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Biomedical subjects

F Manzarbeitia

Publications and source records attributed to F Manzarbeitia.

At least 19 recordsLinked to original sources
PubMed2003

BPH and inflammation: pharmacological effects of Permixon on histological and molecular inflammatory markers. Results of a double blind pilot clinical assay.

INTRODUCTION: The role of infiltrating cells (I.C.), commonly observed in the adenoma interstitial tissue, is unknown. We tested the hypothesis that I.C. are related with BPH progression by: phenotypically characterising these cells; quantifying the expression of lymphokines and growth factors; investigating the response to Permixon (P) in a clinical study. Permixon is a lipido sterolic extract of Serenoa repens possessing pharmacological activities and widely used in the treatment of men with BPH. MATERIAL AND METHODS: A multicenter open pilot study of two parallel groups on BPH patients was carried out. They were randomized to receive either oral Permixon (P) 160 mg bid for three months or to be followed for 3 weeks without any treatment before surgery (control group C). Strict inclusion and exclusion criteria were applied to conform homogeneous groups, avoiding interferences of inflammatory drugs or others. Baseline clinical profile was almost identical in both groups in terms of age (65.7+/-5.1 vs. 67.1+/-5.8 years), IPSS (19.8+/-6.1 vs. 19.0+/-5.8), prostate volume (64.8+/-18.9 vs. 71.5+/-29.3cc), Q(max) (9.6+/-3.2 vs. 10.6+/-2.6 ml/s), and Q(L) (4.0+/-1.1 vs. 3.5+/-0.7). Surgery was ultimately performed on 29 patients (17C, 12P) by TURP or retropubic adenomectomy. Adenoma samples were routinely stained with HE and later prepared for immunohistochemical studies using CD3, CD20 and CD68 antibodies. Counting of positives cells, lymphoid aggregates and foci were done using EnVision technique and the Tech Mate processor. Cytokines, growth factors and eicosanoids were determined by Elisa kits following the manufactured recommendation. RESULTS: HISTOLOGICAL: A difference was observed in the number of lymphocytes B between C (91.4+/-44.1) and P treated (58.2+/-53.7) groups (p=0.097). BIOLOGICAL MARKERS: TNFalpha and IL-1beta were dramatically lower in the Permixon treated group. Other parameters did not show significant changes. CLINICAL: IPSS in the Permixon treated group was significantly reduced (p<0.006) from 20.0+5.9 to 14.9+3.8 after three months of treatment. COMMENTS: The BPH inflammatory hypothesis was tested in humans. Our pilot study shows a significant reduction of some inflammatory parameters in prostatic tissues of patients treated with Permixon. These biological findings justify a pharmacological effect of this drug on the inflammatory status of the adenoma. A correlation with clinical improvement was observed.

Adenoma↗
PubMed2002

[Benign prostatic hyperplasia: biological significance of lymphohistiocytic infiltration of the adenoma].

The presence of mononuclear cells infiltrating the prostate adenoma is a morphological observation well established in the literature. However, its biological meaning is a subject of controversy. It has been postulated that it may represent a local immunological reaction contributing to the pathogenesis of prostatic adenoma. Several studies have been performed to test this hypothesis, both in humans and animals. The purpose of this review is to update available information, including our own ongoing studies. Morphological research has shown that cells infiltrating the adenoma are lymphocyte T, lymphocyte B and macrophages with a high proportion of lymphocyte T. Many of the inflammatory markers, such as lymphoquines (IL1, IL2, IL4, IL6, IL13), are elevated in the adenoma tissue as are some growth factors (EGF, TGF alpha, IFN gamma, TGF beta). The general impression is that an inflammatory process is activated in the adenoma during growth and maturing. It has also been proved that this inflammatory process could be modified with treatment and, in our case, with the lipido-sterolic extract of Serenoa Repens.

Humans↗
PubMed2001

TT virus detection in oral lichen planus lesions.

Epidemiological studies have demonstrated a correlation between oral lichen planus and different liver diseases. The new virus termed TT virus (TTV) is highly prevalent in patients with chronic hepatitis of different etiology and it may be speculated that TT virus may be involved in the pathogenesis of oral lichen planus. This study examined the presence of TT virus DNA in serum by PCR and in oral mucosa biopsies by in situ hybridization from 20 patients with oral lichen planus (13 with chronic hepatitis and seven without liver disease). Serum and oral mucosa biopsies from six patients all with chronic hepatitis with leukoplakia were also studied as controls. TT virus DNA was positive in the serum of 17/20 (85%) of the patients with oral lichen planus and in all the controls. TT virus DNA hybridization signals were detected in mucosa biopsies from all the patients with TT virus DNA in serum but in none of the three cases without this marker. The percentage of positive cells ranged from 1.6-80%. No differences were found in the percentage of positive cells between TT virus positive patients with and without oral lichen planus and there was no relationship between the number of positive cells and the intensity of the inflammatory infiltrate. In conclusion, TT virus infects oral epithelial cells but the results do not support a role for TT virus in causing oral lichen planus.

Aged↗
PubMed2001

In situ detection of hepatitis C virus RNA in salivary glands.

Chronic hepatitis C virus (HCV) infection has been associated with several extrahepatic manifestations, among these, to diseases with oral manifestations such as Sjögren's syndrome or sialadenitis. HCV-RNA has been detected in saliva and in salivary glands from patients with sialadenitis by polymerase chain reaction. However, morphological evidence of HCV replication in salivary gland cells is needed to support a role for HCV in causing sialadenitis or Sjögren's syndrome. We have used in situ hybridization and immunohistochemistry to analyze the presence of HCV-RNA of sense and antisense polarity and HCV core antigen, respectively, in salivary gland biopsies from 19 patients with chronic sialadenitis or Sjögren's syndrome (eight anti-HCV-positive; 11 anti-HCV-negative). HCV-RNA of both positive and negative polarity as well as HCV core antigen were detected in the epithelial cells of the salivary gland biopsies from all of the anti-HCV-positive patients but in none of the anti-HCV-negative cases. The percentage of HCV-infected cells ranged from 25 to 48.8% in the patients studied. In conclusion, we have shown that HCV infects and replicates in the epithelial cells from salivary glands of patients with Sjögren's syndrome or chronic sialadenitis. However, its implication in the pathogenesis of these diseases deserves future research.

Adult↗
PubMed2001

Malignant spiradenoma: report of two cases and literature review.

Spiradenoma is a benign skin adnexal neoplasm that usually appears as a solitary nodule in any area of the body. There have been only 33 reports on malignant transformation of a benign eccrine spiradenoma since the first description by Dabska in 1972. Most cases have originated on a long-standing cutaneous lesion. These tumors can behave in an aggressive fashion, and some have led to the patient's death. We report 2 new cases of this rare neoplasm affecting 2 men, 92 and 72 years of age, comment on the clinical and pathologic features of our cases, and review the literature concerning this lesion.

Adenoma, Sweat Gland↗
PubMed2001

Olmsted syndrome: report of a case with study of the cellular proliferation in keratoderma.

Olmsted syndrome is a rare disorder that consists of sharply marginated keratoderma of the palms and soles, constriction of digits and toes that may result in spontaneous amputation of the distal phalanges, hyperkeratotic plaques around the body orifices, onychodystrophy, and other less common cutaneous and extracutaneous anomalies. Although some patients had other affected family members, most cases of Olmsted syndrome seem to be of sporadic occurrence. We describe a patient with the characteristic features of Olmsted syndrome. The symptoms consisted of diffuse transgrediens palmoplantar keratoderma and keratotic plaques around the mouth and nose. Our patient also had the associated anomalies of hyperhidrosis of the palms and soles and congenital deaf-mutism. Histopathologic study of the keratoderma demonstrated epidermal hyperplasia with acanthosis, papillomatosis, and orthokeratotic hyperkeratosis. Immunohistochemical study showed more basal and suprabasal keratinocytes of the epidermis with immunoreactivity for Ki-67 marker when compared with the keratinocytes of the epidermis of the adjacent non-involved skin. These results support the notion that Olmsted syndrome is a hyperproliferative disorder of the epidermis.

Adult↗
PubMed2001

Expression of factor VII in the liver of patients with liver disease: correlations with the disease severity and impairment in the hemostasis.

Factor VII (FVII) plasma levels in patients with liver disease may be below the normal range. However, no data are available on FVII expression in liver biopsies from patients with liver diseases other than cirrhosis. We have analyzed the expression of FVII by in situ hybridization in liver biopsies from 50 patients in comparison with the procoagulant activity of FVII, and with the plasma levels as activated FVII (FVIIa) and FVII antigen. The level of FVIIa was significantly lower in stage 4 liver fibrosis patients than in the remaining ones (P < 0.05). The percentage of hepatocytes expressing FVII was significantly lower in stage 4 liver fibrosis patients (4.1+/-1.3%) than in stage 3 (22.7+/-6.1%), stage 2 (31.5+/-6.1%), stage 1 (43.7+/-8.2%) and stage 0 patients (63.8+/-4.4%) (P < 0.001). These percentages correlated inversely in a statistically significant way with the histological activity index and the liver function tests. We have demonstrated that the FVIIa plasma levels in patients with chronic liver disease other than cirrhosis may be below the normal range in the absence of blood coagulation impairment. The percentage of hepatocytes expressing FVII decreases as the severity of liver damage increases.

Adult↗
PubMed2001

Activation of NF-kappaB in tubular epithelial cells of rats with intense proteinuria: role of angiotensin II and endothelin-1.

The mechanisms by which persistent proteinuria induces interstitial inflammation and fibrosis are not well known, although nuclear factor-kappaB (NF-kappaB), which regulates the transcription of many genes involved in renal injury, could be implicated. In rats with intense proteinuria, we studied the renal activation of NF-kappaB as well as the potential involvement of the vasoactive hormones angiotensin II (Ang II) and endothelin-1 (ET-1). Uninephrectomized Wistar-Kyoto rats receiving 1 g/d of BSA had proteinuria but no renal morphological lesions at day 1. By contrast, tubular atrophy and/or dilation and mononuclear cell infiltration were observed after 8 or 28 days of BSA administration, coinciding with maximal proteinuria. In relation to control uninephrectomized rats, the renal cortex of nephritic rats showed an increment in the activation of NF-kappaB at all time periods studied. By in situ Southwestern histochemistry, NF-kappaB activity was mainly localized in proximal tubules, interstitial mononuclear cells, and, to a lesser extent, the glomeruli. The administration of the ACE inhibitor quinapril plus the ET(A)/ET(B) receptor antagonist bosentan during 28 days to BSA-overloaded animals diminished proteinuria, renal lesions, and NF-kappaB activity more markedly than single drugs. Cultured tubular epithelial cells exposed to BSA revealed an intense NF-kappaB activation in a time- and dose-dependent manner. Incubation of cells with receptor antagonists of Ang II (AT(1): losartan and AT(2): PD-123,319) or ET-1 (ET(A): BQ123 and ET(B): IRL1038) inhibited significantly the BSA-induced NF-kappaB activity (90%, 75%, 90%, and 60% of inhibition versus basal, respectively). Our results show that overload proteinuria causes NF-kappaB activation in tubular epithelial cells both in vivo and in vitro. The vasoactive peptides Ang II and ET-1 appear to be implicated in this effect. The results reveal a novel mechanism of perpetuation of renal damage induced by persistent proteinuria.

Analysis of Variance↗
PubMed2001

Aspirin protected the nitric oxide/cyclic GMP generating system in human peritoneum.

OBJECTIVE: Changes in the expression of endothelial nitric oxide synthase (eNOS) in the peritoneum could be involved in the peritoneal dysfunction associated with peritoneal inflammation. The aim of the present study was to analyze the effect of Escherichia coli lipopolysaccharide (LPS) on eNOS expression in samples of human peritoneum. The effect of aspirin, a drug with anti-inflammatory properties, was also determined. RESULTS: The eNOS protein expressed in human peritoneal tissue was reduced by LPS (10 microg/mL) in a time-dependent manner. The eNOS was expressed mainly in capillary endothelial cells and mesothelial cells. Anti-inflammatory doses of aspirin (1-10 mmol/L) restored eNOS expression in LPS-stimulated human peritoneal tissue samples. The main intracellular receptor of NO, soluble guanylate cyclase (sGC), was also downregulated by LPS. This effect was prevented by aspirin (5 mmol/L). CONCLUSION: Protein expression of the eNOS-sGC system in the peritoneal tissue was downregulated by LPS. High doses of aspirin protected both eNOS protein expression and sGC in human peritoneum. These findings suggest a new mechanism of action of aspirin that could be involved in the prevention of peritoneal dysfunction during inflammation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Pilot study of combination therapy with ribavirin and interferon alfa for the retreatment of chronic hepatitis B e antibody-positive patients.

Twenty-four patients with chronic hepatitis B virus (HBV), antibody to hepatitis B e antigen (anti-HBe), HBV DNA positivity, and alanine transaminase (ALT) elevation who failed previous interferon alfa (IFN-alpha) therapy were included in a pilot study of combination therapy with ribavirin and IFN-alpha. The patients received daily oral ribavirin (1,000-1,200 mg according to body weight) plus 5 million units (MU) IFN-alpha2b three times a week for 12 months and were followed-up for 12 months. The median viremia level decreased significantly at the end of treatment (1.2 x 10(3) copies/mL) and follow-up (4.0 x 10(2) copies/mL) compared with the baseline (3.0 x 10(6) copies/mL; P <.05). After 12 months, 8 of 24 (33%) patients had cleared HBV DNA and 12 (50%) had normal ALT levels. At the end of the study virological and biochemical response was 50% and 21%, respectively. Thus, virological and biochemical response sustained in 5 of 24 (21%) patients retreated with ribavirin and IFN-alpha; none of them lost hepatitis B surface antigen (HBsAg). Liver histology improved in 2 of 4 sustained responders but in none of the 12 nonresponders with paired biopsies (P =.05). The response was independent of dose and duration of previous treatment, viral load, or the distribution of HBV precore wild-type/mutant variants. However, sustained responders had significantly higher necroinflammation (P =.036) and fibrosis (P =.007) scores. IFN-alpha-related side effects were mild and reversible on discontinuation. In 4 (17%) patients who suffered nausea and diarrhea the ribavirin dosage was reduced by 50% after 1 month of therapy and finally discontinued in all of them. No patient had liver disease decompensation. In summary, combination therapy with ribavirin and IFN-alpha may be efficacious to treat viremic anti-HBe-positive patients with chronic hepatitis B who have failed previous IFN therapy.

Adult↗
PubMed2000

Detection of TT virus DNA in liver biopsies by in situ hybridization.

A novel hepatitis-associated virus named TT virus (TTV) has been isolated. However, its hepatotropism has not been proven. We have retrospectively analyzed the presence of TTV-DNA by polymerase chain reaction (PCR) and in situ hybridization in liver biopsies from 30 patients with liver disease (15 TTV-DNA-positive and 15 TTV-DNA-negative in serum), and prospectively in serum and liver from eight patients with normal liver histology. TTV-DNA was detected by PCR in the liver from the 15 patients with serum TTV-DNA and in serum and liver of two of the eight patients without liver disease. TTV-DNA titers in liver were 10 times higher than in serum, although no correlation between TTV-DNA titers in serum and liver were observed. In situ hybridization shows positive signals in the hepatocytes of the 17 patients infected by TTV but in none of the TTV-DNA-negative patients by PCR. No morphological changes were observed in the hepatocytes showing hybridization signals. The percentage of positive hepatocytes ranged from 2.1% to 30% and correlated with the TTV-DNA titers in liver (r = 0.54; P = 0.037). In conclusion, our results show that TTV is able to infect liver cells although they do not support a role for TTV in causing liver disease.

Adult↗
PubMed2000

Detection of hepatitis C virus replication by In situ hybridization in epithelial cells of anti-hepatitis C virus-positive patients with and without oral lichen planus.

Epidemiological studies have demonstrated that there is a correlation between oral lichen planus and chronic hepatitis C virus (HCV) infection. HCV RNA has been recently detected in epithelial cells from oral lichen planus lesions by reverse-transcription polymerase chain reaction (RT-PCR). However, this technique does not discriminate which types of cells are infected by the virus or if the viral RNA is present in the serum that contaminates the biopsy. Morphological evidence of viral replication in cells from these lesions is needed to establish a role for HCV in oral lichen planus. Consequently, we have analyzed the presence of positive and negative HCV-RNA strands in oral mucosa biopsies from 23 patients (14 anti-HCV-positive) diagnosed as having oral lichen planus and from 5 patients with chronic hepatitis C without oral lichen planus. Positive and negative HCV-RNA strands were detected in epithelial cells of the mucosa biopsies from all anti-HCV-positive patients independently of whether or not they had oral lichen planus, but in none of the anti-HCV-negative cases. The percentage of stained cells ranged from 4.4% to 14.3%. These percentages do not correlate with the serum viremia levels or the intensity of the cellular infiltrate in patients with oral lichen planus. In conclusion, we have shown that HCV replicates in epithelial cells of patients with and without oral lichen planus. The pathological consequences of this finding remain to be elucidated.

Adult↗
PubMed2000

p53 expression in two cases of spiradenocarcinomas.

p53 protein is a nuclear 53-kDa phosphoprotein that acts as a suppressor protein. There are several studies on the expression of p53 in skin tumors, but few deal with adnexal malignant tumors because of their rarity. We performed immunohistochemistry for the detection of p53 and Ki-67 in two cases of malignant spiradenomas and six cases of spiradenomas retrieved from our files. In our cases, p53 was expressed only in the malignant areas of the lesions, whereas the benign areas of the spiradenocarcinomas and all the spiradenomas were negative (nuclear positivity <10%). These results seem to support the idea that p53 is implicated in the malignant transformation of adnexal tumors.

Adenocarcinoma↗
PubMed1999

Retreatment of chronic hepatitis B e antigen-positive patients with recombinant interferon alfa-2a. The European Concerted Action on Viral Hepatitis (EUROHEP).

Fifty-seven patients with chronic hepatitis B, hepatitis B virus (HBV) e antigen (HBeAg) and HBV DNA positivity, and aminotransferase elevation despite a previous course of any type of adequate interferon alfa (IFN-alpha) therapy were included in a multicenter prospective randomized controlled trial. The objective of the study was to compare a second course of IFN-alpha therapy (9 million units [MU] of IFN-alpha-2a, Roferon-A, thrice weekly for 6 months) versus no therapy in terms of loss of HBV DNA and HBeAg. At the end of the study, a sustained clearance of HBV DNA and HBeAg was observed in 9 of the 27 (33.3%) patients who had received retreatment with IFN-alpha compared with 3/30 (10%) patients who spontaneously cleared these markers in the untreated control group (chi2 = 4.66, P =.031; odds ratio: 4.5, 95%; confidence interval: 1.1-18.9). None of the responders lost HBsAg. Patients retreated with IFN-alpha were more likely to have biochemical remission in association with HBV clearance (5/27, 18.5%) compared with untreated patients (1/30, 3. 3%; Fisher's exact test P =.09 ). Histological improvement in the liver necroinflammatory activity was observed among sustained responders to IFN-alpha retreatment, consisting of regression of the portal and periportal inflammation and of the piecemeal necrosis; there was no change in the degree of liver fibrosis. Side effects were similar to those previously reported during IFN-alpha treatment; these were mild and reversible on IFN-alpha discontinuation. None of the baseline features were associated with response by Cox's regression analysis. In summary, viremic patients with chronic HBeAg-positive hepatitis may experience disease remission following retreatment with IFN-alpha. Thus, retreatment with IFN-alpha may be considered a therapeutic option.

Adolescent↗
PubMed1999

Histological damage in chronic hepatitis C is not related to the extent of infection in the liver.

It has not been completely elucidated whether the liver injury induced by the hepatitis C virus (HCV) is due to direct cytopathic damage or to an immune-mediated response against HCV-infected hepatocytes. In this work, we have determined the percentage of HCV-infected hepatocytes, the histological activity index, and the viremia levels in chronically HCV-infected patients with different grades of liver injury to investigate any possible correlation between them. For that purpose, liver biopsies from 27 patients with HCV chronic hepatitis were analyzed by in situ hybridization. This technique revealed that the percentage of infected hepatocytes ranged from 0.04% to 83.6%. Regarding the viremia levels, HCV RNA concentration ranged from 1.8 x 10(3) to 1.4 x 10(6) genome copies/ml. A significant correlation (r = 0.54; P = 0.003) between the percentage of infected hepatocytes and the viremia levels was found. In contrast, no correlation was observed between the percentage of HCV-infected hepatocytes or the viremia levels and the histological activity index. In conclusion, we have shown that the HCV viremia reflects the extent of the infection in the liver and that the liver injury in chronic HCV infection is not directly related to either the number of infected hepatocytes or the serum HCV RNA concentration.

Biopsy↗
PubMed1999

Panniculitis mimicking lupus erythematosus profundus: a new histopathologic finding in malignant atrophic papulosis (Degos disease).

We present the case of a 57-year-old woman with a 1-year history of a cutaneous eruption clinically and histopathologically characteristic of Degos disease. In one of the two cutaneous biopsy specimens taken from the trunk lesions, the histopathology consisted of necrosis and sclerosis of the subcutaneous lobules, a finding that to our knowledge has not been previously described in the cutaneous lesions of Degos disease. Two months after cutaneous biopsies were taken, the patient developed ptosis and an episode of acute abdominal pain; intestinal perforation and many characteristic lesions of visceral Degos disease involving the entire small bowel were noted at laparotomy.

Complement C3↗
PubMed1999

Sebaceous carcinoma of the vulva.

Extraocular sebaceous carcinoma is an uncommon neoplasm usually localized on the head and neck. Sebaceous glands are abundant on the vulva, but vulvar sebaceous carcinoma is an uncommon neoplasm. To our knowledge, there are only five previously reported cases of sebaceous carcinoma on this location. We report an additional case of vulvar sebaceous carcinoma associated with Bowen's disease in the overlying epidermis. The patient also had bowenoid papulosis involving the skin of labia majora. We analyzed by immunohistochemistry, Southern blot hybridization, and polymerase chain reaction (PCR) techniques for the presence of DNA of human papilloma viruses (HPVs) in the specimen of sebaceous carcinoma and in lesions of bowenoid papulosis. Immunohistochemistry, Southern blot hybridization, and PCR studies in specimens of bowenoid papulosis lesions and sebaceous carcinoma did not detect DNA of HPVs. A significant increase in intranuclear p53 staining was demonstrated in several areas of neoplastic aggregations of sebaceous carcinoma.

Adult↗