Human immunodeficiency virus and other sexually transmitted diseases in Cuban women.

A cross-sectional study was performed in 60 Cuban women of child-bearing age who were seropositive for human immunodeficiency virus (HIV) and 60 controls. Human papillomavirus (HPV) was identified most frequently, with oncogenic HPV serotypes 16, 33 and 58 detected in HIV-positive patients, and serotypes 11, 33 and 51 in the controls (relative risk 4.41; 95% CI 2.21-8.29). Syphilis and hepatitis B and C viruses were detected exclusively in HIV-seropositive women (p<0.05). Sexually transmitted diseases (STDs) appeared to pose a substantial health problem, especially for HIV-positive women. Clinics should consider screening and treatment for STDs as part of their HIV prevention programmes.

A case of systemic lupus erythematosus with giant hepatic cavernous hemangioma.

A 39-year old woman with antiphospholipid antibody positive systemic lupus erythematosus (SLE) was admitted to our department because of high fever, liver dysfunction and high level of C-reactive protein. At hospitalization, there was no anemia or jaundice. A tumor was palpable in the epigastric region, and there was tenderness in this region, but no muscular defense. There were no findings which indicated disease activity of SLE. The result of abdominal ultrasonography showed that there was a giant tumor, which occupied the majority of the left lobule of the liver, and a nonuniform ultrasound image was observed inside the tumor. The result of dynamic computed tomography (CT) showed peripheral globular enhancement, and enhancement then extended to the tumor center with time. Consequently, the patient was diagnosed with multiple hepatic hemangiomas. After admission, anemia rapidly deteriorated, and platelet count tended to decline. Therefore, intratumor hemorrhage was suspected, and emergent angiography was performed. For hemostatic purposes, transcatheter arterial embolization (TAE) and extended left hepatic lobectomy were performed. In patients with autoimmune diseases such as SLE and antiphospholipid syndromes, when thrombocytopenia is observed, care should be paid to identifying its cause, considering thrombocytopenia may be induced by hemangioma, although these cases are extremely rare.

Carboxy-terminally truncated Dengue 4 virus envelope glycoprotein expressed in Pichia pastoris induced neutralizing antibodies and resistance to Dengue 4 virus challenge in mice.

We have expressed a recombinant Dengue 4 virus envelope glycoprotein (E4rec), truncated at its C-terminus by 53 amino acids, in Pichia pastoris. The presence of E4rec was confirmed by Western-blot using anti-DEN 4 hyper immune mouse ascitic fluid. E4rec migrated during SDS-PAGE as a 64 kDa protein. Treatment with endoglycosidases showed that the E protein was modified by the addition of short mannose chains and the absence of hyperglycosylation. When administered to BALB-C mice, E4rec elicited a DEN 4 neutralizing antibody response haemagglutination inhibition antibodies and specific memory T cell response. Mice immunized were also significantly protected against lethal DEN 4 virus challenge (86.6%, p < 0.001).

The pilot trial of the prevention of the increase in electrical taste thresholds by zinc containing fluid infusion during chemotherapy to treat primary lung cancer.

It is well known that there are various adverse effects during chemotherapy for cancer treatment. A taste disorder is also seen in 35-70% of patients. It has been reported that a zinc deficiency is associated with the development of these alterations in taste sensation. The purpose of this pilot study was to determine whether the zinc including infusion had the effect on taste disorder in patients with lung cancer. Taste disorder was evaluated as the increase in electrical taste thresholds using an electrogustometer. The plasma zinc concentration was also measured. Although there was no significant correlation, the increase in taste thresholds was detected in many patients who had a low zinc concentration even before receiving chemotherapy. Moreover, after 2 weeks of chemotherapy, almost all patients who did not have a zinc containing infusion showed development of taste disorder (5/5, 100% at chorda tympani area; 4/5, 80% at glossopharyngeal area), whereas no development of taste disorder was observed in those patients receiving a zinc containing infusion. These results suggest the possibility that the administration of zinc during chemotherapy could be a useful supportive therapy for preventing taste disorder and to help maintain a better quality of life.

Long-term local hyperthermia in the treatment of advanced breast cancer (case report).

BACKGROUND: It is difficult to control non-resectable locally advanced primary and recurrent breast cancer by conventional modalities. Recently, hyperthermia (HT) has been recognized as an effective adjuvant to radiotherapy (RT) and chemotherapy (CT) in treatment of various malignancies, including breast cancer. PATIENT AND METHODS: The patient was a 58-year-old female Japanese, with breast cancer, T4N2M0, stage IIIb (papillo-tubular carcinoma). Previous treatment included RT and neoadjuvant CT Local HT was performed with a total number of 87 sessions given over 12 months. The mean time of each session was 40 minutes. Elevation of temperature to a tumoricidal level of 43 degrees C was confirmed. The patient received cyclophosphamide (50 mg p.o./day) and tamoxifen (20 mg p.o./day) during the whole period of HT. Due to the decreased amount of WBC, further CT was not possible, except for one course of CMF performed 3 months after the start of HT. RESULTS: The patient had a decrease in the intensity of pain even after the first 3 sessions. In one month, movement in the right shoulder became possible in an anterio-posterior direction. By 5 months, the healing of ulceration became evident. At present, the patient is in continuous CR for 15 months after HT. The movement in the shoulder joint is markedly improved in all directions. In addition, HT did not cause any notable complications. CONCLUSION: Long-term HT may be useful in the management of locally advanced breast cancer and these results should encourage further clinical study.

Isolation and identification of adenovirus in hospitalized children, under five years, with acute respiratory disease, in Havana, Cuba.

Nine Adenovirus (Ad) strains isolated in Cuba, from 128 nasopharingeal swab specimens of children below five years old, with acute respiratory diseases, during 1996 and 1997, were studied by restriction enzyme analysis of genomic DNA with two endonucleases BamH I and Sma I. All different fragment patterns were compared with the respective prototypes. The identified adenoviruses were Ad 1 (n=4), Ad 2 (n=1) and Ad 6 (n=4). Males were more frequently infected than females. The analysis of the occurrence of these Adenovirus strains of subgenus C revealed that Ad 1 and Ad 6 were the predominant serotypes in 1996 and in 1997, respectively.

Vitamin E treatment of experimental glomerular disease in rats.

BACKGROUND: Kidney mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) are closely related in terms of origin, microscopic anatomy, histochemistry, and contractility. This relationship suggests a similarity between kidney glomerular sclerosis and atherosclerosis. Vitamin E appears beneficial in the prevention and treatment of coronary heart disease and it also inhibits the proliferation of VSMCs in vitro. Thus, we investigated the effect of vitamin E on glomerular sclerosis and MC-proliferative glomerulonephritis (GN) in two rat models of glomerular disease. METHODS: A remnant kidney rat model accelerated with hyperlipidemia was used to examine progressive glomerular sclerosis leading to chronic renal failure. A rat model of MC-proliferative GN was induced by the intravenous administration of absorbed rabbit anti-rat thymocyte serum (ATS). RESULTS: In the remnant kidney rat model, dietary supplementation with vitamin E (500 IU dl-alpha-tocopheryl acetate/kg) and cholesterol (2%) significantly inhibited glomerular sclerosis and macrophage infiltration in glomeruli relative to controls receiving basal and cholesterol-supplemented diets. In the ATS-induced GN model, glomerular cell proliferation (principally MCs) was lower in rats fed diets supplemented with vitamin E (1000 IU dl-alpha-tocopheryl acetate/kg) compared with controls fed the basal diet only. Although the degree of glomerular macrophage infiltration was similar in both groups, fewer proliferative cell nuclear antigen (PCNA)-positive cells were observed in the vitamin E group, suggesting that MC proliferation was suppressed via the inhibition of intracellular transduction. CONCLUSIONS: Supplemental dietary vitamin E suppresses MC proliferation and glomerular sclerosis in models of glomerular disease in rats. This action of vitamin E in experimental nephritis suggests the value of clinical trials testing the potential benefit of vitamin E in chronic GN patients.

Effect of vitamin E on lipid metabolism and atherosclerosis in ESRD patients.

BACKGROUND: Oxidative stress is enhanced in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). Bioincompatibility represents an important source of reactive oxygen species. HD patients exhibit altered anti-oxidative defences and anti-oxidative vitamins such as vitamin E and C are altered in uremia. Frequently, HD patients also suffer from atherosclerotic cardiac disease. We have previously reported that low density lipoprotein (LDL) of HD patients is rich in malondialdehyde (MDA), an end product of lipid peroxidation. MDA rich LDL is thought to be an atherogenic lipoprotein due to its enhancement of macrophage foam cell formation. METHODS: We conducted a controlled study for two years comparing the effects of a vitamin E coated cellulose membrane dialyzer and an ordinary cellulose membrane dialyzer on lipid metabolism and the progress of atherosclerosis. LDL-MDA and oxidized LDL (ox-LDL) were measured in HD patients using these two types of dialyzers. Plasma vitamin E and lipid concentrations were also evaluated. The aortic calcification index (ACI) was evaluated by CT scan to assess the progress of atherosclerosis before and for every year after treatment. RESULTS: Use of a vitamin E coated cellulose membrane dialyzer for six months, one year and two years resulted in a significant reduction in LDL-MDA and ox-LDL compared to the ordinary cellulose membrane dialyzer. Treatment with a vitamin E-coated dialyzer significantly reduced the percentage increase in ACI after 24 months compared to the control. There were no significant changes in plasma vitamin E and lipid concentrations between the two groups. CONCLUSIONS: These results suggest that the oxidative stress could be one of the stimulating factors of abnormal lipid metabolism and atherosclerosis in ESRD patients.

Factors associated with calcification of the abdominal aorta in hemodialysis patients.

BACKGROUND: Cardiovascular and cerebrovascular injury caused by arteriosclerosis has been the major cause of the death in hemodialysis (HD) patients. We quantitatively analyzed and evaluated the severity of abdominal aortic calcification in HD patients in comparison to risk factors for arteriosclerosis. METHODS: One hundred thirty-seven HD patients were examined. Using image analysis software, areas of the calcified abdominal aorta were quantitatively analyzed on plain computerized tomography images. Other factors such as blood pressure (BP), lipid levels, and calcium (Ca) x phosphorus (Pi) value were also analyzed. RESULTS: Patients with a higher one-year average of systolic BP showed a higher severity of abdominal aortic calcification. That is, the severity of abdominal aortic calcification in patients with a one-year systolic BP average above 160 mm Hg was 31.5 +/- 13.6%, and this severity was significantly higher than that in patients with a one-year systolic BP average of less than 120 mm Hg (8.0 +/- 7.7%, P < 0.01). The severity of abdominal aortic calcification in patients demonstrating risk values of ectopic calcification, that is serum Ca x Pi > or = 60 (mg/dl), on more than 4 of 24 measurements within one year (25.8 +/- 13.6%) was significantly higher than the severity of aortic calcification in patients demonstrating this value less than four times in one year (P < 0.05). There was no correlation between levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, lipoprotein(a), and severity of abdominal aortic calcification. CONCLUSIONS: Systolic BP levels and the product of serum Ca and Pi were related to the severity of abdominal aortic calcification in HD patients. These observations suggested that BP control, as well as control of serum Ca and Pi levels, was important in preventing the progression of abdominal aortic arteriosclerosis.

Phosphotyrosine of macrophage by low-density lipoproteins from hemodialysis patients.

BACKGROUND: Because of the possible importance of tyrosine phosphorylation in the signal transduction process, we investigated whether an interaction of low-density lipoprotein (LDL) from hemodialysis patients (HD-LDL) and human macrophages induces tyrosine-phosphorylated proteins in the macrophages. METHODS: Human monocyte-derived macrophages were incubated with HD-LDL (100 micrograms/ml) or native LDL (100 micrograms/ml) for 15 minutes at 37 degrees C. Whole cells were lyzed with Tris-HCl buffer containing vanadate and Triton X-100. After centrifugation, lyzed proteins were divided into Triton-soluble and -insoluble fractions. Both fractions (soluble and insoluble) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were electroblotted onto a polyvinylidene difluoride (PVDF) membrane. Immunoblotting was performed using an antibody against phosphotyrosine or c-Src. RESULTS: Several proteins in the range 40 to 100 kDa were found to be phosphorylated constitutively in the macrophages and not affected by the addition of HD-LDL. HD-LDL did not induce any tyrosine-phosphorylated proteins either in the soluble or insoluble fractions. Macrophages pretreated with tyrosine kinase inhibitor genestein drastically inhibited tyrosine phosphorylation of these proteins. The nonreceptor tyrosine kinase, c-Src p60, was also strongly tyrosine phosphorylated in the macrophages, and this was not enhanced by the stimulation of HD-LDL. CONCLUSION: These data suggest that tyrosine autophosphorylated proteins may play a role in the early step of signal transduction in the macrophages.

Effect of dietary fish oil, vitamin E, and probucol on renal injury in the rat.

Dietary fish oil, vitamin E, and probucol have been considered in a variety of human and experimental models of kidney disease. Using subtotal nephrectomized cholesterol-fed rats as a model for progressive kidney disease, we examined the effect of 5% dietary fish oil, or a combination of 5% dietary fish oil with 500 IU vitamin E/kg diet or 1% probucol on renal injury. Three-month-old Sprague Dawley rats were fed a control diet (C group) or a cholesterol supplemented (2%) diet (Ch group) containing either fish oil (FO group) or fish oil plus vitamin E (FO+E group) or fish oil plus probucol (FO+P group). After 4 weeks of dietary treatment, the right kidney was electrocoagulated and the left kidney nephrectomized. After 8 weeks, 24-hour urine was collected before sacrifice. No effect of the dietary treatments was noted on serum creatinine, blood urea nitrogen, or proteinuria, except that proteinuria was highest in FO+P group. Rats receiving the cholesterol diets had higher serum low density lipoprotein (LDL) + very low density lipoprotein (VLDL) cholesterol (P < 0.05). In contrast, rats in the FO+P group had the lowest serum total cholesterol and LDL+VLDL cholesterol among all groups. The FO group had 26% lower kidney alpha-tocopherol concentrations than the C group. However, inclusion of vitamin E in the diet (FO+E group) increased the kidney alpha-tocopherol status to a level comparable to that in the C group, whereas inclusion of probucol in fish oil diet (FO+P group) did not improve the kidney alpha-tocopherol status. Rats fed the cholesterol diet had a 2.5-fold higher glomerular segmental sclerosis (GSS) score and 1.5-fold higher glomerular macrophage (GM) subpopulation than the C group. These effects of the cholesterol diet were ameliorated by a fish oil diet (FO group: GSS by 30%, GM by 24%). The inclusion of vitamin E in the fish oil diet (FO+E group) did not further improve the GSS score or GM subpopulation. However, inclusion of probucol in fish oil diet (FO+P group) lowered the GSS score by 73% and reduced GM subpopulation by 83% compared with the Ch group. These remarkable changes can be attributed to the powerful hypocholesterolemic activity of probucol. Our findings indicate that progression of glomerular sclerosis in the rat remnant kidney model of progressive kidney disease can be significantly modulated with fish oil treatment.

[Effect of gonadal hormones on sexual dimorphism in malnutrition substrates]. / Efecto de las hormonas gonadales sobre el dimorfismo sexual en substrato de desnutrición.

The environmental effect on growth and sexual dimorphism is mediated by endocrinological dysfunctions. It was shown that malnutrition acts on the hypotalamus-pituitary-glandular axis. An experiment was made in Wistar rats to determine the effect of some gonadic hormones on the functional components of the skull to which sex dimorphism was alterated by a postnatal undernutrition. The effects of these hormones in restoring sexual cranial dimorphism was tested. Four treatments were applied: control, with food intake ad-libitum; undernutrition (50% of the control food intake); undernutrition plus periodic injections of testosterone and estradiol to males and females, respectively and sham-operated animals, which were injected with oil vehicle only. A radiological longitudinal study was performed between 20 and 80 days of postnatal age. The length width and height of the neural and facial components were measured on each radiograph. Data were processed by ANOVA and Mann-Whitney statistical tests were performed by means of the SYSTAT 7.0 statistical package. Results showed that gonadic hormones restored the sexual cranial dimorphism by stimulating (testosterone) or suppressing (estradiol) the growth of the cranial components.

[The application of the polymerase chain reaction technic for the detection of human papillomavirus sequences]. / Aplicación de la técnica de reacción en cadena de la polimerasa para la detección de secuencias de Papillomavirus humano.

The polymerase chain reaction technique was applied to detect sequences of human Papillomavirus (HPV) by controls of cellular lines of cervical cancer and of tissues obtained through biopsy with a HPV-positive clinical diagnosis. A set of consensus oligonucleotides, which are complementary to a highly conserved region within the open reading frame E1 of the viral genome of HPV affecting the cervical mucosa, was used. With these primers it was possible to amplify DNA sequences corresponding to HPV 6 and 11, considered in the low risk group, and to HPV 16, 18, 31 and 33, included in the high risk group. The study of the sensitivity of the amplification technique showed a level of detection of 3,5 viral particles per each cellular diploid genome.

Viral isolation from cases of epidemic neuropathy in Cuba.

OBJECTIVE: To investigate the possibility of a viral agent in the central nervous system of patients with epidemic neuropathy. DESIGN: Virus isolation attempts, in cell cultures and suckling mice, from cerebrospinal fluid (CSF) of neuropathy patients and controls undergoing lumbar puncture for unrelated reasons. Serologic studies in patients, contacts, and controls. SETTING: An epidemic of optic and peripheral neuropathy affected more than 50,000 people in Cuba in 1991 through 1993. Illness was associated with dietary limitations and increased physical demands accompanying the shortages of food and fuel experienced in Cuba since 1989. Most patients responded to parenteral vitamin therapy, and the epidemic began to subside when oral vitamin supplementation was begun for the entire Cuban population. RESULTS: Coxsackievirus A9 (five isolates) and a similar, less cytopathic virus (100 isolates) were recovered from 105 (84%) of 125 CSF specimens from neuropathy patients. The strains with light cytopathic effect were antigenically related to Coxsackieviruses A9 and B4 by cross-neutralization and immunoblotting assays. Virus persisted in CSF of some patients for 1 to 12 months. Cerebrospinal fluid from patients and both types of virus from cell culture produced illness, including complete posterior flaccid paralysis, in newborn mice, and virus was reisolated from the mice. Mouse tissues and sural nerve biopsy specimens from patients were stained by immunoperoxidase and colloidal gold techniques using hyperimmune rabbit antisera against the virus with light cytopathic effect. CONCLUSIONS: Coxsackievirus A9 or an antigenically related agent with a light cytopathic effect was present in CSF of 84% of 125 patients with epidemic neuropathy. The role of these agents, probably in combination with nutritional factors, in the pathophysiology of the disease requires further investigation.

Increased expression of a brain/embryo-type myosin heavy chain isoform (MIIB2) in mesangial proliferative glomerulonephritis.

Proliferation of mesangial cells is frequently found in glomerulonephritis, such as IgA glomerulonephritis. Recent reports suggest that a brain/embryo-type myosin isoform (MIIB2) is involved in cell proliferation. We have studied the expression of MIIB2 in renal biopsy samples from patients with various renal diseases and in the renal tissues from the rat model of mesangial proliferative glomerulonephritis induced with anti-Thy 1.1 antibody. Immunohistochemical analysis of the biopsy samples using an anti-brain-type myosin heavy chain-specific monoclonal antibody (HBM1) indicated that 92% of the samples from patients with IgA glomerulonephritis contained a significant population of mesangial cells that reacted with the antibody. Most of the samples from patients with other types of proliferative glomerular diseases also contained HBM1-reactive mesangial cells, while none of the samples from patients with non-proliferative glomerular diseases contained a significant population of HBM1-reactive mesangial cells. The expression of a brain/embryo-type myosin heavy chain isoform (MIIB2) in the mesangial cells began at five days after injection of anti-Thy 1.1 antibody and peaked at the tenth day. On the other hand, the expression of the proliferating cell nuclear antigen in the mesangial cells was induced at two days after injection of anti-Thy 1.1 antibody and was maximal at the fourth day. These results indicate that the expression of the MIIB2 isoform by mesangial cells is accelerated in proliferative glomerulonephritis and suggest that the myosin isoform is involved in the phenotypic transformations of the glomerular tissues rather than in the cell proliferation.

Effect of alpha-tocopherol on in vitro and in vivo metabolism of low-density lipoproteins in haemodialysis patients.

It has been reported that some modified low-density lipoproteins (LDLs) such as glycated LDL and malondialdehyde-rich LDL (MDA-LDL) probably exist in the circulation. The present study was undertaken to investigate the in vitro and in vivo metabolism of MDA-LDL occurring in chronic haemodialysis patients and the effects of alpha-tocopherol on these abnormalities. MDA-LDL from haemodialysis patients was degraded more rapidly by human monocyte-derived macrophages and disappeared more slowly from the circulation when compared with LDL from healthy controls. Treatment with alpha-tocopherol at doses of 600 mg/day for 2 weeks resulted in improvement of these metabolic abnormalities depending upon the degree of return to normal MDA concentrations in LDL.

[Follicular conjunctivitis caused by an adenovirus. The characterization of its strains by restriction endonucleases]. / Conjuntivitis folicular por Adenovirus. Caracterización de cepas por endonucleasas de restricción.

A study of conjunctivitis cases with a possible viral cause was carried out in Havana City during June and August, 1993. Thirty seven cases from "Ramón Pando Ferrer" Ophthalmological Hospital were studied, of whom 13 isolations (35.1%) in cell culture of Hela cells were obtained. Isolations showed a cytopathic effect characteristic of Adenovirus. A direct immunofluorescence with conjugated serum of rabbit specific to Adenovirus was performed and results were positive in 100% of cases. A DNA restriction analysis of each isolated was performed for their classification. Restriction endonucleases SmaI and Hind III were used and 2 isolates were classified as Adenovirus type 3, and 6 as Adenovirus type 7b, 4 out of 13 isolates were not classified because of the degradation of the genetic material.

Analysis of viral infection in patients with IgA nephropathy.

We investigated viral infections in the tonsils, pharynx and renal tissues of patients with IgA nephropathy using cell culture, polymerase chain reaction (PCR) and immuno-fluorescent techniques, and measured antibody titers against numerous types of viruses. Neutralization tests found no significant inhibition of growth of adenovirus-1, 2, 3, 4, 5, 6, 7, 11 or 19, Coxsackie virus-A7, A9, A16, B1, B2, B3, B4, B5 or B6, or RS virus. Swabs of the oral cavity of patients with IgA nephropathy were cultured with Hel cells, MDCK cells, FL cells, BHK-21 cells and RD-18S cells. No cytopathic effect was detected in any of these cell cultures. We failed to detect the presence of herpes simplex virus-1 and -2, varicella-zoster virus, cytomegalovirus and Epstein-Barr virus (EBV)-1 and -2 in tonsils, renal tissues and mouthwashings from patients with IgA nephropathy. On the other hand, EBV alone was detected with the PCR technique, in mouthwashings from 6 out of 14 patients with IgA nephropathy (42%). Immunohistological and serological analyses were done to examine the relationship between EBV and IgA nephropathy. No evidence was obtained that EBV-infected B lymphocytes were producing IgA. It seems unlikely that the viral infections examined in this study play a significant role in the pathogenesis of IgA nephropathy.