[Hereditary angioedema. A report of a case and literature review]. / Angioedema hereditario. Comunicación de un caso y revisión de la bibliografía.

Hereditary angioedema is a congenital disorder with recurrent attacks of localized swelling of submucosal and subcutaneous tissue, or both caused by a deficiency of the plasma protein C1 inhibitor. It is caused by heterozygous defects in the C1 inhibitor gene located on chromosome 11q, and it has an autosomal dominant inheritance pattern. This disease afflicts 1 in 10,000 to 1 in 150,000 persons. Hereditary angioedema has been reported in all races, and no sex predominance has been found. Skin and visceral organs may be involved by the typically massive local edema. The most commonly involved viscera are the respiratory and gastrointestinal systems, and it can affect the upper airways resulting in severe life-threatening symptoms, including the risk of asphyxiation. There are three types of hereditary angioedema, which difference lies in the inheritance pattern and in the C1 esterase inhibitor and C4 concentrations. The treatment is complicated and it should be treated with intravenous purified C1 inhibitor concentrate; corticosteroids, antihistamines and epinephrine can be useful adjuncts but they are not effective. We report a patient with hereditary angioedema type 1 and make a review of the medical literature.

[Transfer factor as specific immunomodulator in the treatment of moderate-severe atopic dermatitis]. / Factor de transferencia como inmunomodulador específico en el tratamiento de la dermatitis atópica moderada a severa.

BACKGROUND: Atopic dermatitis is a skin inflammatory disease which has been associated to high levels of IgE, eosinophiles and change of T lymphocytes. The transfer factor is an immunomodulator active substance and decreases the number of inflammatory cells and the severity of the symptoms of atopic dermatitis. OBJECTIVE: To determine the efficacy of the transfer factor as treatment of moderate and severe atopic dermatitis. MATERIAL AND METHODS: Articles related to treatment with transfer factor in the atopic dermatitis were looked up in Medline and EMBASE, and the ones referring to controlled studies in patients with moderate and severe atopic dermatitis in accord to SCORAD. RESULTS: We found seven articles with 121 patients and 88 controls demonstrating significant decrease in the symptoms of the SCORAD index, decreased IgE, and eosinophils in patients treated with transfer factor. CONCLUSIONS: The transfer factor is a choice treatment for moderate and severe atopic dermatitis.

[Safety and efficacy of specific sublingual immunotherapy in patients with asthma and allergy to Dermatophagoides pteronyssinus]. / Inocuidad y eficacia de la inmunoterapia sublingual específica en pacientes con asma y alergia a Dermatophagoides pteronyssinus.

BACKGROUND: First reports on sublingual immunotherapy were published in 1980. OBJECTIVE: To compare safety and effectiveness of sublingual immunotherapy, as compared with placebo, in asthmatic patients. MATERIALS: In a blinded randomized controlled trial asthmatic patients with positive skin prick tests to Dermatophagoides pteronyssinus, and with serum IgE at least 200 UI were included. According to GINA, asthma severity was mild persistent and moderate. All patients improved their baseline FEV1 at least by 14% after inhaled albuterol. Spirometry was performed again after three and six months after initiating treatment. Patients were randomized to receive for six months either sublingual immunotherapy with Der p 1 standardized allergens (IPI-ASAC, México) at a total dose of 10,469 UBE or identically looking and tasting placebo. Both groups received conventional pharmacological therapy. RESULTS: Sixty four patients enter the study; four were excluded because of systemic oral steroid therapy. Sixty patients underwent randomization. Both groups (30 patients in each one) were similar in their baseline characteristics. After six months, patients that received sublingual immunotherapy had less exacerbations than those in the control group (61 vs 123, T 2.61, p<0.001, IC 1.8-7.2), better FEV1 as compared with baseline values (25% vs 9%, Z=0.66, p=0.03), and less need of albuterol (50% of initial dose, vs 21% (Z=1.4, p=0.03, IC 1.39-1.49). CONCLUSION: Sublingual immunotherapy improves patient symptoms and pulmonary functional tests, makes exacerbations less frequent, and reduces albuterol needs. It may improve asthma related quality of life.

Minimally invasive video-assisted approach for partial and total thyroidectomy: initial experience.

BACKGROUND: We report our initial experience with partial and total thyroidectomy using a video-assisted approach. The feasibility, safety, and potential benefits of this technique are examined. METHODS: Between January and May 2000, 28 patients were select to undergo a thyroid lobectomy (n = 17) or total thyroidectomy (n = 11) by a video-assisted cervical approach. Patient selection was based on clinical examination and preoperative ultrasonography. The surgical procedures were conducted under general anesthesia through a minimal substernal skin incision. Frozen sections were examined peroperatively in all cases. RESULTS: The initial diagnosis was solitary nodule in 19 patients and multinodular goiter in 8 patients. One patient was treated for hyperthyroidism. The mean cranio-caudal axis and transverse diameter of the resected specimen were 4.9 +/- 0.9 and 2.7 +/- 0.5 cm, respectively, and the mean total lobar weight was 11.9 +/- 5.5 g. Conversion to conventional surgery was required in three patients (10.7%), due to local bleeding in all cases. The mean operative times were 150 +/- 8.2 and 102.5 +/- 17 min for total and partial thyroidectomy, respectively. The laryngeal nerve was identified in 94.8% of cases. The mean length of skin incision was 25.4 +/- 2 mm. There was one case of postoperative hypocalcemia and one case of postoperative hoarseness. One patient had a transient vocal cord palsy. The postoperative hospital stay was 1 day for 66.7% of patients. The pain intensity evaluation, performed on postoperative day 1 using the visual analogue scale (VAS) method, was 1.9 +/- 1.4. CONCLUSION: Video-assisted thyroidectomy is feasible, safe, and effective in selected cases. Benefits for the patients in terms of postoperative pain, hospital stay, and cosmesis still need to be assessed in a prospective trial comparing standard open and video-assisted approaches.

Video-assisted neck exploration for primary and secondary hyperparathyroidism: initial experience.

BACKGROUND: Minimally invasive surgery (MIS) for primary hyperparathyroidism includes unilateral neck exploration, access via a totally endoscopic approach, and access via a video-assisted procedure. We report herein our initial experience with the video-assisted neck exploration procedure for primary (PHPT) and secondary hyperparathyroidism (SHPT). METHODS: Between June 1999 and May 2000, 35 patients were selected for PHPT (n = 25) and SHPT (n = 10). In all cases, video-assisted neck exploration was performed under general anesthesia, leading to selective adenoma removal in PHPT or subtotal parathyroid resection in SHPT. Patient selection was based on the preoperative localization studies (ultrasonography and sestamibi scintigraphy). RESULTS: Five of the 25 patients operated on for PHPT (20%) and three of the 10 patients who underwent surgery for SHPT (30 %) were converted to a conventional surgical technique. The mean operative times in PHPT and SHPT were 48.9 +/- 18.7 min and 136.8 +/- 18.7 min, respectively. The recurrent laryngeal nerve was identified in 45% of the patients. The median size and weight of the resected parathyroid glands were 1.8 cm (range, 0.9-2.5) and 1 g (range, 0.5-7), respectively. The length of skin incision was 24 +/- 1.2 mm. All but one patient are currently cured, with a median follow-up of 6 months (range, 2-13). Postoperative complications included hematoma and transient hoarseness in one patient each (2.85%). The median pain intensity, based on the visual analogue scale (VAS) method, as measured at postoperative day 1 was 0.5 (range, 0-3.6). In the PHPT group, the postoperative hospital stay was

Autoantibodies to phospholipids and to the coagulation proteins in AIDS.

In HIV-1 infection, an increased prevalence of anticardiolipin autoantibodies (aCL) and lupus anticoagulant (LA) has been described. In order to see if these antibodies are isolated or, like in autoimmune diseases, associated with hematological disorders and with antibodies to other phospholipids and to proteins of coagulation, we investigated 3 groups of patients: 1. 342 HIV-1 infected patients, 2. 145 control patients including 61 systemic lupus erythematosus (SLE) patients, 58 patients with a connective tissue disease, 15 patients with stroke, 11 patients with syphilis and 3. 100 blood donors. In HIV-1 infection antiprothrombin (aPrT) antibodies were present in 2% of patients, the prevalence of antiphosphatidylcholine antibodies (aPC) (50%) was almost as high as aCL (64%), and 39% had both antibodies. Absorption on liposomes of the latter revealed an heterogeneous mixture of aCL and aPC or cross-reacting antibodies. In contrast with SLE, anti-beta 2-glycoprotein I (4%), LA (1%), biological false positive test for syphilis (0.3%), thrombosis (p < 0.001) were uncommon. In HIV-1 infection, antiphospholipid antibodies do not associated with features linked to them in SLE or syphilis.

Synthesis and evaluation of a polyamine phosphinate and phosphonamidate as transition-state analogue inhibitors of spermidine/spermine-N1-acetyltransferase.

Polyamine analogues such as bis(ethyl)norspermine and N1-ethyl-N11-[(cyclopropyl)methyl]-4,8-diazaundecane (CPENSpm) act as inhibitors of the enzyme spermidine/spermine-N1-acetyltransferase (SSAT) in vitro and possess impressive antitumor activity against a number of cell lines. However, the propensity of these compounds to superinduce SSAT in intact cells limits their usefulness in studies aimed at elucidating the role of SSAT in cellular metabolism. The recently synthesized alkylpolyamine analogue N1-ethyl-N11-[(cycloheptyl)methyl]-4,8-diazaundecane (CHENSpm, 3) is also an effective inhibitor of SSAT and has potent antitumor activity, but does not appear to superinduce SSAT. These findings suggest that it is possible to synthesize polyamine analogues that can be used for selective inhibition of the enzyme in cellular metabolic studies. Along these lines, the phosphate-based transition state analogues 4 and 5 were synthesized and evaluated as inhibitors of isolated SSAT. Phosphonamidate 4 was rapidly hydrolyzed under the assay conditions, and thus did not inhibit the enzyme. However, the phosphinate analogue 5 was an effective inhibitor of purified human SSAT, with a Ki value of 250 microM. The inhibitory activity of 5 was also compared with that of CHENSpm (IC50 = 13 microM), as well as a series of bis-substituted alkylpolyamine analogues. The unsymmetrically substituted polyamine analogue CHENSpm (3) and the phosphinate transition state analogue 5 represent the first functional, nonsuperinducing inhibitors of human SSAT.

Growth and biochemical effects of unsymmetrically substituted polyamine analogues in human lung tumor cells 1.

Three unsymmetrically substituted polyamine analogues demonstrate significant and selective antitumor effects. Each of the analogues N1-ethyl-N11-propargyl-4,8-diazaundecane (PENSpm), N1-ethyl-N11-(cyclobutyl)methyl-4,8-diazaundecane (CBENSpm), and N1-ethyl-N11-(cyclopropyl)methyl-4,8-diazaundecane (CPENSpm) is cytotoxic to a representative non-small-cell lung carcinoma line, NCI H157, while being only growth-inhibitory to a representative small-cell-lung carcinoma line, NCI H82. Cytotoxicity is accompanied by a significant increase in expression of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT) at the levels of activity and steady-state mRNA. These new analogues are significant both for their cell-type-specific activity and as synthetic prototypes for the addition of SSAT-activated functional groups.

Dapsone-induced hematologic toxicity: comparison of the methemoglobin-forming ability of hydroxylamine metabolites of dapsone in rat and human blood.

The relative methemoglobin (MetHgb) forming ability of two metabolites of dapsone, dapsone hydroxylamine (DDS-NOH) and monoacetyldapsone hydroxylamine (MADDS-NOH), were compared in rat and human whole blood. Concentration-response curves for the two metabolites were generated in vitro in whole blood. Data were fit to both the Emax and Sigmoid Emax models. The Emax values for MetHgb formation in rat blood for MADDS-NOH and DDS-NOH fitted to the Emax model were 83 (8) and 84 (2)%, while the EC50 values were 1087 (283) and 828 (104) microM, respectively (mean +/- SD). Neither these values nor those generated for the Sigmoid Emax model differed significantly between the two metabolites. Similarly, the Emax values in human blood for MADDS-NOH and DDS-NOH fitted to the Emax model were 79 (5) and 80 (2)%, while the EC50 values were 90 (17) and 95 (19) microM, respectively. These values also did not differ between the two metabolites using either pharmacodynamic model. MetHgb was produced at the same rate, reached similar peak concentrations, and exhibited the same rate of decline with both metabolites. The area under the MetHgb content versus time curve did not differ between the two metabolites. These data demonstrate that MADDS-NOH and DDS-NOH are equipotent and equally efficacious in their MetHgb-forming ability. Investigation of the disposition of these metabolites is necessary to assess their relative role in dapsone-induced toxicity in vivo.

Synthesis and evaluation of unsymmetrically substituted polyamine analogues as modulators of human spermidine/spermine-N1-acetyltransferase (SSAT) and as potential antitumor agents.

Spermidine/spermine-N1-acetyltransferase (SSAT), the rate-limiting step in polyamine catabolism, is critical for the interconversion and modulation of cellular polyamines. Inhibitor-initiated induction of this enzyme also appears to correlate with the sensitivity of tumor cells to a class of novel polyamine analogues, the bis(ethyl)polyamines. Thus, terminally alkylated polyamines which modulate the cellular level of SSAT could be of great value for understanding the role of this enzyme both in analogue-mediated cytotoxicity and in overall cellular polyamine metabolism. Such analogues could also become important therapeutic agents by disrupting cellular polyamine metabolism. The structure-activity relationships defining the interaction of polyamine analogues with SSAT have not been fully elucidated, and, in particular, unsymmetrically alkylated polyamines have not been synthesized and evaluated as modulators of SSAT. To this end, we now report the synthesis and preliminary biological evaluation of N1-ethyl-N11-propargyl-4,8-diazaundecane and N1-ethyl-N11-((cyclopropyl)methyl)-4,8-diazaundecane via a synthetic pathway which represents an efficient route to a variety of unsymmetrically substituted polyamine analogues. The title compounds act as effective inhibitors of isolated human SSAT and produce a differential superinduction of SSAT in situ which appears to be associated with a cell specific cytotoxic response in two human lung cancer cell lines. In so doing, these analogues exhibit promising antitumor activity against cultured human lung cancer cells.