Is varicocelectomy indicated in subfertile men with clinical varicoceles who have asthenospermia or teratospermia and normal sperm density?

OBJECTIVE: Varicocele is the most common treatable cause of male infertility and is associated with progressive decline in testicular function. Varicocelectomy, a commonly performed operation, is indicated in infertile males with varicoceles who have oligospermia, asthenospermia, teratospermia or a combination of these factors. It is not clear if varicocelectomy is indicated if the patients have normal sperm density associated with asthenospermia or teratospermia. METHODS: We reviewed 167 patients with varicocele-associated male infertility over a 7-year period (December 1999-November 2005). Pre- and post-varicocelectomy seminal fluid analyses, assessed using the World Health Organization criteria, were obtained at intervals of 4-6 months. Wilcoxon signed rank tests were used to evaluate for statistical significance and P < or = 0.05 was considered significant. RESULTS: The mean age of the patients and their spouses were 35 and 28 years, respectively. The mean duration of infertility was 3.2 years (range, 1.5-7.5). Oligospermia, teratospermia, asthenospermia, oligospermia, asthenospermia and teratospermia (OAT) syndrome and azoospermia were found preoperatively in 106 (63.5%), 58 (34.7%), 154 (92%), 118 (71%) and 15 (9%) patients, respectively. Overall, significant improvements in semen volume (P < 0.001), sperm density (P < 0.001), sperm motility (P < 0.001) and sperm vitality (P < 0.001) were obtained after varicocelectomy. There was, however, no significant improvement in sperm morphology after varicocelectomy (P = 0.220). When patients with preoperative oligospermia (sperm density, <20 million/mL) were considered separately, varicocelectomy led to significant improvement in all the semen parameters except the sperm morphology (P = 0.183). Conversely, when varicocele patients with a sperm density of > or =20 million/mL (normospermia) associated with asthenospermia and/or teratospermia were considered separately, they did not show significant improvement in any of the semen parameters after varicocelectomy (P > 0.05). In addition, azoospermic patients did not show significant improvement in any of the semen parameters (P > 0.05) CONCLUSION: No significant improvement in semen parameters may be obtained in patients with clinical varicocele and preoperative normospermia. It is possible that only patients with preoperative oligospermia may benefit from varicocelectomy. Larger multi-institutional studies are needed to determine more definitively if asthenospermia or teratospermia in normospermic subfertile males with clinical varicoceles are in fact indications for varicocelectomy.     

Sedative and Anxiolytic Effects of the Extracts of the Leaves of Stachytarpheta Cayennensis in Mice

The leaves are used ethnomedicinally in Nigeria and other parts of the world for insomnia and anxiety among other uses. The investigations sought scientific evidence for the ethnomedicinal use of the leaves for the management of insomnia and anxiety as well as the neural mechanisms for the activities. The sedative and anxiolytic effects of the extracts of the leaves of Stachytarpheta cayennensis were examined in this study. The methanolic extract (5–50 mg/kg, i.p.) as well as the ethylacetate (10–50 mg/kg, i.p.), butanol and aqueous fractions (5–50 mg/kg, i.p.) of the extract were examined. Sedation was assessed as reduced novelty-induced rearing (NIR), reduced spontaneous locomotor activity (SLA) and increased pentobarbitone-induced sleeping time (PIST) in mice. The anti-anxiety effect (methanol 2.5–5.0; butanol 5.0; aqueous 20.0; ethylacetate 25.0 mg/kg, i.p.) was assessed using an elevated plus maze. LD₅₀ was calculated for the extract and the fractions after the intraperitoneal route of administration using the Locke method. The methanolic extract, the butanol and the aqueous fractions inhibited rearing and spontaneous locomotion but prolonged pentobarbitone induced sleep. The ethylacetate fraction however increased both rearing and locomotion and decreased pentobarbitone sleeping time. The butanol and aqueous fractions, but not the methanol extract showed indices of open arm avoidance consistent with anti-anxiety effect. Naltrexone (2.5 mg/kg, i.p.) reversed the inhibition of rearing, locomotion and prolongation of pentobarbitone sleep due to the aqueous fraction of the extract. Flumazenil (2mg/kg, i.p.) abolished the effects of both methanolic extract and the butanol fraction on rearing, locomotion, pentobarbitone sleep and anxiety model. The methanolic extract, the butanol and aqueous fractions possess sedative activity while the ethylacetate fraction possesses stimulant property. The anxiolytic effect was found in both the aqueous fraction and the butanol fraction but not in the main methanol extract and also not in the ethylacetate fraction. Flumazenil, blocked the effect of the leaves of Stachytarpheta cayennensis on rearing, locomotion and elevated plus maze suggesting that GABA receptors are involved in the observed sedative and anxiolytic activities. This study also found opioid receptors involved in the sedative activity of the leaves of Stachytarpheta cayennensis. The rationale for the ethnomedicinal use of the leaves for the management of insomnia and anxiety were confirmed scientifically in this study.     

Clinicopathological features of gastric carcinoma in Ibadan,Nigeria, 2000-2011

Aim:

The most recent study on the clinicopathological features of gastric carcinoma from the University College Hospital (UCH), Ibadan, was done in 2000. The aim of this study is to update the knowledge on the clinicopathological features of gastric carcinoma diagnosed in the Pathology Department of the UCH Ibadan between 2000 and 2011.

Materials and Methods:

This was a 12-year retrospective review of clinical and demographic data and the histopathological features of gastric cancers diagnosed at the Pathology Department of the UCH. The chi square test, Fisher''s exact test, and the t-independent test were used as applicable in the statistical analyses.

Results:

A total of 117 cases of gastric carcinoma were histologically diagnosed at the Pathology Department of UCH, Ibadan in this period giving a relative ratio frequency of 1.38% for all cancers. It represented 18.4% of all gastrointestinal tract malignancies diagnosed in the same period. There was a male preponderance with male:female ratio of 1.72:1; the middle-aged and elderly made up about 76.1% of cases. The disease was clinically and histologically advanced in 92.8% of cases. Gastric tumours were predominantly antral/ pyloric in 80% of cases and exophytic in 62.3% of cases. The intestinal histotype constituted 47.0% cases although a rise in the diffuse histological type was observed.

Conclusion:

There is a decline in the relative ratio frequency of gastric carcinoma in Ibadan; and a fall in the rate of the intestinal type of gastric carcinoma relative to the diffuse type when compared to previous studies from our centre.     

Evidence that Meningeal Mast Cells Can Worsen Stroke Pathology in Mice

Stroke is the leading cause of adult disability and the fourth most common cause of death in the United States. Inflammation is thought to play an important role in stroke pathology, but the factors that promote inflammation in this setting remain to be fully defined. An understudied but important factor is the role of meningeal-located immune cells in modulating brain pathology. Although different immune cells traffic through meningeal vessels en route to the brain, mature mast cells do not circulate but are resident in the meninges. With the use of genetic and cell transfer approaches in mice, we identified evidence that meningeal mast cells can importantly contribute to the key features of stroke pathology, including infiltration of granulocytes and activated macrophages, brain swelling, and infarct size. We also obtained evidence that two mast cell-derived products, interleukin-6 and, to a lesser extent, chemokine (C-C motif) ligand 7, can contribute to stroke pathology. These findings indicate a novel role for mast cells in the meninges, the membranes that envelop the brain, as potential gatekeepers for modulating brain inflammation and pathology after stroke.Stroke, the leading cause of adult disability and the fourth most common cause of death in the Unites States,^1,2 occurs when there is insufficient blood flow to the brain, and the resultant injury initiates a cascade of inflammatory events, including immune cell infiltration into the brain.^3–5 This post-stroke inflammation is a critical determinant of damage and recovery after stroke; understanding the interplay between the immune system and the brain after stroke holds much promise for therapeutic intervention.^4–7 However, successfully exploiting this therapeutic potential requires a detailed understanding of the interplay between the immune system and the brain after stroke.⁴An understudied but important aspect of this interplay is the role of meningeal-located immune cells in modulating brain pathology. The meninges have long been recognized as an anatomical barrier that protects the central nervous system (CNS). However, accumulating evidence suggests that the meninges are important for communication between the CNS and immune system during health and disease.^8–10 All blood vessels pass through the meningeal subarachnoid space before entering the brain, and this vascular connection and the close proximity of the meninges to the underlying parenchymal nervous tissue make them ideally located to act as a gatekeeper to modulate immune cell trafficking to the CNS. To support this gatekeeper function is evidence that the meninges modulate brain infiltration of T cells, neutrophils, and monocytes during meningitis and autoimmune conditions,^11–14 with immune cells observed in some instances accumulating in the meninges before they infiltrate into the parenchyma.^11,13Emerging evidence suggests that the actions of immune cells resident in the meninges are important for this gatekeeper function.^11,12,15 Mast cells (MCs), best known as proinflammatory effector cells, can play critical roles in the development of inflammation in many disease settings.^16–18 MCs reside in high numbers within the meninges, but their function in this site has not been fully investigated in stroke pathology. Unlike most immune cells, mature MCs do not circulate in the blood but are long-term residents of tissues, often in perivascular locations, and can rapidly perform their functions in situ. CNS MCs are found in the brain parenchyma and the meninges of rodents and humans.¹⁸ It has been proposed that brain parenchymal MCs can enhance brain neutrophil numbers after stroke and can exacerbate stroke pathology.^19–24 However, much of the evidence to support such conclusions is indirect. For example, some of the studies that implicate MCs in stroke pathology used pharmacologic approaches to interfere with MC activation,^19,20,22 but such drugs can have effects on other cell types.²⁵ Moreover, the role of the meningeal MCs in modulating post-stroke inflammation and pathology is unknown. Finally, little is understood about which among the many MC-derived mediators may be important in stroke pathology.^17,26To address these questions, we used genetic and cell transfer approaches to study the role of MCs in the pathology of ischemic stroke in mice. Specifically, we tested a c-kit–mutant mouse model (ie, WBB6F₁-Kit^W/W-v mice) which is profoundly MC deficient and can be repaired of this deficiency by engraftment of in vitro-derived MCs from wild-type (WT) mice. This MC knock-in approach enables the MC-dependent effects in the mutant mice to be separated from effects due to other abnormalities associated with their mutation,^11,17,26,27 because only the MC deficiency is repaired by MC engraftment. Furthermore, one can investigate the mechanisms by which MCs influence stroke pathology by engrafting MCs from transgenic mice that lack specific MC-associated products. We also tested our newly described Cpa3-Cre; Mcl-1^fl/fl mice, in which MC (and basophil) numbers are reduced constitutively via Cre-mediated depletion of the anti-apoptotic factor, myeloid cell leukemia sequence 1 (Mcl-1), in the affected lineages.²⁸ Cpa3-Cre; Mcl-1^fl/fl mice lack the other abnormalities associated with the c-kit mutations in WBB6F₁-Kit^W/W-v mice.²⁸With the use of these in vivo models, we identified meningeal MCs as important contributors to key features of stroke pathology, including increased numbers of brain granulocytes and activated macrophages, brain swelling, and infarct size. We also obtained evidence that two potentially proinflammatory MC-derived products, IL-6 and, to a lesser extent, chemokine (C-C motif) ligand 7 (CCL7), can contribute to pathology in this setting.     

The Thermolysin Family (M4) of Enzymes: Therapeutic and Biotechnological Potential

Zinc containing peptidases are widely distributed in nature and have important roles in many physiological processes. M4 family comprises numerous zinc‐dependent metallopeptidases that hydrolyze peptide bonds. A large number of these enzymes are implicated as virulence factors of the microorganisms that produce them and are therefore potential drug targets. Some enzymes of the family are able to function at the extremes of temperatures, and some function in organic solvents. Thereby enzymes of the thermolysin family have an innovative potential for biotechnological applications.     

Living with Cancer: A Qualitative Report of the Experiences of Leukaemia Patients in Lagos, Nigeria

The study examined the qualitative, cognitive and psychosocial experiences of those living with leukaemia undergoing treatment at a teaching hospital. Twenty respondents who consented to participate were purposively selected from the cancer patients with leukaemia receiving treatment in the said teaching hospital. The in-depth interview method was used to collect data. The data was analysed using manual content analysis. Data showed that patients lack basic knowledge about leukaemia and had no beliefs regarding leukaemia. Some patients believed in God and a medical breakthrough for a cure, while for some, the hope of living was not certain. The ill-health condition had brought about financial predicament to both patients and family members and has limited their productivity in terms of income-generating activities. Good interpersonal relationships and support from their care providers aided their compliance to treatment regime and provided hope for living positively with their condition. The study concludes that there is a need to educate the patients on the causes of their condition. Financial supports should be rendered to those living with leukaemia, while health care providers should be encouraged to continue to maintain good interpersonal relationships with their patients.