Clonal chromosomal changes in juxta-articular myxoma

 Cytogenetic analysis of a juxta-articular myxoma revealed two distinct cytogenetically abnormal cell populations: inv(2)(p15q36) and +7, t(8;22)(q11–12; q12–13). These clonal chromosomal changes, the first to be reported in this tumour type, suggest that at least some juxta-articular myxomas are neoplastic rather than reactive in nature. Received: 8 June 1998 / Accepted: 17 August 1998     

Corporate response to the HIV/AIDS epidemic in Uganda - time for a paradigm shift?

The HIV/AIDS epidemic is likely to remain the pre-eminent global health concern for the foreseeable future. In Uganda, while significant progress has been made by the government over the past decade in bringing down the rate of new infections, the HIV/AIDS burden in the country remains huge and vigilant efforts must be continued if this burden is to further decrease.

Traditionally the government, supported by its international partners as well as local non-government organizations and the community has borne the brunt of the costs of containing the epidemic in Uganda. While the corporate sector in the country has financially contributed towards the costs of some of the interventions that are currently in place to combat the HIV epidemic, there is largely a paucity of sustained and systematic corporate leadership in providing comprehensive HIV/AIDS programmes for their employees.

A survey done by the authors of this paper reveals that most programmes undertaken in the private sector are of limited scope. We argue that there is more the corporate sector can do to more equitably share the HIV/AIDS burden, without necessarily jeopardizing its primary role - namely to maximize returns to shareholders.

This paper proposes a conceptual framework of how companies can approach the issue of HIV/AIDS within their workforce and suggests that providing more comprehensive interventions may in some instances result in substantial cost savings through the prevention or at least delay of HIV/AIDS related consequences such as: frequent absences from work, erosion of company skills and knowledge through key employee deaths, and the costs of hiring and training replacements etc. This ultimately could result in positive financial returns to those companies that choose to pursue work place led HIV/AIDS control and prevention programmes.

     

Adjunctive alcohol drinking in humans

In an attempt to validate the animal model of adjunctive ethanol drinking in people, human subjects were allowed access to ad lib beer while playing a game that delivered monetary reinforcements on a FI schedule. Subjects exposed to a longer FI schedule drank significantly more than those exposed to a shorter schedule, confirming the prediction made by the animal model. A pattern of ingestion characteristic of adjunctive drinking was also observed in the longer FI condition, providing evidence that ethanol drinking in humans can be schedule-induced.     

A microcomputer-based data acquisition system for continuous recording of feeding and drinking by rats

A monitoring system to continuously record the daily pattern of drinking and eating of rats is described. This system, based on a North Star microcomputer, can record the amount of food ingested with a temporal resolution of +/- 1.0 second and quantitative accuracy within +/- 5%. Drinking behavior is detected using a drinkometer which also has a temporal resolution of +/- 1.0 second. Data are analyzed by computer to determine absolute amounts of consumption and patterns of intake. The patterns of feeding and drinking recorded by this system are similar to those observed using other monitoring devices.     

Effects of microdialysis on brain metabolism in normal and seizure states

The effect of intracranial microdialysis on brain glucose metabolism in control and kainic acid-treated rats was assessed by semi-quantitative [14C]2-deoxyglucose autoradiography. A dialysis fiber loop was implanted into the piriform cortex or a horizontal Vita fiber into the hippocampus, and 24 h later, fibers were perfused with Krebs-Ringer bicarbonate solution before and after injection of kainic acid (16 mg/kg, i.p.) [14C]2-Deoxyglucose was injected i.p. 3 h after the injection of kainic acid. Rats injected with kainic acid were initially lethargic and then proceeded through behavioral phases of staring, "wet-dog shakes", Straub tail, rearing, forepaw clonus, and, in some cases, tonic-clonic convulsions. Three hours after kainic acid, the fiber presence in the piriform cortex enhanced kainic acid-induced metabolic activity in areas adjacent to the fiber assembly, whereas the fiber in hippocampus attenuated kainic acid-induced metabolic activity in areas adjacent to the fiber assembly. The results indicate that intracranial microdialysis alters the already abnormal brain metabolism in a kainic acid-induced seizure state, but has no significant effect in the non-seizure control state.     

The deltaccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe

The chemokine receptor CCR5 is encoded by the CMKBR5 gene located on the p21.3 region of human chromosome 3, and constitutes the major co- receptor for the macrophage-tropic strains of HIV-1. A mutant allele of the CCR5 gene, Delta ccr5 , was shown to provide to homozygotes with a strong resistance against infection by HIV. The frequency of the Delta ccr5 allele was investigated in 18 European populations. A North to South gradient was found, with the highest allele frequencies in Finnish and Mordvinian populations (16%), and the lowest in Sardinia (4%). Highly polymorphic microsatellites (IRI3.1, D3S4579 and IRI3.2, D3S4580 ) located respectively 11 kb upstream and 68 kb downstream of the CCR5 gene deletion were used to determine the haplotype of the chromosomes carrying the Delta ccr5 variant. A strong linkage disequilibrium was found between Delta ccr5 and specific alleles of the IRI3.1 and IRI3.2 microsatellites: >95% of the Delta ccr5 chromosomes carried the IRI3.1-0 allele, while 88% carried the IRI3.2-0 allele. These alleles were found respectively in only 2 or 1.5% of the chromosomes carrying a wild-type CCR5 gene. From these data, it was inferred that most, if not all Delta ccr5 alleles originate from a single mutation event, and that this mutation event probably took place a few thousand years ago in Northeastern Europe. The high frequency of the Delta ccr5 allele in Caucasian populations cannot be explained easily by random genetic drift, suggesting that a selection advantage is or has been associated with homo- or heterozygous carriers of the Delta ccr5 allele.      

Severe stenoses and persistent occlusions of the middle cerebral artery: hemodynamic and metabolic consequences studied by positron tomography

Using positron emission tomography and the 15O continuous inhalation technique, we have measured the regional cerebral blood flow (rCBF) oxygen extraction fraction (rOEF) and oxygen consumption (rCMRO2) of non-infarcted tissue in six patients with either tight stenosis (N = 3) or occlusion (N = 3) of the trunk of the middle cerebral artery (MCA); these arterial lesions were shown to be persistent on late and/or repeated angiograms. The patients were studied 1 to 6 months after their last cerebral ischemic event. The data were analyzed in 4 cm2 regions of interest (fig. 1) and were compared to age-matched control values. Regional right/left ratios were tested for significance individually by comparison to 95 p. 100 confidence limits found in control subjects. We found a significant reduction in mean rCBF in the affected MCA territory; concomitantly, there was a lesser decrease in rCMRO2 significant only in the peri-sylvian area; this was associated with a moderate but significant increase in rOEF in the same areas (Table II, fig. 2 and 3). Individually, the reduction in rCBF and the increased rOEF were significant in 5/6 and 2/6 patients, respectively (Table III). These data indicate that rCBF is decreased distal to persistent hemodynamic MCA obstruction in most patients. This hypoperfusion appears due in part to a mild degree of cerebral ischemia (as demonstrated by the occurrence of "misery perfusion"), indicating inadequate perfusion pressure distal to the MCA obstruction. This was associated with a metabolic depression of the cortex possibly resulting from either neuronal loss, or deactivation (diaschisis), or long-standing hemodynamic local failure or any combination of the three.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of extra-intracranial arterial bypass on cerebral blood flow and oxygen metabolism in humans

Twelve patients, eleven with a carotid obstruction and one with an occlusion of the middle cerebral artery, were studied before and after a successful unilateral extra-intracranial arterial by-pass, (EIAB) using PET and the 15-0 steady-state technique to measure regional cerebral blood flow (CBF), oxygen extraction fraction and oxygen metabolic rate (CMRO2). In the whole group of patients, both CBF and CMRO2 increased significantly on both cerebral hemispheres after EIAB, returning toward control levels defined in age-matched subjects. Mean oxygen extraction fraction, on the other hand, was not affected. Individually, three different effects of EIAB emerged: 1) Alleviation of a state of long standing unilateral "misery-perfusion", as reported earlier; 2) parallel increase of CBF and CMRO2 bilaterally, which appeared due to improvement of a hemodynamic depression of metabolism, the precise mechanism of which remains obscure; 3) Complex, unexpected changes in the CBF-CMRO2 couple again resulting in increases in CMRO2. This metabolic improvement afforded by EIAB in our patients has not been reported before; it suggests that long-standing hemodynamic failure may induce a metabolic depression that is still potentially reversible by surgical revascularization.     

Hybrid Approach to Estimation of Underreporting of Tuberculosis Case Notification in High-Burden Settings With Weak Surveillance Infrastructure: Design and Implementation of an Inventory Study

BackgroundThe greatest risk of infectious disease undernotification occurs in settings with limited capacity to detect it reliably. World Health Organization guidance on the measurement of misreporting is paradoxical, requiring robust, independent systems to assess surveillance rigor. Methods are needed to estimate undernotification in settings with incomplete, flawed, or weak surveillance systems. This study attempted to design a tuberculosis (TB) inventory study that balanced rigor with feasibility for high-need settings.ObjectiveThis study aims to design a hybrid TB inventory study for contexts without World Health Organization preconditions. We estimated the proportion of TB cases that were not reported to the Ministry of Health in 2015. The study sought to describe TB surveillance coverage and quality at different levels of TB care provision. Finally, we aimed to identify structural-, facility-, and provider-level barriers to notification and reasons for underreporting, nonreporting, and overreporting.MethodsRetrospective partial digitalization of paper-based surveillance and facility records preceded deterministic and probabilistic record linkage; a hybrid of health facilities and laboratory census with a stratified sampling of HFs with no capacity to notify leveraged a priori knowledge. Distinct extrapolation methods were applied to the sampled health facilities to estimate bacteriologically confirmed versus clinical TB. In-depth interviews and focus groups were used to identify causal factors responsible for undernotification and test the acceptability of remedies.ResultsThe hybrid approach proved viable and instructive. High-specificity verification of paper-based records in the field was efficient and had minimal errors. Limiting extrapolation to clinical cases improved precision. Probabilistic record linkage is computationally intensive, and the choice of software influences estimates. Record absence, decay, and overestimation of the private sector TB treatment behavior threaten validity, meriting mitigation. Data management demands were underestimated. Treatment success was modest in all sectors (R=37.9%–72.0%) and did not align with treatment success reported by the state (6665/8770, 75.99%). One-fifth of TB providers (36/178, 20%) were doubtful that the low volume of patients with TB treated in their facility merited mastery of the extensive TB notification forms and procedures.ConclusionsSubnational inventory studies can be rigorous, relevant, and efficient in countries that need them even in the absence of World Health Organization preconditions, if precautions are taken. The use of triangulation techniques, with minimal recourse to sampling and extrapolation, and the privileging of practical information needs of local decision makers yield reasonable misreporting estimates and viable policy recommendations.