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Biomedical subjects

M David

Publications and source records attributed to M David.

At least 163 records · Page 9Linked to original sources

Cutaneous ulceration: an unusual sign of methotrexate toxicity--first report in a patient without psoriasis.

OBJECTIVE: To describe a case of skin ulcer related to methotrexate toxicity. CASE SUMMARY: A 67-year-old white man with seronegative arthralgia developed recurrent skin ulcer concurrent with 3-year treatment with methotrexate 5 mg daily. The skin ulcer resolved on discontinuation of methotrexate. DISCUSSION: To the best of our knowledge, this is the first reported case of skin ulcer believed to be induced by methotrexate in a patient without psoriasis. CONCLUSIONS: Skin ulceration should be added to the list of possible toxic adverse effects of methotrexate, not only in psoriatic patients but also in those without psoriasis.

Aged↗

Soft-tissue hemangiomas in infants and children: diagnosis using Doppler sonography.

OBJECTIVE: We describe the sonographic appearance and vascularization of hemangiomas and determine if vessel density and peak systolic Doppler shifts distinguish hemangiomas from other superficial soft-tissue masses. SUBJECTS AND METHODS: Our pilot study included 20 infants and children with hemangiomas who were to undergo biopsy before treatment with interferon alpha-2b. We used Doppler sonography to determine the number of vessels per square centimeter, peak arterial Doppler shift, resistive index, and signs of arteriovenous shunting. All hemangiomas showed high vessel density (more than five per square centimeter) and high Doppler shifts (more than 2 kHz), and these two factors became our diagnostic criteria. A prospective study of 116 patients was then carried out. One hundred sixteen consecutive pediatric patients with superficial soft-tissue masses were examined using Doppler sonography; sonographic findings were compared with the final diagnoses that were established by biopsy, CT, or clinical follow-up. RESULTS: The final diagnoses included 70 hemangiomas, 20 venous malformations, three arteriovenous malformations, three arteriolocapillary malformations, and 20 other masses. Fifty-nine lesions showing high vessel density (more than five per square centimeter) and a peak arterial Doppler shift exceeding 2 kHz were correctly diagnosed as hemangiomas (sensitivity, 84%; specificity, 98%). One arteriovenous malformation showed high vessel density and high Doppler shifts, but none of the other masses that were not hemangiomas did. Eleven patients with hemangiomas who were being treated with interferon at the time of the study fulfilled only one of the two diagnostic criteria. CONCLUSION: High vessel density and high peak arterial Doppler shift can be used to distinguish hemangiomas from other soft-tissue masses.

Arteriovenous Malformations↗

The prevalence of cutaneous manifestations in IDDM patients and their association with diabetes risk factors and microvascular complications.

OBJECTIVE: The aim of our study was to evaluate the frequency of skin manifestations, including the diabetic hand syndrome, in young IDDM patients. In addition, we studied the relation of the cutaneous manifestations to diabetes duration, glycemic control, and microvascular complications. RESEARCH DESIGN AND METHODS: The frequency of skin manifestations, including the diabetic hand syndrome, were examined in 238 IDDM patients (disease duration > 5 years) and 122 healthy control subjects in a cross-sectional study. In addition, we studied the relation of the cutaneous manifestations with diabetes duration, glycemic control, BMI, microvascular complications, and stratum corneum hydration using a stepwise logistic regression. RESULTS: Diabetic skin manifestations were detected in 168 of 238 (71%) IDDM patients and in 18 of 122 (14%) of the control subjects. Ichthyosiform skin changes of the shins, scleroderma-like skin changes, tinea pedis, and dry scaly palms were detected in 48 vs. 7%, 39 vs. 0%, 32 vs. 7%, and 21 vs. 0.8% of the patients and control subjects, respectively. In the diabetic patients, a significant association was found between ichthyosis of the shins and scleroderma-like skin changes of the hand (P < 0.001) and between scleroderma-like skin changes and the skin dryness of the palms (P < 0.0001). When diabetic risk factors were considered, diabetes duration was significantly associated with scleroderma-like skin changes and ichthyosis of the shins (P < 0.0001). The latter was also found to be related to diabetic retinopathy (P < 0.0001). Keratosis pilaris was present in 21% of the patients versus 9% in control subjects and was found to be exclusively associated with high BMI. CONCLUSIONS: Acquired ichthyosis is a common finding and the most prevalent skin manifestation in young IDDM patients. The development of several skin manifestations in insulin-dependent patients seems to be related to duration of diabetes and to development of diabetic microvascular complications.

Adolescent↗

[Tocolysis with a nitroglycerin patch].

We would like to present a 22 year old nullipara where preterm labor was successfully tocolysed using a nitro-glycerine path without sequellae side effects. Potential advantages and disadvantages of a transdermal nitro-glycerine delivery system in comparison to the commonly used intravenous fenoterol tocolysis is discussed.

Administration, Cutaneous↗

Intermediate follow up of the TEKNA bileaflet valve.

BACKGROUND AND AIM OF THE STUDY: The study aim was to collect intermediate clinical data on the TEKNA bileaflet valve. METHODS: This nine-center clinical study involved 884 patients implanted between June 1990 and October 1993. The population consisted of 522 (59.0%) males and 362 (41.0%) females. Mean age at implant was 59.1 +/- 11.8 years (range: 14.7 to 88.4 years). Indication for valve replacement was dependent on the position: stenosis was the predominant reason in the aortic position; regurgitation was more pronounced for the mitral position. A total of 261 (29.5%) patients underwent concomitant procedures. Mean follow up is 2.7 +/- 1.2 years; total follow up is 2386.1 patient-years (pt-yr). RESULTS: Total operative (< or = 30 days postoperative) mortality rate was 3.7%; seven patients (0.8%) died due to valve-related causes. Total postoperative (> 30 days postoperative) mortality rate was 2.5%/pt-yr and included a valve-related mortality rate of 1.1%/pt-yr. The following valve-related complication rates (%/pt-yr) were reported for the long-term postoperative period: thromboembolism 0.6; valve thrombosis 0.3; bleeding events 1.5; non-structural deterioration 0.6; and endocarditis 0.4. No structural valve deterioration was reported. Actuarial freedom at four years was: overall survival rate 86.9 +/- 1.4%; valve-related survival rate 94.7 +/- 1.0%; freedom from thromboembolism 96.8 +/- 0.9%; valve thrombosis 99.3 +/- 0.3%; endocarditis 98.5 +/- 0.5%; bleeding events 94.3 +/- 1.0%; and non-structural deterioration 98.2 +/- 0.6%. CONCLUSIONS: The data indicate that observed mortality is due mainly to non-valve-related disorders. Risk of thromboembolic and bleeding events was low (0.9%/pt-yr and 1.5%/pt-yr, respectively). We conclude that this valve is safe and efficacious for use.

Actuarial Analysis↗

[The prognosis of surgery on the elderly. Proposal for a parametric evaluation].

BACKGROUND AND AIMS: To data there are no preoperative systems of evaluating surgical risk specifically in geriatric patients. Given that it was thought useful to formulate a score-based prognostic system for these patients based on surgical risk, the authors collected a wide range of preoperative data with the aim of identifying the easily determined variables. METHODS: While data from other hospital centres are in the process of being collected, the authors report the data for 122 over 65-year-old patients who underwent elective surgery up until 30-1-1996 out of a total of 329 hospitalized patients. In addition to a wide series of objective, laboratory and instrumental data, the study also took into account the pathology requiring to surgery, any associated morbid conditions, psychic and social conditions, the type of surgery and local and/or general postoperative complications. RESULTS: Hernia of the abdominal wall were found to be the most frequent cause of surgery (41 cases), followed by 27 neoplasias of various organs and biliary lithiasis (20 cases). Cardiovascular diseases were the most common associated pathologies (85 patients). A total of 13 major and 80 medium operations were performed, including 16 cholecystectomies. Among the general complications, an altered acid-base balance was found in 7 patients. Two deaths were recorded within 30 days of surgery. When the data collection is complete, the results will be analysed statistically in order to obtain a numerical calculation of the coefficients of risk correlated to the individual variables. CONCLUSIONS: This will enable the criteria of operability to be broadened, thereby allowing surgery to be performed in those patients who are currently excluded merely on the basis of the personal judgement of the surgeon and anesthetist.

Aged↗

[Long-term follow-up of anatomic heart transplantation. Apropos of 60 patients with a mean follow-up of 36 months].

The aim of this study was to collect different problems seen in long-term evolution of patients who had anatomical cardiac transplantation and to compare with those seen in patients with standard transplantation. During the mean follow-up of 36 months, we analysed different data of 60 patients mean aged 51, who underwent anatomical cardiac transplantation. Six patients (10%) died within the 30 days after surgery. No patient needed the use of permanent pacemaker. Echocardiographic examination found normal atrial shape. One month after surgery, echocardiography described 16 tricuspid regurgitations (22.66%) and 8 mitral regurgitations (13.33%), 1 year later, there was respectively 13.33 and 6.66% tricuspid and mitral regurgitation. We had 8 late deaths: 1 sudden death, 2 chronic rejections, 1 pancreatitis and 4 cancers. The survival analysis pointed out 84% at 1 year, 80 at 2 years, 78 at 3 years and 73 at 5 years. Six months after surgery, 80% of patients were treated for high blood pressure; 85% had serum creatinine level equal or superior to 13 mg/L, with mean serum ciclosporin at 130 ng/mL. At the 3rd month, 6 endomyocardial biopsies were equal or superior to grade 2 rejection (International Society for Heart Transplantation). Between the 3rd and 12th month, 3 endomyocardial biopsies were equal or superior to grade 2 rejection, and the same between the 12th and 24th month. The infections rate was 0.8 episode per patient. Long term follow-up of anatomical cardiac transplantation faces the same problems as in standard cardiac transplantation. It is better to perform anatomical cardiac transplantation because of its early postsurgical advantages. Long term care is the same as in standard cardiac transplantation.

Actuarial Analysis↗

Pregnancies following liver transplantation--how safe are they? A report of 19 cases under cyclosporine A and tacrolimus.

The number of pregnancies following liver transplantation is increasing due to better patient and graft survival and quality of life. Out of 156 women of a reproductive age, there were 19 pregnancies in 16 women, 12 on CsA and seven on tacrolimus, which occurred between 7/92 and 1/97. The median age of the women was 27.9 yr, median time after transplantation 33 months. There were four spontaneous and two induced abortions in the first trimenon. Ten women delivered ten healthy babies; three newborns had problems (alcoholic embryopathy due to recurrent alcohol abuse of his mother, pneumonia, weight < 2000 g). In eight women mostly mild complications were observed, such as hypertension (n = 5), nonspecific elevation of liver enzymes (n = 2), infection (n = 3) and premature labor (n = 1). Mean gestational age was 39 wk and mean birth weight 2900 g. One case of prematurity and three cases of growth retardation occurred. Cesarean sections were performed in 7 patients (54%) for maternal hypertension (n = 2), presumed fetal hypoxia (n = 4) and breech position (n = 1). All children are normally developed, the oldest being 5 yr old. Although experience with tacrolimus is limited, pregnancies following liver transplantation carry an acceptable risk if carefully monitored by an experienced team of transplant surgeons and obstetricians.

Adult↗

Engrafted human T and B lymphocytes form mixed follicles in lymphoid organs of human/mouse and human/rat radiation chimera.

BACKGROUND: We recently described a new approach that enables the generation of human/mouse chimera by adoptive transfer of human peripheral blood mononuclear cells into lethally irradiated normal strains of mice or rats, radioprotected with bone marrow from donors with severe combined immune deficiency. In such human/mouse chimera, a marked humoral response to recall antigens, as well as a significant primary response to keyhole limpet hemocyanin, has been generated. METHODS: In the present study, the organ distribution of the engrafted human cells in the human/mouse and human/rat chimera was investigated by immunohistochemistry. RESULTS: Our results show that the T cells seem to be distributed throughout the reticular endothelial system, almost behaving like particles without any homing specificity. The B cells, however, can barely be found in internal organs, such as the liver or the pancreas, and are concentrated in the secondary lymphoid system (e.g., spleen, lymph node, and nonencapsulated lymphoid tissue). The B cells, together with the engrafted human T cells, form mixed lymphoid follicles. CONCLUSIONS: The different homing patterns exhibited by the T and B lymphocytes indicate that the homing receptors on human B cells might be cross-reactive with their mouse counterparts, in contrast to the human T cells, which seem to be unable to interact with the mouse homing receptors. The presence of human B and T lymphocytes in close proximity to each other in the lymphoid tissues is in accordance with the ability of human/BALB radiation chimera to mount significant primary human antibody responses.

Adoptive Transfer↗

A model for human B-chronic lymphocytic leukemia in human/mouse radiation chimera: evidence for tumor-mediated suppression of antibody production in low-stage disease.

B-chronic lymphocytic leukemia (BCLL) is a lymphoproliferative disease that is characterized by clonal expansion of CD5+ B cells. BCLL is associated with secondary immunodeficiency and hypogammaglobulinemia. It has been suggested that T-cell dysregulation may play a role in the hypogammaglobulinemia and in the increased incidence of autoimmunity in BCLL patients. We attempted to transfer human peripheral blood mononuclear cells (PBMC) from BCLL patients in different stages of the disease into immunodeficient mice. PBMC from BCLL patients in stage 0, stages I to II, and stages III to IV were transplanted into the peritoneal cavity of lethally irradiated Balb/c or beige/nude/Xid (BNX) mice radioprotected with bone marrow (BM) from severe combined immunodeficiency (SCID) mice. Different engraftment profiles were found in the chimeric mice 2 weeks after transplantation of PBMC according to the disease stage of the BCLL donors. Infusion of PBMC from donors in stage 0 led to marked engraftment of human T cells, whereas the human tumor cells could hardly be detected. In contrast, chimeric mice receiving PBMC from patients in stage III to IV disease exhibited engraftment with a dominance of tumor cells, compared with a miniscule level of T cells. The ability of the engrafted cells to produce human Ig was also found to be correlated with the disease stage of the donor, although all donors had the same magnitude of hypogammaglobulinemia. Total human Ig production in the chimeric mice was normal in mice receiving PBMC from donors in stage 0, whereas in chimeric mice engrafted with PBMC from donors in stages III to IV almost no human Igs could be detected. This differential reconstitution of antibody production in the mouse model according to the stage of the patient's disease will allow further studies on possible cellular interactions between malignant and immune cells in BCLL.

Adoptive Transfer↗

A thyroxine dosage of 8 micrograms/kg per day is appropriate for the initial treatment of the majority of infants with congenital hypothyroidism.

UNLABELLED: The adequate L-thyroxine dosage for the initial treatment of infants with congenital hypothyroidism is a subject of controversy. Some recommend higher dosages (> 10 micrograms/kg/day) to ensure adequate levels, while others advocate lower dosages to permit normalisation of thyroid status. The aim of this study was to evaluate the results of a treatment strategy using an initial dosage of 7.5-8.0 micrograms/kg per day, TSH measurements being taken at 15 and 30 days of treatment. Fifty one newborns infants with primary congenital hypothyroidism detected by neonatal screening were treated with the same therapeutic strategy. A mean L-thyroxine dosage of 7.9 micrograms/kg per day at the onset of treatment and 6.6 micrograms/kg/d at 2 months, normalised the FT4 and FT3 levels at 15 days in 100% and TSH levels at 2 months in 90% of cases. Many patients showed elevated levels of FT4 and a systematic higher initial dosage could expose many infants to a dangerous hyperthyroidism. Patients with abnormal TSH levels at 2 months already had higher TSH levels in the first 8 weeks of life and, despite higher L-thyroxine dosage, also exhibited lower FT4 and FT3 levels. These patients who needed an early increase in dosage had already shown a more profound ante and neonatal hypothyroidism. This subgroup of patients require a higher dosage of thyroxine and early assessment of FT4, FT3 and TSH levels are required for optimum dosage choice. CONCLUSION: Even though a subgroup of patients may require a higher dosage of L-thyroxine, an initial dosage of 7.5-8.0 micrograms/kg per day, with an early assessment of FT4, FT3, and TSH levels, is adequate for the treatment of the majority of infants with congenital hypothyroidism.

Congenital Hypothyroidism↗

Juvenile granulosa cell tumor of the ovary in infants: a clinicopathologic study of three cases and review of the literature.

The clinical and pathological features of three cases of juvenile granulosa cell tumors occurring in infants were studied. Precocious pseudopuberty developed in two patients and acute abdominal symptoms related to the rupture of the tumor developed in one. Surgery was the only treatment in each case and no adjuvant therapy was delivered. No patient experienced relapse. Histological examination showed a predominantly diffuse pattern with prominent luteinization. Call-Exner bodies were absent. Two tumors had multilocular thin walled cysts containing large amounts of estradiol, the third one contained rudimentary microfollicles. The prognosis of juvenile granulosa cell tumors in infancy appears more favorable than those occurring in older patients. No case of tumor recurrence has been reported in infancy so far. Surgery appears to be the state-of-the-art treatment of these tumors and additional therapy (chemotherapy or radiotherapy) must be discussed with caution, even in advanced stages.

Female↗

A method using a liquid chromatographic-electrospray-mass spectrometric assay for the determination of antimigraine compounds: preliminary pharmacokinetics of MDL 74,721, sumatriptan and naratriptan, in rabbit.

MDL 74,721 (I), sumatriptan(II) and naratriptan(III) are new 5-HT1-like agonists that have potential as a novel treatment for migraine. Liquid chromatographic-electrospray-mass spectrometric (LC-ESI-MS) assay have been developed to compare the pharmacokinetics of these three antimigraine compounds. The concentration of each parent drug was determined using a solid-phase extraction method and LC-ESI-MS analysis demonstrating the high sensitivity and specificity of the methods down to subnanogram levels in rabbit plasma samples. Pharmacokinetic parameters evaluated after administration of single intravenous and oral doses were very similar and the ANOVA analysis did not show any statistically significant differences for t1/2, Cmax, V or AUC (normalised). The pharmacokinetic parameters showed short t1/2 (range 1.14-1.9 h) either after intravenous (i.v.) or oral (p.o.) administration and high total body clearance (CL) after the p.o. dose both probably due to extensive and rapid metabolism of the parent drugs as suggested by the low values for bioavailability (range 13.4-22.8%).

Administration, Oral↗