von Willebrand's disease in Mexico: a pilot study.

von Willebrand's disease (VWD) is the most commonly inherited bleeding disorder. For a long time, it has been said that VWD was absent in some countries due to ethnical differences. Information about the prevalence of VWD in Mexico remains unclear, owing largely to poor awareness and diagnosis of the disease. The aim of this study was to objectively diagnose VWD in a cohort of highly selected Mexican patients with a chronic history of bleeding. Mexican Mestizos were recruited between July 2010 and August 2011. Included were 133 adult and paediatric patients with a high suspicion of VWD. Fifty-three were diagnosed with VWD: 47 (88.7%) with type 1 VWD, four (7.5%) with type 2a VWD and two (3.8%) with type 3 VWD. Mean age for female patients was 19.5 years (range 3-44 years) and 18.5 years (range 4-63 years) for male patients. Mean age at start of bleeding symptoms was 8.8 years (range 1-61). The most frequent clinical symptoms were epistaxis (84.9%), ecchymosis (79.2%), haematomas (71.7%), gum bleeds (62.3%) and petechia (50.9%). Severe transoperative or postoperative bleeding was found in 17 patients (32.1%). Twenty-six women at childbearing age had a history of abnormal gynaecological bleeding. Our results clearly demonstrate the presence of VWD in Mexican and underscore the importance of a more detailed description of VWD. Efforts to increase the awareness and diagnosis of VWD could help in better identification of patients with bleeding disorders and lead to early, appropriate management with safe and efficacious therapies such as desmopressin and plasma concentrates.

Pifithrin-alpha, an inhibitor of p53, enhances the genetic instability induced by etoposide (VP16) in human lymphoblastoid cells treated in vitro.

Recent studies indicate that p53-dependent apoptosis induced in normal tissues during chemo- and radiotherapy can cause severe side effects of anti-cancer treatments that limit their efficiency. The aim of the present work was to further characterise the role of p53 in maintaining genomic stability and to verify whether the inhibition of p53 function in normal cells by pifithrin-alpha (PFT-alpha) may contribute in reducing the side effects of cancer therapy. Two human lymphoblastoid cell lines, derived from the same donor, TK6 (p53 wild type) and WTK1 (p53 mutated) have been treated with an anti-neoplastic drug, the etoposide (VP16), an inhibitor of DNA topoisomerase II in presence or in absence of the p53 inhibitor PFT-alpha. Following treatments with VP16 on TK6 and WTK1, we observed a higher induction of chromosome aberrations in WTK1 (p53 mutated) and of apoptosis in TK6 (p53 wild-type) cells. The p53 inhibition by PFT-alpha in VP16 treated TK6 cells produced an increase of chromosomal aberrations and a reduction of apoptosis. Therefore, the temporary suppression of the function of p53 by PFT-alpha, increasing the survival of the normal cells, could be a promising approach to reduce the side-effects of cancer therapy but it is important to consider that the surviving cells could be genetically modified and consequently the risk of secondary tumours could be increased.

Detection of DNA primary damage by premature chromosome condensation in human peripheral blood lymphocytes treated with methyl methanesulfonate.

Methyl methanesulfonate (MMS) is a direct acting methylating agent which produces apurinic sites that are transformed into DNA single-strand breaks by base excision repair. MMS-induced DNA lesions have to be transformed by DNA synthesis in order to give rise to chromosomal damage. In this study the premature chromosome condensation (PCC) technique was used in G(1) human lymphocytes treated with MMS to investigate whether, with this technique, chromosomal damage could be detected without the cell needing to undergo DNA synthesis. A dose-dependent increase in chromosomal fragmentation was indeed observed in G(1) lymphocytes. MMS treatment at 1.3, 2.5 and 5 mM was characterized by the appearance of highly fragmented chromosomes. This observation induced us to further investigate whether this effect was more connected with triggering of apoptotic cell death than a consequence of the PCC technique. Data obtained by nuclear morphology analysis, by Trypan blue exclusion assay and pulsed field gel electrophoresis seem to suggest that the observed chromosome fragmentation could be due to the onset of apoptosis. Consequently, one should bear in mind that the PCC technique can overestimate chromosomal damage when apoptosis is also induced.

Inhibition of platelet aggregation by putrescine, spermidine, and spermine in hypercholesterolemic rabbits.

BACKGROUND: Hypercholesterolemia causes alterations in platelet function. Platelet hyperaggregation is considered a predisposing factor for atherosclerosis. In this paper, the antiaggregating effect of the polyamines putrescine, spermidine, and spermine was studied on platelets of normal and hypercholesterolemic rabbits. METHODS: New Zealand rabbits were fed with a cholesterol-enriched diet for 10 weeks. Lipids and glucose were determined in serum. The assays of platelet aggregation were carried out using platelet-rich plasma (PRP) obtained from both control and cholesterol-fed rabbits. We used 2.5 micromol /mL ADP and 2 microg/mL collagen as inductors of platelet aggregation. In addition, arginase activity and L-arginine content were determined in PRP. RESULTS: Serum total cholesterol and LDL-cholesterol concentrations were increased from 26.3 +/- 8.1 to 1,485.0 +/- 26.8 mg/dL and from 15.9 +/- 5.9 to 1,383.8 +/- 58.9 mg/dL, respectively, whereas triglyceride concentration increased from 88.3 +/- 35.6 to 411.0 +/- 154.5 mg/dL upon cholesterol feeding. Seventy-five percent of platelet aggregation inhibition was observed with 10 microM of polyamines in PRP of normal rabbits. Spermine inhibited platelet aggregation by 54% in PRP of hypercholesterolemic rabbits when ADP was used as agonist. The order of polyamine action was spermine > spermidine > putrescine. In addition, we found that platelet arginase activity and L-arginine content were unaltered upon hypercholesterolemia. CONCLUSIONS: These results show that the polyamines putrescine, spermidine, and spermine have antagonist action in platelet aggregation and suggest a key role of polyamines in platelet aggregation under normal and hypercholesterolemic conditions.

[Phaeohyphomicosis by Wangiella dermatitidis in Republic Argentine.]. / Feohifomicosis producida por Wangiella dermatitidis en la República Argentina.

We are presenting the case of a 54 year-old woman, who had a kidney transplant. She came to our laboratory to consult for two cutaneous lesions: a cystic one at the back of her right leg and one localized on dorsum of left forearm. Biopsies of both lesions were performed for a histopathologic study as well as microbiological (both bacteriologic and mycologic) cultures. The histopathologic study showed a lesion compatible with a B type cutaneous lymphoma in the lesion in her leg, while in the mycologic study of the cystic lesion elements compatible with phaeohyphomycosis were observed. Development of Wangiella dermatitidis was obtained in the cultures. The cystic lesion localized on forearm was completely removed by surgery, while the lesion in the leg received oncological treatment. The aim of this paper is to describe the first published case of phaeohyphomycosis, by W. dermatitidis, in the Argentine Republic.

[Separation and divorce in Mexico: a demographic perspective]. / Separacion y divorcio en Mexico: una perspectiva demografica.

PIP: Data from the 1976 Mexican Fertility Survey are analyzed to determine the extent of legitimization of children born out of wedlock. The socioeconomic characteristics of women in consensual and legal unions are compared. The frequency and timing of legalization of consensual unions is analyzed, and the number of consensual unions and the frequency of legalization in rural and urban areas are compared. The role of pregnancy in forcing legalization and the stability of legal unions with and without prior cohabitation are studied. (SUMMARY IN ENG)^ieng

Systemic IFN-alpha treatment of multiple bladder papilloma grade I or II patients: pilot study.

Bladder papillomatosis offers a good target to evaluate IFN-alpha systemic treatment. We carried out a pilot study on eight multiple bladder papilloma patients under the same treatment scheme (1 x 10(6) IU/amp. every 48 h over six months), and they were followed-up for over two years after treatment. Recurrent patients underwent a similar second treatment. IFN-alpha therapy showed the following variations of effects: total disappearance, size decrease or persistence of papillomas, neither size increase nor appearance of new ones, remarkable valuable recurrence frequency rate decrease in all cases, and recurrences with smaller papillomas. This IFN-alpha treatment scheme would be fit to carry out broader controlled studies to show frequencies of the different kinds of responses. The inclusion of a minimum (dose-frequency-period) IFN-alpha treatment period after the first six months' therapy is proposed in order to achieve total disappearance of recurrences.

Influence of human leukocyte interferon on IgG on the replication of herpes simplex virus in nervous tissue in vitro.

Herpes simplex virus type 1 (HSV-1) replicated productively in rabbit and guinea pig ganglia and nerve organ cultures when inoculated in high titres. Treatment with IgG 20 hr before and 48 hr after infection produced a delay of 4 to 7 days in the recovery of HSV-1 by the method of co-cultivation. The same result was obtained when IgG was combined with human leukocyte interferon. There was no difference in the period up to HSV recovery between the groups treated with interferon alone and the HSV control. Morphological evidence by light and electron microscopy of viral productive infection was obtained in all the cell types of nervous tissues infected in vitro.

Combined therapy of human interferon (HI) and secretory immunoglobulin (S-IgA) in the treatment of human herpetic keratitis.

The topical action of a combined therapy of human interferon (3000 U/ml) and secretory immunoglobulin IgA (1,5 mg/ml) was studied in 56 patients with herpetic keratitis. The pain and photophobia disappeared within 48 h after the beginning of treatment and a marked reduction of the corneal lesion during the first week of treatment was observed in all the patients. The therapy was effective, with complete healing of the lesion in 94.8% of cases; 72.2% of them healed in less than 15 days. The highest frequency of healing was between 5 and 10 days, and the rest up to 30 days. Humoral, immunological and delayed hypersensitivity studies were carried out in 36 patients.

Interferon in the replication of herpes simplex virus in normal and pathological nerve cells.

Previous results obtained in experimental and clinical trials have demonstrated that topical combined thrapy with human interferon (HI) and human colostral secretory immunoglobulin A (S-IgA) is effective against herpetic corneal infection. This therapy prevented encephalitis in rabbits but could not completely prevent recurrences either in rabbits or in patients. A number of in vitro studies were designed to elucidate the role of these factors in herpes simplex virus replication in the nervous system, with the following results: (1) HSV latency in trigeminal ganglia (TG) explanted from rabbits with experimental herpetic keratitis, topically treated with HI or HI/S-IgA: HSV was recovered in 30% TG after 15-19 days co-cultivation on RK-13 cells. (2) HSV replication in nervous ganglia and nerve of newborn rabbits in organ culture; influence of HI or HI plus IgG: a restrictive HSV productive infection was demonstrated in this system, although yields were always higher in nerve cultures. We were unable to demonstrate a direct effect of HI on HSV-1 replication. When explants were treated with HI and IgG before and after infection for 48 hours a delay in the expression of HSV-1 was detected by co-cultivation. (3) Replication of HSV-1 and HSV-2 in a C1300 murine neuroblastoma clone (NB41A3): both HSV types replicated with titres of 10(3.4) for HSV-1 AND 10(4.8) for HSV-2 at 48 hours p.i.; CPE was more marked for HSV-2 at 24 hours. HSV-specific antigens were demonstrated by the immunoperoxidase technique.

Interferon in breast cancer.

The interferon production ability by leukocytes in vitro from 37 patients with mammary cancer was studied. The leukocytes were derived from patients between 27 and 80 years of age, 6 months and up to 28 years after removal of the primary tumor. The interferon titer of 34/37 human breast cancer leukocytes was 2-8 times lower than that of 35 normal donor leukocytes and 3 non-neoplastic diseases. No correlation between interferon titers, the patient's age, and the histologic tumor features was observed; however, interferon production was observed to return to normal in those patients who had a long remission period or whose tumors were locally confined. Interferon response of patients under different therapy was modified: radiotherapy affected interferon production more severely than chemotherapy. A tendency for association between the skin DNCB test and interferon response was found. An inverse correlation was observed between interferon titers and the PHA-induced transformation index.