The behavior of epididymis, processus vaginalis and testicular descent in cryptorchid boys treated with buserelin

This randomized double-blind placebo-controlled study was initiated to analyze the behavior of epididymis, processus vaginalis and testicular descent in cryptorchid boys treated with a low dose (20 g) of a luteinizing hormone-releasing hormone analogue (Buserelin), administered daily, as a nasal spray, for a short period (28 days). Fifty-nine true cryptorchid boys were randomly assigned to 3 groups: buserelin, treatment [22], surgical treatment [18] or placebo control group [19]. The 3 groups of patients were similar before treatment in regard to testicular position, chronological and bone age, height and weight, luteinizing hormone, follicle-stimulating hormone, testosterone, penile size and the volume of the contralateral descended testis. None of the patients had retractile testes. Buserelin significantly induced testicular descent compared to the boys treated with a placebo (P<0.01). A normal epididymis was found more often in boys with successful descent (P<0.003). A closed processus vaginalis was also more frequently observed in the group treated with buserelin than in surgically treated one (P<0.05). In conclusion, buserelin was capable of inducing testicular descent besides provoking further development of the epididymis and closing the processus vaginalis.     

Dopa-responsive dystonia in British patients: new mutations of the GTP- cyclohydrolase I gene and evidence for genetic heterogeneity

Dopa-responsive dystonia (DRD) was originally described in a series of Japanese patients, but is now increasingly recognized in other countries. Recently the GTP cyclohydrolase I (GTPCH) gene was isolated as the first causative gene for dopa-responsive dystonia (DRD). Mutations were identified in three Japanese families with autosomal dominantly inherited DRD and in one sporadic Japanese patient. Characterisation of the exon-intron boundaries of this gene has now allowed the analysis of mutations at the level of genomic DNA. Amplifying all six exons, we analyzed the GTPCH gene in nine British families with 33 affected family members and in three sporadic cases and found six new mutations. Only point mutations were found, causing a stop codon in one family and an amino acid change in highly conserved regions of the gene in a further four families and in one sporadic case. None of these mutations were detected more than once and none of the mutations previously described were found in our patients. No mutations were identified in four families and in two sporadic cases.      

Antibody responses to antigenic sites 1 and 3 of serotype 3 poliovirus after vaccination with oral live attenuated or inactivated poliovirus vaccine and after natural exposure

Three important antigenic sites involved in virus neutralization on polioviruses in mouse experiments have been identified. These sites are located at the surface of the virion and have been designated antigenic sites 1, 2, and 3. In mice, the antibody response to antigenic site 1 of serotype 3 poliovirus is considered to be immunodominant, but little is known about the immunogenicity of these sites in humans. In the present study, we developed inhibition enzyme-linked immunosorbent assays specific for antigenic sites 1 and 3 to measure antibody responses to these sites in fully vaccinated inactivated poliovirus vaccine (IPV) (n = 63) and oral live attenuated poliovirus vaccine (OPV) (n = 63) recipients and in naturally infected persons (n = 25). Similar levels of antibodies to site 1 in IPV and OPV vaccinees were detected. However, significantly more OPV recipients (88.7%) had detectable antibodies to antigenic site 3 (P < 0.01) than did IPV-vaccinated persons (63. 1%). After an IPV booster vaccination, both previously IPV- and OPV-vaccinated persons responded with a significant increase in antibodies to sites 1 and 3 (P < 0.01). We conclude that the immune response to serotype 3 poliovirus in humans consists of both site 1- and site 3-specific antibodies and that these responses can be induced by either OPV or recent IPV vaccination.     

Lactogenic Activity of Rats Stimulated by Gunnera Perpensa L. (Gunneraceae) from South Africa

Gunnera perpensa L. (Gunneraceae) is a medicinal plant used by Zulu traditional healers to stimulate milk production. The effect of an aqueous extract of the rhizome of the plant on milk production in rats was investigated. Female lactating rats that received oral doses of the extract of G.perpensa significantly (p<0.05) produced more milk than controls. The plant extract did not however, significantly influence the levels of prolactin, growth hormone, progesterone, cortisol, ALT, AST and albumin in the blood. The mammary glands of rats treated with the extract showed lobuloalveolar development. The extract (0.8 µg/ml) was also found to stimulate the contraction of the uterus and inhibit (23%) acetylcholinesterase activity. The cytotoxicity of the extract (LC₅₀) to two human cell lines (HEK293 and HepG2) was 279.43 µg/ml and 222.33µg/ml, respectively. It is inferred that the plant extract exerts its activity on milk production and secretion by stimulating lobuloalveolar cell development and the contraction of myoepithelial cells in the alveoli. It is concluded that Gunnera perpensa contains constituents with lactogenic activity that apparently contribute to its effectiveness in folk medicine.     

Nitric oxide production during the early neonatal period in small-for-gestational-age infants

In a study of endogenous nitric oxide production in growth-retarded, very preterm newborns (<32 wk GA), urinary NOx/creatinine ratio and plasma guanosine 3',5'-cyclic monophosphate levels were determined during the early neonatal period. Newborns were divided into three groups: appropriate-for-gestational-age (AGA, n = 19), moderately small-for-gestational-age (SGA, n = 13) and severely SGA (n = 6) infants. Severely SGA infants showed significant higher values of nitric oxide derivatives during the first 24 h of life compared with the other groups. CONCLUSION: An increased NO production is found in SGA infants during the first 24 h after birth. This may reflect an increased intrauterine nitric oxide production in the feto-placental circulation found in cases with intrauterine growth retardation,     

Socioeconomic impact of cancer in member countries of the Association of Southeast Asian Nations (ASEAN): the ACTION study protocol

Cancer can be a major cause of poverty. This may be due either to the costs of treating and managing the illness as well as its impact upon people's ability to work. This is a concern that particularly affects countries that lack comprehensive social health insurance systems and other types of social safety nets. The ACTION study is a longitudinal cohort study of 10,000 hospital patients with a first time diagnosis of cancer. It aims to assess the impact of cancer on the economic circumstances of patients and their households, patients' quality of life, costs of treatment and survival. Patients will be followed throughout the first year after their cancer diagnosis, with interviews conducted at baseline (after diagnosis), three and 12 months. A cross-section of public and private hospitals as well as cancer centers across eight member countries of the Association of Southeast Asian Nations (ASEAN) will invite patients to participate. The primary outcome is incidence of financial catastrophe following treatment for cancer, defined as out-of-pocket health care expenditure at 12 months exceeding 30% of household income. Secondary outcomes include illness induced poverty, quality of life, psychological distress, economic hardship, survival and disease status. The findings can raise awareness of the extent of the cancer problem in South East Asia and its breadth in terms of its implications for households and the communities in which cancer patients live, identify priorities for further research and catalyze political action to put in place effective cancer control policies.     

CRAVT: a prospective, randomized study comparing transvenous cryothermal and radiofrequency ablation in atrioventricular nodal re-entrant tachycardia.

BACKGROUND: Transvenous catheter ablation of atrioventricular nodal re-entrant tachycardia (AVNRT) with radiofrequency (RF) is effective and safe, but carries a 1-3% incidence of early and potentially late heart block. Cryothermy can create transient effects, and identify potentially successful ablation sites and decrease the risk for permanent heart block. METHODS: In this prospective, randomized trial 102 patients with recurrent narrow QRS-complex tachycardia suggestive of AVNRT were randomized to either RF or cryoablation before a diagnostic study. RESULTS: In 63 patients with AVNRT, 33 were randomized to RF and 30 to cryoablation. Procedural success was achieved, respectively, in 30 (91%) patients in the RF and 28 (93%) in the cryoablation group. The median number of cryothermal applications was significantly lower than the number of RF applications (2 versus 7, p<0.005). No accelerated junctional rhythm was seen with cryothermy, while it was present in 31/33 RF patients. Both fluoroscopy and procedural times were comparable. The radiological position of the successful site in relation to anatomical landmarks was slightly different (p<0.05). No cryothermy related complications were observed, and no permanent AV conduction disturbances occurred. During a mean follow up of 13+/-7 months long-term clinical success was seen in one additional patient in each group. In the same period, 3 patients in both groups experienced recurrent AVNRT. CONCLUSION: Cryoablation is as effective and safe as RF for AVNRT. Significantly fewer applications are necessary, with comparable procedure times. This makes cryothermy useful for the treatment of tachyarrhythmias near the compact AV node.     

The polio eradication effort has been a great success--let's finish it and replace it with something even better

The polio eradication campaign has greatly reduced the effects of this disease, but many new challenges have emerged. These challenges include the occurrence of polio outbreaks caused by wild-type polioviruses or circulating vaccine-derived polioviruses (cVDPVs) in areas where vaccination coverage is low, the existence of people who excrete poliovirus persistently, and the inability to know definitely that poliovirus has gone. As a result, there is uncertainty about if, when, and how we can end polio immunisation. In this article, we discuss several scenarios for the future of polio control. Because the emergence of cVDPVs necessitates discontinuing the use of live oral polio vaccine, we propose to strive towards a global coverage of near 100% vaccination against all major childhood infections using combination vaccines that contain inactivated poliovirus vaccine. Such a policy will present multiple challenges.     

Restoration of adenylate cyclase responsiveness in murine myeloid leukemia permits inhibition of proliferation by hormone. Butyrate augments catalytic activity of adenylate cyclase

Mechanisms of leukemic cell clonal dominance may include aberrations of transmembrane signaling. In particular, neoplastic transformation has been associated with reduced capacity for hormone-stimulated adenylate cyclase activity. In the present study, prostaglandin E, a hormonal activator of adenylate cyclase that has antiproliferative activity in myeloid cells, and cholera toxin, an adenylate cyclase agonist that functions at a postreceptor site by activating the adenylate cyclase stimulatory GTP-binding protein (Gs), were studied for antiproliferative activity in two murine myeloid cell lines. FDC-P1, an interleukin 3 (IL 3)-dependent myeloid cell line and a tumorigenic IL 3- independent subline, FI, were resistant to these antiproliferative agents. The in vitro ability of the "differentiation" agent, sodium butyrate, to reverse their resistance to adenylate cyclase agonists was studied. The antiproliferative action of butyrate involved augmentation of transmembrane adenylate cyclase activity. Increased adenylate cyclase catalyst activity was the primary alteration of this transmembrane signaling group leading to the functional inhibitory effects on leukemia cells, although alterations in regulatory G- proteins appear to play a secondary role.