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Biomedical subjects

D Lambert

Publications and source records attributed to D Lambert.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Contact dermatitis to topical antiviral drugs].

BACKGROUND: Topical antiviral drugs are frequently used. Repeated applications on a skin injured by the viral infection can lead to irritating dermatitis or contact eczema. This secondary effect is often unrecognized because imputed to an increase of the initial dermatosis. CASES REPORTS: Case 1 - A 58 year-old woman had an eczema around the mouth after the use of Zovirax(R) cream (acyclovir). The patch test with this cream was positive (++ at 96 h) but the detail of all the constituents was negative. Case 2 - A 39 year-old woman had an eczema surrounding the mouth after each use of Zovirax(R) cream and Cuterpes(R) (ibacitabin). The patch tests were doubtful for Zovirax(R) cream, positive for Cuterpes(R) (++ at 96 h) and ibacitabin 1 p. 100 and 10 p. 100 in petrolatum (++ at 96 h). Case 3 - A 58 year-old man had an acute eczema of the face after the use of Zovirax(R) cream and Vira-MP(R) (vidarabin phosphate). The patch tests were positive for the both antiviral topical drugs but negative for each one of their constituents. DISCUSSION: Contact dermatitis to antiviral topical drugs are rare, due to active molecule or its excipients. The propyleneglycol, component found in the three antiviral drugs, can induce irritation or allergy. In the most of cases, like in our case number 1 and 3, the patch tests with each constituents of the topical drugs were negative, we conclude to a compound allergy.

Administration, Topical↗
PubMed1999

Structural basis for the guanosine requirement of the hairpin ribozyme.

To form a catalytically active complex, the essential nucleotides of the hairpin ribozyme, embedded within the internal loops of the two domains, must interact with one another. Little is known about the nature of these essential interdomain interactions. In the work presented here, we have used recent topographical constraints and other biochemical data in conjunction with molecular modeling (constraint-satisfaction program MC-SYM) to generate testable models of interdomain interactions. Visual analysis of the generated models has revealed a potential interdomain base pair between the conserved guanosine immediately downstream of the reactive phosphodiester (G(+1)) and C(25) within the large domain. We have tested this former model through activity assays, using all 16 combinations of bases at positions +1 and 25. When the standard ribozyme was used, catalytic activity was severely suppressed with substrates containing U(+1), C(+1), or A(+1). Similarly, mutations of the putative pairing partner (C(25) to A(25) or G(25)) reduce activity by several orders of magnitude. The U(25) substitution retains a significant level of activity, consistent with the possible formation of a G.U wobble pair. Strikingly, when combinations of Watson-Crick (or wobble) base pairs were introduced in these positions, catalytic activity was restored, strongly suggesting the existence of the proposed interaction. These results provide a structural basis for the guanosine requirement of this ribozyme and indicate that the hairpin ribozyme can now be engineered to cleave a wider range of RNA sequences.

Base Pairing↗
PubMed1999

European multicenter study on propionyl-L-carnitine in intermittent claudication.

OBJECTIVES: This study was performed to identify a target population of claudicants for propionyl-L-carnitine treatment. BACKGROUND: Previous studies suggest that the efficacy of propionyl-L-carnitine in intermittent claudication is greater in patients with severe functional impairment than in those with mild walking disability. METHODS: After run-in, 485 claudicant patients were randomized to placebo or propionyl-L-carnitine (1 g bid, p.o.) and then stratified on the basis of maximal walking distance (cutoff point 250 m) and maximal walking distance variability (cutoff point 25%). Treatment lasted 12 months. Walking capacity was assessed by treadmill and quality of life by a questionnaire exploring various aspects of daily life. RESULTS: In the target population, that is, patients who at baseline walked < or = 250 m and showed a maximal walking distance variability < or = 25%, per-protocol analysis showed that the effect of propinyl-L-carnitine was significantly greater than that with placebo for both maximal walking distance and initial claudication distance (ICD). In the intention-to-treat population, maximal walking distance increased by 62 +/- 14% on propionyl-L-carnitine and by 46 +/- 9% (p < 0.05) on placebo, while no difference between treatments was observed for ICD. The beneficial effect of propionyl-L-carnitine was confirmed when data of the target population were pooled with those of patients who at baseline walked < or = 250 m and showed a > 25% maximal walking distance < 50% variability. Actually, maximal walking distance increased by 98 +/- 16% in the propionyl-L-carnitine group and by only 54 +/- 10% in the placebo group (p < 0.01). The corresponding values for ICD were 99 +/- 21% and 51 +/- 8% (p < 0.05). For patients with baseline maximal walking distance > 250 m, no difference between treatments was observed. CONCLUSIONS: Claudicants with maximal walking distance < or = 250 m benefited from the use of propionyl-L-carnitine, with improvement in walking distance and quality of life. However, patients with mild functional impairment (i.e., walking distance > 250 m) showed no response to propionyl-L-carnitine.

Cardiotonic Agents↗
PubMed1999

Leg ulcers and hydroxyurea: forty-one cases.

BACKGROUND: Hydroxyurea is an antitumor agent used to treat chronic myeloproliferative disorders. Leg ulcerations have been reported in patients undergoing long-term hydroxyurea therapy for myeloproliferative diseases. To better define this dermatological adverse effect of hydroxyurea therapy and to try to understand the pathophysiological process of this disease, we collected medical information for such patients in a multicenter retrospective study. OBSERVATIONS: Forty-one patients (mean age, 67 years) developed leg ulcerations while undergoing hydroxyurea therapy (mean therapy duration, 5 years). The sex ratio was 1, and there was no underlying vascular disease. Hematologic abnormalities were identified. Complete recovery from the ulcerations occurred quickly after withdrawal of treatment in 33 (80%) of the cases. CONCLUSIONS: This longest-reported series of patients confirms the role of hydroxyurea therapy in the onset of leg ulcerations. Healing or improvement requires cessation of treatment. Cutaneous atrophy and impaired wound healing may explain the relationship between hydroxyurea and leg ulcers. In addition, the megaloblastic erythrocytes resulting from the presence of hydroxyurea may circulate poorly through the capillary network. A prospective study in hematologic centers would be valuable.

Adult↗
PubMed1999

Essential Tremor.

Multiple pharmacologic treatments have been studied, but propranolol and primidone have proven to be the most effective medications. It is unlikely that a patient will respond miraculously to another medication if his or her response to propranolol and primidone is minimal. Some subsets of essential tremor, however, such as the kinetic predominant type, may respond better to other medications. Mildly affected patients may not need treatment at all, and the potential benefits must always be weighed against the possible side effects. The main benefit of botulinum toxin injection is for head tremor, whereas its efficacy in hand tremor is variable. If a patient does not respond to adequate doses of propranolol or primidone, deep brain stimulation should be considered because it carries the lowest risk of the available surgical procedures; usually, it should be given preference over thalamotomy. It is important for the physician to realize the multitude of symptomatic treatments available. Beyond the conventional and often effective oral medications, use of newer treatments such as botulinum toxin, thalamotomy, and deep brain stimulation can often reduce tremor and lead to a greater quality of life for patients with ET.

Journal Article↗
PubMed1999

Comparison of two methods for the measurement of rat liver methylmalonyl-coenzyme A mutase activity: HPLC and radioisotopic assays.

Methylmalonyl-coenzyme A mutase (MCM) is a 5'-deoxyadenosylcobalamin-linked mitochondrial enzyme that catalyzes the isomerization of L-methylmalonyl-coenzyme A to succinyl-coenzyme A. In vitro assays of total and holo-MCM activities are important tools for investigating the cobalamin pathway. Several methods have been described for measuring MCM activity. The most commonly-used method is a radioassay based on the permanganate oxidation of DL[CH(3)-(14)C]methylmalonyl-coenzyme A, but radiometric methods are insensitive, laborious, and time-consuming. Therefore, we have compared this method with a nonradiometric assay, potentially most sensitive, based on the separation of methylmalonyl-coenzyme A and succinyl-coenzyme A by high performance liquid chromatography (HPLC). We determined the optimal assay conditions and the reproducibility and sensitivity of each technique. The results obtained by the two techniques were very different: the specific activities obtained by the permanganate oxidation method (0.039 +/- 0.013 nmol/min/mg protein for the holo-MCM activity and 1.90 +/- 0.69 nmol/min/mg protein for the total-MCM activity) were threefold lower than those obtained with the HPLC method (0.124 +/- 0.011 nmol/min/mg protein for the holo-MCM activity and 6.15 +/- 0.76 nmol/min/mg protein for the total-MCM activity). The coefficients of variation for the radiometric method (18.4-40.6%) were three to five times greater than those for the HPLC assay (3.5-12.2%). This demonstrates the lack of sensibility and reproducibility of the permanganate radioassay. Thus, the radiometric method is not suitable for measuring low mutase activities such as the holo activities in tissues. The intrinsic inconvenience of the radiometric assay indicates that the HPLC method is a method of choice for measuring MCM activity.

Journal Article↗
PubMed1999

Increased cell surface exposure of phosphatidylserine on propidium iodide negative thymocytes undergoing death by necrosis.

Phosphatidylserine (PS) exposure on propidium iodide negative cells using FITC labelled annexin-V has been used to quantify apoptosis in vitro and in vivo. Detection of PS within cells undergoing necrosis is also possible if labelled annexin-V specific for PS enters the cell following early membrane damage. Necrotic or late apoptotic cells can be excluded from flow cytometric analysis using propidium iodide which enters and stains cells with compromised membrane integrity. Here we show that thymocytes undergoing death exclusively by necrosis show early exposure of PS prior to loss of membrane integrity. This early exposure of PS occurs in cells treated with agents which both raise intracellular calcium levels and are also capable of interacting with protein thiol groups. We also demonstrate that PS exposure in thymocytes induced to undergo apoptosis by three different agents does not correlate with calcium rises but correlates with and precedes DNA fragmentation.

Animals↗
PubMed1999

CD4+ CD56+ cutaneous neoplasms: a distinct hematological entity? Groupe Français d'Etude des Lymphomes Cutanés (GFELC).

We report seven cases of particular cutaneous tumors selected from the register of the French Study Group on Cutaneous Lymphomas. The patients (three men, four women) were aged 37-86 years. They initially presented with cutaneous nodules or papules. Three cases presented with regional lymph nodes. Stagings were negative, except for one patient with bone marrow involvement. Histological features were relevant with pleomorphic medium T-cell lymphoma, but these cells exhibited a distinguishing phenotype. They were positive for CD4, CD56, and also CD45, CD43, and HLA-DR. All other T-cell and B-cell markers were negative. The myelomonocytic markers (CD13, CD14, CD15, CD33, CD117, myeloperoxidase, and lysozyme) were negative excepted CD68, which was clearly positive in four cases and weakly in two cases. Others natural killer cell markers (CD16, CD57, TiA1, granzyme B), TdT, and CD34 were negative. Polymerase chain reaction studies did not detect any B or T clonal rearrangement. The cytogenetic studies, performed in five cases, showed a del(5q) in two cases. All patients were treated successfully by polychemotherapy, but relapsed quickly in the skin, between 4 and 28 months. Five patients developed bone marrow involvement, with leukemia in three cases, and they died in 5-27 months. One patient died at 17 months with skin progression. The seventh patient is alive at 33 months, with cutaneous progression. The origin of these cells is unclear. Despite expression of CD4 or CD56, we failed to demonstrate a T-cell, natural killer cell origin. However, CD4 and CD56 are not specific for T or natural killer lineages. Although these two markers are also known to be expressed by monocytic cells, classic myeloid antigens were negative. These seven cases, together with other rare similar cases already reported, seem to represent a distinct entity likely developed from hematological precursor cells.

Adult↗
PubMed1999

Service use of rural and urban Medicaid beneficiaries suffering from depression: the role of supply.

Despite the prevalence and consequence of depression in rural areas, the literature on treating depression in rural areas is relatively scarce and inconclusive. The use of mental health services by rural people suffering from depression and the role that supply may play in explaining these differences are not well understood. Understanding these issues for rural Medicaid beneficiaries is important as Medicaid managed carefor physical and behavioral health care is expanded to rural areas. This study compares the mental health service use of rural and urban Medicaid beneficiaries, ages 18 to 64, in Maine suffering from depression and examines what influence mental health and primary care supply have in explaining observed differences. Two models are used to estimate the use of ambulatory mental health services: (1) a logit likelihood estimate of whether a beneficiary uses any outpatient mental health services for depression; (2) an ordinary least squares regression estimating the number of annualized ambulatory mental health care visits among users. Rural beneficiaries suffering from depression have lower utilization than urban beneficiaries. Rural and urban Aid for Families with Dependent Children (AFDC)--and Supplemental Security Income (SSI)--beneficiaries suffering from depression rely more on mental health than on general health care providers to receive ambulatory mental health care. Rural beneficiaries (AFDC and SSI) rely relatively more on general health care providers than urban beneficiaries. Multivariate analysis suggests that mental health supply and patient-level factors, but not primary care supply, account for utilization differences. This article describes the need to better understand factors limiting participation of primary care providers and to study the role of supply across multiple states.

Adult↗
PubMed1999

Infections and melanoma risk: results of a multicentre EORTC case-control study. European Organization for Research and Treatment of Cancer.

Immune function plays a prominent role in the defence against cutaneous malignant melanoma and the increased risk of melanoma development during immunosuppression. Since the immune system is challenged beyond its routine activity by an infection, the effect of previous infectious diseases on the risk of melanoma may also be crucial. In a European Organization for Research and Treatment of Cancer (EORTC) case-control study performed in six European countries and Israel, we compared the history of severe infections in 603 melanoma patients with that in 627 population controls. We calculated adjusted odds ratios (ORs) to estimate the effect of infectious diseases on melanoma risk. The ORs for melanoma risk were below 1 for nearly all types of infections (except two) if body temperature was not taken into consideration, and for all infections with a body temperature above 38.5 degrees C. In the latter category significantly lowered ORs were found for pulmonary tuberculosis (0.16; 95% confidence interval [CI] 0.01-0.98), Staphylococcus aureus infections (0.54; 95% CI 0.31-0.94), sepsis (0.23; 95% CI 0.06-0.70), influenza and related infections (0.65; 95% CI 0.48-0.86) and pneumonia (0.45; 95% CI 0.27-0.73). Analysis of the cumulative influence revealed a consistent pattern of results pointing to a reduction in melanoma risk with increasing numbers of recorded infections and fever height. This apparent dose-response relationship suggests a causal association. Speculations on the underlying mechanism include a Shwartzman-like phenomenon when melanoma formation precedes the infection and/or an infection-related Th1-cell activation preventing the establishment of the tumour.

Adult↗
PubMed1999

[Distal cutaneous necrosis, an unusual etiology: hyperhomocysteinemia].

INTRODUCTION: Homocysteine is a sulfur amino acid occurring in methionine intermediary metabolism. It was recently shown to be a vascular risk factor even without high serum levels. CASE REPORT: A 29-year-old woman had painful plantar nodules and necrosis of the fifth toe on the right foot with cyanosis of the forefoot. The histology examination of a nodule biopsy gave the diagnosis of subcutaneous thrombophlebitis. Vascular explorations disclosed advanced-stage arteriopathy of the leg. The methionine loading test was abnormal and search for the heterozygous form of cystathionine ss was positive. DISCUSSION: Different diagnoses could be possible for cases associating an inflammatory venous disease and stage IV arteritis. Latent hyperhomocysteinemia was diagnosed in this case on the basis of the methionine loading test and identification of the heterozygous form of cystathionine ss. Patients with latent hyperhomocysteinemia have an increased risk of both thrombosis and arteritis. Our case emphasizes the importance of searching for hyperhomocysteinemia in patients with early arterial and/or venous thromboembolism, either as repeated episodes or occurring in an unusual territory.

Adult↗
PubMed1998

Anticonvulsant activity and interactions with neuronal voltage-dependent sodium channel of analogues of ameltolide.

Fifteen compounds related to ameltolide (LY 201116) were studied for (i) anticonvulsant potential in the maximal electroshock-induced seizures (MES) and the subcutaneous pentylenetetrazol (sc Ptz) tests in mice and rats and (ii) interactions with neuronal voltage-dependent sodium channels. Compounds were chosen ranging in anticonvulsant activity in mice from very active to inactive. The active compounds were defined as those protecting 50% of the animals at doses between 10 and 50 micromol/kg and inactive compounds as those protecting 50% of the animals at doses greater than 1 mmol/kg. The series studied included three N-(2,6-dimethylphenyl)benzamides (compounds 1, 2 (ameltolide), and 3), three N-(2,2,6, 6-tetramethyl)piperidinyl-4-benzamides (compounds 4, 5, 6), one phenylthiourea (compound 7), five N-(2,6-dimethylphenyl)phthalimides (compounds 8, 9, 10, 13, and 14), two N-phenylphthalimide derivatives (compounds 11 and 12), and one N-(2,2,6, 6-tetramethyl)piperidinyl-4-phthalimide (compound 15). Phenytoin (PHT) was employed as the reference prototype antiepileptic drug. After inital screening in mice, compounds 1, 2, 3, 5, 8, 9, 10, 13, and 14 were selected for further testing in rats. Anticonvulsant ED50s (effective doses in at least 50% of animals tested) of compounds in the MES test were determined in rats dosed orally and amounted to 52 (1), 135 (2), 284 (3), 231 (8), 131 (9), 25 (10), 369 (13), 354 (14), and 121 (PHT) micromol/kg, compound 5 presenting with an ED50 value higher than 650 micromol/kg. In our hands, the apparent IC50s (inhibitory concentrations 50) of compounds toward binding to rat brain synaptosomes of [3H]batrachotoxinin-A-20alpha-benzoate were 0.25 (1), 0.97 (2), 0.35 (3), 25.8 (5), 161.3 (8), 183.5 (9), 0.11 (10), 1.86 (13), 47.8 (14), and 0.86 (PHT) microM. The relationship between the activity in the MES test and the capacity to interact in vitro with neuronal voltage-dependent sodium channels and the fact that the IC50 values obtained in the in vitro test are close to the brain concentrations at which anticonvulsant activities are reported to occur for ameltolide strongly suggest that the anticonvulsant properties of most compounds tested could be a direct result of their interaction with the neuronal voltage-dependent sodium channel.

Administration, Oral↗
PubMed1998

Design, synthesis, and anticonvulsant activity of 1-(pyrid-3-ylsulfonamido)-2-nitroethylenes.

The lipophilic 1-cycloalkylamino-1-(pyrid-3-yl-sulfonamido)-2-nitr oethylenes were synthesized as bioisosteres of BM-34, an anticonvulsant sulfonylthiourea. Compound 17 (ip) emerged from the maximal electroshock seizure (MES) test with a 50% effective dose (ED50) of 8.25 mg/kg. Its anticonvulsant profile was similar to that of phenytoin (ED50 = 9.51 mg/kg) and of BM-34 (ED50 = 1.19 mg/kg): active in the MES test and inactive in seizures induced by subcutaneous injection of pentetrazole, strychnine, bicuculline, picrotoxin, or N-methyl-D,L-aspartate. The neurotoxicity of 17 (TD50 = 113.8 mg/kg) was lower than that of phenytoin (TD50 = 65.5 mg/kg) but higher than that of BM-34 (TD50 = 147.2 mg/kg). Crystallographic study revealed that BM-401 (17) was a zwitterionic structure. Its sulfonamido nitroethylene side chain adopted a conformation which placed the two cycloalkyl rings face to face to form a single hydrophobic area.

Animals↗
PubMed1998

[Dyshidrosis].

Dyshidrosis is a vesicular, non inflammatory and recurrent disease of the palms and soles related to eczema. Sometimes hyperhidrosis can induce inflammatory reactions. The diagnosis becomes obvious when a period of ferocious pruritus, vesicle develop on the sides of the fingers and the palms. These vesicles are imbedded in the epidermis below the thick stratum corneum. They are strongly distended and painful when they grow in size. They dry up and disappear within three weeks. Relapses are frequent in patients with a topy, sweat gland disorders or neurovegetative disturbances. Several clinical aspects are observed: bullous dyshidrosis, superinfection, psoriasiform keratodermia. Dyshidrosis in infectious, fungal or allergic origin can be cured by suppressing the causative agent, but complex or idiopathic lesions follow their own course and persist.

Eczema, Dyshidrotic↗
PubMed1998

Fibroblast growth factors and their receptors in parathyroid disease.

Fibroblast growth factors (FGFs) comprise a family of polypeptide growth factors implicated in the control of proliferation of glandular tissues. The aim of this study was to determine whether FGFs are produced in normal and abnormal parathyroid glands and if these tissues have the potential to respond to this growth factor family. We have examined the expression of FGF receptor (FGF-R) types 1 and 2 and of FGFs 1, 2, 3, and 7 in a series of human parathyroid tissues using the reverse transcription polymerase chain reaction (RT-PCR). Samples of 10 parathyroid adenomas and 10 hyperplastic glands from patients with renal hyperparathyroidism (HPT) were compared with samples from normal parathyroid glands from patients with primary HPT in the study. FGF-R1 was expressed in all samples and FGF-R2 in most. FGF1 and FGF2 were expressed in all samples at variable levels, with no correlation between disease type and amplified RT-PCR product levels. FGF7 was expressed in normal parathyroid tissue and in all adenomas but was absent in all but one of the hyperplastic parathyroid glands from renal failure patients. FGF3 was expressed at low levels in normal tissue and variably expressed in diseased tissue, in some instances at high levels. These findings suggest that parathyroid tissue is potentially responsive to FGFs. The absence of FGF7 expression in all but one of the renal parathyroid samples compared with normal and adenomatous tissue requires further investigation. The presence of elevated levels of FGF3 expression in abnormal parathyroid tissue may be significant, as the FGF3 gene (int-2 proto-oncogene) is located on chromosome 11q13.3, a region already identified as being susceptible to rearrangement/mutation in parathyroid disease.

Adenoma↗
PubMed1998

[Eosinophilic ascites and urticaria].

INTRODUCTION: The finding of eosinophilic ascites is unusual. It requires the search for the main etiology, i.e., parasitic or malignant disease, vasculitis or hypereosinophilic syndrome. The diagnosis of exclusion is either mucosal, muscular or serous eosinophilic gastroenteritis. This last type, the most unusual--as less than 50 cases have been documented until now--is associated with eosinophilic ascites. EXEGESIS: We report a new case of serous eosinophilic gastroenteritis that occurred in a 23-year-old woman. This case was unusual because of its clinical history, as abdominal pain fits (along with the occurrence of ascites) were associated with urticaria fits. The lack of eosinophils in both the blood counts and the various digestive biopsies were unusual too. The disease evolution was favorable with corticosteroid therapy; however, a minimal dose of 8 mg/day was necessary to control the disease symptoms. CONCLUSION: Because of its association with urticaria fits, this case emphasizes the need for differential diagnosis in patients with hypereosinophilic syndrome and food allergy.

Abdominal Pain↗
PubMed1998

Rural models for integrating primary care and mental health services.

This paper presents findings from a study designed to identify and describe models for integrating primary care and mental health services in rural communities. Data were obtained from telephone interviews with staff at rural primary care sites around the country. Findings are based on the responses of 53 primary care organizations in 22 states. The authors identify four integration models--diversification, linkage, referral and enhancement--which appear to exist in combination, rather than as pure types. The proposed analytic framework outlines aspects of integration that are readily amenable to study.

Attitude of Health Personnel↗