Male infertility and varicocele: myths and reality.

Varicocele is among the most common causes of male infertility. It is also one of the most controversial issues in the field of Andrology, especially regarding why, when and to whom varicocelectomy should be applied. Many experts believe that the surgical repair of varicocele should be applied only in a meticulously selected group of infertile men, although there are no generally accepted criteria. Up to now, the only confirmed prognostic factor for achievement of pregnancy after varicocelectomy is the age of the female partner. Given the wide application of intra-cytoplasmic sperm injection (ICSI) during the last few years, the modern research approaches should compare the benefits of varicocelectomy and ICSI, taking under consideration both the efficacy and the cost-effectiveness of the methods.

Changes of hepatitis B core antigen (HBcAg) in liver biopsies of patients with chronic active hepatitis B treated with interferon.

Data have shown that hepatitis B core antigen (HBcAg) is detected in both the hepatocyte nucleus and cytoplasm. Its expression is associated with chronic hepatitis and active viral replication. The intrahepatic distribution of HBcAg was studied in liver biopsies of 14 patients with chronic active hepatitis B (CAH-B) (5 were hepatitis B e antigen [HBeAg]+/anti-HBe--, 9 were HBeAg--/anti-HBe+) by an immunohistochemical method (PAP) before and after 6-month treatment with interferon (IFN), and our findings were analyzed according to the response of patients to treatment. Our findings showed that, at the end of treatment, nuclear HBcAg was decreased or absent in 4 of 5 and cytoplasmic HBcAg in 2 of 4 HBeAg+/anti-HBe--patients, irrespective of the response to treatment. Loss of cytoplasmic expression was related to the outcome of treatment in 5 of 9 HBeAg--/anti-HBe+ patients. Four patients expressed no HBcAg before or at the end of treatment. These findings possibly reflect a different pattern of viral core antigen expression as a result of IFN therapy in the two groups of patients.

Immunotherapy in chronic brucellosis. Effect of levamisole and interferon; mechanisms of action and clinical value.

Thirty two anergic patients with chronic brucellosis treated with a) interferon-alpha 2b(group 1), b) levamisole (group 2) and c) conventional therapy(group 3) were studied. The effect of treatment on T lymphocyte blast formation in the presence of PHA, specific cell mediated immunity against brucella antigens, titers of brucella antibodies and clinical symptoms were evaluated .T lymphocyte blast formation was shown to range in normal levels in all patients before treatment compared to 10 normal controls suggesting against a generalized impairment of cell mediated immunity. Titers of brucella antibodies were significantly decreased in group 1, almost significantly in group 2 and were significantly increased in group 3 at the end of treatment. A significant improvement of symptoms as well as production of leukocyte migration inhibition against brucella antigens were noted in both groups 1 and 2, in contrast to group 3. This response to treatment was however greater in group 1. These findings demonstrate that immunotherapy resulted in both clinical and immunological improvement and that interferon seems to be a more promising therapeutic approach of chronic brucellosis.

The effect of loratadine on activated cells of the nasal mucosa in patients with allergic rhinitis.

The effect of loratadine on the numbers of activated cells--cells expressing interleukin-2 receptors(IL-2R), HLA-DR antigens and proliferating cell nuclear antigen (PCNA)--in the nasal mucosa was studied in 48 patients with allergic rhinitis. Patients were treated with either loratadine (10 mg) or placebo for 1 month. At the end of treatment, a significant decrease in the symptom scores was noted in both groups of patients. However, the clinical score was significantly lower in the loratadine group compared to the placebo group. At the end of treatment, the numbers of IL-2R+, HLA-DR+ and PCNA+ cells were significantly decreased only in the group on loratadine. An almost significant correlation was also observed between the numbers of IL-2R+ cells and symptoms in the loratadine group. Our results show that loratadine exerts its beneficial effect possibly by inhibiting both the action of histamine and immune activation.

Interferon treatment of chronic active hepatitis B: effect of a six month treatment regimen.

In this study of 17 patients with chronic active hepatitis B, the loss of hepatitis B virus DNA, the return to normal of alanine aminotransferase activities, and histological improvement after six months' treatment with 3 million units three times weekly with interferon alfa-2b, was achieved in 40% of hepatitis B e antigen (HBeAg) positive/anti HBe negative patients, and 41.66% of HBeAg negative/anti HBe positive patients. The reappearance of hepatitis B virus DNA was seen in most patients when treatment was stopped, although a higher percentage of HBeAg positive/anti HBe negative patients (20%) had a sustained loss of hepatitis B virus DNA, return to normal alanine aminotransferase activities, and histological improvement compared with HBeAg negative/anti HBe positive patients (8.3%).

alpha-Interferon therapy in patients with chronic active hepatitis B: immunological profile.

The effect of interferon-alpha 2b (IFN) on viral markers, liver function and immunological parameters (CD3, CD4, CD8, B, NK, II-2 receptor and HLA-DR positive cells in blood and T cell proliferation) was studied in 9 patients with HBsAg(+), HBeAg(-) chronic active hepatitis (CAH). Three patients were HBV-DNA(+) and 6 also had complications of cirrhosis of the liver (LC). IFN was given at a dose of 2.5 mil IU x 3 weekly for 6 months. One patient with LC developed hepatic coma and died 2 months later. Severe leukopenia limited duration of treatment to 2 and 4 months in another 2 patients. By the end of treatment, the 8 patients were in good clinical status, SGOT, SGPT levels and prothrombin time were decreased, HBV-DNA became negative in 2 out of 3 patients and proportions of CD3, CD4, B, NK and activated cells were significantly decreased. When compared to controls, NK and activated cells were significantly increased in patients before and were gradually decreased by the end of treatment. In contrast, T transformed cells were significantly decreased before and ranged in normal levels by the end of treatment. These findings suggest that immunomodulatory activity possibly contributes to the beneficial effect of IFN therapy.

In vitro effect of interferon alpha-2b on T lymphocyte transformation and leukocyte migration inhibition in patients with chronic brucellosis.

The in vitro effect of IFN-a on lymphocyte transformation and specific immune response against Brucella antigens was studied in 33 patients with chronic brucellosis and 10 normal controls. The following immunologic in vitro tests were applied: PHA activated lymphocyte transformation test using Bromodeoxyuridine and a monoclonal antibody in the presence and absence of 50 and 100 IU IFN Alpha-2b and leukocyte migration inhibition test against Brucella antigens in the presence and absence of 100 and 500 IU of IFN Alpha-2b. Patients were further divided to 2 subgroups according to a positive or negative migration inhibition test. Our results showed that T lymphocyte transformation was similar in patients and controls and that the addition of 50 IU IFN resulted in a significant increase of transforming cells whereas in the concentration of 100 IU IFN only anergic patients and controls responded positively. IFN also resulted in a significant leukocyte migration inhibition only in anergic patients and controls. These findings suggest that the chronic infection is not due to a generalized cellular immunodeficiency state and that IFN Alpha-2b might be a promising therapeutic approach in anergic patients.

Lymphocyte subpopulations in gastric disease; effect of histamine and cimetidine on immunoregulatory T cell subsets.

The numbers of T lymphocytes, helper and suppressor T lymphocytes, were measured in peripheral blood of 10 patients, 13 patients with gastric cancer and 20 normal controls. T lymphocyte subpopulations were enumerated by the use of monoclonal antibodies OKT3 (pan-T lymphocytes), OKT4 (helper/inducer lymphocytes) and OKT8 (cytotoxic/suppressor lymphocytes) in an indirect immunofluorescence technique. Furthermore, the possible pharmacological modulation of 10(-4) histamine and 10(-4), 10(-6) M cimetidine of T lymphocyte subsets was investigated. Lymphocyte subpopulations were found to range in normal values in patients with ulcer and chronic gastritis. A marked decrease of OKT3 and OKT8 positive lymphocytes was noted in patients with gastric cancer, whereas OKT4 lymphocytes from the three groups of patients to histamine and cimetidine resulted in no significant changes of lymphocyte subsets.

Reevaluation of the effect of levamisole in chronic brucellosis: in vitro and in vivo effect on monocyte phagocytosis.

The in vitro effect of levamisole on peripheral blood monocyte (P.B.M.) phagocytosis was studied in 32 patients with chronic brucellosis and 20 normal subjects. It was shown that levamisole enhances P.B.M. phagocytic capacity, not reaching however normal levels. A subgroup of 11 patients were treated with levamisole for 6 months and the drug effect on cellular and humoral immunity and monocyte phagocytosis was also studied. By the end of the 6 month treatment-study period, the following results were obtained: 1. six patients were symptom free while five had significantly improved. 2. T lymphocyte number and monocyte phagocytosis reached normal values. 3. Significant specific cellular immunity against both brucella antigens was noted. 4. B. lymphocytes showed no significant changes. 5. Antiglobulin titers varied. These findings suggest that the good therapeutical effect of levamisole in patients with chronic brucellosis could probably be a attributed to the enhancement of both T-cell function and monocyte phagocytosis.

A study of cell-mediated immunity to gastric antigens in patients with atrophic type A and B gastritis.

The leucocyte migration in the presence of gastric antigens was studied in 10 patients with type A gastritis, 38 patients with type B gastritis (28 with atrophic and 10 with superficial gastritis) and 10 healthy controls. A positive leucocyte migration was found in a significant proportion of patients with both types of gastritis, whereas no difference between the two types was observed. These results indicate that cellular immunity is implicated in the aetiology of both types of gastritis, is of greater importance than auto-antibody production and is associated with the severity of the atrophic lesion.

Peripheral blood T lymphocytes in patients with duodenal ulcers treated with cimetidine.

The influence of cimetidine on the numbers of circulating T lymphocytes was studied in 24 patients with duodenal ulcer treated with cimetidine. The patients were divided into two groups according to the way of cimetidine administration and T lymphocytes were measured during treatment. No significant difference in the numbers of T lymphocytes was found in both groups of patients suggesting that cimetidine given therapeutically has no effect on circulating T lymphocytes.

Peripheral blood monocyte phagocytosis in patients with chronic brucellosis.

Peripheral blood monocyte phagocytosis of SRBC was studied in 32 patients with chronic brucellosis and 20 normal controls. It was found that phagocytosis was significantly decreased in patients with chronic brucellosis. Our findings suggest that disfunction of this cell-system in chronic brucellosis could be responsible for the chronicity of the disease.

Double-blind evaluation of domperidone in acute vomiting and dyspeptic disorders.

The anti-emetic effects of domperidone were evaluated under double-blind conditions in twenty-four patients with acute vomiting randomly assigned to treatment either with 10 mg i.m. domperidone (six female, five males) or with placebo (seven females, six males). The therapeutic results were better with domperidone and the differences from placebo were statistically significant (p less than 0.02). In a second randomized, crossover, double-blind trial, domperidone (10 mg t.i.d.) evaluated according to a nine-symptom rating scale, in eighteen dyspeptic patients, proved significantly more effective than placebo. The duration of treatment was 6 weeks and the drugs were crossed-over after 3 weeks. The difference between the two groups was most marked during the second phase of the trial. No side-effects were reported.

Levamisole in the treatment of chronic brucellosis.

Ten patients with chronic brucellosis were treated with levamisole, 150mg daily for 3 consecutive days every week for 6 months. Patients were followed up for another 6 months after the end of treatment. By the end of the treatment period, patients improved clinically, their E rosettes showed a significant increase and specific leukocyte inhibition migration factor (LIF) was produced. By the end of the follow up period, all patients except one became symptom free, antiglobulin titers were very low or negative, E rosettes showed a further increase ranging to normal levels and specific LIF activity was not detected to most of the patients. Our results suggest that levamisole might prove to be beneficial in the treatment of chronic brucellosis.

Serum inhibitory factors and E rosettes in chronic renal failure.

The inhibiting effect of uraemic serum on both normal and uraemic lymphocytes capacity to form E rosettes was studied in 10 uraemic patients and 14 healthy controls. Uraemic serum was found to significantly inhibit E rosette forming cells of normal and uraemic lymphocytes. On the other hand, E rosettes of uraemic patients ranged in normal values after incubation in normal serum. These findings suggest that rosette inhibiting factors are present in uraemia and that uraemic T lymphocyte sheep erythrocyte rosette function is intact.

Physiological variations of T cells during the menstrual cycle.

Peripheral blood T lymphocytes were measured in healthy subjects during the various phases of the menstrual cycle. A significant decrease in T lymphocytes occurred during the menstrual period; T-lymphocyte numbers returned to the pre-levels 1 week after the end of the menstrual period.