persistent wound of 6 months' duration who showed dramatic improvement after treatment with G-CSF. CONCLUSION: We conclude that G-CSF may represent a useful adjunct in patients with persistent wound healing problems and neutropenia despite adequate treatment by conventional means. Further clinical experience with G-CSF in patients with delayed healing is indicated.

Cutaneous Fistula↗
PubMed1999

Ophthalmic manifestations of allergic fungal sinusitis.

PURPOSE: To highlight allergic fungal sinusitis as a cause of ophthalmic and sinus problems by identifying the profile of the patient with allergic fungal sinusitis and presenting a successful treatment approach. METHODS: Six consecutive cases of patients with ophthalmic manifestations of allergic fungal sinusitis were reviewed. Ophthalmic findings, sinus involvement, mycology, immune response, imaging studies, and treatment were examined. The characteristics of this patient group with ophthalmic manifestations of allergic fungal sinusitis were compared with those of the general group of patients with allergic fungal sinusitis. RESULTS: All six patients had proptosis. One had symptomatic diplopia and one had visual loss. Imaging studies, fungal characterization, and immune profiles were similar to the reported allergic fungal sinusitis population. After treatment there was no recurrence of ophthalmic or sinus symptoms at a mean follow-up of 34 months (range, 8 to 48 months). There were no complications of treatment. CONCLUSIONS: Initial diagnosis of allergic fungal sinusitis requires suspicion on the part of the ophthalmologist. Proptosis is the most common ophthalmic sign. Differentiation from invasive forms of fungal sinus disease is crucial, because systemic antifungal medication and extensive surgical tissue debridement are not required in allergic fungal sinusitis. Treatment consists of extirpation of the allergic mucin and fungus, sinus aeration, and systemic and topical corticosteroids.

Adolescent↗
PubMed1999

Vocal fold paralysis secondary to cardiac countershock (cardioversion).

Application of electrical energy to the heart is effective in treating many dysrhythmias. There are, however, also disadvantages associated with cardioversion. Employment of external electrical current has been shown to induce epicardial and myocardial damage at the site of electrode application. We present the only case in the English literature of vocal fold paralysis in which the single identified associated event was cardioversion. In this case of temporary vocal fold paralysis, there was no invasive procedure to directly damage the nerve. Echocardiography of the patient revealed a large left atrium, placing the recurrent laryngeal nerve in an abnormal anatomic position where it was vulnerable to the electric current.

Aged↗
PubMed1999

Sequential magnetic resonance imaging analysis of the maxillary sinuses: implications for a model of gene therapy in cystic fibrosis.

Serial maxillary sinus aminoglycoside lavage is an adjunctive technique increasingly employed in a variety of areas in cystic fibrosis (CF). It may be helpful in reducing revision rates for sinus surgery, in lowering rates of bronchial pseudomonal colonization after lung transplantation and in the evolving field of gene therapy for CF. The goal of this study was to assess the utility of the maxillary sinus as a model for gene transfer in cystic fibrosis. We performed serial maxillary sinus lavage, in accordance with published protocols, using tobramycin in a randomized series of five CF subjects. Lavage was performed for up to 10 days and sequential magnetic resonance imaging (MRI) scans were taken at zero, 10, 30, 60, 120 and 180 days. The 30 MRI scans were blindly scored by two examiners on the parameters of maxillary sinus aeration, averaged over the five time intervals, was significantly improved (p < 0.05) in the lavaged sinus. This study provides the first systematic image-based measure of efficacy of maxillary sinus aminoglycoside lavage, a major element of a number of clinical protocols used in the treatment of CF. The prolonged increase in aeration after lavage suggests that any further improvement potentially achievable after gene transfer would be difficult to detect, limiting the value of this system as a model of clinical efficacy of gene transfer in CF.

Adult↗