Noncommunicable diseases in sub-Saharan Africa: where do they feature in the health research agenda?

There is no doubt that communicable diseases will remain the predominant health problem for the populations in sub-Saharan Africa, including adults, for the next 10-20 years. Concern has been expressed that the available resources to deal with this problem would be reduced by increasing the emphasis on noncommunicable diseases. The latter, however, already present a substantial burden because their overall age-specific rates are currently higher in adults in sub-Saharan Africa than in populations in Established Market Economies. There is also evidence that the prevalence of certain noncommunicable diseases, such as diabetes and hypertension, is increasing rapidly, particularly in the urban areas, and that significant demands are being made on the health services by patients with these diseases. To ignore the noncommunicable diseases would inevitably lead to an increase in their burden; the provision of health services for them would be largely undirected by issues of clinical and cost effectiveness, and their treatment and prevention would be left to the mercy of local and global commercial interests. Improved surveillance of all diseases within sub-Saharan Africa is needed in order to place noncommunicable diseases properly within the context of the overall burden of disease. Research is needed to guide improvements in the clinical and cost effectiveness of resources currently committed to the care of patients with noncommunicable diseases, and to direct and evaluate preventive measures.     

The efficacy and safety of intraoperative and/or postoperative 5-fluorouracil in trabeculectomy and phacotrabeculectomy

Purpose : First, to assess the safety and efficacy of using 5‐fluorouracil (5‐FU) to improve trabeculectomy and phacotrabeculectomy success rates, and second, to assess the efficacy of intraoperative and reduced postoperative 5‐FU following trabeculectomy compared with a more intensive course of postoperative 5‐FU alone. Methods : In a retrospective, unmatched, non‐randomized consecutive series study, 186 eyes of 186 patients who had filtration surgery were followed for 2 years in four groups: 51 patients had undergone trabeculectomy surgery with postoperative 5‐FU, 51 had phacotrabeculectomy with postoperative 5‐FU, 56 had trabeculectomy with both intraoperative and postoperative 5‐FU, and 28 patients had trabeculectomy without antifibrotics. Results : At all times mean intraocular pressure (IOP) was reduced in all groups (P < 0.001 for each group). Success was defined as IOP < 16 mmHg and > 30% IOP reduction at the 2‐year follow up. It was achieved in 71% of the trabeculectomy patients with intraoperative and postoperative 5‐FU, 76% of the trabeculectomy group with only postoperative 5‐FU, 55% of the phacotrabeculectomy/ 5‐FU group, and in 29% of the trabeculectomy‐only eyes (between‐group differences P < 0.01). Success rates were not significantly different for the intraoperative and postoperative 5‐FU trabeculectomy versus the postoperative 5‐FU‐only eyes, but the former had fewer postoperative 5‐FU injections and corneal ulceration (P < 0.01 for both). Conclusions : 5‐Fluorouracil was safe and improved trabeculectomy survival. Intraoperative 5‐FU allowed fewer postoperative 5‐FU injections and fewer side‐effects without compromising success rates. Phacotrabeculectomy with postoperative 5‐FU had a lower surgical success rate than did trabeculectomy with 5‐FU and this was not statistically different from trabeculectomy without 5‐FU.     

A prominent soma-dendritic distribution of Kv3.3 K+ channels in electrosensory and cerebellar neurons.

The expression pattern and subcellular distribution of a teleost homologue of the mammalian Kv3.3 potassium channel, AptKv3.3, was examined in the electrosensory lateral line lobe (ELL) and two cerebellar lobes in the hindbrain of the weakly electric gymnotiform Apteronotus leptorhynchus. AptKv3.3 expression was brain specific, with the highest level of expression in the cerebellum and 56% relative expression in the ELL. In situ hybridization revealed that AptKv3.3 mRNA was present in virtually all cell classes in the ELL as well as in the cerebellar lobes eminentia granularis pars posterior (EGp) and corpus cerebellum (CCb). Immunocytochemistry indicated a distribution of AptKv3.3 channels over the entire soma-dendritic axis of ELL pyramidal, granule, and polymorphic cells and over the soma and at least proximal dendrites (100 microm) of multipolar cells and neurons of the ventral molecular layer. AptKv3.3 immunolabel was present at the soma of cerebellar granule, golgi, eurydendroid, and CCb Purkinje cells, with an equally intense label throughout the dendrites of CCb Purkinje cells and EGp eurydendroid cells. Immunolabel was virtually absent in afferent or efferent axon tracts of the ELL but was detected on climbing fiber axons and on the axons and putative terminal boutons of CCb Purkinje cells. These data reveal a prominent soma-dendritic distribution of AptKv3.3 K+ channels in both principal output and local circuit neurons, a pattern that is distinct from the soma-axonal distribution that characterizes all other Kv3 K+ channels examined to date. The widespread distribution of AptKv3.3 immunolabel in electrosensory cells implies an important role in several aspects of signal processing.     

Spatial learning deficits without hippocampal neuronal loss in a model of early-onset epilepsy.

Studies were undertaken to examine the effects recurrent early-life seizures have on the ability of rats to acquire spatial memories in adulthood. A minute quantity of tetanus toxin was injected unilaterally into the hippocampus on postnatal day 10. Within 48 h, rats developed recurrent seizures that persisted for 1 week. Between postnatal days 57 and 61, rats were trained in a Morris water maze. Toxin-injected rats were markedly deficient in learning this task. While these rats showed gradual improvement in escape latencies over 20 trials, their performance always lagged behind that of controls. Poor performance could not be explained by motor impairments or motivational difficulties since swimming speed was similar for the groups. Only eight of 16 toxin-injected animals showed focal interictal spikes in the hippocampus during electroencephalographic recordings. This suggests that learning deficiencies and chronic epilepsy may be independent products of recurrent early-life seizures. A quantitative analysis of hippocampus revealed a significant decrease in neuronal density in stratum pyramidale of experimental rats. However, the differences were largely explained by a concomitant increase in the area of stratum pyramidale. Studies of glial fibrillary acidic protein expression and spread of horseradish peroxidase-conjugated tetanus toxin in the hippocampus suggest that the dispersion of cell bodies in stratum pyramidale can neither be explained by a reactive gliosis nor the direct action of the toxin itself.Taken together, we suggest that recurrent seizures beginning in early life can lead to a significant deficiency in spatial learning without ongoing hippocampal synchronized network discharging or a substantial loss of hippocampal pyramidal cells.     

Concurrence of systemic lupus erythematosus and pemphigus: coincidence or correlation?

BACKGROUND: Pemphigus and systemic lupus erythematosus (SLE) have previously been reported to coexist in the same patient. However, the relationship between the 2 diseases has not been elucidated. OBJECTIVE: This review was conducted to examine the relationship between pemphigus and SLE when they occur together in the same patient. METHODS: We conducted a retrospective review of the literature to identify previously reported cases of pemphigus and SLE coexisting in the same patient. The temporal relationship, clinical course, response to therapy and effects of 1 disease on the other were examined. RESULTS: Eight patients with a dual diagnosis of pemphigus and SLE have been previously reported. Most were female and non-Caucasian, with a mean age of 41 years. In the 8 patients reviewed here clinical outcomes, organ system involvement and demographic profiles are more typical of SLE. Seven of these 8 patients had pemphigus vulgaris, and 1 had pemphigus erythematosus. The limited follow-up did not permit studying issues of disease interaction. An additional 17 patients with pemphigus have been reported who have features suggestive of SLE. Organ system involvement in these patients was less typical of SLE. CONCLUSION: It appears that a true dual diagnosis of pemphigus and SLE is less common than suggested by the literature. Comparing patients with only pemphigus or only SLE to those with both may provide insights into genetic predisposition and pathogenesis, and provide an opportunity to study the effects of drugs that influence their course.     

Basaloid carcinoma of the prostate: a case report and review of the literature

Malignant tumours arising from the basal cells of the prostate gland are extremely rare, and the majority of reports in the literature suggest a relatively indolent clinical course. We report a case of infiltrative basaloid carcinoma of the prostate in a 68-year old man that did not respond to systemic chemotherapy. It is essential that this aggressive disease is differentiated from more indolent basaloid proliferations, as metastatic spread can occur and outcome may be poor.     

Effects of prostacyclin and milrinone on pulmonary hemodynamics in newborn lambs with persistent pulmonary hypertension induced by ductal ligation

Prostacyclin (PGI(2)) stimulates adenyl cyclase to synthesize cAMP within the vascular smooth muscle resulting in vasodilatation. Milrinone inhibits cAMP clearance by phosphodiesterase type III. We studied the dose response of pulmonary and systemic hemodynamics to intratracheal (IT) PGI(2) in newborn lambs with pulmonary hypertension (PH) and whether intravenous milrinone potentiate these effects. IT-PGI(2) at varying doses was administered to lambs with PH induced by prenatal ductal ligation. IT-PGI(2) doses were repeated in the presence of intravenous milrinone (bolus-100 microg/kg followed by infusion at 1 microg/kg/min). Increasing doses of IT-PGI(2) significantly decreased mean pulmonary arterial pressures (PAP) and pulmonary vascular resistance (PVR) and increased pulmonary blood flow (PBF). Intravenous milrinone by itself produced a significant reduction in PVR and a significant increase in PBF. Intravenous milrinone significantly shortened the onset, prolonged the duration and degree of pulmonary vasodilation produced by PGI(2). We conclude that intravenous milrinone potentiates the pulmonary vasodilator effects of PGI(2) at lower doses.     

Development and cardiac contractility: cardiac troponin T isoforms and cytosolic calcium in rabbit

Cardiac contractility depends on calcium sensitivity of the myofilaments and cytosolic free calcium concentration ([Ca(2+)](i)) during activation. During development, the cardiac troponin T isoform cTnT(1) is replaced by shorter cTnT isoforms, including cTnT(4), and changes occur in other myofibrillar proteins and in calcium regulation. We expressed rabbit recombinant (r)cTnT(1) and rcTnT(4) in Spodoptera frugiperda cells and determined their effect on calcium binding to TnC in solution and on the calcium sensitivity of myofilaments in skinned rabbit ventricular fibers in vitro. We measured [Ca(2+)](i) and L-type calcium current (I(Ca)) in ventricular myocytes from 3-wk-old and adult rabbits. The dissociation constant (K(d)) of Ca-Tn(cTnT1) in solution was smaller than that of Ca-Tn(cTnT4) (mean +/- SE: 0.52 +/- 0.08 mumol/L versus 0.83 +/- 0.09 mumol/L). The Ca(2+) sensitivity of force development was greater in fibers reconstituted with rcTnT(1) (pCa(50) 6.07 +/- 0.04) than those reconstituted with rcTnT(4) (pCa(50) 5.75 +/- 0.07). Systolic [Ca](i) was lower in 3-wk-old than adult cells (443 +/- 35 nmol/L versus 882 +/- 88 nmol/L) as was I(Ca) (5.8 +/- 0.9 pA/pF versus 14.2 +/- 1.6 pA/pF). The higher calcium sensitivity of Tn-Ca binding and of force development conferred by rcTnT(1) suggest that higher neonatal cTnT(1) expression may partially compensate for the lower systolic [Ca(2+)](i).     

Antigen specificity in subsets of mucous membrane pemphigoid

Mucous membrane pemphigoid (MMP) has several subsets based on target antigens recognized by their sera. MMP and ocular cicatricial pemphigoid (OCP) sera recognize beta4 integrin subunit, oral pemphigoid sera recognize alpha6 integrin subunit, and anti-epiligrin cicatricial pemphigoid sera recognize laminin 5. Our aim is to determine if autoantibodies in the sera of patients with MMP, OCP, and oral pemphigoid (OP) recognize only their target antigens, and to see if this specificity is maintained throughout the clinical course. An immunoblot assay using bovine gingival lysate was used as substrate. Fifteen MMP patients, eight with OCP, and 15 OP patients were studied before therapy and at multiple intervals during the clinical course. Absorption and blocking studies were performed to determine binding specificity. Sera of patients with MMP and OCP recognize only beta4 integrin subunit, and sera of OP patients recognize alpha6 integrin throughout the clinical course. The sera of patients in the subsets of MMP described in this report show adherence and selectivity to target antigen during the entire clinical course, without crossover, interaction, or change. Hence, these subsets of MMP provide an excellent model to study clinical correlation with antigen and antibody specificity, in autoimmunity.