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Biomedical subjects

D S Walsh

Publications and source records attributed to D S Walsh.

At least 37 records · Page 2Linked to original sources
PubMed2000

Fetal surgical intervention.

Despite advances in perinatal management, some congenital disorders continue to have significant morbidity and mortality both in utero and in the early postnatal period. In selected anomalies, fetal surgical intervention can alter the natural history of the disorder, leading to improved survival rates and functional outcomes. While therapies are primarily aimed at life-threatening disorders, some significantly morbid disorders may also be addressed prenatally. Potential indications for fetal surgery include mass lesions causing hydrops fetalis, congenital diaphragmatic hernia, myelomeningocele, urinary obstruction and disorders of twins. A thorough prenatal evaluation and extensive family counseling are necessary prior to intervention. Improvements in minimally invasive techniques may minimize the greatest challenge of fetal surgery, management of postoperative preterm labor.

Female↗
PubMed2000

Assessment of fetal lung volumes and liver herniation with magnetic resonance imaging in congenital diaphragmatic hernia.

OBJECTIVE: We evaluated the use of fetal magnetic resonance imaging in predicting outcomes after ultrasonographic diagnosis of left-sided congenital diaphragmatic hernia. STUDY DESIGN: Forty-one pregnant women carrying fetuses with congenital diaphragmatic hernia underwent 43 magnetic resonance imaging scans. Lung volumes were calculated by summing the areas on 6-mm axial sections. The presence or absence of liver herniation was noted. A liver/diaphragm ratio was obtained by using the distances from the superior aspect of the liver and the diaphragmatic remnant to the apex of the chest. RESULTS: Mean gestational age was 26 weeks and overall survival was 59%. Neither right, left, nor total lung volume measurements were predictive of survival. Liver herniation into the left side of the chest was predictive of outcome at P<.05. The liver/diaphragm ratio was predictive of outcome at P = .03. CONCLUSION: Fetal magnetic resonance imaging permits calculation of lung volumes, but these volumes are not predictive of outcome. However, both the presence of liver herniation and the volume of liver within the chest, as reflected by the liver/diaphragm ratio, help predict outcome in left-sided congenital diaphragmatic hernia.

Fetus↗
PubMed2000

Measurement of tafenoquine (WR 238605) in human plasma and venous and capillary blood by high-pressure liquid chromatography.

A simple, rapid, and accurate high-pressure liquid chromatographic method with fluorescence detection is described for the measurement of tafenoquine (TQ) (also known as WR 238605) from human plasma and venous and capillary blood. Tafenoquine was measured in plasma and venous blood following protein precipitation. Chromatographic separation was achieved using a Waters S5P Spherisorb phenyl analytical cartridge (150 mm x 4.6 mm I.D., 5 microm particle size) (Waters, Milford, MA, USA) and a mobile phase of 22 mM ammonium acetate, pH 4:acetonitrile (45:55, vol/vol). The flow rate was 1.5 mL/min and the retention times were approximately 3.5 min for WR VIIIAc (internal standard) and approximately 7.8 min for TQ. The interday and intraday coefficients of variation of TQ over a concentration range of 20-1000 ng/mL in plasma were < or =8.4% and in venous blood were < or =9.6%. The mean percent difference between added concentration and obtained concentration was 7.3% in plasma and 8.5% in venous blood over the corresponding concentration range. The limit of quantitation for both fluids was 10 ng/mL. Tafenoquine concentrations were comparable between capillary and venous blood with no significant difference between measurement in both biological fluids. The clinical application of the method was demonstrated by measuring plasma and whole blood concentrations of TQ from participants in a chemosuppression trial of the drug against malaria infections in Thailand.

Aminoquinolines↗
PubMed2000

Frequency of pruritus in Plasmodium vivax malaria patients treated with chloroquine in Thailand.

Chloroquine-induced itch in black-skinned African malaria patients is common and frequently leads to poor compliance or treatment defaulting.To assess the frequency and severity of chloroquine-induced pruritus in an Asian population, we reviewed case records of 1189 Plasmodium vivax malaria patients treated with chloroquine (25 mg/kg over 3 days) at the Bangkok Hospital for Tropical Diseases from 1992 through 1997. The majority of patients were Thais or ethnic Burmese (light brown skin), referred from the western border of Thailand. Overall, there were 23 patients (1.9%) with complaints of pruritus during chloroquine therapy. Of these, 12 (52%) had palm and sole involvement, eight (35%) had generalized pruritus including the palms and soles, and three (13%) had palm itching only. One patient developed pruritus on the palms and soles on two consecutive admissions. The pruritus did not interfere with daily activity, was reduced in intensity by anti-histamine therapy, and did not affect the patient's willingness to complete the chloroquine regimen. Therapeutic responses in the 23 patients with chloroquine itch was similar to those without itch. Among the itch patients, there was no association with gender or level of parasitaemias. Our findings indicate that the frequency of chloroquine-induced pruritus in Asian patients treated with chloroquine for P. vivax malaria is low in comparison with black-skinned Africans.This may be related to pharmacogenetic factors, the infective Plasmodium species, drug metabolism or drug-parasite interactions, or a lower affinity of chloroquine for less pigmented skin.

Adolescent↗
PubMed1999

Serum neopterin as a marker for reactional states in leprosy.

Reactions, a relatively common phenomenon among leprosy patients in treatment, require early detection and proper management to prevent serious sequelae. It is generally accepted that reactional states are immunologically mediated and, as such, usually improve with immunomodulatory treatments such as corticosteroids or thalidomide. Neopterin, a product of gamma-interferon-activated macrophages, is a marker for cell-mediated immune activation and may be useful to detect reactional states in leprosy. Here, we compared neopterin levels in single serum samples from leprosy patients with and without reaction with untreated controls and, when available, serial samples among patients with and without reaction. Levels in the single sample measurements, conducted in 22 patients with a reversal reaction (mean 14.5 nmol l(-1), S.D. 8.7) and 13 with erythema nodosum leprosum (mean 16.9 nmol l(-1), S.D. 13.6), were significantly higher (P=0.02 and P=0.001, respectively) than levels in 26 untreated patients (mean 9.1 nmol l(-1), S.D. 7.3). Values above the upper limit of normal (10 nmol l(-1)) were found in seven of 26 untreated patients, 14 of the 22 reversal reaction patients (P=0.01) and 10 of the 13 ENL patients (P=0.003). Serial serum samples, obtained from six patients that developed reactions and 14 that remained free of reaction, indicated that reversal reaction or erythema nodosum leprosum paralleled a concomitant increase in the serum neopterin level. Neopterin levels generally declined upon corticosteroid therapy. Neopterin may be a useful marker for reactional states in leprosy by providing a laboratory parameter to assess the onset, progression, response to therapy and resolution.

Biomarkers↗
PubMed1999

Impairment of Plasmodium falciparum growth in thalassemic red blood cells: further evidence by using biotin labeling and flow cytometry.

Certain red blood cell (RBC) disorders, including thalassemia, have been associated with an innate protection against malaria infection. However, many in vitro correlative studies have been inconclusive. To better understand the relationship between human RBCs with thalassemia hemoglobinopathies and susceptibility to in vitro infection, we used an in vitro coculture system that involved biotin labeling and flow cytometry to study the ability of normal and variant RBC populations in supporting the growth of Plasmodium falciparum malaria parasites. Results showed that both normal and thalassemic RBCs were susceptible to P falciparum invasion, but the parasite multiplication rates were significantly reduced in the thalassemic RBC populations. The growth inhibition was especially marked in RBCs from alpha-thalassemia patients (both alpha-thalassemia1/alpha-thalassemia2 and alpha-thalassemia1 heterozygote). Our observations support the contention that thalassemia confers protection against malaria and may explain why it is more prevalent in malaria endemic areas.

Animals↗
PubMed1999

Fetal interventions for obstructive uropathy.

Obstructive uropathy is a significant source of morbidity and mortality in the neonate and infant, despite advances in postnatal management. Diagnosis is typically made early in the second trimester on the basis of sonographic measurements. In utero therapy holds promise for improved outcomes by preventing progressive urinary tract damage and permitting drainage of urine into the amniotic space to minimize the pulmonary sequelae of oligohydramnios. Multiple studies with animal models have showed the benefits of midgestational intervention, but large prospective, randomized studies have not yet been performed to confirm these findings in humans. Standardization of the diagnostic evaluation allows for refined patient selection, resulting in improved postnatal outcomes after fetal vesicoamniotic shunting. Research into the role of specific growth factors and immunoproteins in renal development and function may further improve patient selection and outcome. This article reviews diagnosis, technique, and outcomes for fetal treatment of obstructive uropathy.

Female↗
PubMed1999

Randomized dose-ranging study of the safety and efficacy of WR 238605 (Tafenoquine) in the prevention of relapse of Plasmodium vivax malaria in Thailand.

WR 238605 is an 8-aminoquinoline developed for the radical cure of Plasmodium vivax. Forty-four P. vivax-infected patients were randomly assigned to 1 of 4 treatment regimens: 3 groups received a blood schizonticidal dose of chloroquine followed by WR 238605: group A (n=15) received 300 mg daily for 7 days; group B (n=11), 500 mg daily for 3 days, repeated 1 week after the initial dose; group C (n=9), 1 dose of 500 mg. A fourth group (D; n=9) received chloroquine only. Among patients who completed 2-6 months of follow-up (n=23), there was 1 relapse in group B (day 120) and 1 in group C (day 112). Among patients treated with chloroquine only, there were 4 relapses (days 40, 43, 49, and 84). WR 238605 was safe, well tolerated, and effective in preventing P. vivax relapse.

Adolescent↗
PubMed1999

Transmission of Mycobacterium ulcerans to the nine-banded armadillo.

Animal models for Mycobacterium ulcerans infections (Buruli ulcer) include guinea pigs, rats, and mice, but each has limitations in replicating the spectrum of human disease. Here, 19 adult nine-banded armadillos were inoculated intradermally with M. ulcerans. Injection sites were examined and skin samples obtained for histologic and microbiology studies. Necropsies were conducted to assess systemic involvement. In group 1 (n = 4), 2 animals developed progressive skin ulcers with undermined borders at the injection sites within 6-10 weeks. Biopsies showed features similar to human disease including extensive necrosis in the deep dermis and subcutaneous fat, mixed cellular infiltrates, and acid-fast bacilli (AFB). In group 2 (n = 15), 5 animals developed progressive skin ulcers, 3 had evanescent papulo-nodules, 3 died shortly after inoculation of unknown causes, and 4 showed no signs of infection. Lesion samples from 3 animals with progressive ulcers were culture positive for AFB. Our findings indicate that nine-banded armadillos are susceptible to M. ulcerans and may develop cutaneous lesions that closely mimic Buruli ulcer.

Animals↗
PubMed1999

Complicated malaria is associated with differential elevations in serum levels of interleukins 10, 12, and 15.

Complicated malaria, caused by Plasmodium falciparum, is characterized by multiple organ dysfunction. The pathogenesis of complicated malaria involves complex host-parasite interactions that include polarized cytokine responses. Recently, correlates between Th1-like and Th2-like cytokines, especially interleukin-10 (IL), IL-12, and TNF-alpha, and specific types of organ dysfunction have been noted. Here, we measured IL-10, IL-12, and for the first time, IL-15, in 19 patients aged 16-55 years old with complicated malaria on days 0 (admission), 3, 7, and 14. For analysis, patients were grouped together or sub-categorized into hyperparasitemias or cerebral malaria (CM). For IL-10, a dramatic increase was noted on admission, followed by a reduction toward control values that closely paralleled parasite clearance. For IL-12, modest but persistent increases were noted over the entire 14 day period that did not correlate with parasitemia. In general, especially on days 0 and 3, hyperparasitemic patients had, in comparison with CM patients, higher IL-10 and IL-12 levels. In contrast, IL-15 was generally below detection in most samples. These results provide further insight into the pathogenesis of complicated malaria by strengthening the contention that cytokines such as IL-10 and IL-12 are involved in modulating the immune response to P. falciparum.

Adolescent↗
PubMed1999

Cutaneous delayed-type hypersensitivity responsiveness in lepromatous and borderline lepromatous leprosy patients as determined by MULTITEST CMI.

To assess cell mediated immune (CMI) function in patients with lepromatous and borderline lepromatous leprosy (LL and BL), 35 patients were examined with the MULTITEST CMI system to evaluate cutaneous delayed-type hypersensitivity (DTH) responsiveness to 7 recall antigens. Reactions were assessed quantitatively and qualitatively. In addition, patients were classified as "responsive" (> or = 2 positive reactions), "hypo-responsive" (1 positive reaction), or anergic. Only hyporesponsive and anergic patients were re-tested. In 23 patients tested before treatment started (Group 1), 9 were responsive, 4 hypo-responsive, and 10 anergic. Upon re-testing, 10 of the 14 hyporesponsive-anergic subjects showed improvement. In 12 patients assessed after therapy initiation (Group 2), 9 were responsive and 3 others became responsive upon re-testing. Quantitative assessment indicated variable deficiencies in cutaneous DTH reactivity that, in many cases, improved with therapy. Correlations between reactivity and disease severity (LL versus BL) or duration of disease were not observed. The MULTITEST CMI system provided a convenient, safe, and reproducible method to assess cutaneous DTH responsiveness in LL and BL patients. Our findings indicated that most LL and BL patients are able to generate detectable but generally fewer and less robust cutaneous DTH responses to recall antigens, many improving with therapy. However, a semi-quantitative classification whereby patients that reacted to 2 or more antigens were considered "responsive" showed little difference between patients and controls. Overall, the data support the contention that deficits in cutaneous DTH responsiveness probably neither predispose nor necessarily accompany lepromatous disease, a practical consideration as efforts to develop a leprosy vaccine continue.

Adolescent↗
PubMed1998

Patterns of X chromosome inactivation in sporadic basal cell carcinomas: evidence for clonality.

BACKGROUND: Some basal cell carcinomas (BCCs) contain genetic mutations, suggesting that the lesion is composed of a monoclonal population of cells. Clonality, a distinguishing feature of neoplasia, can be inferred by referencing clonal markers such as the pattern of X chromosome inactivation. The X-linked human androgen receptor gene (HUMARA; GenBank) contains a polymorphic DNA marker that reliably illustrates the pattern of X chromosome inactivation in a tissue. OBJECTIVE: Our purpose was to determine the clonality of sporadic BCCs by examining patterns of X chromosome inactivation. METHODS: The patterns of X chromosome inactivation in paired samples of normal skin and sporadic BCCs from 24 women were compared by means of the HUMARA gene assay. RESULTS: All samples from normal skin displayed random X chromosome inactivation, consistent with lyonization. In 15 of 25 tumor samples (60%), nonrandom X chromosome inactivation was detected, consistent with monoclonality. CONCLUSION: At least some sporadic BCCs are composed of a monoclonal population of cells, strengthening the contention that a collection of mutations confers a growth advantage to this epithelial lesion.

Adult↗
PubMed1998

Pulmonary edema in cerebral malaria patients in Thailand.

Pulmonary edema is a serious complication of falciparum malaria that usually occurs in association with cerebral malaria, acute renal failure, high parasitemias, or delayed antimalarial treatment. From 1993 to 1996, 120 adult patients admitted to the intensive care unit of the Bangkok Hospital for Tropical Diseases were enrolled in a prospective study to assess the combination of artesunate and mefloquine for the treatment of cerebral malaria. Twenty-five patients (21%) presented with pulmonary edema and a majority developed complications in other organs as well, especially acute renal failure. In most patients (19 of 25), pulmonary edema was noted on the first day of admission and was associated with higher parasitemias and levels of acidemia, than in patients without pulmonary edema. Ten of the 25 patients diagnosed with pulmonary edema developed signs consistent with adult respiratory distress syndrome (ARDS). The mean central venous pressure when pulmonary edema was diagnosed was markedly lower in ARDS than in non-ARDS patients, supporting the argument that fluid imbalance is not essential for malaria-induced lung injury. Seven of 10 patients with ARDS died, 5 within 24 hours of admission, but there were no deaths in the 15 pulmonary edema patients without ARDS. Early diagnosis and prompt treatment remain important principles to reduce the morbidity and mortality associated with complicated falciparum malaria. This report emphasizes that ARDS, when concurrently occurs, is a poor prognostic clinical indicator in cerebral malaria.

APACHE↗